case presentation of hypertension in pregnancy

Loading metrics

Open Access

Learning Forum

Learning Forum articles are commissioned by our educational advisors. The section provides a forum for learning about an important clinical problem that is relevant to a general medical audience.

See all article types »

A 21-Year-Old Pregnant Woman with Hypertension and Proteinuria

• Andrea Luk,

* To whom correspondence should be addressed. E-mail: [email protected]

• Ching Wan Lam,
• Wing Hung Tam,
• Anthony W. I Lo,
• Enders K. W Ng,
• Alice P. S Kong,
• Wing Yee So,
• Chun Chung Chow
• Andrea Luk, 
• Ronald C. W Ma, 
• Ching Wan Lam, 
• Wing Hung Tam, 
• Anthony W. I Lo, 
• Enders K. W Ng, 
• Alice P. S Kong, 
• Wing Yee So, 

Published: February 24, 2009

• https://doi.org/10.1371/journal.pmed.1000037
• Reader Comments

Citation: Luk A, Ma RCW, Lam CW, Tam WH, Lo AWI, Ng EKW, et al. (2009) A 21-Year-Old Pregnant Woman with Hypertension and Proteinuria. PLoS Med 6(2): e1000037. https://doi.org/10.1371/journal.pmed.1000037

Copyright: © 2009 Luk et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Funding: The authors received no specific funding for this article.

Competing interests: RCWM is Section Editor of the Learning Forum. The remaining authors have declared that no competing interests exist.

Abbreviations: CT, computer tomography; I, iodine; MIBG, metaiodobenzylguanidine; MRI, magnetic resonance imaging; SDH, succinate dehydrogenase; SDHD, succinate dehydrogenase subunit D

Provenance: Commissioned; externally peer reviewed

Description of Case

A 21-year-old pregnant woman, gravida 2 para 1, presented with hypertension and proteinuria at 20 weeks of gestation. She had a history of pre-eclampsia in her first pregnancy one year ago. During that pregnancy, at 39 weeks of gestation, she developed high blood pressure, proteinuria, and deranged liver function. She eventually delivered by emergency caesarean section following failed induction of labour. Blood pressure returned to normal post-partum and she received no further medical follow-up. Family history was remarkable for her mother's diagnosis of hypertension in her fourth decade. Her father and five siblings, including a twin sister, were healthy. She did not smoke nor drink any alcohol. She was not taking any regular medications, health products, or herbs.

At 20 weeks of gestation, blood pressure was found to be elevated at 145/100 mmHg during a routine antenatal clinic visit. Aside from a mild headache, she reported no other symptoms. On physical examination, she was tachycardic with heart rate 100 beats per minute. Body mass index was 16.9 kg/m 2 and she had no cushingoid features. Heart sounds were normal, and there were no signs suggestive of congestive heart failure. Radial-femoral pulses were congruent, and there were no audible renal bruits.

Baseline laboratory investigations showed normal renal and liver function with normal serum urate concentration. Random glucose was 3.8 mmol/l. Complete blood count revealed microcytic anaemia with haemoglobin level 8.3 g/dl (normal range 11.5–14.3 g/dl) and a slightly raised platelet count of 446 × 10 9 /l (normal range 140–380 × 10 9 /l). Iron-deficient state was subsequently confirmed. Quantitation of urine protein indicated mild proteinuria with protein:creatinine ratio of 40.6 mg/mmol (normal range <30 mg/mmol in pregnancy).

What Were Our Differential Diagnoses?

An important cause of hypertension that occurs during pregnancy is pre-eclampsia. It is a condition unique to the gravid state and is characterised by the onset of raised blood pressure and proteinuria in late pregnancy, at or after 20 weeks of gestation [ 1 ]. Pre-eclampsia may be associated with hyperuricaemia, deranged liver function, and signs of neurologic irritability such as headaches, hyper-reflexia, and seizures. In our patient, hypertension developed at a relatively early stage of pregnancy than is customarily observed in pre-eclampsia. Although she had proteinuria, it should be remembered that this could also reflect underlying renal damage due to chronic untreated hypertension. Additionally, her electrocardiogram showed left ventricular hypertrophy, which was another indicator of chronicity.

While pre-eclampsia might still be a potential cause of hypertension in our case, the possibility of pre-existing hypertension needed to be considered. Box 1 shows the differential diagnoses of chronic hypertension, including essential hypertension, primary hyperaldosteronism related to Conn's adenoma or bilateral adrenal hyperplasia, Cushing's syndrome, phaeochromocytoma, renal artery stenosis, glomerulopathy, and coarctation of the aorta.

Box 1: Causes of Hypertension in Pregnancy

• Pre-eclampsia
• Essential hypertension
• Renal artery stenosis
• Glomerulopathy
• Renal parenchyma disease
• Primary hyperaldosteronism (Conn's adenoma or bilateral adrenal hyperplasia)
• Cushing's syndrome
• Phaeochromocytoma
• Coarctation of aorta
• Obstructive sleep apnoea

Renal causes of hypertension were excluded based on normal serum creatinine and a bland urinalysis. Serology for anti-nuclear antibodies was negative. Doppler ultrasonography of renal arteries showed normal flow and no evidence of stenosis. Cushing's syndrome was unlikely as she had no clinical features indicative of hypercortisolism, such as moon face, buffalo hump, violaceous striae, thin skin, proximal muscle weakness, or hyperglycaemia. Plasma potassium concentration was normal, although normokalaemia does not rule out primary hyperaldosteronism. Progesterone has anti-mineralocorticoid effects, and increased placental production of progesterone may mask hypokalaemia. Besides, measurements of renin activity and aldosterone concentration are difficult to interpret as the renin-angiotensin-aldosterone axis is typically stimulated in pregnancy. Phaeochromocytoma is a rare cause of hypertension in pregnancy that, if unrecognised, is associated with significant maternal and foetal morbidity and mortality. The diagnosis can be established by measuring levels of catecholamines (noradrenaline and adrenaline) and/or their metabolites (normetanephrine and metanephrine) in plasma or urine.

What Was the Diagnosis?

Catecholamine levels in 24-hour urine collections were found to be markedly raised. Urinary noradrenaline excretion was markedly elevated at 5,659 nmol, 8,225 nmol, and 9,601 nmol/day in repeated collections at 21 weeks of gestation (normal range 63–416 nmol/day). Urinary adrenaline excretion was normal. Pregnancy may induce mild elevation of catecholamine levels, but the marked elevation of urinary catecholamine observed was diagnostic of phaeochromocytoma. Conditions that are associated with false positive results, such as acute myocardial infarction, congestive heart failure, acute cerebrovascular event, withdrawal from alcohol, withdrawal from clonidine, and cocaine abuse, were not present in our patient.

The working diagnosis was therefore phaeochromocytoma complicating pregnancy. Magnetic resonance imaging (MRI) of neck to pelvis, without gadolinium enhancement, was performed at 24 weeks of gestation. It showed a 4.2 cm solid lesion in the mid-abdominal aorto-caval region, while both adrenals were unremarkable. There were no ectopic lesions seen in the rest of the examined areas. Based on existing investigation findings, it was concluded that she had extra-adrenal paraganglioma resulting in hypertension.

What Was the Next Step in Management?

At 22 weeks of gestation, the patient was started on phenoxybenzamine titrated to a dose of 30 mg in the morning and 10 mg in the evening. Propranolol was added several days after the commencement of phenoxybenzamine. Apart from mild postural dizziness, the medical therapy was well tolerated during the remainder of the pregnancy. In the third trimester, systolic and diastolic blood pressures were maintained to below 90 mmHg and 60 mmHg, respectively. During this period, she developed mild elevation of alkaline phosphatase ranging from 91 to 188 IU/l (reference 35–85 IU/l). However, liver transaminases were normal and the patient had no seizures. Repeated urinalysis showed resolution of proteinuria. At 38 weeks of gestation, the patient proceeded to elective caesarean section because of previous caesarean section, and a live female baby weighing 3.14 kg was delivered. The delivery was uncomplicated and blood pressure remained stable.

Following the delivery, computer tomography (CT) scan of neck, abdomen, and pelvis was performed as part of pre-operative planning to better delineate the relationship of the tumour to neighbouring structures. In addition to the previously identified extra-adrenal paraganglioma in the abdomen ( Figure 1 ), the CT revealed a 9 mm hypervascular nodule at the left carotid bifurcation, suggestive of a carotid body tumour ( Figure 2 ). The patient subsequently underwent an iodine (I) 131 metaiodobenzylguanidine (MIBG) scan, which demonstrated marked MIBG-avidity of the paraganglioma in the mid-abdomen. The reported left carotid body tumour, however, did not demonstrate any significant uptake. This could indicate either that the MIBG scan had poor sensitivity in detecting a small tumour, or that the carotid body tumour was not functional.

• PPT PowerPoint slide
• PNG larger image
• TIFF original image

https://doi.org/10.1371/journal.pmed.1000037.g001

https://doi.org/10.1371/journal.pmed.1000037.g002

In June 2008, four months after the delivery, the patient had a laparotomy with removal of the abdominal paraganglioma. The operation was uncomplicated. There was no wide fluctuation of blood pressures intra- and postoperatively. Phenoxybenzamine and propranolol were stopped after the operation. Histology of the excised tumour was consistent with paraganglioma with cells staining positive for chromogranin ( Figures 3 and 4 ) and synaptophysin. Adrenal tissues were notably absent.

The tumour is a well-circumscribed fleshy yellowish mass with maximal dimension of 5.5 cm.

https://doi.org/10.1371/journal.pmed.1000037.g003

The tumour cells are polygonal with bland nuclei. The cells are arranged in nests and are immunoreactive to chromogranin (shown here) and synaptophysin.

https://doi.org/10.1371/journal.pmed.1000037.g004

The patient was counselled for genetic testing for hereditary phaeochromocytoma/paraganglioma. She was found to be heterozygous for c.449_453dup mutation of the succinate dehydrogenase subunit D (SDHD) gene ( Figure 5 ). This mutation is a novel frameshift mutation, and leads to SDHD deficiency (GenBank accession number: 1162563). At the latest clinic visit in August 2008, she was asymptomatic and normotensive. Measurements of catecholamine in 24-hour urine collections had normalised. Resection of the left carotid body tumour was planned for a later date. She was to be followed up indefinitely to monitor for recurrences. She was also advised to contact family members for genetic testing. Our patient gave written consent for this case to be published.

https://doi.org/10.1371/journal.pmed.1000037.g005

Phaeochromocytoma in Pregnancy

Hypertension during pregnancy is a frequently encountered obstetric complication that occurs in 6%–8% of pregnancies [ 2 ]. Phaeochromocytoma presenting for the first time in pregnancy is rare, and only several hundred cases have been reported in the English literature. In a recent review of 41 cases that presented during 1988 to 1997, maternal mortality was 4% while the rate of foetal loss was 11% [ 3 ]. Antenatal diagnosis was associated with substantial reduction in maternal mortality but had little impact on foetal mortality. Further, chronic hypertension, regardless of aetiology, increases the risk of pre-eclampsia by 10-fold [ 1 ].

Classically, patients with phaeochromocytoma present with spells of palpitation, headaches, and diaphoresis [ 4 ]. Hypertension may be sustained or sporadic, and is associated with orthostatic blood pressure drop because of hypovolaemia and impaired vasoconstricting response to posture change. During pregnancy, catecholamine surge may be triggered by pressure from the enlarging uterus and foetal movements. In the majority of cases, catecholamine-secreting tumours develop in the adrenal medulla and are termed phaeochromocytoma. Ten percent of tumours arise from extra-adrenal chromaffin tissues located in the abdomen, pelvis, or thorax to form paraganglioma that may or may not be biochemically active. The malignant potential of phaeochromocytoma or paraganglioma cannot be determined from histology and is inferred by finding tumours in areas of the body not known to contain chromaffin tissues. The risk of malignancy is higher in extra-adrenal tumours and in tumours that secrete dopamine.

Making the Correct Diagnosis

The diagnosis of phaeochromocytoma requires a combination of biochemical and anatomical confirmation. Catecholamines and their metabolites, metanephrines, can be easily measured in urine or plasma samples. Day collection of urinary fractionated metanephrine is considered the most sensitive in detecting phaeochromocytoma [ 5 ]. In contrast to sporadic release of catecholamine, secretion of metanephrine is continuous and is less subjective to momentary stress. Localisation of tumour can be accomplished by either CT or MRI of the abdomen [ 6 ]. Sensitivities are comparable, although MRI is preferable in pregnancy because of minimal radiation exposure. Once a tumour is identified, nuclear medicine imaging should be performed to determine its activity, as well as to search for extra-adrenal diseases. I 131 or I 123 MIBG scan is the imaging modality of choice. Metaiodobenzylguanidine structurally resembles noradrenaline and is concentrated in chromaffin cells of phaeochromocytoma or paraganglioma that express noradrenaline transporters. Radionucleotide imaging is contraindicated in pregnancy and should be deferred until after the delivery.

Treatment Approach

Upon confirming the diagnosis, medical therapy should be initiated promptly to block the cardiovascular effects of catecholamine release. Phenoxybenzamine is a long-acting non-selective alpha-blocker commonly used in phaeochromocytoma to control blood pressure and prevent cardiovascular complications [ 7 ]. The main side-effects of phenoxybenzamine are postural hypotension and reflex tachycardia. The latter can be circumvented by the addition of a beta-blocker. It is important to note that beta-blockers should not be used in isolation, since blockade of ß2-adrenoceptors, which have a vasodilatory effect, can cause unopposed vasoconstriction by a1-adrenoceptor stimulation and precipitate severe hypertension. There is little data on the safety of use of phenoxybenzamine in pregnancy, although its use is deemed necessary and probably life-saving in this precarious situation.

The definitive treatment of phaeochromocytoma or paraganglioma is surgical excision. The timing of surgery is critical, and the decision must take into consideration risks to the foetus, technical difficulty regarding access to the tumour in the presence of a gravid uterus, and whether the patient's symptoms can be satisfactorily controlled with medical therapy [ 8 , 9 ]. It has been suggested that surgical resection is reasonable if the diagnosis is confirmed and the tumour identified before 24 weeks of gestation. Otherwise, it may be preferable to allow the pregnancy to progress under adequate alpha- and beta-blockade until foetal maturity is reached. Unprepared delivery is associated with a high risk of phaeochromocytoma crisis, characterised by labile blood pressure, tachycardia, fever, myocardial ischaemia, congestive heart failure, and intracerebral bleeding.

Patients with phaeochromocytoma or paraganglioma should be followed up for life. The rate of recurrence is estimated to be 2%–4% at five years [ 10 ]. Assessment for recurrent disease can be accomplished by periodic blood pressure monitoring and 24-hour urine catecholamine and/or metanephrine measurements.

Genetics of Phaeochromocytoma

Approximately one quarter of patients presenting with phaeochromocytoma may carry germline mutations, even in the absence of apparent family history [ 11 ]. The common syndromes of hereditary phaeochromocytoma/paraganglioma are listed in Box 2 . These include Von Hippel-Lindau syndrome, multiple endocrine neoplasia type 2, neurofibromatosis type 1, and succinate dehydrogenase (SDH) gene mutations. Our patient has a novel frameshift mutation in the SDHD gene located at Chromosome 11q. SDH is a mitochondrial enzyme that is involved in oxidative phosphorylation. Characteristically, SDHD mutation is associated with head or neck non-functional paraganglioma, and infrequently, sympathetic paraganglioma or phaeochromocytoma [ 12 ]. Tumours associated with SDHD mutation are rarely malignant, in contrast to those arisen from mutation of the SDHB gene. Like all other syndromes of hereditary phaeochromocytoma, SDHD mutation is transmitted in an autosomal dominant fashion. However, not all carriers of the SDHD mutation develop tumours, and inheritance is further complicated by maternal imprinting in gene expression. While it may not be practical to screen for genetic alterations in all cases of phaeochromocytoma, most authorities advocate genetic screening for patients with positive family history, young age of tumour onset, co-existence with other neoplasms, bilateral phaeochromocytoma, and extra-adrenal paraganglioma. The confirmation of genetic mutation should prompt evaluation of other family members.

Box 2: Hereditary Phaeochromocytoma/Paraganglioma Syndromes

• Von Hippel-Lindau syndrome
• Multiple endocrine neoplasia type 2A and type 2B
• Neurofibromatosis type 1
• Mutation of SDHB , SDHC , SDHD
• Ataxia-telangiectasia
• Tuberous sclerosis
• Sturge-Weber syndrome

Key Learning Points

• Hypertension complicating pregnancy is a commonly encountered medical condition.
• Pre-existing chronic hypertension must be considered in patients with hypertension presenting in pregnancy, particularly if elevation of blood pressure is detected early during pregnancy or if persists post-partum.
• Secondary causes of chronic hypertension include renal artery stenosis, renal parenchyma disease, primary hyperaldosteronism, phaeochromocytoma, Cushing's syndrome, coarctation of the aorta, and obstructive sleep apnoea.
• Phaeochromocytoma presenting during pregnancy is rare but carries high rates of maternal and foetal morbidity and mortality if unrecognised.
• Successful outcomes depend on early disease identification, prompt initiation of alpha- and beta-blockers, carefully planned delivery, and timely resection of the tumour.

Phaeochromocytoma complicating pregnancy is uncommon. Nonetheless, in view of the potential for catastrophic consequences if unrecognised, a high index of suspicion and careful evaluation for secondary causes of hypertension is of utmost importance. Blood pressure should be monitored in the post-partum period and persistence of hypertension must be thoroughly investigated.

Author Contributions

All authors participated in the management of the patient or writing of the article. AL and RCWM wrote the article, with contributions from all the authors.

• View Article
• Google Scholar

NARGES FARAHI, MD, FAREEDAT OLUYADI, MD, AND ANDREA B. DOTSON, MD, MSPH

Am Fam Physician. 2024;109(3):251-260

Author disclosure: No relevant financial relationships.

Hypertensive disorders of pregnancy are a major contributor to maternal morbidity and mortality in the United States and include chronic and gestational hypertension, preeclampsia, HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome, eclampsia, and chronic hypertension with superimposed preeclampsia. For patients with chronic hypertension, oral antihypertensive therapy should be initiated or titrated at a blood pressure threshold of 140/90 mm Hg or greater. Gestational hypertension and preeclampsia without severe features can be managed with blood pressure monitoring, laboratory testing for disease progression, antenatal testing for fetal well-being, and delivery at 37 weeks' gestation. The use of antihypertensive drugs to control nonsevere hypertension in the setting of gestational hypertension and preeclampsia does not improve outcomes and is not recommended. Antihypertensive therapy should be initiated expeditiously for acute-onset severe hypertension to prevent hemorrhagic stroke. Preeclampsia with severe features requires immediate stabilization and inpatient treatment with magnesium sulfate for seizure prophylaxis and antenatal corticosteroids (if preterm). Patients in the preterm period should receive antenatal corticosteroids without delaying delivery to complete courses. Hypertensive disorders of pregnancy can worsen or initially present after delivery and account for up to 44% of pregnancy-related deaths in the first six days postpartum. Patients should be monitored closely in the early postpartum period. Hypertensive disorders of pregnancy are linked to poor long-term maternal and fetal outcomes, including increased maternal lifetime risk of cardiovascular disease. Daily low-dose aspirin therapy starting at 12 to 16 weeks' gestation is safe and effective for reducing the risk of preeclampsia for patients with risk factors.

Hypertensive disorders of pregnancy affect 1 in 7 hospital deliveries in the United States, are strongly associated with maternal complications, and account for 7% of pregnancy-related deaths. 1 – 3 Hypertensive disorders of pregnancy, which include chronic hypertension and pregnancy-associated hypertension (gestational hypertension, preeclampsia, HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome, eclampsia, chronic hypertension with superimposed preeclampsia), increased in prevalence from 2017 to 2019. 1 , 4 Pregnancy-associated hypertension more than doubles the risk of peripartum coronary disease, cardiomyopathy, and stroke, and accounts for 44% of maternal deaths in the first six days following delivery. 4 – 6

Preeclampsia is a multisystem disease process with pathogenesis involving maternal and placental pathways. 2 , 5 Nonmodifiable risk factors for developing hypertensive disorders of pregnancy include genetic factors; reproductive history, including in vitro fertilization; and certain patient demographics. 4 , 6 Modifiable risk factors for preeclampsia reflect cardiovascular risk and include obesity, dyslipidemia, diabetes mellitus, kidney disease, and chronic hypertension. 2 , 5 , 7 , 8 Placental influences begin in early pregnancy with abnormal placentation and spiral artery remodeling, leading to decreased uteroplacental perfusion and oxidative stress. 6 , 7 , 9 , 10 Pregnancy, a natural cardiac stress test, can also reveal underlying endothelial dysfunction. 6 , 7

There are significant racial and ethnic disparities in the prevalence of hypertensive disorders of pregnancy. Non-Hispanic Black women have an up to five times higher risk of preeclampsia compared with non-Hispanic White women, are more likely to experience complications from hypertensive disorders of pregnancy, and have a threefold increased risk of inpatient maternal mortality after risk factor adjustment. 1 , 4 , 11 , 12 Multiple factors likely contribute to these disparities, including a higher prevalence of risk factors, less access to care, lower-quality care, underrepresentation in research, racial bias in health care, and the physiologic effect of stress from racism. 1 , 5 , 13 – 15

Hypertensive disorders of pregnancy span the entire reproductive period from preconception to postpartum ( Figure 1 ) . Chronic hypertension can present before pregnancy, before 20 weeks' gestation, or during pregnancy without resolving postpartum. 4 , 16 Preeclampsia refers to new-onset hypertension after 20 weeks' gestation with proteinuria or end-organ dysfunction. Gestational hypertension describes new-onset hypertension after 20 weeks without proteinuria or end-organ dysfunction. When a patient with gestational hypertension or preeclampsia has severe-range blood pressure (160 mm Hg or greater systolic or 110 mm Hg or greater diastolic on at least two measurements) or end-organ involvement, the diagnosis shifts to preeclampsia with severe features. 7 Superimposed preeclampsia is when a person with chronic hypertension has new-onset proteinuria or severe features, including acutely worsening or resistant hypertension. HELLP syndrome is a severe form of preeclampsia that involves hemolysis, liver dysfunction, and thrombocytopenia. 7 Table 1 describes diagnostic criteria for hypertensive disorders of pregnancy. 4 , 7 , 16 , 17

CHRONIC HYPERTENSION

The diagnostic threshold for hypertension in pregnancy is a systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater on two measurements at least four hours apart. Severe-range blood pressure quickly confirms the diagnosis, and treatment should be expedited. 4 One study found that pregnant women with a systolic blood pressure of 130 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg are at greater risk of gestational diabetes, preterm birth, and infant neonatal intensive care admissions compared with those who have normal blood pressure. 18 , 19 Although 20 weeks' gestation is conventionally used to distinguish chronic from gestational hypertension, a retrospective study found that 39% of patients with normal blood pressure before pregnancy developed hypertension without proteinuria before 20 weeks that resolved postpartum. Of patients with chronic hypertension, up to 50% develop superimposed preeclampsia. 4 , 11

GESTATIONAL HYPERTENSION AND PREECLAMPSIA

Pregnancy-associated hypertension represents a spectrum of illnesses that have an onset after 20 weeks' gestation. Screening recommendations focus on blood pressure monitoring during pregnancy. 20 Biomarkers and uterine artery Doppler ultrasonography have limited use in predicting preeclampsia. 2 , 7 Gestational hypertension with severe-range blood pressure has the same risk as preeclampsia with severe features and should be treated accordingly. 4 Up to one-half of women with gestational hy pertension develop preeclampsia, and the risk is higher when gestational hypertension presents before 32 weeks. 7

HELLP SYNDROME

HELLP syndrome is a severe form of preeclampsia associated with high morbidity and mortality. Malaise and right upper quadrant pain occur in 90% of patients with HELLP. Rapid clinical deterioration is a characteristic of HELLP. All components of the diagnostic criteria are necessary and distinguish HELLP from conditions such as preeclampsia complicated by disseminated intravascular coagulation, acute fatty liver disease of pregnancy, or thrombotic thrombocytopenic purpura. Additionally, 15% of patients with HELLP do not have hypertension or proteinuria, and up to one-third present in the postpartum period. 7 , 21

Eclampsia is a new-onset tonic-clonic, focal, or multifocal seizure in a pregnant or postpartum patient with a hypertensive disorder of pregnancy and without an alternative diagnosis for seizure. Eclampsia is a primary cause of maternal death globally. 7 One-half of eclampsia cases present before labor, with the other half presenting in the intrapartum or postpartum period. Eclamptic seizures can occur without warning; however, 80% are preceded by neurologic symptoms, including headaches, visual disturbances, and altered cognition. 22

POSTPARTUM HYPERTENSION

Although preeclampsia typically begins to resolve after delivery, patients can experience significant hypertension-related morbidity and mortality postpartum, especially in the first 48 hours following delivery. Postpartum hypertension is most common in patients with hypertension during pregnancy but can develop as new-onset hypertension or preeclampsia up to six weeks after delivery. 7 , 17 Notably, 1 in 5 eclamptic seizures initially presents postpartum, and 15% occur before preeclampsia is recognized. 22

Evaluation and Management

Evaluation and management of hypertensive disorders of pregnancy are summarized in Table 2 . 4 , 7 , 11 , 16 , 23 – 27

When hypertension is diagnosed before 20 weeks' gestation, cardiac function is a primary concern. Patients with long-standing hypertension (typically 10 years or longer but depends on severity and age at onset) are at risk of heart disease, including hypertrophy, cardiomegaly, and ischemic disease. Clinical evaluation includes a cardiovascular examination for potential cardiac dysfunction. Electrocardiography is recommended for patients older than 30 years and those with at least four years of poorly controlled disease. Echocardiography is warranted if electrocardiography findings are abnormal. 4 A baseline laboratory evaluation at the initial prenatal visit or after diagnosis should include a urine protein/creatinine ratio or 24-hour urine protein measurement, complete blood count, and serum creatinine, blood urea nitrogen, serum potassium, aspartate transaminase, and alanine transaminase testing. 4

Oral antihypertensive therapy should be initiated or titrated when blood pressure is 140/90 mm Hg or greater. A treatment threshold of 140/90 mm Hg reduces adverse pregnancy outcomes compared with 160/105 mm Hg (number needed to treat [NNT] = 15; 95% CI, 9.4 to 33.7) without affecting fetal growth. 11 Treatment for a systolic blood pressure of 130 to 139 mm Hg or diastolic blood pressure of 80 to 89 mm Hg may be appropriate when patients have underlying cardiovascular comorbidities. 4 Labetalol and extended-release nifedipine are first-line oral medications for chronic hypertension in pregnancy. 4 , 11 Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers should be avoided because of their teratogenic effects. Thiazide diuretics may be continued when used before pregnancy and can be added as second-or third-line medications ( Table 3 ) . 4 , 16

Chronic hypertension is associated with fetal growth restriction, and thus third-trimester ultrasonography is recommended. 4 Subsequent ultrasonography may be recommended based on the initial growth assessment. Antenatal fetal testing with a nonstress test, biophysical profile, or modified biophysical profile, including a nonstress test and an assessment of amniotic fluid volume, is recommended for patients with chronic hypertension requiring medications or associated with conditions affecting fetal outcomes. 3 , 23 For patients with chronic hypertension requiring medications, weekly antenatal testing starting at 32 weeks' gestation is recommended. 23 Timing of delivery should be based on a balance of maternal, fetal, and neonatal risks and range from 37 to 39 weeks' gestation for uncomplicated chronic hypertension. 4 , 16

GESTATIONAL HYPERTENSION AND PREECLAMPSIA WITHOUT SEVERE FEATURES

After the initial diagnosis, the evaluation for patients with gestational hypertension and preeclampsia without severe features includes at least weekly office visits with blood pressure monitoring, symptom assessment, urine protein measurement to assess for preeclampsia, and laboratory evaluation to assess for severe features. 7 Although there are limited data for the timing and interval of antenatal fetal surveillance, testing is recommended because of the risk of fetal growth restriction and death. The American College of Obstetricians and Gynecologists suggests fetal testing once or twice per week and weekly assessment of amniotic fluid volume. 7 , 23 Growth ultrasonography is recommended at diagnosis and every three to four weeks. In contrast with chronic hypertension, the use of antihypertensive drugs for nonsevere hypertension does not alter disease progression or improve outcomes and is not recommended. 7 Delivery is recommended at 37 weeks' gestation or at the time of diagnosis if after 37 weeks. 7 , 24

PREECLAMPSIA WITH SEVERE FEATURES

Preeclampsia with severe features is associated with significant morbidity and rapid disease progression, and inpatient management is required from diagnosis until after delivery. When severe features are diagnosed at 34 weeks' gestation or later, delivery is recommended after maternal stabilization. 7 If severe features are diagnosed before 34 weeks' gestation, inpatient expectant management can be considered with serial maternal and fetal surveillance to delay delivery to 34 weeks. Progression to delivery is recommended if maternal or fetal status deteriorates 7 , 24 ( Table 4 7 ) .

Due to the risk of cardiac events, renal injury, and ischemic or hemorrhagic stroke, antihypertensive therapy should be initiated within 30 to 60 minutes if acute-onset severe hypertension persists for 15 minutes. 4 , 7 First-line treatments for acute severe hypertension include intravenous labetalol, intravenous hydralazine, and oral immediate-release nifedipine, which is particularly useful when intravenous access has not been established 7 ( Table 3 4 , 16 ) .

Magnesium sulfate helps prevent eclamptic seizures (NNT = 100) and placental abruption (NNT = 100) in preeclampsia with severe features. 25 For patients who have preeclampsia with severe features, intravenous magnesium sulfate is initiated with a loading dose of 4 to 6 g followed by a maintenance infusion of 1 to 2 g per hour. Close monitoring of respiratory status, urine output, mental status, and reflexes is required to assess for potential magnesium toxicity. 7 , 24 Early signs of toxicity include the loss of deep tendon reflexes, and severe toxicity can present with respiratory depression, apnea, and cardiac arrest. 7 , 24 , 25

For patients with HELLP syndrome, delivery at a tertiary care center is recommended at the time of diagnosis. 7 , 21 Just as magnesium sulfate is used for preeclampsia with severe features, it should be initiated for seizure prophylaxis. 24 A Cochrane review including limited studies of high-dose steroids found that they were not beneficial for HELLP syndrome. 28 Laboratory testing (complete blood count, lactate dehydrogenase, blood urea nitrogen, creatinine, aspartate transaminase, alanine transaminase) should be performed at least every 12 hours and continued postpartum until levels improve or stabilize. 7

Treatment of eclampsia includes protecting the maternal airway, avoiding injury, and promptly initiating magnesium sulfate. Compared with other anticonvulsants, magnesium sulfate is more effective for treating eclamptic seizures, preventing recurrent seizures, and decreasing mortality. The addition of other medications is not beneficial. For patients who received a loading dose of magnesium sulfate for prophylaxis, an additional 24-g bolus should be administered after a seizure. For other patients, a loading dose of 4 to 6 g should be administered over 20 minutes. 7 , 25

Mode of Delivery

Vaginal delivery is preferred for patients with chronic hypertension, gestational hypertension, and preeclampsia without severe features in the absence of specific indications for cesarean delivery. 7 For patients who have preeclampsia with severe features, induction of labor is a reasonable option; however, cesarean delivery rates of up to 97% for patients less than 28 weeks' gestation and 65% for patients 28 to 32 weeks' gestation have been reported. Decisions about the mode of delivery for patients remote from term should be individualized based on gestational age, disease progression, and fetal status. 7 Although antenatal corticosteroids are recommended before 34 weeks' gestation and can be considered before 37 weeks, in preeclampsia with severe features, delivery should not be delayed to complete steroid administration. 26 , 27

Postpartum Care

After delivery, most people with preeclampsia experience diuresis, lower blood pressure, and general improvement. Magnesium sulfate should be continued for 24 hours postpartum. Hypertension may worsen while third-space fluid returns to the vasculature and can peak three to six days postpartum. 17 , 29 Close monitoring and outpatient follow-up within the first seven to 10 days is recommended for patients with gestational hypertension or preeclampsia. 29 Home blood pressure monitoring may increase the likelihood of obtaining blood pressure measurements at the recommended time, reduce hypertension-related hospital readmissions, and narrow disparities in adherence to postpartum follow-up. 30

Antihypertensive medications administered postpartum should be started or titrated to maintain a systolic blood pressure of less than 150 mm Hg and a diastolic blood pressure of less than 100 mm Hg to prevent the development of severe hypertension. 24 , 31 Antihypertensive medications are safe during lactation, although thiazides may decrease milk volume. 4 , 16 , 17 Treatment of acute-onset severe hypertension follows the same protocols after delivery 7 ( Table 3 4 , 16 ) . All postpartum patients should receive information about hypertensive warning signs before discharge. 7 , 17

Aspirin therapy is a safe and effective risk-reduction strategy in patients with risk factors for developing preeclampsia 5 , 8 , 32 , 33 ( Table 5 34 ) . In these patients, daily low-dose aspirin (81 mg) lowers the likelihood of developing preeclampsia by 15% and decreases the risk of preterm birth, small-for-gestational-age infants, and perinatal mortality. 5 , 8 , 35 Aspirin should be initiated after 12 weeks' gestation (optimally before 16 weeks) and continued until delivery. 5 , 7 Calcium supplementation may decrease the risk of preeclampsia, particularly for patients with low-calcium diets; however, high-quality evidence is lacking. 9 , 33

Hypertensive disorders of pregnancy are associated with short- and long-term maternal and fetal complications. 2 , 5 – 7 , 11 , 16 , 36 , 37 There is also a risk of recurrence in subsequent pregnancies. 36 , 37 Fetal and neonatal complications include low-birth-weight infants, preterm delivery, perinatal mortality, congenital malformations, and cognitive issues in childhood and beyond. 5 , 16 , 37 Studies suggest there is an increased risk of hypertension, obesity, and cardiovascular disease (CVD) in infants that extends into adulthood. 6

People who have had hypertensive disorders of pregnancy have twice the risk of CVD throughout their lifetime compared with patients who have not, and an increased risk of stroke, heart failure, and kidney disease. 5 , 7 , 11 , 36 – 38 Patients with pregnancy-associated hypertension have a fivefold greater lifetime risk of hypertension and are diagnosed an average of 10 years younger than patients without pregnancy-associated hypertension. 2 , 7 These risks are higher with recurrent preeclampsia or more severe manifestations. 7 , 16 , 38 One explanation is that underlying endothelial dysfunction predisposes patients to hypertensive disorders of pregnancy and CVD. Physiologic stress of pregnancy and cardiovascular changes associated with hypertensive disorders of pregnancy may cause cellular remodeling that contributes to future CVD. 2

Postpartum counseling should emphasize the importance of ongoing primary care because of the risk of future CVD. Regular health care visits should include blood pressure monitoring, the evaluation for and treatment of comorbidities such as high cholesterol, diabetes, and tobacco use, and ongoing education about a healthy lifestyle (e.g., stress reduction, sleep hygiene, weight management). 37 – 39

This article updates previous articles on this topic by Leeman, et al. 40 ; Leeman and Fontaine 41 ; Wagner 42 ; and Padden . 43

Data Sources: PubMed searches were conducted using the key words hypertensive disorders of pregnancy, hypertension, pregnancy-induced, chronic hypertension in pregnancy, preeclampsia, and eclampsia. We used an evidence summary generated by Essential Evidence Plus with the key words hypertension, pregnancy-induced, preeclampsia, and eclampsia. We searched the Cochrane database and U.S. Preventive Services Task Force recommendations using the key words preeclampsia and hypertensive disorders of pregnancy. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. Whenever possible, if studies used race or gender as patient categories but did not define how these categories were assigned, they were not included in our final references. If studies that used these categories were determined to be essential and therefore included, limitations were stated or explanations provided in the manuscript. Search dates: December 22, 2022; January 9, 2023; February 20, 2023; and December 28, 2023.

Ford ND, Cox S, Ko JY, et al. Hypertensive disorders in pregnancy and mortality at delivery hospitalization - United States, 2017–2019. MMWR Morb Mortal Wkly Rep. 2022;71(17):585-591.

Garovic VD, Dechend R, Easterling T, et al. Hypertension in pregnancy: diagnosis, blood pressure goals, and pharmacotherapy: a scientific statement from the American Heart Association [published correction appears in Hypertension . 2022; 79(3): e70]. Hypertension. 2022;79(2):e21-e41.

Creanga AA, Syverson C, Seed K, et al. Pregnancy-related mortality in the United States, 2011–2013. Obstet Gynecol. 2017;130(2):366-373.

American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin no. 203: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133(1):e26-e50.

Henderson JT, Vesco KK, Senger CA, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: updated evidence report and systematic review for the U.S. Preventive Services Task Force. JAMA. 2021;326(12):1192-1206.

Cameron NA, Everitt I, Seegmiller LE, et al. Trends in the incidence of new-onset hypertensive disorders of pregnancy in the United States, 2007 to 2019. J Am Heart Assoc. 2022;11(2):e023791.

Gestational hypertension and preeclampsia. ACOG practice bulletin no. 222. Obstet Gynecol. 2020;135(6):e237-e260.

Bartsch E, Medcalf KE, Park AL, et al.; High Risk of Pre-eclampsia Identification Group. Clinical risk factors for pre-eclampsia determined in early pregnancy. BMJ. 2016;353:i1753.

Hofmeyr GJ, Manyame S, Medley N, et al. Calcium supplementation commencing before or early in pregnancy, for preventing hypertensive disorders of pregnancy. Cochrane Database Syst Rev. 2019(9):CD011192.

Ives CW, Sinkey R, Rajapreyar I, et al. Preeclampsia-pathophysiology and clinical presentations. J Am Coll Cardiol. 2020;76(14):1690-1702.

Tita AT, Szychowski JM, Boggess K, et al.; Chronic Hypertension and Pregnancy Trial Consortium. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386(19):1781-1792.

Shahul S, Tung A, Minhaj M, et al. Racial disparities in comorbidities, complications, and maternal and fetal outcomes in women with preeclampsia/eclampsia. Hypertens Pregnancy. 2015;34(4):506-515.

Howell EA. Reducing disparities in severe maternal morbidity and mortality. Clin Obstet Gynecol. 2018;61(2):387-399.

Petersen EE, Davis NL, Goodman D, et al. Vital signs: pregnancy-related deaths, United States, 2011–2015, and strategies for prevention, 13 states, 2013–2017. MMWR Morb Mortal Wkly Rep. 2019;68(18):423-429.

Puia-Dumitrescu M, Greenberg RG, Younge N, et al. Disparities in the use of antenatal corticosteroids among women with hypertension in North Carolina. J Perinatol. 2020;40(3):456-462.

Battarbee AN, Sinkey RG, Harper LM, et al. Chronic hypertension in pregnancy. Am J Obstet Gynecol. 2020;222(6):532-541.

Hauspurg A, Jeyabalan A. Postpartum preeclampsia or eclampsia: defining its place and management among the hypertensive disorders of pregnancy. Am J Obstet Gynecol. 2022;226(2S):S1211-S1221.

Greenberg VR, Silasi M, Lundsberg LS, et al. Perinatal outcomes in women with elevated blood pressure and stage 1 hypertension. Am J Obstet Gynecol. 2021;224(5):521.e1-521.e11.

Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines [published correction appears in Hypertension . 2018; 71(6): e140–e144]. Hypertension. 2018;71(6):e13-e115.

Barry MJ, Nicholson WK, Silverstein M, et al. Screening for hypertensive disorders of pregnancy: U.S. Preventive Services Task Force final recommendation statement. JAMA. 2023;330(11):1074-1082.

Sibai BM. Diagnosis, controversies, and management of the syndrome of hemolysis, elevated liver enzymes, and low platelet count. Obstet Gynecol. 2004;103(5 pt 1):981-991.

Mattar F, Sibai BM. Eclampsia. VIII. Risk factors for maternal morbidity. Am J Obstet Gynecol. 2000;182(2):307-312.

Indications for outpatient antenatal fetal surveillance: ACOG Committee Opinion Summary no. 828. Obstet Gynecol. 2021;137(6):1148-1151.

Hypertension in pregnancy: diagnosis and management. NICE guideline no. 133. National Institute for Health and Care Excellence. 2019.

Duley L, Gülmezoglu AM, Henderson-Smart DJ, et al. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010(11):CD000025.

Committee on Obstetric Practice. Committee opinion no. 713: antenatal corticosteroid therapy for fetal maturation. Obstet Gynecol. 2017;130(2):e102-e109.

Gyamfi-Bannerman C, Thom EA, Blackwell SC, et al.; NICHD Maternal–Fetal Medicine Units Network. Antenatal betamethasone for women at risk for late preterm delivery [published correction appears in N Engl J Med . 2023; 388(18): 1728]. N Engl J Med. 2016;374(14):1311-1320.

Woudstra DM, Chandra S, Hofmeyr GJ, et al. Corticosteroids for HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome in pregnancy. Cochrane Database Syst Rev. 2010(9):CD008148.

Bernstein PS, Martin JN, Barton JR, et al. National Partnership for Maternal Safety: consensus bundle on severe hypertension during pregnancy and the postpartum period [published correction appears in Obstet Gynecol . 2019; 133(6): 1288]. Obstet Gynecol. 2017;130(2):347-357.

Steele DW, Adam GP, Saldanha IJ, et al. Management of Postpartum Hypertensive Disorders of Pregnancy . Agency for Healthcare Research and Quality; May 2023.

Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on hypertension in pregnancy. Obstet Gynecol. 2013;122(5):1122-1131.

Richards EMF, Giorgione V, Stevens O, et al. Low-dose aspirin for the prevention of superimposed preeclampsia in women with chronic hypertension. Am J Obstet Gynecol. 2023;228(4):395-408.

Liu YH, Zhang YS, Chen JY, et al. Comparative effectiveness of prophylactic strategies for preeclampsia: a network meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2023;228(5):535-546.

U.S. Preventive Services Task Force. Aspirin use to prevent preeclampsia and related morbidity and mortality: preventive medication. September 28, 2021. Accessed January 8, 2024. https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/low-dose-aspirin-use-for-the-prevention-of-morbidity-and-mortality-from-preeclampsia-preventive-medication

Davidson KW, Barry MJ, Mangione CM, et al. Aspirin use to prevent preeclampsia and related morbidity and mortality: US Preventive Services Task Force Recommendation statement. JAMA. 2021;326(12):1186-1191.

Brouwers L, van der Meiden-van Roest AJ, Savelkoul C, et al. Recurrence of pre-eclampsia and the risk of future hypertension and cardiovascular disease. BJOG. 2018;125(13):1642-1654.

Brown MA, Magee LA, Kenny LC, et al.; International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24-43.

Magee LA, Brown MA, Hall DR, et al. The 2021 International Society for the Study of Hypertension in Pregnancy classification, diagnosis & management recommendations for international practice. Pregnancy Hypertens. 2022;27:148-169.

Behrens I, Basit S, Melbye M, et al. Risk of post-pregnancy hypertension in women with a history of hypertensive disorders of pregnancy: nationwide cohort study. BMJ. 2017;358:j3078.

Leeman L, Dresang LT, Fontaine P. Hypertensive disorders of pregnancy. Am Fam Physician. 2016;93(2):121-127.

Leeman L, Fontaine P. Hypertensive disorders of pregnancy. Am Fam Physician. 2008;78(1):93-100.

Wagner LK. Diagnosis and management of preeclampsia. Am Fam Physician. 2004;70(12):2317-2324.

Padden MO. HELLP syndrome: recognition and perinatal management. Am Fam Physician. 1999;60(3):829-839.

Continue Reading

More in AFP

Copyright © 2024 by the American Academy of Family Physicians.

This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP.  See permissions  for copyright questions and/or permission requests.

Copyright © 2024 American Academy of Family Physicians. All Rights Reserved.

Hypertension in Pregnancy

• Diagnosis |
• Treatment |
• Key Points |

Recommendations regarding classification, diagnosis, and management of hypertensive disorders (including preeclampsia) are available from the American College of Obstetricians and Gynecologists (ACOG [ 1 ]).

(See also Hypertension .)

In 2017, the American College of Cardiology (ACC) and the American Heart Association (AHA) released new guidelines for the evaluation of high blood pressure (BP). They lowered the definitions for hypertension as follows:

Elevated: 120 to 129/

Stage 1 hypertension: 130 to 139/80 to 89 mm Hg

Stage 2 hypertension: ≥ 140/90 mm Hg

ACOG defines chronic hypertension as systolic BP ≥ 140 mm Hg or diastolic BP ≥ 90 mm Hg on 2 occasions before 20 weeks gestation. Data on the effect of hypertension as defined by the ACC/AHA during pregnancy are limited. Thus, pregnancy management is likely to evolve.

Hypertension during pregnancy can be classified as one of the following:

Chronic: BP is high before pregnancy or before 20 weeks gestation. Chronic hypertension complicates about 1 to 5% of all pregnancies.

Gestational: Hypertension develops after 20 weeks gestation (typically after 37 weeks) and remits by 6 weeks postpartum; it occurs in about 5 to 10% of pregnancies, more commonly in multifetal pregnancy .

Both types of hypertension increase risk of preeclampsia and eclampsia and of other causes of maternal mortality or morbidity, including

Hypertensive encephalopathy

Renal failure

Left ventricular failure

HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count)

Risk of fetal mortality or morbidity increases because of decreased uteroplacental blood flow, which can cause vasospasm, growth restriction, hypoxia, and placental abruption. Outcomes are worse if hypertension is severe (systolic BP ≥ 160 mm Hg, diastolic BP ≥ 110 mm Hg, or both) or accompanied by renal insufficiency (eg, creatinine clearance < 60 mL/min, serum creatinine > 2 mg/dL [ > 180 μ mol/L]).

General reference

1. American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy : Hypertension in pregnancy. Report of the American College of Obstetricians and Gynecologists’ Task Force on Hypertension in Pregnancy. Obstet Gynecol 122 (5):1122–1131, 2013. doi: 10.1097/01.AOG.0000437382.03963.88

Diagnosis of Hypertension in Pregnancy

Tests to rule out other causes of hypertension

Blood pressure is measured routinely at prenatal visits. If severe hypertension occurs for the first time in pregnant women who do not have a multifetal pregnancy or gestational trophoblastic disease , tests to rule out other causes of hypertension (eg, renal artery stenosis , coarctation of the aorta , Cushing syndrome , systemic lupus erythematosus , pheochromocytoma ) should be considered.

Treatment of Hypertension in Pregnancy

For mild hypertension, conservative measures followed by antihypertensives if needed

For moderate or severe hypertension, antihypertensive therapy, close monitoring, and, if condition worsens, possibly termination of pregnancy or delivery, depending on gestational age

Recommendations for chronic and gestational hypertension are similar and depend on severity. However, chronic hypertension may be more severe. In gestational hypertension, the increases in BP often occur only late in gestation and may not require treatment.

Treatment of mild to moderate hypertension without renal insufficiency during pregnancy is controversial; the issues are whether treatment improves outcome and whether the risks of drug treatment outweigh risks of untreated disease. Because the uteroplacental circulation is maximally dilated and cannot autoregulate, decreasing maternal BP with medications may abruptly decrease uteroplacental blood flow. Diuretics reduce effective maternal circulating blood volume; consistent reduction increases risk of fetal growth restriction. However, hypertension with renal insufficiency is treated even if hypertension is mild or moderate.

For mild to moderate hypertension (systolic BP 140 to 159 mm Hg or diastolic BP 90 to 109 mm Hg) with labile BP, reduced physical activity may decrease BP and improve fetal growth, making perinatal risks similar to those for women without hypertension. However, if this conservative measure does not decrease BP, many experts recommend drug therapy. In pregnant women with mild chronic hypertension, a strategy of targeting a BP 1

For severe hypertension (systolic BP ≥ 160 mm Hg or diastolic BP ≥ 110 mm Hg), drug therapy is indicated. Risk of complications—maternal (progression of end-organ dysfunction, preeclampsia) and fetal (prematurity, growth restriction, stillbirth)—is increased significantly. Several antihypertensives may be required.

For systolic BP > 180 mm Hg or diastolic BP > 110 mm Hg, immediate evaluation is required. Multiple medications are often required. Also, hospitalization may be necessary for much of the latter part of pregnancy. If the woman’s condition worsens, pregnancy termination may be recommended.

All women with chronic hypertension during pregnancy should be taught to self-monitor BP, and they should be evaluated for target organ damage. Evaluation, done at baseline and periodically thereafter, includes

Serum creatinine, electrolytes, and uric acid levels

Liver function tests

Platelet count

Urine protein assessment

Usually funduscopy

Maternal echocardiography should be considered if women have had hypertension for > 4 years. After initial ultrasonography to evaluate fetal anatomy, ultrasonography is done monthly starting at about 28 weeks to monitor fetal growth; antenatal testing often begins at 32 weeks. Ultrasonography to monitor fetal growth and antenatal testing may start sooner if women have additional complications (eg, renal disorders) or if complications (eg, growth restriction) occur in the fetus. Delivery should occur by 37 to 39 weeks but may be induced earlier if preeclampsia or fetal growth restriction is detected or if fetal test results are nonreassuring.

Pharmacologic treatment

First-line medications for hypertension during pregnancy include

Beta-blockers

Calcium channel blockers

Several classes of antihypertensives are usually avoided during pregnancy:

ACE inhibitors are contraindicated because risk of fetal urinary tract abnormalities is increased.

ARBs are contraindicated because they increase risk of fetal renal dysfunction, lung hypoplasia, skeletal malformations, and death.

Aldosterone antagonists

Treatment reference

1. Tita AT, Szychowski JM, Boggess K, et al : Treatment for Mild Chronic Hypertension during Pregnancy.  N Engl J Med 386(19):1781-1792, 2022. doi:10.1056/NEJMoa2201295

Both chronic and gestational hypertension increase risk of preeclampsia, eclampsia, other causes of maternal mortality or morbidity (eg, hypertensive encephalopathy, stroke, renal failure, left ventricular failure, HELLP syndrome), and uteroplacental insufficiency.

Check for other causes of hypertension if severe hypertension occurs for the first time in a pregnant woman who does not have a multifetal pregnancy or gestational trophoblastic disease.

Do not use ACE inhibitors, ARBs, or aldosterone antagonists.

Consider hospitalization or termination of pregnancy if BP is > 180/110 mm Hg.

• Cookie Preferences

Copyright © 2024 Merck & Co., Inc., Rahway, NJ, USA and its affiliates. All rights reserved.

Hypertension in Pregnancy: A Diagnostic and Therapeutic Overview

• Review article
• Open access
• Published: 13 June 2023
• Volume 30 , pages 289–303, ( 2023 )

Cite this article

You have full access to this open access article

• Renata Cífková   ORCID: orcid.org/0000-0003-2765-3821 1 , 2  

8364 Accesses

3 Citations

Explore all metrics

Hypertensive disorders in pregnancy are associated with increased risk of maternal, fetal, and neonatal morbidity and mortality. It is important to distinguish between pre-existing (chronic) hypertension and gestational hypertension, developing after 20 weeks of gestation and usually resolving within 6 weeks postpartum. There is a consensus that systolic blood pressure ≥ 170 or diastolic blood pressure ≥ 110 mmHg is an emergency and hospitalization is indicated. The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. The current European guidelines recommend initiating drug treatment in pregnant women with persistent elevation of blood pressure ≥ 150/95 mmHg and at values > 140/90 mmHg in women with gestational hypertension (with or without proteinuria), with pre-existing hypertension with the superimposition of gestational hypertension, and with hypertension with subclinical organ damage or symptoms at any time during pregnancy. Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice. The results of the CHIPS and CHAP studies are likely to reduce the threshold for initiating treatment. Women with a history of hypertensive disorders in pregnancy, particularly those with pre-eclampsia, are at high risk of developing cardiovascular disease later in life. Obstetric history should become a part of the cardiovascular risk assessment in women.

Similar content being viewed by others

Hypertension in pregnancy: natural history and treatment options.

Treating Hypertension in Pregnancy

Hypertensive Disorders in Pregnancy

Avoid common mistakes on your manuscript.

1 Introduction

Hypertensive disorders in pregnancy (HDP) are a major cause of maternal, fetal, and neonatal morbidity and mortality complicating about 10% of pregnancies worldwide. This rate is likely to rise due to the increasing age and obesity of conceiving women. Pregnant women with HDP are at risk of developing placental abruption, stroke, pulmonary edema, thromboembolic events, disseminated intravascular coagulation, and multiple organ failure. The fetal risk includes intrauterine growth retardation, prematurity, and intrauterine death, all of which are particularly high in pre-eclampsia. Neonates are at increased risk of preterm birth with low birthweight, prolonged high-level neonatal care, and postnatal death [ 1 ].

2 Physiological Changes in Blood Pressure During Pregnancy

Due to vasodilation induced by local mediators such as prostacycline and nitric oxide, there is a fall in blood pressure (BP) early in the first trimester. This reduction in BP primarily affects diastolic BP (DBP), with the lowest values being achieved at weeks 20–24 (reduction of DBP by 8–15 mmHg), further followed by a gradual increase to pre-pregnancy values at week 36 [ 2 ].

This BP fluctuation is seen both in normotensive and hypertensive pregnant women. Women with pre-existing hypertension may have a greater BP decrease in early pregnancy and therefore the BP rise in the third trimester may be misdiagnosed as gestational hypertension.

Blood pressure usually falls immediately after delivery and then progressively rises over the first five postnatal days peaking on days 3–6 after delivery. It should be emphasized that 10% of maternal deaths due to hypertensive disorders in pregnancy occur in the postpartum period.

A summary of hemodynamic changes in pregnancy is provided in Table 1 .

3 Blood Pressure Measurement

The initial BP measurement should be taken in both upper arms, with following measurements taken in the arm with the higher BP value, preferably in the sitting position or in the left lateral recumbent position during labor. A cuff of appropriate size should always be used with the arm being supported at heart level.

The mercury sphygmomanometer is still considered the gold standard for BP measurement in pregnancy with Korotkoff V phase to be used for DBP. However, as the sale of mercury sphygmomanometers has been banned in Europe, other devices for standard sphygmomanometry or automatic/semiautomatic (usually oscillometric) BP devices, validated according to standardized protocols (specifically for pregnancy and pre-eclampsia) should be used [ 3 ]. It is important to note that not all automatic devices are validated for use in pregnancy and pre-eclampsia. Those that are not specifically validated for this condition showed a tendency to underestimate actual BP levels and are thus unreliable in severe pre-eclampsia. A reasonable solution may be an auscultatory hybrid device with a liquid-crystal display on a vertical column simulating a mercury sphygmomanometer [ 4 ], however, these devices are not presently widely used. Wrist BP monitors are not recommended [ 5 ].

In hypertensive emergencies, BP should also be measured in both arms and in lower limbs if there is a clinical suspicion of aortic dissection [ 6 ].

Ambulatory BP monitoring (ABPM) is superior to routine BP measurement for the prediction of pregnancy outcome [ 7 ]. It can help to rule out white-coat hypertension, which is quite frequent in pregnancy [ 8 ], and may identify nocturnal hypertension, a finding commonly reported in pre-eclampsia [ 9 ].

Home BP measurement (HBPM) is suitable for long-term monitoring, particularly in patients treated with antihypertensive drugs, despite two recently published studies (BUMP 1 and BUMP 2) not showing any convincing evidence. In BUMP 1 (Blood Pressure Monitoring in High Risk Pregnancy to Improve the Detection and Monitoring of Hypertension 1) in women at high risk of pre-eclampsia, self-monitoring with telemonitoring did not lead to earlier clinic-based detection of hypertension [ 10 ]. BUMP 2, a randomized clinical trial initiated by the same group of investigators [ 11 ], did not find differences in mean systolic BP recorded by healthcare professionals in women whose BP was measured at regular antenatal clinics compared with those who performed BP self-monitoring. Together with tele-transmission of BP data, self-monitoring may become a future solution, saving repeated office visits and hospital admissions [ 12 ].

4 Diagnosis of Hypertension

Hypertension in pregnancy is diagnosed if systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg, measured in the office or in hospital; it has to be confirmed, preferably on 2 separate occasions or at least 15 min apart in severe hypertension (i.e. ≥ 160/110 mmHg in the obstetric literature which usually recognizes only mild and severe hypertension rather than the three grades used by the European hypertension guidelines) [ 13 ].

5 Classification of Hypertensive Disorders

Hypertension in pregnancy is not a single entity but comprises [ 1 , 13 ] (Table 2 ):

Pre-existing hypertension: either preceding pregnancy or developing before 20 weeks’ gestation. It usually persists for more than 42 days postpartum and may be associated with proteinuria.

Gestational hypertension: developing after 20 weeks’ gestation and usually resolving within 42 days postpartum.

Pre-eclampsia: gestational hypertension with significant proteinuria (> 0.3 g/24 h or ≥ 30 mg/mmol urinary protein: creatinine ratio in a spot random urine sample).

Pre-eclampsia is a systemic disorder with both maternal and fetal manifestation occurring more frequently during the first pregnancy, in multiple pregnancy, in hydatidiform mole, in antiphospholipid syndrome, in renal disease or diabetes, or with pre-existing hypertension. It is often associated with fetal growth restriction due to placental insufficiency and is a common cause of prematurity. The only cure is delivery [ 14 ]. As proteinuria may be a late manifestation of pre-eclampsia, it should be suspected when de novo hypertension is accompanied by headache, visual disturbances, abdominal pain, or abnormal laboratory tests, specifically low platelet count and abnormal liver enzymes; it is recommended to treat such patients as having pre-eclampsia.

Pre-existing hypertension plus superimposed gestational hypertension with proteinuria.

Antenatally unclassifiable hypertension: this term is used when BP is first recorded after 20 weeks' gestation and hypertension is diagnosed; re-assessment is necessary at or after 42 days postpartum.

The above definition of pre-eclampsia is in concordance with the 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy [ 1 ]. However, the International Society for the Study of Hypertension in Pregnancy (ISSHP) introduced a new, broader definition of pre-eclampsia, now being defined as gestational hypertension accompanied by one or more of the following new‐onset conditions at or after 20 weeks of gestation: (1) proteinuria; (2) evidence of other maternal organ dysfunction (including acute kidney injury [serum creatinine ≥ 1 mg/dl; 90 µ/l], liver involvement [elevated transaminases > 40 UI/L; 67 µkat/L]) with or without right upper quadrant or epigastric pain, neurological complications [convulsions, altered mental status, blindness, scotomata or headache], hematological complications [platelet count < 150,000/μL, disseminated intravascular coagulation, hemolysis]; or (3) uteroplacental dysfunction (e.g., fetal growth restrictions, abnormal umbilical artery Doppler wave form analysis for stillbirth) [ 15 ]. The combination of hemolysis, thrombocytopenia, and elevated transaminases defines HELLP syndrome as one manifestation of pre-eclampsia and therefore additional features of pre-eclampsia should be evaluated.

Pre-existing hypertension is associated with a 25% increased risk of developing superimposed pre-eclampsia [ 16 ], which is usually associated with a sharp increase in BP, and de novo development of proteinuria or any other maternal organ dysfunction as defined by the ISSHP.

The 2018 ISSHP recommendations [ 15 ] included transient gestational hypertension, which is usually detected in the clinic but settles with repeated BP measurements taken over the course of several hours. It is not a benign disorder, as it is associated with a 40% risk of developing true gestational hypertension or pre-eclampsia later in the same pregnancy. Therefore, these patients should have a careful follow-up with home BP measurements.

6 Laboratory Tests and Other Recommended Examinations

Hypertensive disorders in pregnancy, particularly gestational hypertension with or without proteinuria, may induce changes in the hematologic, renal, and hepatic profiles that may adversely affect both neonatal and maternal outcomes.

Basic laboratory investigations recommended for monitoring patients with hypertension in pregnancy are presented in Table 3 . All pregnant women should be assessed for proteinuria in early pregnancy to rule out pre-existing renal disease and, in the second half of pregnancy, to screen for pre-eclampsia. A positive dipstick test (≥ 1+) should prompt further investigations including an albumin-to-creatinine ratio (ACR), which can be quickly determined in a single spot urine sample. A value < 30 mg/mmol (0.3 mg/mg) can reliably rule out proteinuria, but a positive test should possibly be followed by a 24-h urine collection. If proteinuria exceeds 2 g/day, close monitoring is warranted. It should be noted that 24-h urine collection is often inaccurate and delays the diagnosis of pre-eclampsia. Thus, an ACR cutoff of ≥ 30 mg/mmol (0.3 mg/mg) can be used to identify significant proteinuria.

The following investigations may be considered additionally to the basic laboratory tests:

Determination of the soluble fms-like tyrosine kinase-1 (sFlt-1) to placental growth factor (PlGF) ratio is now widely available to exclude the development of pre-eclampsia when suspected clinically [ 17 ]; a value of (sFlt-1: PlGF) < 38 is used to possibly rule out the development of pre-eclampsia in the next week. The test has a high negative predictive value. The sFlt-1/PlGF ratio is suggested to be used from 20 weeks through to 32 + 6 weeks for short-term prediction and diagnostic support in high-risk women or in women clinically suspected of pre-eclampsia [ 18 ]. It could also be used in women after 37 weeks with suspected pre-eclampsia or to evaluate uteroplacental dysfunction [ 19 ]. Women with a sFlt-1/PlGF ratio ≥ 85 most likely have or will develop pre-eclampsia within the next 4 weeks and require intensive monitoring, preferably during hospitalization [ 20 ]. A recent study showed that the increased sFlt-1/PlGF ratio in pre-eclampsia is mostly driven by the increased placental sFlt-1 [ 21 ].

Doppler ultrasound of uterine arteries after 20 weeks of gestation is useful in detecting women at high risk of gestational hypertension, pre-eclampsia, and intrauterine growth retardation.

Performing an ultrasound examination of the adrenals, urine metanephrine, and normetanephrine assays in all pregnant women with hypertension is recommended by some authors [ 22 ] as a screening for pheochromocytma.

7 Pre-conception Counselling

All women with known pre-existing hypertension should receive pre-conception counselling aimed at ruling out possible secondary causes of hypertension and informing them about the high risk of developing pre-eclampsia, which could be reduced by a low dose of aspirin [ 23 ]. Renal Doppler ultrasound is suggested to be performed in all hypertensive women planning pregnancy. If fibromuscular dysplasia (FMD) is diagnosed before pregnancy, a search for other potential arterial damage in other vascular beds should follow [ 24 ]. Determination of urine metanephrine and normetanephrine assays in all pregnant women with hypertension is recommended by some authors [ 22 ] as a screening for pheochromocytma, which may be completely asymptomatic and, if not diagnosed before labor, fatal.

8 Management of Secondary Hypertension in Pregnancy

8.1 pheochromocytoma.

During pregnancy, a pheochromocytoma is among the most life-threatening conditions for both the mother and fetus. Although extremely rare (0.002% of all pregnancies), this tumor is infamous for its devastating consequences [ 25 ]. The signs and symptoms are variable but not specific, as is the case with non-pregnant women. Hypertension is only of one of the most dominant signs. If left undiagnosed, maternal and fetal mortality is around 50%. Early detection and adequate treatment during pregnancy lower the maternal and fetal mortality to < 5 and < 15%, respectively. For the biochemical diagnosis, plasma or urinary metanephrines are the test of choice since they have the highest sensitivity and the highest negative predictive value. For reliable localization, magnetic resonance imaging is the most suitable technique, having a sensitivity of more than 90%. When a pheochromocytoma is diagnosed in pregnancy, a laparoscopic adrenalectomy should be performed after 10–14 days of drug pretreatment (as in non-pregnant patients), using alpha-adrenoreceptor blockade combined with beta-adrenergic blockade started some days later. If the pheochromocytoma is diagnosed during the third trimester, the patient should be managed until the fetus is viable using the same drug regimen as for the surgical preparation. Caesarian section with tumor removal in the same session or at a later stage is preferred, as vaginal delivery is possibly associated with higher mortality.

8.2 Primary Aldosteronism

Primary aldosteronism (PA), the most common cause of secondary hypertension outside of pregnancy, is underdiagnosed in pregnancy. Women with known PA before pregnancy or with clinical suspicion in early pregnancy should have a close laboratory work-up. However, optimal management of PA during pregnancy has not been established regarding the safety of mineralocorticoid antagonists and amiloride. It is also unclear if laparoscopic adrenalectomy of adrenal adenoma will improve the prognosis [ 26 ]. Eplerenone on top of the usual BP lowering treatment may be considered for uncontrolled hypertension in the second trimester [ 27 ]. Hypokalemia and BP may be aggravated postpartum due to the decrease in progesterone [ 26 , 27 ].

9 Prevention of Pre-eclampsia

Women at high or moderate risk of pre-eclampsia should be advised to take 100–150 mg of aspirin daily from 12 weeks to weeks 36–37 [ 1 , 13 , 23 ].

High risk of pre-eclampsia includes any of the following:

hypertensive disease during a previous pregnancy

chronic kidney disease

autoimmune disease such as systemic lupus erythematosus or antiphospholipid syndrome

type 1 or type 2 diabetes

chronic hypertension

Moderate risk of pre-eclampsia includes ≥ 1 of the following risk factors:

first pregnancy

age 40 years or older

pregnancy interval of more than 10 years

body mass index (BMI) of 35 kg/m 2 or more at first visit

family history of pre-eclampsia

multiple pregnancy.

There is growing evidence that assisted reproductive technology (ART) is associated with an increased risk of developing pre-eclampsia [ 28 , 29 ]. The risk is particularly high in frozen embryo transfers [ 30 ]. Thus, it is very likely that ART in the current pregnancy will be listed as an additional high-risk condition of pre-eclampsia recommending a low dose of aspirin to prevent it.

Calcium supplementation (at least 1 g/day, orally) is recommended for prevention of pre-eclampsia in women with a low dietary intake of calcium (< 600 mg/day)[ 31 ]. Vitamin D deficiency is very common in pregnant women and increases the risk of pre-eclampsia [ 32 ]. The beneficial role of vitamin D in the prevention of pre-eclampsia, independent of timing of supplementation, dosage, and maternal age, was shown by a meta-analysis of randomized clinical trials. [ 33 ]. Further research should be focused on the recommended regimen (daily, weekly or a single dose).

There is no evidence that vitamins C and E decrease the risk of pre-eclampsia [ 34 , 35 ]. On the contrary, they are associated with low birth weight (< 2.5 kg) and adverse perinatal outcomes [ 36 ].

10 Management of Hypertension in Pregnancy

The majority of women with pre-existing hypertension in pregnancy have mild to moderate hypertension (140–179/90–109 mmHg) and are at low risk for cardiovascular complications within the short timeframe of pregnancy. Women with essential hypertension and normal renal function have good maternal and neonatal outcomes. Some women with treated pre-existing, mild hypertension may be able to have their medication withdrawn or reduced in the first half of pregnancy because of the physiological fall in BP during this period. However, close monitoring and, if necessary, resumption of treatment is essential.

There are not sufficient data regarding treatment of hypertension in pregnancy as pharmaceutical companies have been reluctant to test drugs in this small market with a high potential of litigation. Child-bearing potential without reliable contraception is an exclusion criterion in basically all clinical trials testing antihypertensive drugs.

The only trial of treatment of hypertension in pregnancy with adequate infant follow-up (7.5 years) was performed almost 50 years ago with alpha-methyldopa, now rarely used in non-pregnant women [ 37 , 38 ]. Past clinical trials also have not supported a beneficial effect on pregnancy outcome of treating mild to moderate hypertension. There has been no reduction in perinatal mortality, placental abruption, or superimposed pre-eclampsia [ 39 , 40 ]. The most recent Cochrane Review on this topic showed only a halving of the risk of developing severe hypertension [ 41 ]. More recently, a systematic review and network meta-and trial sequential analyses found that all commonly prescribed antihypertensive drugs in pregnancy reduce the risk of severe hypertension, but labetalol may also decrease the development of proteinuria/pre-eclampsia and fetal/newborn death [ 42 ].

10.1 Non-drug Treatment

A normal diet without salt restriction is advised, particularly close to the time of delivery as salt restriction may induce a low intravascular volume. However, women with pre-existing hypertension should continue any salt-restricted diet they already follow [ 43 ].

Aerobic exercise three to four times per week (30–60 min/session) is recommended to prevent weight gain and reduce adverse pregnancy outcomes, including hypertensive disorders and gestational diabetes mellitus, unless contraindicated [ 44 , 45 , 46 , 47 ]. Exercise of low to moderate intensity during pregnancy is particularly effective in decreasing the development of gestational diabetes and gestational hypertension, especially when supervised and when initiated in the first trimester [ 48 ].

As maternal obesity may be associated with poor outcomes for both mother and fetus, obese women (BMI ≥ 30 kg/m 2 ) are advised to avoid a weight gain of more than 6.8 kg. The recommended weight gain range for overweight pregnant women (BMI 25.0–29.9 kg/m 2 ) is 6.8–11.2 kg [ 49 , 50 , 51 ].

11 Drug Treatment

The goal of treating hypertension is to reduce maternal risk without compromising the health of the fetus.

11.1 Treatment of Severe Hypertension

With values ranging between 160 and 180 mmHg/> 110 mmHg, there is no agreement on the definition of severe hypertension in pregnancy. However, there is a consensus that SBP ≥ 170 or DBP ≥ 110 mmHg in a pregnant woman should be considered an emergency, and hospitalization is indicated [ 1 ] (Table 4 ). The selection of the antihypertensive drug and its route of administration depend on the expected time of delivery. ACE inhibitors, ARBs, and direct renin inhibitors are strictly contraindicated.

Labetalol, methyldopa, or nifedipine XL can be used for oral treatment. If parenteral treatment is needed, intravenous labetalol seems to be the drug of choice. Intravenous hydralazine should no longer be thought of as the drug of choice, as its use is associated with more adverse effects than other drugs [ 52 ] and should only be used when labetalol is contraindicated or other drugs prove ineffective. However, recent analyses of safety and efficacy, found hydralazine to be comparable to both labetalol and nifedipine [ 53 , 54 ]. Oral short-acting nifedipine should only be used temporarily, e.g. until i.v. access is available, with the second dose administered only after one hour if severe hypertension persists. Short-acting sublingual nifedipine is contraindicated.

11.2 Hypertensive Emergencies

The definition of hypertensive emergency in pregnancy is: pre-eclampsia/eclampsia and SBP ≥ 160 mmHg and DBP ≥ 110 mm Hg or severely elevated BP (DBP > 120 mmHg) and progressive acute end-organ damage such as acute myocardial infarction, pulmonary edema, respiratory failure, or aortic dissection. BP should be decreased immediately by 15–25% with the goal being SBP 140–150 mmHg and DBP 90–100 mmHg. The list of the most frequently used drugs for treatment of hypertensive emergencies is shown in Table 5 .

Prolonged treatment with sodium nitroprusside is associated with an increased risk of fetal cyanide poisoning as nitroprusside is metabolized into thiocyanate excreted into urine [ 55 ]. Therefore, sodium nitroprusside should be reserved for extreme emergencies and used for the shortest possible duration.

The drug of choice in pre-eclampsia associated with pulmonary edema is nitroglycerine (given as intravenous infusion of 5 µg/min, gradually increased every 3–5 min to a maximum dose of 100 µg/min).

11.3 Prevention of Eclampsia

For prevention of eclampsia and for treatment of seizures, magnesium sulfate i.v. is recommended [ 56 , 57 ]. Most guidelines suggest primary prevention of eclampsia in severe pre-eclampsia with persistent neurological symptoms (severe headache, visual disturbances, hyperactive deep-tendon reflexes). The recommended loading dose is 4 g i.v., followed by continuous infusion of 1 g per hour until delivery for a maximum of 24 h while monitoring the mother closely.

11.4 Treatment of Mild-to-Moderate Hypertension

In the absence of randomized controlled trials, recommendations can only be guided by expert opinion. The European guidelines [ 1 , 13 ] recommend initiating drug treatment in all women with persistent elevation of BP ≥ 150/95 mmHg and at values > 140/90 mmHg in women with:

gestational hypertension (with or without proteinuria)

pre-existing hypertension with the superimposition of gestational hypertension

hypertension with subclinical organ damage or symptoms at any time during pregnancy.

Methyldopa, labetalol, and calcium antagonists (the most data are available for nifedipine) are the drugs of choice (Table 6 ). Beta-blockers appear to be less effective than calcium antagonists and may induce fetal bradycardia, growth retardation, and hypoglycemia; the type and dose should be carefully selected with atenolol avoided, as it was shown to be fetotoxic. Calcium-channel blockers are considered safe if not given concomitantly with magnesium sulfate (risk of hypotension due to potential synergism). Women with pre-existing hypertension may continue their current antihypertensive medication except for RAS blockers which are strictly contraindicated in pregnancy. As there is a reduction of plasma volume in pre-eclampsia, diuretic therapy is therefore inappropriate unless there is oliguria when low-dose furosemide may be considered. (Table 7 ). Magnesium sulfate i.v. is recommended for the prevention of eclampsia and treatment of seizures [ 56 ].

Future guidelines are likely to be influenced by two randomized clinical trials conducted in women with non-severe hypertension in pregnancy. The Control of Hypertension in Pregnancy Study (CHIPS) assessed whether “more tight” or “less tight” control of hypertension was associated with better outcomes [ 58 ]. Most women included in this study had non-severe and non-proteinuric chronic hypertension (75%, 736 out of 987) and 25% had gestational hypertension. Similar to previous meta-analyses [ 39 , 40 ], the development of severe hypertension was significantly reduced in the “more tight” arm of the study. In the subgroup of women with chronic hypertension, “less tight” BP control was associated with lower rates of small-for-gestational age newborns. Unfortunately, the study has several limitations: (a) the sample size was limited, not allowing for subgroup analyses, including that of small-for-gestational age newborns; (b) chronic and gestational hypertension were analyzed together as one group; (c) women with newly detected hypertension before week 14 did not qualify for enrollment ; (d) labetalol, being considered the drug of choice, was used only by 2/3 of women in the study; (e) systolic BP was ignored when assessing the study outcomes; (f) women with prior severe hypertension were more often randomly allocated to the “less tight” control group. Nevertheless, despite all the above limitations, most experts concluded that the study demonstrated that lowering BP in pregnancy to levels which are routinely achieved by non-pregnant women is safe for the fetus [ 59 ]. The investigator-initiated Chronic Hypertension and Pregnancy (CHAP) project included a much larger study group of women with mild chronic hypertension of gestational age less than 23 weeks [ 60 ]. A total of 2,408 women were randomized to a BP goal of < 140/90 mmHg (active treatment) or to control treatment, in which antihypertensive medication was withdrawn or never given unless severe hypertension (SBP ≥ 160 mmHg or DBP ≥ 105 mmHg) developed. In the active treatment group, the study participants were supplied with labetalol or extended release nifedipine or other medication such as amlodipine or methyldopa, based on the patient´s preference. The primary outcome was defined as a composite of pre-eclampsia with severe features, medically indicated preterm birth before 35 weeks gestation, placental abruption, or fetal or neonatal death. The primary-outcome events were reduced in the active treatment group (adjusted risk ratio 0.82; 95% CI 0.74–0.92). The overall mean BP was lower in the active treatment group (129.5/79.1 mmHg vs. 132.6/81.5 mmHg). The pre-specified composite maternal or neonatal secondary outcomes did not differ between groups, including small-for-gestational-age newborns. Severe hypertension was less frequent in the active treatment group, with no stroke in either group. The study results support antihypertensive treatment in women with mild pre-existing hypertension to achieve a target BP of < 140/90 mmHg. It should be noted that BP differences were more evident in the first half of the pregnancy. Low doses of aspirin were administered equally in the active treatment and control group (44.6% vs 44.7%).

12 Delivery

Induction of labor is advisable for women with gestational hypertension or mild pre-eclampsia beyond 37 weeks of gestation, as it has been shown to be associated with improved maternal outcome [ 61 ]. Factors such as fetal well-being, gestational age, and type of hypertensive disorder determine the optimal timing of delivery. Pre-eclampsia lacking severe features is possibly manageable by expectation. On the other hand, eclampsia requires delivery shortly after the mother is stabilized.

Cesarean delivery should be considered only for obstetric indications and in the rare case of pheochromocytoma. Otherwise, vaginal delivery is preferable for women with hypertension in pregnancy. Severe pre-eclampsia, regardless of gestational age, requires prompt delivery either vaginally or by cesarean section.

During labor and delivery, antihypertensive treatment should continue with the aim of keeping SBP < 160 mmHg and DBP < 90 mmHg.

13 Blood Pressure Postpartum

Fluctuations of blood pressure in the postpartum period are common. After the usual fall in BP following delivery, there is a progressive rise over the subsequent five days. The postpartum period is also associated with a risk of the late onset of pre-eclampsia. Therefore, BP should be checked in all women within six hours of delivery. Transient hypertension may develop postpartum in women who were previously normotensive. This could be due to pain (because of inadequate analgesia), some drugs (non-steroid anti-inflammatory drugs for pain relief, ergot derivatives for postpartum bleeding, or ephedrine), hypervolemia after regional anesthesia, salt and water redistribution into the intravascular compartment, or restoration of non-pregnant vascular tone. Mild hypertension postpartum usually resolves spontaneously. However, as late presentation pre-eclampsia is a possibility, it is necessary to check BP at least once a day for the first five days after delivery. It is advised to continue with BP measuring every other day for at least one week after discharge from hospital.

In the postpartum period up to 4 weeks, hypertensive women with the following symptoms should be suspected of having de novo pre-eclampsia: headaches, epigastric pain (possibly accompanied by nausea and vomiting), visual disturbances (blurred vision, flashing lights, double vision, floating spots, etc., dyspnea (potentially due to pulmonary edema), sudden swelling in the face, hands, or feet, or seizures.

14 Lactation

Generally, breast feeding is not associated with an increase in BP in mothers. Bromocryptin, used to suppress lactation in some countries, may induce hypertension. All antihypertensive drugs are excreted into breast milk, mostly at very low concentrations, except for propranolol, atenolol, acebutolol (potentially inducing signs of neonatal betablockade), and nifedipine, achieving similar levels to those in maternal plasma. According to many guidelines, methyldopa is still considered the drug of choice for breastfeeding mothers, except for women prone to depression.

Labetalol, nifedipine, and enalapril are suggested as first line antihypertensive drugs for breastfeeding mothers by most guidelines. A list of antihypertensive drugs usually compatible with breastfeeding is provided in Table 8 . ACE inhibitors can be used in lactating mothers except in cases of premature birth or renal failure in the newborn. Enalapril is the most widely prescribed ACE inhibitor to breastfeeding mothers because of its safety and favorable pharmacokinetics. It is also used for treatment of peripartum cardiomyopathy.

Calcium channel blockers, particularly felodipine and nifedipine, are considered safe and are therefore frequently used, despite nifedipine not being recommended to nursing mothers by the manufacturer. Nifedipine may be the drug of choice in Black women of African or Caribbean origin.

Labetalol and some beta-1 selective blockers, with the most favorable data being available on metoprolol, are also compatible with breastfeeding and are therefore recommended.

Diuretics should be used with caution, as they may reduce milk production.

15 Prognosis After Pregnancy

Women with a history of gestational hypertension or pre-eclampsia are at higher risk of developing hypertension and stroke later in life [ 62 ]. Pre-eclampsia was associated with a four-fold increase in heart failure and hypertension, and doubled the risk of ischemic heart disease, stroke, and cardiovascular death [ 63 , 64 ]. Women with a history of HDP developing hypertension within a decade postpartum were shown to have the most pronounced abnormal echocardiographic findings in left ventricular remodeling and diastolic function, compared to hypertensive women without previous history of HDP [ 65 ]. The 2018 American College of Cardiology/American Heart Association cholesterol guidelines suggest initiating treatment with statins in asymptomatic, middle-aged women with an intermediate 10-year risk and history of pre-eclampsia [ 66 ]. HDPs are also associated with an increased risk of developing peripartum cardiomyopathy [ 67 , 68 ].

Women with previous gestational hypertension may develop endothelial dysfunction and early alterations of carbohydrate and lipid metabolism. They may also experience a relative hyperandrogenism which could, together with the metabolic abnormalities, partly explain the increased risk of developing CVD in later life [ 69 ].

A recent meta-analysis of 5 cohort studies with a total of more than 180,000 women with HDP and more than 2,300,000 women without HDP showed that the risk of all-cause and vascular dementia was substantially elevated in women with HDP (adjusted HR, 1.38; 95% CI 1.18–1.61, p < 0.01) [ 70 ]. There is also growing evidence for an increased risk of alterations in developmental cognition in the offspring [ 71 ].

Despite women with HDPs being recognized as high-risk individuals by the 2018 ESC/ESH hypertension guidelines, recommendations on systematic check-ups are still lacking. BP monitoring in the first postpartum months is strongly suggested, possibly by implementing BP self-measurement to be reported to the primary care physician or using e-health technology [ 72 ]. Larger validation studies with BP self-measurement are ongoing [ 73 ].

Cardiologists and general practitioners should include an obstetric history, regardless of the woman’s age, as part of the cardiovascular risk assessment. Unfortunately, this area is currently lacking data from randomized studies. There is general agreement that women with a history of HDP, particularly when associated with gestational diabetes, metabolic syndrome, or fetal growth restriction, should be closely monitored for the development of CVD. The timing of this recommendation is unclear, but experts suggest setting up an initial review 6–12 weeks postpartum and then at 6–12 months [ 74 ]. The examination should include BP evaluation and assessment of other modifiable risk factors [ 74 ]. There is a need to develop a CVD risk calculator assessing female-specific risk factors, including hypertensive and metabolic disorders of pregnancy [ 75 ].

16 Assisted Reproductive Technology

In high-income countries 2–6% of children are conceived using ART, meaning that, worldwide, at least 8,000,000 children have been born using ART [ 76 ]. There is convincing evidence that HDPs are increased in all pregnancies following ART, regardless of the type of treatment [ 77 ]. This meta-analysis included 66 longitudinal studies (7,038,029 pregnancies and 203,375 following any ART). These results are confirmed by another meta-analysis showing higher odds of HDP and pre-eclampsia in pregnancies after in vitro fertilization (IVF) or in intracytoplasmic sperm fertilization (ICSI). The risk was particularly high in frozen embryo transfer and oocyte donation pregnancies [ 29 ]. Women who conceived via ART in their current pregnancy are advised to take a low dose of aspirin to prevent pre-eclampsia [ 78 ].

In 2015 a group of Swiss researchers declared that children conceived by ART have cardiovascular dysfunction and could potentially have increased CV risk later in life [ 79 ]. A total of 54 young individuals (mean age 16.5 ± 2.3 years) conceived by ART were compared with 43 spontaneously conceived controls of similar age [ 80 ]. Both groups were re-examined 5 years later. Premature vascular aging persisted in ART conceived individuals (impaired flow-mediated dilatation of the brachial artery, increased pulse-wave velocity, and carotid intima-media thickness). They also showed significantly higher SBP and DBP values by ambulatory BP monitoring (ABPM), and 8 of them (15.4%) met the ABPM criteria for hypertension. A significantly lower left ventricular diastolic function was found in another study including children conceived by ART (mean age 12.85 ± 5.8 years) compared to spontaneously conceived controls of roughly the same age [ 81 ]. The risk of developing left ventricular diastolic alterations was particularly high in individuals born preterm.

17 Conclusions

HDPs complicate about 10% of pregnancies and are associated with increased risk of morbidity and mortality for the mother, fetus, and the newborn. Diagnosis of hypertension in pregnancy is based on BP values (SBP ≥ 140 mmHg and/or diastolic DBP ≥ 90 mmHg) measured in the office or in hospital, preferably on two separate occasions. Ambulatory BP monitoring should be used to rule out white coat hypertension to avoid unnecessary treatment.

Hypertension in pregnancy should be classified as pre-existing hypertension or gestational hypertension. Pre-eclampsia used to be defined as gestational hypertension with significant proteinuria. In 2018 a new definition of pre-eclampsia was introduced, no longer insisting on the presence of proteinuria, but requiring evidence of other maternal organ dysfunction.

Pre-existing hypertension is associated with a 25% increased risk of developing superimposed pre-eclampsia. A low dose of aspirin should be initiated in these women from week 12 to weeks 36 to 37. The same preventive measure is recommended to all women at high risk of pre-eclampsia, such as having had hypertension during a previous pregnancy, currently having chronic kidney disease, autoimmune disease, or diabetes. A low dose of aspirin should also be given to women at moderate risk of pre-eclampsia.

Calcium supplementation is recommended for the prevention of pre-eclampsia only in women with a low dietary intake of calcium (< 600 mg daily). Vitamin D is also suggested in the prevention of pre-eclampsia.

Women with pre-existing hypertension should continue their salt-restricted diet, otherwise a normal diet without salt restriction is advised. Exercise of low to moderate intensity during pregnancy is effective in reducing the risk of developing gestational diabetes and gestational hypertension. Obese women are advised to avoid a weight gain of more than 6.8 kg.

There is a consensus that SBP ≥ 170 or DBP ≥ 110 mmHg is considered an emergency and hospitalization should follow. The selection of antihypertensive drugs and their route of administration should be determined based on the expected time of delivery. Intravenous labetalol seems to be an almost universal drug of choice. For mild and moderate hypertension, methyldopa, oral labetalol, and calcium antagonists (with the most data available for long-acting nifedipine), are drugs of choice. Based on the CHIPS and CHAP projects, the threshold for initiating drug treatment for hypertension in pregnancy may be reduced to 140/90 mmHg.

Vaginal delivery is preferred for women with hypertension in pregnancy, provided there is no obstetric indication for cesarean delivery. Induction of labor after the 37th week, compared with the expectant approach, is associated with a better prognosis in women with gestational hypertension or mild pre-eclampsia. Pre-eclampsia can also newly develop in the postpartum period and should be suspected if a rise in BP is associated with some symptoms (headache, epigastric pain, visual disturbances, dyspnea, edema in the face, hands, feet, or seizures).

All antihypertensive drugs are excreted into breast milk, most of them at very low concentrations. Labetalol, nifedipine, and enalapril are considered safe and are recommended by most guidelines. However, ACE inhibitors should not be used in cases of premature birth or renal failure of the newborn.

Women with a history of HDPs are at higher risk of developing CVD prematurely in later life.

Data availability

Not applicable.

Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, et al. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018;39(34):3165–241.

Article   PubMed   Google Scholar  

Shen M, Tan H, Zhou S, Smith GN, Walker MC, Wen SW. Trajectory of blood pressure change during pregnancy and the role of pre-gravid blood pressure: a functional data analysis approach. Sci Rep. 2017;7(1):6227.

Article   PubMed   PubMed Central   Google Scholar  

Stergiou GS, Palatini P, Asmar R, Ioannidis JP, Kollias A, Lacy P, et al. Recommendations and Practical Guidance for performing and reporting validation studies according to the Universal Standard for the validation of blood pressure measuring devices by the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO). J Hypertens. 2019;37(3):459–66.

Article   CAS   PubMed   Google Scholar  

Davis GK, Roberts LM, Mangos GJ, Brown MA. Comparisons of auscultatory hybrid and automated sphygmomanometers with mercury sphygmomanometry in hypertensive and normotensive pregnant women: parallel validation studies. J Hypertens. 2015;33(3):499–505 ( discussion -6 ).

Mounier-Vehier C, Amar J, Boivin JM, Denolle T, Fauvel JP, Plu-Bureau G, et al. Hypertension and pregnancy: expert consensus statement from the French Society of Hypertension, an affiliate of the French Society of Cardiology. Fundam Clin Pharmacol. 2017;31(1):83–103.

van den Born BH, Lip GYH, Brguljan-Hitij J, Cremer A, Segura J, Morales E, et al. ESC Council on hypertension position document on the management of hypertensive emergencies. Eur Heart J Cardiovasc Pharmacother. 2019;5(1):37–46.

O’Brien E, Parati G, Stergiou G, Asmar R, Beilin L, Bilo G, et al. European Society of Hypertension position paper on ambulatory blood pressure monitoring. J Hypertens. 2013;31(9):1731–68.

Magee LA, Ramsay G, von Dadelszen P. What is the role of out-of-office BP measurement in hypertensive pregnancy? Hypertens Preg. 2008;27(2):95–101.

Article   CAS   Google Scholar  

Ditisheim A, Wuerzner G, Ponte B, Vial Y, Irion O, Burnier M, et al. Prevalence of hypertensive phenotypes after preeclampsia: a prospective cohort study. Hypertension. 2018;71(1):103–9.

Tucker KL, Mort S, Yu LM, Campbell H, Rivero-Arias O, Wilson HM, et al. Effect of self-monitoring of blood pressure on diagnosis of hypertension during higher-risk pregnancy: the BUMP 1 randomized clinical trial. JAMA. 2022;327(17):1656–65.

Chappell LC, Tucker KL, Galal U, Yu LM, Campbell H, Rivero-Arias O, et al. Effect of self-monitoring of blood pressure on blood pressure control in pregnant individuals with chronic or gestational hypertension: the BUMP 2 Randomized Clinical Trial. JAMA. 2022;327(17):1666–78.

Denolle T, Weber JL, Calvez C, Getin Y, Daniel JC, Lurton O, et al. Diagnosis of white coat hypertension in pregnant women with teletransmitted home blood pressure. Hypertens Preg. 2008;27(3):305–13.

Article   Google Scholar  

Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension: The Task Force for the management of arterial hypertension of the European Society of Cardiology and the European Society of Hypertension. J Hypertens. 2018;36(10):1953–2041.

Ives CW, Sinkey R, Rajapreyar I, Tita ATN, Oparil S. Preeclampsia-pathophysiology and clinical presentations: JACC state-of-the-art review. J Am Coll Cardiol. 2020;76(14):1690–702.

Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. The hypertensive disorders of pregnancy: ISSHP classification, diagnosis & management recommendations for international practice. Preg Hypertens. 2018;13:291–310.

Seely EW, Ecker J. Chronic hypertension in pregnancy. Circulation. 2014;129(11):1254–61.

Zeisler H, Llurba E, Chantraine F, Vatish M, Staff AC, Sennström M, et al. Predictive value of the sFlt-1:PlGF ratio in women with suspected preeclampsia. N Engl J Med. 2016;374(1):13–22.

Verlohren S, Brennecke SP, Galindo A, Karumanchi SA, Mirkovic LB, Schlembach D, et al. Clinical interpretation and implementation of the sFlt-1/PlGF ratio in the prediction, diagnosis and management of preeclampsia. Preg Hypertens. 2022;27:42–50.

Huhn EA, Kreienbühl A, Hoffmann I, Schoetzau A, Lange S, de Tejada BM, et al. Diagnostic accuracy of different soluble fms-like tyrosine kinase 1 and placental growth factor cut-off values in the assessment of preterm and term preeclampsia: a gestational age matched case-control study. Front Med (Lausanne). 2018;5:325.

Cerdeira AS, O’Sullivan J, Ohuma EO, James T, Papageorghiou AT, Knight M, et al. Performance of soluble fms-like tyrosine kinase-1-to-placental growth factor ratio of ≥85 for ruling in preeclampsia within 4 weeks. Am J Obstet Gynecol. 2021;224(3):322–3.

Gaccioli F, Sovio U, Gong S, Cook E, Charnock-Jones DS, Smith GCS. Increased placental sFLT1 (Soluble fms-Like Tyrosine Kinase Receptor-1) drives the antiangiogenic profile of maternal serum preceding preeclampsia but not fetal growth restriction. Hypertension. 2023;80(2):325–34.

Rossi GP, Seccia TM, Pessina AC. Clinical use of laboratory tests for the identification of secondary forms of arterial hypertension. Crit Rev Clin Lab Sci. 2007;44(1):1–85.

Rolnik DL, Wright D, Poon LC, O’Gorman N, Syngelaki A, de Paco MC, et al. Aspirin versus placebo in pregnancies at high risk for preterm preeclampsia. N Engl J Med. 2017;377(7):613–22.

Gornik HL, Persu A, Adlam D, Aparicio LS, Azizi M, Boulanger M, et al. First international consensus on the diagnosis and management of fibromuscular dysplasia. J Hypertens. 2019;37(2):229–52.

Lenders JW. Pheochromocytoma and pregnancy: a deceptive connection. Eur J Endocrinol. 2012;166(2):143–50.

Morton A. Primary aldosteronism and pregnancy. Pregnancy Hypertens. 2015;5(4):259–62.

Landau E, Amar L. Primary aldosteronism and pregnancy. Ann Endocrinol (Paris). 2016;77(2):148–60.

Almasi-Hashiani A, Omani-Samani R, Mohammadi M, Amini P, Navid B, Alizadeh A, et al. Assisted reproductive technology and the risk of preeclampsia: an updated systematic review and meta-analysis. BMC Preg Childb. 2019;19(1):149.

Chih HJ, Elias FTS, Gaudet L, Velez MP. Assisted reproductive technology and hypertensive disorders of pregnancy: systematic review and meta-analyses. BMC Preg Childb. 2021;21(1):449.

Sindre HP, Westvik-Johari K, Spangmose AL, Pinborg A, Romundstad LB, Bergh C, et al. Risk of hypertensive disorders in pregnancy after fresh and frozen embryo transfer in assisted reproduction: a population-based cohort study with within-sibship analysis. Hypertension. 2023;80(2):e6–16.

Google Scholar  

Hofmeyr GJ, Lawrie TA, Atallah ÁN, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2018;10(10):Cd001059.

PubMed   Google Scholar  

Woo J, Giurgescu C, Wagner CL. Evidence of an association between vitamin D deficiency and preterm birth and preeclampsia: a critical review. J Midwif Womens Health. 2019;64(5):613–29.

Fogacci S, Fogacci F, Banach M, Michos ED, Hernandez AV, Lip GYH, et al. Vitamin D supplementation and incident preeclampsia: a systematic review and meta-analysis of randomized clinical trials. Clin Nutr. 2020;39(6):1742–52.

Rossi AC, Mullin PM. Prevention of pre-eclampsia with low-dose aspirin or vitamins C and E in women at high or low risk: a systematic review with meta-analysis. Eur J Obstet Gynecol Reprod Biol. 2011;158(1):9–16.

Villar J, Purwar M, Merialdi M, Zavaleta N, Thi Nhu Ngoc N, Anthony J, et al. World Health Organisation multicentre randomised trial of supplementation with vitamins C and E among pregnant women at high risk for pre-eclampsia in populations of low nutritional status from developing countries. BJOG. 2009;116(6):780–8.

Poston L, Briley AL, Seed PT, Kelly FJ, Shennan AH. Vitamin C and vitamin E in pregnant women at risk for pre-eclampsia (VIP trial): randomised placebo-controlled trial. Lancet. 2006;367(9517):1145–54.

Cockburn J, Moar VA, Ounsted M, Redman CW. Final report of study on hypertension during pregnancy: the effects of specific treatment on the growth and development of the children. Lancet. 1982;1(8273):647–9.

Redman CW, Beilin LJ, Bonnar J. Treatment of hypertension in pregnancy with methyldopa: blood pressure control and side effects. Br J Obstet Gynaecol. 1977;84(6):419–26.

Abalos E, Duley L, Steyn DW. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2014;2014(2):Cd002252.

Abalos E, Duley L, Steyn DW, Henderson-Smart DJ. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2007;207(1):Cd002252.

Abalos E, Duley L, Steyn DW, Gialdini C. Antihypertensive drug therapy for mild to moderate hypertension during pregnancy. Cochrane Database Syst Rev. 2018;10(10):Cd002252.

Bone JN, Sandhu A, Abalos ED, Khalil A, Singer J, Prasad S, et al. Oral antihypertensives for nonsevere pregnancy hypertension: systematic review, network meta- and trial sequential analyses. Hypertension. 2022;79(3):614–28.

Webster K, Fishburn S, Maresh M, Findlay SC, Chappell LC. Diagnosis and management of hypertension in pregnancy: summary of updated NICE guidance. BMJ. 2019;366: l5119.

Physical activity and exercise during pregnancy and the postpartum period: ACOG Committee Opinion Summary, Number 804. Obstet Gynecol. 2020;135(4):991–3.

Di Mascio D, Magro-Malosso ER, Saccone G, Marhefka GD, Berghella V. Exercise during pregnancy in normal-weight women and risk of preterm birth: a systematic review and meta-analysis of randomized controlled trials. Am J Obstet Gynecol. 2016;215(5):561–71.

Barakat R, Pelaez M, Cordero Y, Perales M, Lopez C, Coteron J, et al. Exercise during pregnancy protects against hypertension and macrosomia: randomized clinical trial. Am J Obstet Gynecol. 2016;214(5):649.e1-8.

Santos S, Voerman E, Amiano P, Barros H, Beilin LJ, Bergström A, et al. Impact of maternal body mass index and gestational weight gain on pregnancy complications: an individual participant data meta-analysis of European, North American and Australian cohorts. BJOG. 2019;126(8):984–95.

CAS   PubMed   PubMed Central   Google Scholar  

Martínez-Vizcaíno V, Sanabria-Martínez G, Fernández-Rodríguez R, Cavero-Redondo I, Pascual-Morena C, Álvarez-Bueno C, et al. Exercise during pregnancy for preventing gestational diabetes mellitus and hypertensive disorders: an umbrella review of randomised controlled trials and an updated meta-analysis. BJOG. 2023;130(3):264–75.

Dodd JM, Turnbull D, McPhee AJ, Deussen AR, Grivell RM, Yelland LN, et al. Antenatal lifestyle advice for women who are overweight or obese: LIMIT randomised trial. BMJ. 2014;348: g1285.

Maxwell C, Gaudet L, Cassir G, Nowik C, McLeod NL, Jacob C, et al. Guideline no. 391-pregnancy and maternal obesity part 1: pre-conception and prenatal care. J Obstet Gynaecol Can. 2019;41(11):1623–40.

Maxwell C, Gaudet L, Cassir G, Nowik C, McLeod NL, Jacob C, et al. Guideline no. 392-pregnancy and maternal obesity part 2: team planning for delivery and postpartum care. J Obstet Gynaecol Can. 2019;41(11):1660–75.

Magee LA, Cham C, Waterman EJ, Ohlsson A, von Dadelszen P. Hydralazine for treatment of severe hypertension in pregnancy: meta-analysis. BMJ. 2003;327(7421):955–60.

Article   CAS   PubMed   PubMed Central   Google Scholar  

Antza C, Dimou C, Doundoulakis I, Akrivos E, Stabouli S, Haidich AB, et al. The flipside of hydralazine in pregnancy: a systematic review and meta-analysis. Preg Hypertens. 2020;19:177–86.

Sridharan K, Sequeira RP. Drugs for treating severe hypertension in pregnancy: a network meta-analysis and trial sequential analysis of randomized clinical trials. Br J Clin Pharmacol. 2018;84(9):1906–16.

Cífková R, Johnson MR, Kahan T, Brguljan J, Williams B, Coca A, et al. Peripartum management of hypertension: a position paper of the ESC Council on Hypertension and the European Society of Hypertension. Eur Heart J Cardiovasc Pharmacother. 2020;6(6):384–93.

Altman D, Carroli G, Duley L, Farrell B, Moodley J, Neilson J, et al. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet. 2002;359(9321):1877–90.

Duley L, Gülmezoglu AM, Henderson-Smart DJ, Chou D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane Database Syst Rev. 2010;2010(11):Cd000025.

PubMed   PubMed Central   Google Scholar  

Magee LA, von Dadelszen P, Rey E, Ross S, Asztalos E, Murphy KE, et al. Less-tight versus tight control of hypertension in pregnancy. N Engl J Med. 2015;372(5):407–17.

August P. Lowering diastolic blood pressure in non-proteinuric hypertension in pregnancy is not harmful to the fetus and is associated with reduced frequency of severe maternal hypertension. Evid Based Med. 2015;20(4):141.

Tita AT, Szychowski JM, Boggess K, Dugoff L, Sibai B, Lawrence K, et al. Treatment for mild chronic hypertension during pregnancy. N Engl J Med. 2022;386(19):1781–92.

Koopmans CM, Bijlenga D, Groen H, Vijgen SM, Aarnoudse JG, Bekedam DJ, et al. Induction of labour versus expectant monitoring for gestational hypertension or mild pre-eclampsia after 36 weeks’ gestation (HYPITAT): a multicentre, open-label randomised controlled trial. Lancet. 2009;374(9694):979–88.

Wilson BJ, Watson MS, Prescott GJ, Sunderland S, Campbell DM, Hannaford P, et al. Hypertensive diseases of pregnancy and risk of hypertension and stroke in later life: results from cohort study. BMJ. 2003;326(7394):845.

Søndergaard MM, Hlatky MA, Stefanick ML, Vittinghoff E, Nah G, Allison M, et al. Association of adverse pregnancy outcomes with risk of atherosclerotic cardiovascular disease in postmenopausal women. JAMA Cardiol. 2020;5(12):1390–8.

Wu P, Haththotuwa R, Kwok CS, Babu A, Kotronias RA, Rushton C, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10(2):e003497.

Countouris ME, Villanueva FS, Berlacher KL, Cavalcante JL, Parks WT, Catov JM. Association of hypertensive disorders of pregnancy with left ventricular remodeling later in life. J Am Coll Cardiol. 2021;77(8):1057–68.

Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73(24):e285–350.

Hilfiker-Kleiner D, Haghikia A, Nonhoff J, Bauersachs J. Peripartum cardiomyopathy: current management and future perspectives. Eur Heart J. 2015;36(18):1090–7.

Gammill HS, Chettier R, Brewer A, Roberts JM, Shree R, Tsigas E, et al. Cardiomyopathy and preeclampsia. Circulation. 2018;138(21):2359–66.

Paradisi G, Biaggi A, Savone R, Ianniello F, Tomei C, Caforio L, et al. Cardiovascular risk factors in healthy women with previous gestational hypertension. J Clin Endocrinol Metab. 2006;91(4):1233–8.

Schliep KC, McLean H, Yan B, Qeadan F, Theilen LH, de Havenon A, et al. Association between hypertensive disorders of pregnancy and dementia: a systematic review and meta-analysis. Hypertension. 2023;80(2):257–67.

Escudero C, Kupka E, Ibañez B, Sandoval H, Troncoso F, Wikström AK, et al. Brain vascular dysfunction in mothers and their children exposed to preeclampsia. Hypertension. 2023;80(2):242–56.

Heida KY, Bots ML, de Groot CJ, van Dunné FM, Hammoud NM, Hoek A, et al. Cardiovascular risk management after reproductive and pregnancy-related disorders: a Dutch multidisciplinary evidence-based guideline. Eur J Prev Cardiol. 2016;23(17):1863–79.

Kitt J, Frost A, Mollison J, Tucker KL, Suriano K, Kenworthy Y, et al. Postpartum blood pressure self-management following hypertensive pregnancy: protocol of the Physician Optimised Post-partum Hypertension Treatment (POP-HT) trial. BMJ Open. 2022;12(2): e051180.

Spaan J, Peeters L, Spaanderman M, Brown M. Cardiovascular risk management after a hypertensive disorder of pregnancy. Hypertension. 2012;60(6):1368–73.

Arnott C, Patel S, Hyett J, Jennings G, Woodward M, Celermajer DS. Women and cardiovascular disease: pregnancy, the forgotten risk factor. Heart Lung Circ. 2020;29(5):662–7.

Yang H, Kuhn C, Kolben T, Ma Z, Lin P, Mahner S, et al. Early life oxidative stress and long-lasting cardiovascular effects on offspring conceived by assisted reproductive technologies: a review. Int J Mol Sci. 2020;21(15):5175.

Thomopoulos C, Salamalekis G, Kintis K, Andrianopoulou I, Michalopoulou H, Skalis G, et al. Risk of hypertensive disorders in pregnancy following assisted reproductive technology: overview and meta-analysis. J Clin Hypertens (Greenwich). 2017;19(2):173–83.

Brown MA, Magee LA, Kenny LC, Karumanchi SA, McCarthy FP, Saito S, et al. Hypertensive disorders of pregnancy: ISSHP classification, diagnosis, and management recommendations for international practice. Hypertension. 2018;72(1):24–43.

Scherrer U, Rexhaj E, Allemann Y, Sartori C, Rimoldi SF. Cardiovascular dysfunction in children conceived by assisted reproductive technologies. Eur Heart J. 2015;36(25):1583–9.

Meister TA, Rimoldi SF, Soria R, von Arx R, Messerli FH, Sartori C, et al. Association of assisted reproductive technologies with arterial hypertension during adolescence. J Am Coll Cardiol. 2018;72(11):1267–74.

Cui L, Zhao M, Zhang Z, Zhou W, Lv J, Hu J, et al. Assessment of cardiovascular health of children ages 6 to 10 years conceived by assisted reproductive technology. JAMA Netw Open. 2021;4(11): e2132602.

Download references

Author information

Authors and affiliations.

Center for Cardiovascular Prevention, Charles University in Prague, First Faculty of Medicine and Thomayer University Hospital, Prague, Czech Republic

Renata Cífková

Department of Medicine II, Charles University in Prague, First Faculty of Medicine, Prague, Czech Republic

You can also search for this author in PubMed   Google Scholar

Corresponding author

Correspondence to Renata Cífková .

Ethics declarations

Open access publishing supported by the National Technical Library in Prague.

Conflict of interest

The author declares no financial or non-financial conflicts of interest, directly or indirectly related to the work submitted.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ .

Reprints and permissions

About this article

Cífková, R. Hypertension in Pregnancy: A Diagnostic and Therapeutic Overview. High Blood Press Cardiovasc Prev 30 , 289–303 (2023). https://doi.org/10.1007/s40292-023-00582-5

Download citation

Received : 04 May 2023

Accepted : 16 May 2023

Published : 13 June 2023

Issue Date : July 2023

DOI : https://doi.org/10.1007/s40292-023-00582-5

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Classification of hypertensive disorders in pregnancy
• Pre-conception counselling
• Prevention of pre-eclampsia
• Drug treatment of hypertension in pregnancy
• Cardiovascular risk after hypertensive disorders in pregnancy
• Find a journal
• Publish with us
• Track your research

• Open access
• Published: 24 April 2024

Analysis of risk factors of preeclampsia in pregnant women with chronic hypertension and its impact on pregnancy outcomes

• Xiaorui Nie 1 ,
• Zijie Xu 1 &
• Hong Ren 1  

BMC Pregnancy and Childbirth volume  24 , Article number:  307 ( 2024 ) Cite this article

20 Accesses

Metrics details

To investigate the risk factors and maternal and fetal outcomes of preeclampsia after pregnancy in patients with primary chronic hypertension.

A total of 500 singleton pregnant women with a history of hypertension who were admitted for delivery at our Hospital from March 2015 to May 2022 were retrospectively collected by random sampling and divided into the non-occurrence group ( n  = 200) and the occurrence group ( n  = 300) according to whether they were complicated by preeclampsia. Afterward, the general data and the pregnancy-related data of patients were collected for comparison.

The univariate analysis showed significant differences between the non-occurrence group and the occurrence group in terms of the proportion of preeclampsia history (4.00% VS 24.67%, χ2  = 37.383, P  < 0.001), duration of hypertension > 3 years (18.00% VS 31.67%, χ2  = 11.592, P  < 0.001), systemic therapy (20.50% VS 10.00%, χ2  = 10.859, P  < 0.001), gestational age at admission [37.72 (34.10, 38.71) VS 35.01 (31.91, 37.42) weeks, Z = -9.825, P  < 0.001]. Meanwhile, the multivariate analysis showed that a history of preeclampsia (OR = 6.796, 95% CI: 3.575  ∼  10.134, χ2  = 8.234, P  < 0.001), duration of hypertension > 3 years (OR = 3.456, 95% CI: 2.157  ∼  5.161, χ2  = 9.348, P  < 0.001), and a lack of systemic antihypertensive treatment (OR = 8.983, 95% CI: 7.735  ∼  9.933, χ2  = 9.123, P  < 0.001) were risk factors for chronic hypertension complicated by preeclampsia during pregnancy.

A history of preeclampsia, a longer duration of hypertension, and a lack of systematic antihypertensive treatment are risk factors for chronic hypertension complicated by preeclampsia during pregnancy. The occurrence of preeclampsia in pregnant women with chronic hypertension increases the incidence of maternal HELLP syndrome and fetal distress.

Peer Review reports

Introduction

Chronic hypertension complicated by pregnancy refers to the occurrence of elevated blood pressure before pregnancy or before 20 weeks of gestation, with no significant aggravation during pregnancy, or diagnosed as hypertension after 20 weeks of gestation while blood pressure remains elevated for 12 weeks after delivery [ 1 ]. Studies have shown that about 6% of pregnant women in China suffer from chronic hypertension [ 2 ], and the number of patients is increasing worldwide. Meanwhile, the incidence of chronic hypertension complicated by pregnancy has increased by 67% in recent years according to foreign reports [ 3 ]. Chronic hypertension complicated by pregnancy not only affects the organ function of pregnant women but also increases the risk of adverse pregnancy outcomes. A study showed that pregnant women with a history of chronic hypertension have at least a nearly 5-fold to 6-fold increased risk of cardiovascular and cerebrovascular diseases and multi-organ dysfunction than those with normal blood pressure [ 4 ]. More studies also indicate that women with primary hypertension experience earlier and more severe maternal and fetal complications once complicated by preeclampsia after pregnancy [ 5 ]. The previous research conducted by Bramham K et al. [ 6 ] in the United States on 822 pregnant women with chronic hypertension already demonstrated that the potential risk of severe intrauterine hypoxia, fetal growth restriction, and even stillbirth was significantly increased in pregnant women with preeclampsia [ 7 ]. The incidence of preeclampsia in the general Chinese pregnant population is about 3 − 5%, while the incidence of preeclampsia in pregnant women with chronic hypertension can reach 17 − 25% [ 8 ]. In contrast, foreign studies have indicated an incidence of 13 − 40% for preeclampsia in women with chronic hypertension [ 9 ].

Preeclampsia is a complex and dynamic process, and its exact pathogenesis remains unclear. Currently, it is believed that the infiltration of trophoblast cells and the remodeling of uterine spiral arteries during placental formation are important links in the occurrence of preeclampsia [ 2 ]. Some scholars have proposed the “two-stage” theory for the occurrence of preeclampsia [ 10 ] and further developed the “six-stage” model [ 11 ]. In addition to causing adverse pregnancy outcomes, the occurrence of preeclampsia also has some impact on the long-term prognosis of pregnant patients, such as depression [ 12 , 13 , 14 , 15 ]. Therefore, it is of great significance to identify high-risk factors for chronic hypertension complicated by preeclampsia, screen out high-risk pregnant women promptly, and take early intervention measures for the pregnancy outcomes and long-term prognosis of both mother and child.

Most current research and clinical trials focus on statistical analysis of pregnancy-induced hypertension with or without preeclampsia and comparisons of different pregnancy outcomes. However, there is limited research on the special population of chronic hypertension with preeclampsia. Therefore, the risk factors for the occurrence of preeclampsia in pregnant women with chronic hypertension have not been clearly identified. This study is designed to analyze the population of pregnant women with chronic hypertension and explore the high-risk factors for the occurrence of preeclampsia, as well as its impact on maternal and fetal outcomes, so as to better guide the screening of high-risk groups before pregnancy and reduce the occurrence of adverse maternal and fetal outcomes.

Study subjects and methods

Study subjects.

A total of 500 singleton pregnant women with a history of hypertension who were admitted for delivery at Beijing Chaoyang District Maternal and Child Health Care Hospital from March 2015 to May 2022 were retrospectively collected by random sampling and divided into the non-occurrence group ( n  = 200) and the occurrence group ( n  = 300) based on whether they developed concurrent preeclampsia. Inclusion Criteria: (1) Patients with a singleton pregnancy; (2) Patients diagnosed with chronic hypertension complicated by pregnancy (without preeclampsia) or chronic hypertension complicated by pregnancy with preeclampsia. Exclusion Criteria: (1) Patients with secondary hypertension such as renal hypertension and pheochromocytoma diagnosed during pregnancy or postpartum; (2) Patients with normal maternal blood pressure during follow-up at 12 weeks after delivery; (3) Patients with malformed infants found in the second trimester requiring induction of labor; (4) Patients with multiple pregnancies.

Study methods

Diagnostic criteria for chronic hypertension: Diastolic blood pressure ≥ 90 mmHg and/or systolic blood pressure ≥ 140 mmHg before pregnancy or before 20 weeks of gestation, with the latter seeing persistent blood pressure ≥ 140/90 mmHg 3 months after delivery.

Criteria for cardiovascular risk stratification of chronic hypertension: (1) Mild (low risk): diastolic blood pressure = 90  ∼  99 mmHg, systolic blood pressure = 140  ∼  159 mmHg, without target organ damage; (2) Moderate (medium risk): diastolic blood pressure = 100  ∼  109 mmHg, systolic blood pressure = 160  ∼  179 mmHg; (3) Severe (high risk): diastolic blood pressure ≥ 110 mmHg, systolic blood pressure ≥ 180 mmHg, without target organ damage, or diastolic blood pressure = 90  ∼  99 mmHg, systolic blood pressure = 140  ∼  150 mmHg, with diabetes or target organ damage.

Diagnostic criteria for preeclampsia: (1) Presence of proteinuria after 20 weeks of gestation; (2) pregnant women with hypertension and proteinuria before 20 weeks of gestation suddenly developed elevated blood pressure or increased proteinuria; (3) Elevated creatinine and liver enzymes, or platelets < 100 × 109/L, or accompanied by right upper abdominal pain, headache, and other symptoms.

Treatment methods for hypertension [ 16 ]: All pregnant women were treated with low-dose aspirin (100 mg/d) before 20 weeks of gestation. For patients with mild hypertension, low-dose aspirin alone was used; for patients with blood pressure ≥ 150/100 mmHg for more than 2 times and target organ damage, antihypertensive drugs were added; for patients with a sharp increase in blood pressure or proteinuria, additional tests were conducted to determine if they had preeclampsia. Those with preeclampsia were hospitalized for observation, and if the condition stabilized, they could continue the pregnancy and be discharged with follow-up. However, they could continue hospitalization if severe preeclampsia develops. Low-dose aspirin was discontinued after 36 weeks of gestation in pregnant women without preeclampsia, with premature infants and low birth weight infants transferred to the neonatal ICU for treatment.

Data collection

General characteristics data of the patients were collected, including: age, pre-delivery BMI, previous pregnancy and delivery history, previous blood pressure control, family history of hypertension, and history of previous preeclampsia in pregnancy. Delivery-related data included: newborn birth weight, newborn Apgar score results, and the occurrence of related maternal and fetal complications.

The newborn Apgar score is used to determine the severity of neonatal asphyxia and asphyxia, which is based on five signs within one minute after birth, i.e., heart rate, respiration, muscle tone, laryngeal reflex, and skin color, each of which scored from 0 to 2, with a maximum score of 10. Scores of 8  ∼  10: normal; 4  ∼  7: mild asphyxia; 0  ∼  3: severe asphyxia. The lower the score, the more severe acidosis and hypoxemia, and the higher the mortality rate, which required immediate rescue to improve asphyxia [ 17 ].

Common maternal complications include placental abruption, postpartum hemorrhage, and HELLP syndrome, while fetal complications mainly include intrauterine growth restriction (IUGR), fetal distress, abnormal amniotic fluid volume, abnormal diastolic blood flow signals, premature delivery, and stillbirth. (1) Diagnostic criteria for placental abruption: the placental abruption surface does not exceed 1/3 of the placental area, the signs are not obvious, the main symptoms are a large amount of vaginal bleeding, no abdominal pain or mild abdominal pain, and the fetal heart rate is normal [ 18 ]; (2) Diagnostic criteria for postpartum hemorrhage: the amount of blood loss reaches or exceeds 500 mL within 24 h after delivery of the fetus [ 18 ]. (3) Diagnostic criteria for fetal growth restriction (FGR): fetal head circumference, femur length, and abdominal circumference are measured by ultrasound, and fetal weight (EFW) is estimated by substituting the HadlockC formula, and FGR is diagnosed if EFW is less than the 10th percentile of the same gestational age [ 19 ]. (4) Diagnostic criteria for fetal distress: the fetus in the womb due to acute or chronic hypoxia endangering health and life syndrome, mainly manifested as abnormal fetal heart rate during delivery, amniotic fluid meconium contamination and abnormal fetal heart rate monitoring (late deceleration, frequent mutation deceleration), abnormal fetal movement (hypoxia in the initial stage of frequent fetal movements, then weakened and reduced, and then disappeared). Intrauterine distress is diagnosed if any of the above are achieved [ 18 ]. (5) Diagnostic criteria for oligohydramnios: those with less than 300 ml of amniotic fluid in the third trimester of pregnancy are called oligohydramnios. The prenatal diagnosis of oligohydramnios is mainly determined by the maximum depth (AFV) of the dark area of the amniotic fluid and the index of amniotic fluid (AFI) by color ultrasound, with AFV  ≦  2 cm being oligohydramnios and AFI  ≦  5 cm being the standard for oligohydramnios. Hypohydramnios can be clearly diagnosed if the total amount is less than 300 ml when the membrane is broken and the amount of amniotic fluid is collected by various methods after delivery. Polyhydramnios: The amount of amniotic fluid during pregnancy is more than 2000 ml, which is called polyhydramnios. The prenatal diagnosis of polyhydramnios is mainly determined by the maximum depth (AFV) of the dark area of the amniotic fluid and the amniotic fluid index (AFI) monitored by color ultrasound, AFV  ≧  8 cm is diagnosed as polyhydramnios, and AFI  ≧  25 cm is diagnosed as polyhydramnios. A total amount of more than 2000 mL of amniotic fluid collected postpartum confirms the diagnosis of polyhydramnios [ 18 ].(6) Premature delivery: It refers to delivery at 28 weeks of gestation and less than 37 weeks of gestation, resulting in premature infants with a birth weight between 1,000 and 2,499 g [ 20 ].

Statistical analysis

SPSS 26.00 software was used for statistical analysis. The K-S method was used for the normality test, measurement data complying with normality were expressed as (x ± s), and the independent sample t-test was used for inter-group comparison. Count data were expressed as frequency (n) or rate (%), with the χ2 test used for the comparison of general data and the rank-sum test for the comparison of grade data. Meanwhile, the skewed distribution was described using the median (interquartile range), and the rank-sum test was used for inter-group comparison. In addition, multivariate analysis was conducted using Logistic regression, and the ROC curve was used to analyze the predictive value of each factor for the occurrence of preeclampsia in patients with chronic hypertension during pregnancy. The significance level was set at α = 0.05.

Comparison of general data between patients with/without preeclampsia

The comparison of general data between the two groups showed that the mean age of the group without preeclampsia was 33.69 ± 5.80, with 104 primiparas, a median pre-delivery BMI of 30.00 (27.38, 32.23) kg/m2, and a history of preeclampsia ( n  = 8); the mean age of the group with preeclampsia was 32.74 ± 5.25, with 146 primiparas, the median pre-delivery BMI of 31.51 (29.21, 34.91) kg/m2, and a history of preeclampsia ( n  = 74). There were significant differences between the two groups in the history of preeclampsia (4.00% VS 24.67%, χ 2  = 37.383, P  < 0.001), duration of hypertension > 3 years (18.00% VS 31.67%, χ 2  = 11.592, P  < 0.001), systemic therapy (20.50% VS 10.00%, χ 2  = 10.859, P  < 0.001), and gestational age at admission (37.72 (34.10, 38.71) VS 35.01 (31.91, 37.42) weeks, Z = -9.825, P  < 0.001). However, no significant difference was found in factors such as age, proportion of primiparous, pre-delivery BMI, proportion of positive antiphospholipid antibody, gravidity, parity, and family history of hypertension between the two groups ( P  > 0.05), as shown in Table  1 .

Multivariate logistic regression analysis of patients with chronic hypertension complicated by preeclampsia

A logistic regression analysis model was constructed with the presence or absence of preeclampsia as the dependent variable (occurrence = 1, absence = 0), and statistically significant factors in the aforementioned analysis as independent variables [history of preeclampsia (presence = 1, absence = 0), duration of hypertension > 3 years (presence = 1, absence = 0), performing systemic therapy (presence = 1, absence = 0), and gestational age at admission entered at the original value]. The findings revealed that a history of preeclampsia (OR = 6.796, 95% CI: 3.575  ∼  10.134, χ 2  = 8.234, P  < 0.001), duration of hypertension > 3 years (OR = 3.456, 95% CI: 2.157  ∼  5.161, χ 2  = 9.348, P  < 0.001), and a lack of systemic antihypertensive treatment (OR = 8.983, 95% CI: 7.735  ∼  9.933, χ 2  = 9.123, P  < 0.001) were risk factors for the occurrence of chronic hypertension complicated by preeclampsia. See Table  2 .

Predictive value of duration of hypertension, history of preeclampsia, and systemic therapy for chronic hypertension complicated by preeclampsia in pregnant women

The duration of hypertension, history of preeclampsia, and systemic therapy were of certain value in predicting the occurrence of preeclampsia in pregnant women with chronic hypertension ( P  < 0.05). Specifically, the area under the curve (AUC) of the duration of hypertension, history of preeclampsia, and systemic therapy in predicting preeclampsia in pregnant women with chronic hypertension were 0.752 (95% CI: 0.683, 0.792), 0.746 (95% CI: 0.679, 0.821), and 0.756 (95% CI: 0.691, 0.823), respectively. In terms of combined prediction, the combined prediction effect was better than that of the single prediction, and the AUC of the three factors combined for predicting the occurrence of preeclampsia in pregnant women with chronic hypertension was 0.856 (95%CI: 0.790, 0.898), as shown in Table  3 .

Effect of preeclampsia on pregnancy outcomes in pregnant women with chronic hypertension

A comparison of pregnancy outcomes between pregnant women with and without preeclampsia in chronic hypertension showed that there were significant differences in the occurrence of HELLP syndrome (1 VS 22 cases, χ 2  = 12.769, P  < 0.001), gestational age at delivery [38.10 (36.11, 38.91) VS 35.61 (32.42, 37.61) weeks, Z = -9.874, P  < 0.001], newborn birth weight (3200.32 ± 956.81 VS 2513.41 ± 903.82 g, t = -7.452, P  < 0.001), 1-min newborn Apgar score (9.41 ± 0.54 VS 8.46 ± 0.33 points, t = 9.417, P  < 0.001), 5-min newborn Apgar score (9.67 ± 0.45 VS 9.12 ± 0.24 points, t = 8.593, P  < 0.001), umbilical artery S/D value [2.21 (1.91, 2.50) VS 2.61 (2.22, 2.93), Z =-9.523, P  < 0.001], abnormal amniotic fluid volume (2 VS 15 cases, χ 2  = 5.846, P  = 0.016), and fetal distress (4 VS 42 cases, χ 2  = 20.686, P  < 0.001) were significantly different. However, there was no significant difference in postpartum hemorrhage, placental abruption, stillbirth, and IUGR between the two groups ( P  > 0.05). See Table  4 .

Chronic hypertension is a lifelong disease that affects the function of various organs in the body and is the leading disease that endangers people’s health, it has been reported in literature that the incidence of adverse pregnancy outcomes increases with the elevated blood pressure levels in pregnant women with different degrees of hypertension [ 21 ]. The relationship between hypertension and preeclampsia (PE) is traceable. In 2017, Boriboonhirunsarn et al. [ 22 ] performed a statistical analysis on 300 singleton pregnant women diagnosed with primary hypertension, which showed an incidence of 43.3% for concurrent PE in pregnant women with primary hypertension, and the incidence of adverse fetal outcomes increased. Numerous reports have shown that pregnant women complicated by PE see a significantly increased risk of maternal complications such as placental abruption and fetal growth restriction, leading to poor perinatal outcomes like premature delivery [ 23 ], cardiovascular disease [ 24 ]. Therefore, monitoring and management of pregnant women with chronic hypertension complicated by preeclampsia has become a common concern worldwide.

Some studies have found [ 25 ] that the aggregation of risk factors greatly increases the occurrence of adverse maternal and fetal outcomes in preeclampsia. Therefore, identifying high-risk factors for preeclampsia and strengthening prenatal monitoring of high-risk patients have become a hot topic in obstetric research. In our study, we identified several risk factors according to analyses of univariate cox regression and multiple cox regression, among them, the discovery on the risky nature of PE history aligned with previous established researches [ 26 , 27 ]. Though the negative effects of hypertension duration and patient age have been proved in PE development among hypertension patients [ 28 ], there is still a gap in related researches based on chronic hypertension population. We successfully illustrated the promoting effect of hypertension duration (> 3 years) to PE occurrence on chronic hypertension subjects, while the patient age showed no significant contribution, according to the investigation outcomes of this study. Moreover, for pregnant women with mild to moderate primary hypertension, strict and reasonable control of blood pressure levels can also reduce the incidence of preeclampsia [ 29 ], it seems to be equally applicable to pregnant subjects with chronic hypertension. The findings of this study demonstrated that untreated chronic hypertension and a longer course of hypertension increase the incidence of preeclampsia in patients with chronic hypertension.

In addition, it has been shown that family history of preeclampsia, history of preeclampsia, pregnancy interval ≥ 10 years, and primiparity are all risk factors for developing preeclampsia [ 29 ]. This study also found that a history of preeclampsia is a risk factor for developing preeclampsia after pregnancy in patients with primary chronic hypertension, which is consistent with previous research findings.

During a normal pregnancy, umbilical artery blood flow resistance gradually decreases with increasing gestational age, reflecting an increase in maternal-fetal blood exchange and normal fetal growth and development [ 30 ]. Studies have shown that the umbilical artery resistance index (S/D) should be ≤ 3 after 30 weeks of gestation [ 31 ]. This index is also a major parameter reflecting the fetal-placental circulation status and plays a role in predicting pregnancy outcomes. If this value shows no downward trend or even increases in the third trimester of pregnancy, it indicates increased blood flow resistance and increased placental perfusion pressure. This may manifest as reversed or absent umbilical artery blood flow signals, and in severe cases, it can lead to fetal hypoxia and distress.

In patients with chronic hypertension after pregnancy, due to long-term maintenance of high blood pressure levels, the small blood vessels throughout the body are in a state of spasm, affecting multiple organs and causing corresponding changes in their functions. Once complicated by preeclampsia, maternal and fetal complications (e.g., placental abruption, postpartum hemorrhage, HELLP syndrome) tend to occur earlier and more severely [ 32 ]. In order to balance the risks between the mother and the perinatal outcomes, they often lead to preterm termination of pregnancy, resulting in an increase in preterm delivery and cesarean section. The findings of this study also revealed that pregnant women with chronic hypertension complicated by preeclampsia experience a higher proportion of HELLP syndrome and shorter gestational age at delivery, which is consistent with the above findings.

Chronic hypertension complicated with preeclampsia is a common cause of iatrogenic preterm delivery, and the gestational age directly affects the maturity of the fetus, which is crucial for perinatal outcomes. Many studies have reported that preeclampsia increases the risk of fetal complications (e.g., fetal growth restriction, fetal distress, stillbirth, etc.). A statistical analysis of clinical mortality in China comparing pre-eclampsia with or without chronic hypertension suggested [ 33 ] that the probability of neonatal death due to chronic hypertension complicated with preeclampsia may be the highest among the studies of the classification of hypertensive disorders of pregnancy at various stages. Some scholars believe that chronic hypertension itself may not necessarily increase the incidence of IUGR. Only when preeclampsia causes insufficient early placental blood flow in the mother, it may become a key factor in the occurrence of fetal growth restriction [ 34 ]. The findings of of this study revealed that newborn birth weight and Apgar scores were relatively lower and the incidence of fetal distress events was higher in patients with chronic hypertension complicated by preeclampsia. However, there was no significant increase in the risk of complications such as severe fetal growth restriction and stillbirth.

Of course, this study comes with some limitations. Firstly, it is a single-center retrospective analysis, relying on medical records and laboratory query systems for data collection, and there was missing data for some pregnant women. Secondly, since its sample size is relatively small, further large-scale studies are needed to increase the persuasiveness. Specifically, further multi-center large-scale prospective studies are needed in the future.

In conclusion, a history of pre-eclampsia, long duration of hypertension, and a lack of systematic antihypertensive treatment are risk factors for chronic hypertension complicated with pre-eclampsia during pregnancy. The occurrence of preeclampsia in pregnant women with chronic hypertension increases the incidence of maternal HELLP syndrome and fetal distress.

Data availability

All data generated or analyzed during this study are included in this article.

ACOG Practice Bulletin No. 203 Summary: chronic hypertension in pregnancy. Obstet Gynecol. 2019;133:215–9. https://doi.org/10.1097/AOG.0000000000003021 .

Article   Google Scholar  

Ye C, Ruan Y, Zou L, Li G, Li C, Chen Y, et al. The 2011 survey on hypertensive disorders of pregnancy (HDP) in China: prevalence, risk factors, complications, pregnancy and perinatal outcomes. PLoS ONE. 2014;9:e100180. https://doi.org/10.1371/journal.pone.0100180 .

Article   CAS   PubMed   PubMed Central   Google Scholar  

Martin JA, Hamilton BE, Ventura SJ, Osterman MJ, Kirmeyer S, Mathews TJ, et al. Births: final data for 2009. Natl Vital Stat Rep. 2011;60:1–70.

PubMed   Google Scholar  

Gilbert WM, Young AL, Danielsen B. Pregnancy outcomes in women with chronic hypertension: a population-based study. J Reprod Med. 2007;52:1046–51.

Zheng DM, Li SH, Wang J, Li C. Effect of hypertensive disorder complicating pregnancy on neonatal birth outcome and umbilical artery blood flow. Med J Chin People’s Liberation Army. 2013;38:757–9. doi: CNKI:SUN:JFJY.0.2013-09-013.

Google Scholar  

Bramham K, Parnell B, Nelson-Piercy C, Seed PT, Poston L, Chappell LC. Chronic hypertension and pregnancy outcomes: systematic review and meta-analysis. BMJ. 2014;348:g2301. https://doi.org/10.1136/bmj.g2301 .

Article   PubMed   PubMed Central   Google Scholar  

Glover AV, Tita A, Biggio JR, Anderson SB, Harper LM. Incidence and risk factors for Postpartum severe hypertension in women with underlying chronic hypertension. Am J Perinatol. 2019;36:737–41. https://doi.org/10.1055/s-0038-1675153 .

Article   PubMed   Google Scholar  

Kumar M, Singh A, Garg R, Goel M, Ravi V. Hypertension during pregnancy and risk of stillbirth: challenges in a developing country. J Matern Fetal Neonatal Med. 2021;34:3915–21. https://doi.org/10.1080/14767058.2019.1702943 .

American College of Obstetricians and Gynecologists, Task Force on Hypertension in Pregnancy. Hypertension in pregnancy. Report of the American College of Obstetricians and gynecologists’ Task Force on hypertension in pregnancy. Obstet Gynecol. 2013;122:1122–31. https://doi.org/10.1097/01.AOG.0000437382.03963.88 .

Aouache R, Biquard L, Vaiman D, Miralles F. Oxidative stress in Preeclampsia and placental diseases. Int J Mol Sci. 2018;19:1496. https://doi.org/10.3390/ijms19051496 .

Redman C. The six stages of pre-eclampsia. Pregnancy Hypertens. 2014;4:246. https://doi.org/10.1016/j.preghy.2014.04.020 .

Youn H, Lee S, Han SW, Kim LY, Lee TS, Oh MJ, et al. Obstetric risk factors for depression during the postpartum period in South Korea: a nationwide study. J Psychosom Res. 2017;102:15–20. https://doi.org/10.1016/j.jpsychores.2017.09.003 .

McVittie C, Craig S, Temple M. A conversation analysis of communicative changes in a time-limited psychotherapy group for mothers with post-natal depression. Psychother Res. 2020;30:1048–60. https://doi.org/10.1080/10503307.2019.1694721 .

Pálinkás A, Sándor J, Papp M, Kőrösi L, Falusi Z, Pál L, et al. Associations between untreated depression and secondary health care utilization in patients with hypertension and/or diabetes. Soc Psychiatry Psychiatr Epidemiol. 2019;54:255–76. https://doi.org/10.1007/s00127-018-1545-7 .

Li Z, Li Y, Chen L, Chen P, Hu Y. Prevalence of Depression in patients with hypertension: a systematic review and Meta-analysis. Med (Baltim). 2015;94:e1317. https://doi.org/10.1097/MD.0000000000001317 .

Article   CAS   Google Scholar  

Obstetrics and Gynecology Branch of the Chinese Medical Association. Guidelines for the Diagnosis and Treatment of Hypertensive Disorders in Pregnancy. (2020). Chinese Journal of Obstetrics and Gynecology. 2020;55, 227–238. https://doi.org/10.3760/cma.j.cn112141-20200114-00039 .

Simon LV, Hashmi MF, Bragg BN, APGAR Score. 2023 May 22. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan&#8211.

Xie X, Kong B, Duan T et al. (2018). Obstetrics and Gynecology (9th ed.) [M]. People’s Medical Publishing House. July 18, 2018.

Albu AR, Horhoianu IA, Dumitrascu MC. Growth assessment in diagnosis of fetal growth restriction. Rev J Med Life. 2014;7:150–4.

CAS   Google Scholar  

Bian XM, Fu CW. Definition classification and diagnosis of premature delivery. Progress Obstet Gynecol. 2011;20:164–5. doi: CNKI:SUN:XDFC. 0.2011-03-003.

Wang XX, Song XL. Effect of different degrees of hypertensive disorder complicating pregnancy combined with cervical infection on pregnancy outcome and postoperative infection. Maternal Child Health Care China. 2016;31:3247–9. https://doi.org/10.7620/zgfybj.j.issn.1001-4411.2016 .

Boriboonhirunsarn D, Pradyachaipimol A, Viriyapak B. Incidence of superimposed preeclampsia among pregnant Asian women with chronic hypertension. Hypertens Pregnancy. 2017;36:226–31. https://doi.org/10.1080/10641955.2017.1311340 .

Sibai BM, Caritis SN, Thom E, Klebanoff M, McNellis D, Rocco L, et al. Prevention of preeclampsia with low-dose aspirin in healthy, nulliparous pregnant women. The National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units. N Engl J Med. 1993;329:1213–8. https://doi.org/10.1056/NEJM199310213291701 .

Article   CAS   PubMed   Google Scholar  

Mongraw-Chaffin ML, Cirillo PM, Cohn BA. Preeclampsia and cardiovascular disease death: prospective evidence from the child health and development studies cohort. Hypertension. 2010;56:166–71. https://doi.org/10.1161/HYPERTENSIONAHA.110.150078 .

Williams B, Masi S, Wolf J, Schmieder RE. Facing the challenge of lowering blood pressure and cholesterol in the same patient: report of a Symposium at the European Society of Hypertension. Cardiol Ther. 2020;9:19–34. https://doi.org/10.1007/s40119-019-00159-1 .

Wang XL, Yang SY, Zeng XY, Chen FZ. Effect of blood pressure control level during pregnancy on pregnancy outcomes in pregnant women with mild to moderate chronic hypertension. Chin J Hypertens. 2021;29:268–71. https://doi.org/10.16439/j.issn.1673-7245.2021.03.012 .

Wang JL. Clinical analysis of pregnant women with chronic hypertension. J Med Forum. 2014;28:123–4. doi: CNKI:SUN:HYYX.0.2014-10-059.

Teng XH, Pan SL. Relationship between maternal age and high risk factors of pregnancy and pregnancy outcomes. J Practical Obstet Gynecol. 2017;33:692–6. doi: CNKI:SUN:SFCZ.0.2017-09-019.

Lecarpentier E, Tsatsaris V, Goffinet F, Cabrol D, Sibai B, Haddad B. Risk factors of superimposed preeclampsia in women with essential chronic hypertension treated before pregnancy. PLoS ONE. 2013;8:e62140. https://doi.org/10.1371/journal.pone.0062140 .

Xiao HY, Wang YM. Clinical Value of Nursing Intervention for Diabetic Nephropathy Based on Maslow Hierarchy Theory. Chin J Gen Pract. 2019;17:1065–8. doi: CNKI:SUN:SYQY.0.2019-06-049.

Ayati S, Vahidroodsari F, Talebian M. Maternal death due to Placenta Percreta with bladder involvement: a Case Report. Tehran Univ Med J. 2011. b26a817249d1442fa9de7b6335385e85.

Yu S, Ren Q, Wu W. Effects of losartan on expression of monocyte chemoattractant protein-1 (MCP-1) in hyperuricemic nephropathy rats. J Recept Signal Transduct Res. 2015;35:458–61. https://doi.org/10.3109/10799893.2015.1006332 .

Li XM, Chen DJ, Li XY, Wang X, Gong JJ, Tang WT, et al. Clinical comparison of simple preeclampsia and chronic hypertension complicated by Preeclampsia. J Trop Med. 2016;16:1494–7. https://doi.org/10.3969/j.issn.1672-3619.2016.12.004 .

Benigni A, Gregorini G, Frusca T, Chiabrando C, Ballerini S, Valcamonico A, et al. Effect of low-dose aspirin on fetal and maternal generation of thromboxane by platelets in women at risk for pregnancy-induced hypertension. N Engl J Med. 1989;321:357–62. https://doi.org/10.1056/NEJM198908103210604 .

Download references

Acknowledgements

Not applicable.

Author information

Authors and affiliations.

Department of obstetrics and gynecology Beijing Chaoyang District Maternal and Child Health Care Family Planning Service Center (Beijing Chaoyang District Maternal and Child Health Care Hospital), No. 25 Huaweili, Panjiayuan Street, Chaoyang District, Beijing, 100021, China

Xiaorui Nie, Zijie Xu & Hong Ren

You can also search for this author in PubMed   Google Scholar

Contributions

Nie XR designed and performed the experiments, analyzed the data, and wrote the manuscript; Xu ZJ and Ren H performed the experiments; all authors performed experiments and wrote the manuscript; all authors have read and approved the manuscript.

Corresponding author

Correspondence to Hong Ren .

Ethics declarations

Competing interests.

The authors declare no competing interests.

Ethics approval and consent to participate

This study was conducted in accordance with the declaration of Helsinki. This study was conducted with approval from the Ethics Committee of Beijing Chaoyang District Maternal and Child Health Care Hospital. Written informed consent was obtained from all participants.

Consent for publication

Additional information, publisher’s note.

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ . The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Cite this article.

Nie, X., Xu, Z. & Ren, H. Analysis of risk factors of preeclampsia in pregnant women with chronic hypertension and its impact on pregnancy outcomes. BMC Pregnancy Childbirth 24 , 307 (2024). https://doi.org/10.1186/s12884-024-06476-1

Download citation

Received : 12 December 2023

Accepted : 01 April 2024

Published : 24 April 2024

DOI : https://doi.org/10.1186/s12884-024-06476-1

Share this article

Anyone you share the following link with will be able to read this content:

Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

• Preeclampsia
• Chronic hypertension
• Pregnancy outcome

BMC Pregnancy and Childbirth

ISSN: 1471-2393

• Submission enquiries: [email protected]
• General enquiries: [email protected]

An official website of the United States government

The .gov means it’s official. Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

The site is secure. The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

• Publications
• Account settings

Preview improvements coming to the PMC website in October 2024. Learn More or Try it out now .

• Advanced Search
• Journal List
• HHS Author Manuscripts

The Management of Hypertension in Pregnancy

Hypertensive pregnancy disorders complicate 6–8% of pregnancies and cause significant maternal and fetal morbidity and mortality. The goal of treatment is to prevent significant cerebrovascular and cardiovascular events in the mother, without compromising fetal well-being. Current guidelines differentiate between the treatment of women with acute hypertensive syndromes of pregnancy and women with preexisting chronic hypertension in pregnancy. This review will address the management of hypertension in pregnancy, review the various pharmacologic therapies, and discuss the future directions in this field.

Introduction

Hypertensive pregnancy disorders cover a spectrum of conditions, including preeclampsia/eclampsia, gestational hypertension, chronic hypertension, and preeclampsia superimposed on chronic hypertension ( Table 1 ). According to the National High Blood Pressure Education Program (NHBPEP) Working Group Report on High Blood Pressure (BP) in Pregnancy, hypertension occurs in 6–8% of pregnancies in the United States. 1 Hypertensive pregnancy disorders represent the most significant complications of pregnancy and contribute significantly to maternal and perinatal morbidity and mortality. 2 Most of the current recommendations for the treatment of these disorders are based on expert opinion and observational studies, with a lack of evidence from randomized controlled trials. The overall strategy in the treatment of hypertension in pregnancy is to prevent maternal cerebrovascular and cardiac complications, while preserving the uteroplacental and fetal circulation and limiting medication toxicity to the fetus.

Hypertensive Pregnancy Disorder classification

Treatment strategies fall into two general categories – the management of acute hypertensive syndromes of pregnancy, such as preeclampsia/eclampsia, and the management of chronic hypertension. While the definitive treatment for acute hypertensive syndromes of pregnancy is delivery, expectant management with close observation may be appropriate in carefully selected patients, especially before 32 weeks gestation. Women with chronic hypertension should ideally be evaluated prior to pregnancy, with a focus on the presence of end-organ damage, evidence of secondary causes of hypertension (such as renal artery stenosis due to fibromuscular dysplasia, primary hyperaldosteronism and pheochromocytoma), medication adjustments, and counseling regarding the risks of preeclampsia and adverse fetal events.

Women with hypertensive pregnancy disorders should have a comprehensive plan of care, which includes prenatal counseling, frequent visits during pregnancy, timely delivery, appropriate intrapartum monitoring and care, and postpartum follow up. Care of these patients involves counseling at every step of the pregnancy to ensure that the woman is aware of the risks to her and her fetus such that she can make informed decisions.

Blood Pressure Measurement

Hypertension in pregnancy is defined as a systolic BP ≥ 140 mm Hg and a diastolic BP ≥ 90 mm Hg on two separate measurements at least 4–6 hours apart. However, the diagnosis of hypertension, in pregnancy or otherwise, requires first and foremost an accurate measurement of BP. Many automated BP cuffs have not been tested during pregnancy, and therefore obtaining a manual BP is the preferred technique. The 2000 NHBPEP Working Group Report on High BP in Pregnancy recommends that the Korotkoff phase V (disappearance) sound be used to determine the diastolic BP. 1 In the outpatient setting, proper BP technique is essential and includes the subject being in a seated position, legs uncrossed, back supported, and no tobacco or caffeine for 30 minutes prior. In recumbent, hospitalized patients, the provider should measure the BP in the left lateral decubitus position to minimize the BP change caused by the compression of the inferior vena cava by the gravid uterus.

Blood pressure measurements should be interpreted in the context of the stage of pregnancy and the expected changes in blood pressure for each trimester. BP drops during the first and second trimesters, nadirs at around 20 weeks of gestation, and returns to preconception levels by the third trimester. Women who have not had regular medical care prior to pregnancy may be labeled as ‘gestational hypertension’ based on elevated BPs in the third trimester, when in reality, they were hypertensive prior to pregnancy, which was masked by the physiologic changes during mid-pregnancy. If a woman has gestational hypertension that does not resolve after delivery, she will subsequently be diagnosed as having chronic hypertension.

Ambulatory blood pressure monitoring (ABPM) and the hyperbaric index (HBI) have been suggested as alternative methods for diagnosing elevated blood pressure in pregnancy. 3 The HBI is defined as the amount of BP excess during a given time period above a 90% tolerance limit, with units of mm Hg X hours. One promising study suggested that HBI calculated from a 48-hour ABPM performed in the first trimester had a 93% sensitivity and 100% specificity for predicting preeclampsia, 4 although other researchers have not been able to replicate this high degree of accuracy and reliability. 5 , 6 There is currently no official role of ABPM in the diagnosis of hypertensive pregnancy disorders. 7 Home monitoring of blood pressure by automated cuffs in pregnancy has not been validated and some monitors have been shown to inaccurate in pregnancy and, therefore, in-office, manual BPs remain the gold-standard for the diagnosis and monitoring of hypertension in pregnancy. 8 , 9 This may involve frequent outpatient visits, especially in those with severe hypertension.

Blood Pressure Management in Pregnancy

Hypertension in preeclamptic patients.

The NHBPEP Working Group Report on High BP in Pregnancy and the American College of Obstetrics and Gynecology (ACOG) guidelines recommend treatment in preeclampsia when the diastolic BP (DBP) is persistently above 105–110 mm Hg, 1 but there is no official recommendation regarding a systolic BP threshold for treatment. Most experts agree that pharmacologic therapy should be initiated when the BP approaches 150/100 mm Hg, 10 with the goal of preventing cerebral and cardiovascular events in the mother. If a woman has mild preeclampsia (DBP<100 mm Hg) with normal laboratory tests, other than low-level proteinuria, management as an outpatient can be appropriate, provided that there are frequent outpatient visits and that fetal nonstress testing (NST) is favorable. The frequency of formal ultrasound testing depends on the clinical condition and is at the discretion of an obstetrician. In the setting of severe preeclampsia that is being managed expectantly in the hospital, daily ultrasounds for fetal well-being may be indicated.

While treatment of hypertension may improve the risk profile of the mother, and therefore delay delivery, it does not cure preeclampsia, nor does it delay the progression to preeclampsia. 11 The diagnosis of severe preeclampsia includes greater than 1 of the following criteria – severe hypertension (defined as DBP>100 mm Hg), proteinuria > 5 g/24 hours or > 3+ on 2 random urine samples 4 hours apart, oliguria, cerebral or visual disturbances, pulmonary edema, epigastric or right upper quadrant pain, impaired liver function, thrombocytopenia or fetal growth restriction. The only definitive therapy for preeclampsia is delivery. When urgent control of BP is necessary, or when delivery is expected within the next 48 hours, intravenous agents, such as labetalol or hydralazine, are the drugs of choice. Oral agents may be considered if delivery is not imminent, and the choices of medications will be discussed further below.

Eclampsia may occur in the absence of gestational hypertension or preeclampsia in up to 20% of cases. 12 Magnesium sulfate has been shown to decrease the risk of eclampsia and maternal death without evidence of significant harm to the mother or baby. 13 Therefore, intravenous magnesium sulfate should be administered for seizure prophylaxis both during delivery and for 24 hours after delivery. The rate of continuous infusion, but not the loading dose, should be decreased for women with renal failure (as magnesium is renally excreted), and serum magnesium should be checked every 1–2 hours, as compared to women with normal renal function, for whom the level can be checked every 4–6 hours.

Timing of Delivery

The decision regarding the timing of delivery should be made after a careful assessment of the risks to the fetus and the mother. In appropriately selected patients, especially those before 32 weeks gestation, delivery can be postponed to allow for fetal maturation, particularly of the respiratory system. Women with mild preeclampsia, i. e., those with a diastolic BP < 100 mm Hg, without evidence of cerebral involvement, hemolysis with elevated liver enzymes and low platelets (HELLP) syndrome, or significant proteinuria (> 1 g/24 hours), may be candidates for this approach.

In women with severe preeclampsia before 34 weeks gestation, the timing of delivery is more complicated. In an interventional trial of 38 women with severe preeclampsia between 28–34 weeks gestation who were randomized to either aggressive therapy (betamethasone and delivery 48 hours later) or expectant management (betamethasone, and delivery only for prespecified indications, including low urine output, thrombocytopenia, abnormal liver function tests, imminent eclampsia, pulmonary edema or severe hypertension despite therapy), there was no difference in the maternal complications between the two groups. There was advanced gestational age at delivery (an addition of 7.1 vs. 1.3 days, p<0.05), with fewer neonatal complications in the expectant management group (33% vs. 75%, p<0.05). 14 . Another larger trial of 95 women with severe preeclampsia between 28–32 weeks gestation, randomized to aggressive versus expectant management, also showed advanced gestational age at delivery in the expectant group, with fewer visits to the neonatal intensive care unit and fewer episodes of respiratory distress in the infants. 15 However, this study excluded women with underlying medical disease or obstetrical complications. A meta-analysis published in 2002 evaluating expectant versus interventional strategies in the management of women with early onset severe preeclampsia found insufficient evidence to recommend one approach over the other. 16 One approach that has been suggested by the Society for Maternal-Fetal Medicine is to admit women with early (< 34 weeks gestation), severe preeclampsia for observation and corticosteroid administration if delivery is not imminent, followed by daily laboratory tests, including liver and renal function tests, daily fetal assessments by ultrasound, and delivery at 34 weeks or earlier if any of the following develop – severe hypertension despite therapy, HELLP syndrome, pulmonary edema, eclampsia, severe renal dysfunction, disseminated intravascular coagulation, placental abruption, fetal growth restriction, oligohydramnios or abnormal fetal stress testing. 17 In cases of severe hypertension (BP > 160/110 mm Hg), a trial of anti-hypertensive therapy may be undertaken, but if the BP is not reduced within 24–48 hours, delivery should be strongly considered. Given the complexity of such cases, including the risks to both mother and fetus, the decision must be made on an individual basis after thoughtful discussion with the mother. A nephrology consultation should be considered, especially in the management of severe preeclampsia, hypertension, and medication choices. In addition, a nephrologist can follow proteinuria levels and help risk-stratify patients into those who need closer follow-up for monitoring of renal disease in the post-partum setting.

If a woman is at greater than 34 weeks gestation and develops severe preeclampsia, delivery is still the treatment of choice, while expectant management may be reasonable in those with mild preeclampsia. At greater than 36–37 weeks gestation, induction of labor should pursued. Recent evidence for this approach comes from the Hypertension and Preeclampsia Intervention Trial at Term (HYPITAT) trial published in 2009 that compared the induction of labor versus expectant monitoring for gestational hypertension or mild preeclampsia after 36 weeks gestation. The HYPITAT trial was a multicenter randomized-controlled trial that included 756 women with a singleton pregnancy at 36–41 weeks, with mild gestational hypertension or mild preeclampsia. 18 The subjects were randomized to either expectant monitoring or induction of labor, with the primary outcomes being progression to severe disease, HELLP syndrome, eclampsia, pulmonary edema, placental abruption, postpartum hemorrhage, thromboembolic disease or death. There were no maternal or neonatal deaths and no cases of eclampsia or placental abruption in either group. The women randomized to the induction group had a relative risk reduction of 0.71 (95% CI 0.59–0.86) for the primary outcome, mainly due to a difference in the rate of progression to severe disease. The study was not powered to compare differences in primary outcomes between those with preeclampsia versus gestational hypertension. However, it does support the induction of labor in preeclamptic pregnancies beyond 36 weeks gestation.

Chronic Hypertension in Pregnancy

Data from the National Health and Nutrition Examination Survey (1999–2008), indicates that the prevalence of hypertension in women aged 20–44 years is 7.7%, and an estimated 4.9% of women use anti-hypertensive pharmacologic therapy, 19 with the two most common categories of medications being diuretics (47.9%) and angiotension-converting enzyme (ACE) inhibitors (44.0%). Prenatal counseling in women with chronic hypertension is an important component of their care. The goals of the visit should be to evaluate for end-organ damage, to adjust medications as necessary, to discuss appropriate lifestyle modifications, and to consider secondary causes of hypertension. Given the teratogenic potential of ACE inhibitors (see below), women should be counseled on the importance of birth control while on ACE inhibitors, and this class of medication should be changed prior to attempting to conceive.

There is continued controversy over whether women with mild-moderate chronic hypertension on anti-hypertensive therapy prior to pregnancy should stop these medications, be kept under close observation, and only reinstitute therapy for blood pressure elevations of 140–160/90–100 mm Hg, versus continuing their usual anti-hypertensive regimen. 1 Currently, both approaches are used and there is insufficient evidence to recommend one approach over the other. Central to this controversy is the concern that anti-hypertensive therapy for mild-moderate hypertension may provide no maternal benefits, while, at the same time, harming the fetus (a) from the intrauterine exposure to anti-hypertensive medications with their possible adverse effects, and (b) as a result of unfavorable hemodynamics, whereby a decrease in the maternal blood pressure may impair uteroplacental perfusion, and, ultimately, fetal growth. The evidence for an association between fetoplacental growth and the use of oral anti-hypertensive medications is limited. In the absence of well-designed and adequately powered studies, a meta-analysis of 14 treatment trials is frequently cited. 20 This meta-analysis concluded that a 10 mm Hg decrease in mean arterial blood pressure was associated with a 145 gram decrease in neonatal birth weight. However, only 16% of the variation in birth weight was accounted for by the change in blood pressure, as several other variables may have contributed independently to the fetal growth impairment. These negative effects of anti-hypertensive therapy on birth weight have not been demonstrated consistently 21 and, in turn, the presence of hypertension itself, irrespective of blood pressure medication use, has been shown to result in lower birth weights. Those in favor of treatment support their view by citing evidence that treatment of chronic hypertension may prevent progression to severe hypertension and that chronic hypertension has been associated with increased feto-maternal risks, including perinatal mortality and placental abruption 22 . In general, most experts agree with the use of anti-hypertensive therapy for a blood pressure ≥ 150/100 mm Hg. 10 Evaluation for end-organ damage is important in that it helps to guide therapy decisions. In the presence of renal disease, proteinuria, left ventricular hypertrophy, hypertensive retinopathy, microvascular disease, stroke and age greater than 40, therapy should be initiated for a diastolic BP ≥ 90 mm Hg. 1 , 23 It should be noted that therapeutic guidelines as to when to institute treatment and subsequent BP targets vary among different obstetrical and medical societies due to the lack of evidence supporting a single BP goal. 24 , 25

Secondary hypertension should be considered in women with difficult to control BP requiring three or more anti-hypertensive agents, including a diuretic, and/or indicative laboratory and clinical findings, such as hypokalemia or an abdominal bruit. A thorough history and physical exam should be performed by a nephrologist or hypertension specialist and should include a review of lifestyle factors, such as nicotine use, caffeine intake and recreational drug use, in particular cocaine and methamphetamines, which can mimic conditions such as pheochromocytoma. The primary differential for secondary causes of hypertension includes primary hyperaldosteronism, pheochromocytoma and renal artery stenosis (primarily due to fibromuscular dysplasia in this age group). Women with secondary hypertension are at a particularly high risk for adverse pregnancy outcomes. 26 Pheochromocytoma, in particular, is associated with significant maternal and fetal mortality, mainly due to hypertensive crisis in the mother and intrauterine growth restriction in the fetus. 27 The diagnosis may be missed, mainly due to the fact that patients may present with atypical features, such as gestational diabetes and difficult to control hypertension ( Figure 1 ), and may be inappropriately diagnosed as having preeclampsia. 28 Primary hyperaldosteronism is also difficult to diagnose during pregnancy, mainly due to the stimulation of the renin-angiotensin-aldosterone axis in normal pregnancy, resulting in false negatives when measuring the renin-aldosterone ratio. 29

Surgical specimen of the adrenal pheochromocytoma.

Case presentation - Patient was a 31 year old P6G5 with a history of chronic hypertension requiring medications intermittently in the past, and a history of preeclampsia with her first pregnancy, with subsequent unremarkable pregnancies. She was admitted at 34 weeks due to systolic BP > 200 mm Hg, as well as 3+ protein on dipstick, elevated AST (57 U/L), serum creatinine of 1.2 mg/dL and uric acid of 10.1 mg/dL. The constellation of clinical findings and laboratory abnormalities was considered to be consistent with preeclampsia. She received IV magnesium sulfate and labetalol, and underwent C-section at 34 and 4/7 weeks, and gave birth to a healthy male infant. Systolic BPs remained in the 180s mm Hg post-delivery, and she was transferred to the ICU for hypertensive urgency. Work-up for secondary causes revealed a 3.2 × 6.2 × 5.3 cm heterogenous lesion in the right adrenal gland, and MRI was consistent with pheochromocytoma. The level of plasma free normetanephrine was 26.2 nmol/L (normal < 0.90 nmol/L), and the 24-hour urine showed significantly elevated levels of norepinephrine and normetanephrine. She received phenoxybenzamine, nicardipine and propranolol. She underwent a right total adrenalectomy (photograph of mass shown) and was able to be tapered off her BP medications.

Specific interventions to treat the underlying cause should be pursued, when possible, prior to pregnancy, whether it is surgery for pheochromocytoma or revascularization for renal artery stenosis, which may result in cure of the hypertension. In the case that the diagnosis is not made before pregnancy, there are no official guidelines as to the management of these conditions, and decisions must be made on a case-by-case basis. Renal artery revascularization has been successfully used during pregnancy, 26 and surgical resection of pheochromocytoma has been performed in all trimesters, after the initiation of 10–14 days of alpha blockage prior to surgery. 28

Lastly, women with chronic hypertension should be aware of the risks associated with pregnancy. In a study of 763 women with chronic hypertension enrolled in a multi-center trial of low-dose aspirin for the prevention of preeclampsia, 25% developed superimposed preeclampsia. 30 In addition, the women in this study who developed preeclampsia were at increased risk for placental abruption, versus those with chronic hypertension alone (3% vs. 1%, p=0.04). 30 Among women with severe or high risk hypertension (BP>160/110), placental abruption may affect as many as 5–10% of women. 11 One study by Sibai and colleagues looked at the maternal and fetal outcomes of 44 women with severe chronic hypertension in the first trimester of pregnancy and found that while there were no maternal deaths, morbidity, including hospitalizations and reduction in renal function, was high. 11 Of the twenty women with deterioration in renal function during pregnancy, 19 had returned to their baseline renal function by their post-partum visit, although one patient continued to have significant renal impairment. Nearly one-half of these women developed superimposed preeclampsia, and the perinatal mortality was 25% (ten stillbirths and 1 neonatal death), predominantly in the group of women with preeclampsia, and all in infants less than 800 grams at delivery and less than 29 weeks of age. The risk of recurrence of preeclampsia in subsequent pregnancies after a pregnancy complicated by severe preeclampsia is 25%, but the relative risk is 2 times greater in those with a history of chronic hypertension. 31

Complications of hypertensive pregnancy

The most significant short term complications of hypertensive pregnancy in the mother are cerebrovascular complications, including cerebral hemorrhage and seizures, renal impairment and cardiovascular complications, such as pulmonary edema ( Table 2 ). Women with chronic hypertension and evidence of end-organ damage prior to pregnancy are at increased risk of pulmonary edema, hypertensive encephalopathy, retinopathy, cerebral hemorrhage and acute renal failure. 1

Possible acute complications of hypertensive pregnancy by organ system

HELLP syndrome occurs in 10–20% of severe preeclamptic/eclamptic pregnancies. 32 , 33 The syndrome was first described in 1982 by Weinstein and colleagues 34 as being characterized by hemolysis, low platelets and elevated liver enzymes. It is associated with significant maternal morbidity and mortality. In a prospective study of 442 patients with HELLP syndrome, there were 5 maternal deaths, 3 attributed to diffuse hypoxic encephalopathy, and significant morbidity – including placental abruption (16%), acute renal failure (7.7%), pulmonary edema (6%) and subcapsular hematoma (0.9%). 32 Hypertension and proteinuria may not be present, 32 and so providers must be alert to the deceptive signs and symptoms of HELLP syndrome – including midepigastric or right upper quadrant pain, nausea, vomiting and general malaise. Women with HELLP syndrome should typically be delivered as soon as possible due to the significant morbidity and mortality. They are not candidates for expectant management. 35 , 36 HELLP syndrome must be differentiated from hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenia purpura (TTP), two forms of thrombotic microangiopathy that may present during pregnancy. 33 TTP and HUS, either typical or atypical, are not characterized by elevated liver enzymes and, in addition, TTP is associated with deficiency in the enzyme ADAMTS13, a metalloproteinase that degrades von Willebrand factor multimers.

Eclampsia is the convulsive form of preeclampsia and occurs in 0.5% of patients with mild preeclampsia, and in 2–3% of those with severe preeclampsia. 37 The most feared complication and cause of maternal death in eclampsia is stroke. 38 In a population-based study in France in 1995, 31 cases of stroke in pregnancy were identified and eclampsia accounted for nearly half of both hemorrhagic and non-hemorrhagic strokes. 39 A more recent study by Martin and colleagues looked at 28 women who had suffered strokes in the setting of severe preeclampsia and eclampsia 40 and found that their systolic blood pressures were > 155 mm Hg immediately before their cerebrovascular accidents. Only 5 patients reached a diastolic blood pressure of 105 mm Hg, and therefore would not necessarily be candidates for treatment according to the current NHBPEP and ACOG guidelines. 1 In this study, maternal mortality was 53.6%, and only 3 of the 28 patients had no residual deficits post-stroke. The authors concluded that a paradigm shift is needed toward treatment of SBP of 155–160 mm Hg in severe preeclamptic and eclamptic patients.

Posterior reversible encephalopathy syndrome (PRES) was first described in the setting of eclampsia in 1996. 41 PRES is a syndrome characterized by neurologic signs and symptoms, such as headache, impaired consciousness, visual changes and seizures, in combination with neuroimaging findings of vasogenic edema in the posterior circulation. In a retrospective study of patients with eclampsia at Mayo Clinic, Rochester, 13 cases of eclampsia were identified, of which 7 had neuroimaging studies, and all of the women had characteristic findings of PRES syndrome. Importantly, pregnant patients developed PRES at lower peak systolic BPs (mean 173 mm Hg) than the non-pregnant PRES subjects. 42 The authors hypothesize that the reduction in BP in these women may delay progression of vasogenic to cytotoxic edema and cerebral infarction. The true incidence of PRES in eclampsia, or even in severe preeclampsia, has not been established, but the association is one that requires future study.

Long-term complications

It was long believed that if hypertension and proteinuria resolve after delivery, there would not be any long term risk of cardiovascular or renal complications in the mother. However, recent studies have shown that a history of hypertensive pregnancy is a risk factor for hypertension, 43 , 44 as well as cardiovascular disease, 44 , 45 with an approximate relative risk of 2, compared to those without hypertensive pregnancies. The risk of future kidney disease is not clear, although several studies have suggested an association. It has been shown that a history of preeclampsia is associated with a higher frequency of microalbuminuria up to 5 years after delivery. 46 A study using registry data from Norway found that preeclampsia occurring during a first pregnancy increased the risk of future end-stage renal disease (ESRD). 47 The study population consisted of women with a first singleton birth between 1967 and1991, and follow-up extended until December 2005. The absolute risk of ESRD after any preeclamptic pregnancy was low, 14.5/100,000 person-years, but the adjusted relative risk was 4.3 (95% CI 3.3–5.6), and in women with greater than 2 preeclamptic pregnancies, the adjusted relative risk increased to 10.9 (95% CI 5.0–23.8). It should be noted that as this was a registry study, and patients with renal disease prior to pregnancy were not able to be excluded, which would certainly impact the associated risk. As to the mechanisms that underlie this association, it is not clear whether it is the hypertensive pregnancy itself that leads to the increased risk of these complications, or whether there is underlying endothelial dysfunction in the mother that manifests differently at varying stages of life. Either way, women with a history of preeclampsia should be advised regarding life style modifications and should be monitored closely for traditional risk factors.

Treatment of hypertensive pregnancy disorders

Non-pharmacological therapeutic approach.

Lifestyle interventions, such as weight loss and a reduction in salt intake, are of proven benefit in non-pregnant hypertensive patients. There is currently no evidence from prospective, randomized trials that instituting an exercise program during pregnancy is effective in preventing preeclampsia in at risk individuals, 1 , 48 , although some benefit has been seen in an animal model. 49 Similarly, there is no current evidence that instituting a weight loss program in pregnancy can prevent preeclampsia, 48 although obesity is a risk factor for gestational hypertension and preeclampsia. 50 In 2009, the Institute of Medicine revised their guidelines for gestational weight gain and recommended that women who are overweight prior to pregnancy (body-mass index (BMI) 25–29.9) gain only 15–25 lbs during pregnancy, as opposed those with normal weight (BMI 18.5–24.9) prior to pregnancy, who should gain 25–35 lbs. 51 Obese women with a BMI > 30 should gain only 11–20 lbs, according to the new recommendations.

As volume contraction is common in preeclampsia, salt restriction is not routinely recommended. However, bed rest is frequently advised, and has been shown to lower blood pressure, promote diuresis, and reduce premature labor 52 , 53 .

Medications

Pharmacologic therapy during pregnancy may prevent progression to severe hypertension and maternal complications (such as heart failure and cerebrovascular events) while improving fetal maturity by permitting prolongation of pregnancy. During both induction and titration of anti-hypertensive medications, fetal well-being and safety should be closely monitored by several methods that are available in daily clinical practice. A discussion of the most common classes of anti-hypertensive therapy is presented below and summarized in Table 3 .

Medication choices for pharmacologic treatment of hypertension in pregnancy

α-adrenergic agonists

One of the medications with the longest track record in pregnancy is methyldopa. A long-term follow-up study on children born to women treated with methyldopa during pregnancy could find no increased incidence of general health problems or cognitive problems. 54 This record of safety makes it the first line agent recommended by the NHBPEP working group. 1 Methyldopa acts centrally by decreasing sympathetic tone, and therefore can have many side effects, including sedation and impaired sleep patterns. One potential side effect is that it may cause mild elevations of liver enzymes, which can lead to diagnostic confusion with HELLP syndrome. Although it is relatively safe, methyldopa is not a potent BP lowering agent and side effects, which are commensurate with the dose, can limit its use. Methyldopa can be combined with other anti-hypertensives, such as a diuretic (discussed below), to achieve target blood pressure values.

Clonidine has a similar mode of action to methyldopa, but has a much stronger effect in lowering BP. Clonidine may impair fetal growth, especially if the mother has a reduction in heart rate after therapy is initiated. 21 It can cause significant rebound hypertension and does not have as strong a record of safety as methyldopa. It should be considered in cases of intolerance to methyldopa.

Beta-blockers

Beta-blockers are generally well-tolerated and safe in pregnancy. Labetalol is becoming one of the favored therapies for hypertension in pregnancy. It is a non-selective beta blocker that antagonizes both beta and alpha-1 receptors. Its side effects include fatigue, decreased exercise tolerance, as well as bronchospasm in individuals with reactive airway disease. Labetalol has been compared to methyldopa in prospective trials and neither medication was associated with adverse maternal or fetal outcomes. 25 , 55 It is available in both oral and intravenous forms, so it may be used for both outpatient and inpatient management.

Atenolol has been shown to have minimal effects on systolic BP in preeclamptic women, and it is also associated with intrauterine growth retardation. 56 Given the availability of other more effective medications, including labetalol, atenolol should be avoided in pregnancy.

Calcium channel blockers

In a small trial of preeclamptic mothers who received nifedipine versus placebo, there were significant reductions in maternal BP, serum creatinine and urea values, and 24-hour urinary protein measurements, without a reduction in umbilical artery blood flow. 57 According to a prospective, multicenter cohort study of 78 women exposed to calcium channel blockers in the first trimester, mainly nifedipine and verapamil, there was no increase in major congenital malformations. There was an increase in preterm delivery in those who received calcium channel blockers versus controls, matched for age and smoking status (28% vs. 9%, p=0.003), although this was attributed to underlying maternal disease by stepwise regression. 58 There is little data available on diltiazem, although it may be used as a rate control agent in pregnancy, 59 and has been shown to lower BP and proteinuria in pregnant patients with underlying renal disease in a small study of 7 patients. 60 Calcium channel blockers are also potent tocolytics and can affect the progression of labor. A major concern with calcium channel blockers in pregnancy is the concurrent use of magnesium sulfate for seizure prophylaxis, as co-administration of these agents has been reported to cause circulatory collapse and neuromuscular blockade. 16 Despite these issues, calcium channel blockers, nifedipine in particular, as there is more data available for it, is an effective and safe alternative to methyldopa as a first-line agent for the treatment of hypertension in pregnancy.

As noted above, diuretics are the most commonly used medication among women of child-bearing age with chronic hypertension. 19 A possible side effect of any diuretic is vascular volume contraction, which may paradoxically cause further elevations of BP in preeclamptic women. Women with preeclampsia have lower plasma volumes compared to those with normal pregnancies, and volume contraction may stimulate the renin-angiotensin-aldosterone axis, causing further increases in peripheral vascular resistance, thus worsening hypertension. 24 , 61 However, the 2000 NHBPEP Working Group report on High BP in Pregnancy recognized that the major concern for diuretic use in pregnancy is mainly theoretical, as supporting evidence for their adverse effects is lacking. Therefore, if a woman is on a diuretic prior to pregnancy, this can be continued during pregnancy, with the exception of spironolactone, which may have fetal anti-androgen effects.

Hydralazine

Hydralazine is a direct vasodilator that can be administered orally or intravenously, and is often used in the setting of hypertensive urgency, given its fast onset of action. However, hydralazine has been associated with hypotension, oliguria and fetal distress. 62 It is also associated with a lupus-like syndrome and peripheral neuropathy. The lupus-like syndrome is usually seen with higher oral daily doses (> 200 mg daily) 63 , though has been seen with doses as low as 50 mg daily when the exposure is prolonged (months to years) 64 . Due to these potential side effects, labetalol is increasingly viewed as a safer agent for inpatient management of hypertension. Hydralazine remains, however, commonly used when other treatment regimens have failed to achieve adequate BP control, as most obstetricians are quite familiar with its pharmacological actions and find its side-effect profile acceptable.

Renin-Angiotensin-Aldosterone System Blockade

Renin-Angiotensin-Aldosterone System (RAAS) blockers, including most commonly ACE inhibitors and ARBs, are extremely effective in lowering BP and have significant benefit in proteinuric diseases. Initially, these medications were considered to be relatively safe during the first trimester, and only associated with defects when taken in the second trimester, potentially leading to oligohydramnios, anuria, and fetal renal failure. However, a study published in 2006 by Cooper and colleagues demonstrated that exposure to ACE inhibitors in the first trimester can be associated with significant congenital malformations affecting both the cardiovascular and central nervous systems. 65 The relative risk of major congenital malformations after a first trimester exposure was 2.71 (95% CI 1.72–4.27) as compared to infants with no exposure to anti-hypertensives. A 2011 study of over 400,000 women-infant pairs in the Northern California Kaiser Permanente region did find an increased risk of congenital heart defects in the offspring after exposure to ACE inhibitors in the first trimester as compared to healthy controls (OR 1.54, CI 0.9–2.62), but not as compared to women on other anti-hypertensive agents (OR 1.14, CI 0.65–1.98). 66 However, ACE inhibitors are still considered contraindicated in pregnancy, despite the controversy regarding the magnitude of the risk associated with exposure. If a woman becomes pregnant while on one of these agents, she should be switched immediately to an alternative therapy and offered an ultrasound and fetal echocardiography at 18 weeks gestation, and providers should discuss the possible risks for congenital malformations with the patient. There is little data regarding direct renin inhibitors, such as aliskerin, in pregnancy, but they are also considered category D by the US Federal Drug Administration as they block the RAAS system (see Table 3 ). As mentioned previously, spironolactone is contraindicated in pregnancy as it can cross the placenta and have anti-androgen effects on the fetus. There is a case report of eplerenone being used successfully for blood pressure control in a women with primary hyperaldosteronism during pregnancy. 67

Future Directions

Over the last several years, evidence has emerged suggesting that women with hypertensive pregnancy disorders are at an increased risk for both immediate and long-term cardiovascular disease. On the other hand, current recommendations for the treatment of hypertension in pregnancy, unlike those for the general population, have remained the same for many years, mainly due to a lack of studies that address the safety and benefits of lowering BP in pregnancy. At present, several interventional studies for the treatment of hypertension in pregnancy are underway (ClinicalTrials.gov – {"type":"clinical-trial","attrs":{"text":"NCT01192412","term_id":"NCT01192412"}} NCT01192412 , {"type":"clinical-trial","attrs":{"text":"NCT01351428","term_id":"NCT01351428"}} NCT01351428 , {"type":"clinical-trial","attrs":{"text":"NCT00293735","term_id":"NCT00293735"}} NCT00293735 , {"type":"clinical-trial","attrs":{"text":"NCT00194974","term_id":"NCT00194974"}} NCT00194974 , {"type":"clinical-trial","attrs":{"text":"NCT01361425","term_id":"NCT01361425"}} NCT01361425 ) that may provide long needed information, with respect to therapeutic targets and preferred agents in pregnant hypertensive patients. 24 While awaiting the results of these trials, a recent editorial by Moser and colleagues suggested using a new approach to the treatment of hypertension in pregnancy, whereby women with a history of chronic hypertension should continue their anti-hypertensive medications throughout pregnancy, provided that they are safe, with careful monitoring of BP and dose adjustments, as necessary. 24 The authors suggest that a new target BP in previously normotensive women should be 140/90 mm Hg, with beta-blockers, diuretics or calcium-channel blockers as first line therapies. The emphases of this proposal are to simplify the classification of hypertensive pregnancy disorders into chronic hypertension and de novo hypertension after 20 weeks, simplify the target BP goal to less than 140/90 mm Hg, and recommend specific pharmacologic agents. The authors suggest that the currently available methods for monitoring fetal well-being and safety should be instrumental in this approach, and applied during both the introduction and titration of anti-hypertensive medications. The studies currently underway may help address what the appropriate targets for BP should be in pregnancy, and which anti-hypertensive agents are most effective.

Current guidelines for the prevention of cardiovascular disease in women recommend referral of patients with a history of hypertensive pregnancy to primary care or cardiology, in order to facilitate monitoring and control of risk factors, 68 and though there are currently no guidelines, routine screening for renal disease with blood urea nitrogen, serum creatinine and urinalysis may be indicated in affected women. Future research should address the question as to whether more aggressive BP control during hypertensive pregnancies may result in the reduction of the future cardiovascular disease outcomes and renal disease in the affected women.

Hypertension in pregnancy is a common complication of pregnancy and one associated with significant maternal and fetal morbidity and mortality. The central issue in the management of hypertension in pregnancy is achieving a balance between the maternal benefits derived from improved BP control, and the fetal risks resulting from intrauterine medication toxicity and possible uteroplacental hypoperfusion. For the severe forms of hypertensive pregnancy disorders, including eclampsia, severe preeclampsia and HELLP syndrome, delivery remains the standard of care. Women with mild preeclampsia prior to 32 weeks gestation may be candidates for expectant management, but after 37 weeks, current evidence supports induction of labor to prevent adverse maternal and fetal outcomes. Women with chronic hypertension should undergo a pre-pregnancy evaluation, with a focus on end-organ damage, medication profile, potential secondary causes of hypertension, and counseling on the risks of pregnancy, including the development of superimposed preeclampsia. Women must be followed carefully during pregnancy and in the intra- and post-partum settings. There is ongoing research focusing on the appropriate management of hypertension in pregnancy and the long-term consequences for the mother that may influence future recommendations in this field.

Clinical Summary

• Hypertensive pregnancy disorders complicate 6–8% of pregnancies in the United States.
• The strategy for the treatment of hypertension in pregnancy is to prevent maternal cerebrovascular and cardiac complications, while preserving uteroplacental blood flow and limiting medication toxicity to the fetus.
• The definitive therapy for acute hypertensive syndromes of pregnancy is delivery, although anti-hypertensive medications are often necessary to lower the blood pressure in the mother to a) prevent maternal complications, and b) decrease neonatal complications related to prematurity by allowing for the continuation of pregnancy
• Women with chronic hypertension should have a prenatal visit that includes an evaluation for secondary causes of hypertension, medication adjustments, and counseling regarding the high risk of developing preeclampsia.

Acknowledgments

Grant support - The project described was supported by Award Number K08 HD051714 (Vesna D. Garovic) from the Eunice Kennedy Shriver National Institute of Child Health & Human Development and by Award Number P-50 AG44170 (Vesna D. Garovic) from the National Institute on Aging. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The writing of the manuscript and the decision to submit it for publication were solely the authors’ responsibilities.

Financial disclosures – The authors have no relevant financial disclosures.

Hypertensive disorders of pregnancy increase risk of cardiovascular death after giving birth

Rutgers Health researchers have found that hypertensive disorders in pregnancy are strongly associated with fatal cardiovascular disease for up to a year after birth.

Among the hypertensive disorders that cause dangerously high blood pressure during pregnancy -- chronic hypertension, gestational hypertension, preeclampsia without severe features, preeclampsia with severe features, superimposed preeclampsia and eclampsia -- all but gestational diabetes were associated with a doubling in the risk of fatal cardiovascular disease compared to women with normal blood pressure.

Eclampsia, a condition whereby hypertensive disorders cause seizures, was associated with a nearly 58-fold increase in fatal cardiovascular disease, according to a study published in Paediatric and Perinatal Epidemiology .

"Maternal and postpartum mortality rates in the U.S. are higher than in other high-income countries and rising, but more than half of cardiovascular disease-related deaths are preventable," said lead author Rachel Lee, a data analyst at Rutgers Robert Wood Johnson Medical School. "This study provides new information about how each hypertensive disorder is related to fatal cardiovascular disease, so healthcare providers can monitor patients with such complications more closely and develop strategies for keeping them healthy postpartum."

The researchers used the Nationwide Readmissions Database to examine pregnancy-related mortality rates for females 15 to 54 years old from 2010 to 2018. Data from more than 33 million delivery hospitalizations identified hypertensive disorders in 11 percent of patients, but that number increased with time. In 2010, 9.4 percent of patients in the study had hypertensive disorders of pregnancy. By 2018, that figure had risen by more than half to 14.4 percent.

"We've gotten better at predicting, diagnosing, and treating preeclampsia in this country, so the risk of death is falling for any individual patient with that condition," said Cande Ananth, chief of the Division of Epidemiology and Biostatistics in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Rutgers Robert Wood Johnson Medical School and senior author of the study.

Unfortunately, Ananth noted, the sharp increase in the number of patients who develop chronic hypertension has more than offset the improved ability to treat it.

"Cases of chronic hypertension are rising sharply among people of childbearing age, but optimal treatment strategies remain uncertain," he said. "While we're treating more pregnant people with mild hypertension with antihypertensive medications, there remain many questions about the right definitions of hypertension in pregnant compared to non-pregnant individuals."

Pregnant people with hypertensive disorders, especially those with pre-existing hypertension, need high-quality care as heart disease and related cardiac symptoms can be confused with common symptoms of normal pregnancy. Delays in diagnosis are associated with an increased incidence of preventable complications, the study authors said. Early identification and optimal treatment of hypertensive disorders, especially preeclampsia-eclampsia, are crucial for the primary prevention of maternal stroke.

Guidelines for ongoing care for up to one year after delivery are needed for each hypertensive disorder, the researchers conclude.

• Heart Disease
• Hypertension
• Diseases and Conditions
• Pregnancy and Childbirth
• Stroke Prevention
• Today's Healthcare
• Parkinson's Research
• Thyroid Disease
• Premature birth
• Nutrition and pregnancy
• Sudden infant death syndrome
• Protein microarray
• Personalized medicine
• Whooping cough

Story Source:

Materials provided by Rutgers University . Original written by Andrew Smith. Note: Content may be edited for style and length.

Journal Reference :

• Rachel Lee, Justin S. Brandt, K. S. Joseph, Cande V. Ananth. Pregnancy‐associated mortality due to cardiovascular disease: Impact of hypertensive disorders of pregnancy . Paediatric and Perinatal Epidemiology , 2024; 38 (3): 204 DOI: 10.1111/ppe.13055

Cite This Page :

Explore More

• Profound Link Between Diet and Brain Health
• Loneliness Runs Deep Among Parents
• Food in Sight? The Liver Is Ready!
• Acid Reflux Drugs and Risk of Migraine
• Do Cells Have a Hidden Communication System?
• Mice Given Mouse-Rat Brains Can Smell Again
• How Do Birds Flock? New Aerodynamics
• Cancer: Epigenetic Origin Without DNA Mutation
• Climate Change Driving Biodiversity Loss
• Why Can't Robots Outrun Animals?

Trending Topics

Strange & offbeat.

• Search Menu
• Volume 2024, Issue 4, April 2024 (In Progress)
• Volume 2024, Issue 3, March 2024
• Case of the Year
• MSF Case Reports
• Audiovestibular medicine
• Cardiology and cardiovascular systems
• Critical care medicine
• Dermatology
• Emergency medicine
• Endocrinology and metabolism
• Gastroenterology and hepatology
• Geriatrics and gerontology
• Haematology
• Infectious diseases and tropical medicine
• Medical ophthalmology
• Medical disorders in pregnancy
• Paediatrics
• Palliative medicine
• Pharmacology and pharmacy
• Radiology, nuclear medicine, and medical imaging
• Respiratory disorders
• Rheumatology
• Sexual and reproductive health
• Sports medicine
• Substance abuse
• Author Guidelines
• Submission Site
• Open Access
• Editorial Board
• Advertising and Corporate Services
• Journals Career Network
• Self-Archiving Policy
• Journals on Oxford Academic
• Books on Oxford Academic

Article Contents

Introduction, case presentation, conflict of interest statement.

• < Previous

Primary small lymphocytic lymphoma of the breast: a rare presentation of non-Hodgkin’s lymphoma

• Article contents
• Figures & tables
• Supplementary Data

Matthew Passeggiata, Geovanna Badaro, Hui Un Kim, Landry Umbu, Penelope Mashburn, Manju Nath, Primary small lymphocytic lymphoma of the breast: a rare presentation of non-Hodgkin’s lymphoma, Oxford Medical Case Reports , Volume 2024, Issue 4, April 2024, omae028, https://doi.org/10.1093/omcr/omae028

• Permissions Icon Permissions

Primary Small Lymphocytic Lymphoma of the breast is a rare presentation of Non-Hodgkin’s lymphoma. In this report, we present the case of primary small lymphocytic lymphoma of the breast in a 65-year-old female who presented with an abnormal breast ultrasound significant for a nodule of the right breast consistent with BI-RADS 4, indicating follow-up with ultrasound-guided biopsy for further diagnostic evaluation. The patient had no prior history of extramammary lymphoma or widespread disease. A sample of the breast mass was obtained via ultrasound-guided core needle biopsy and the pathology report revealed low-grade B-cell Lymphoma. After discussion with medical oncology and the explanation of risks, benefits and alternatives to surgery, a lumpectomy was performed, and the final pathology report of the mass revealed primary low-grade B-cell lymphocytic lymphoma of the breast. On follow up, the PET scan was unremarkable and showed no evidence of abnormal glucose metabolism or adenopathy.

Breast lymphomas are classified into primary breast lymphoma (PBL) and secondary breast lymphoma (SBL) [ 1–3 ]. The incidence of PBL from 1975 to 2017 was 1.35/1 000 000 [ 4 ]. PBL is most commonly due to Non-Hodgkin’s Lymphoma (NHL) without previous diagnosis of extramammary lymphoma, whereas SBL is due to metastasis also most commonly from NHL that developed from extrammamary tissue. PBL and SBL are clinically similar, and both may exhibit B-symptoms such as fever, night sweats and weight loss [ 3 ]. NHL is a solid tumor of the lymphatic system, representing 90% of lymphomas [ 1 ]. NHL can be indolent or aggressive, Indolent NHL typically manifests with waxing and waning lymphadenopathy. Of the indolent types, the most common are follicular lymphoma, chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), and splenic marginal zone lymphoma [ 5 ].

An asymptomatic 65-year-old postmenopausal female with a past medical history of hypertension, diabetes mellitus, hyperlipidemia, and hysterectomy was referred to the surgery clinic after a non-diagnostic mammogram (BI-RADS Category 1) and ultrasound (US) significant for a nodule at the 7 o’clock position of the right breast measuring 4.6 × 3.5 × 3.6 centimeters (cm) ( Fig. 1 ), consistent with BI-RADS 4, indicating the need for an US-guided biopsy for further diagnostic evaluation.

Imaging of the right breast mass at the 7 o’clock position measuring 4.6 × 3.5 × 3.6 cm.

Her prior routine mammograms had been unremarkable for the past 6 years. Family history was significant for breast cancer in her sister who succumbed to aggressive metastatic breast cancer with unknown hormonal or HER2 status. The patient denied breast pain, nipple discharge, fever, night sweats, fatigue, chest pain, or palpitations. On exam there were no dimpling, retraction, or secretions of bilateral breasts. On palpation there was a palpable mass at the 7 o’clock position. There was no cervical, supraclavicular, or axillary lymphadenopathy.

The US-guided core needle biopsy revealed low-grade mature small B-cell lymphoma. The peripheral blood smear was within normal limits and complete blood count was normal outside of rare target cells, slight poikilocytosis, and rare schistocytes. There were no immature white blood cells and platelet count was normal with rare giant forms. The results were discussed with oncology, lumpectomy was recommended with follow up positron emission tomography (PET) scan imaging. After the explanation of risks, benefits, and alternative treatment options to lumpectomy the patient agreed to lumpectomy.

A lumpectomy was performed with no complications and the pathology report of the mass revealed atypical lymphoid cell population infiltrating the breast duct ( Fig. 2 ) and lymphoid tissue infiltration fat ( Fig. 3 ). Immunohistochemical staining confirmed low-grade NHL with positive B-cell markers for CD3, CD5, and CD20 ( Fig. 4 ) and negative CD10, cyclin D1, BCL6, and CD23 markers. The final diagnosis of primary small lymphocytic lymphoma was made. On follow up, the PET scan was unremarkable with no evidence of abnormal glucose metabolism or adenopathy. The planned surveillance for this patient consisted of follow up mammogram imaging every 6 months for 1 to 2 years with yearly mammograms subsequently. A 6-month follow-up mammogram revealed no evidence of malignancy or significant changes.

Atypical lymphoid cell population infiltrating the breast duct.

Lymphoid tissue infiltrating fat.

Immunohistochemical staining positive for B-cell marker CD20.

NHL is a heterogeneous group of lymphoproliferative malignancies originating from B and T-cell precursors, as well as mature B and T-cells [ 5 ]. 25% of NHL cases disseminate to extranodal areas, most commonly the stomach, Waldeyer’s ring, central nervous system, lung, bone, and skin [ 1 ]. Breast lymphoma is rare with a prevalence of 0.04%–0.7% [ 2 , 6 ], which can be attributed to the scarcity of lymphoid tissue in the breast [ 4 ]. Breast lymphomas are classified into primary breast lymphoma (PBL) and secondary breast lymphoma (SBL) [ 1–3 ]. The current diagnostic criteria for PBL was initially proposed by Wiseman and Laio in 1972 [ 7 ]. The criteria consists of mammary tissue and lymphoma infiltrates in close proximity to each other, no evidence of concurrent widespread disease, and no prior diagnosis of extramammary lymphoma.

SLL consists of monomorphic small round B lymphocytes involving the lymph nodes, peripheral blood, and bone marrow [ 8 ]. In this patient, the histopathologic report of the mass showed two small foci of lymphoid infiltration predominantly composed of small lymphocytes positive for CD20, CD3, and CD5 markers. The peripheral blood smear showed a normal CBC without the presence of small lymphocytes. The presence of the neoplastic lymphocytes primarily in the lymphatic tissue rather than circulating in peripheral blood is more consistent with SLL rather than CLL [ 8 ].

PBL management consists of surgery, chemotherapy such as cyclophosphamide, hydroxy daunomycin, and vincristine sulfate, prednisone, radiotherapy, and immunotherapy, which can be done alone or in different combinations [ 9 ]. The classic treatment for PBL is chemotherapy, radical surgical excision has been shown to have no influence on survival or risk of recurrence therefore it is not recommended as a therapeutic measure [ 9 , 10 ]. Despite this it is important to note that due to the scarcity of PBL, definite therapeutic guidelines have not been established. Therefore, surgical excision may be indicated when the core needle biopsy sample is insufficient for classification or due to individualized treatment plans and patient preference [ 10 ]. In this case, we have performed surgical excision for therapeutic purposes with follow-up PET scan dictating required additional treatment. If the PET scan detected metastasis of the PBL, then an assessment for further treatment would be followed.

Primary breast lymphoma is a rare malignancy of the breast which shares many radiological and clinical presentations with breast carcinoma and other breast malignancies. Despite this, it is vital to have primary breast lymphoma as a differential diagnosis and to obtain an adequate sample for flow cytometry, allowing for an accurate diagnosis and appropriate treatment options. Although there are no definite therapeutic guidelines as there are for breast carcinoma, treatment options should be individualized to each patient’s case, taking stage, symptoms, overall health, patient preference and lymphoma subtype into consideration when deriving a treatment plan. Here we discussed the case of PBL successfully treated with surgical excision thereby avoiding the side effects and associated risks of chemotherapy and radiation.

There are no conflicts of interests to disclose.

Written informed consent was obtained for both the procedure and manuscript publication, including photographs and images.

Singh   R , Shaik   S , Negi   BS , Rajguru   JP , Patil   PB , Parihar   AS . et al.    Non-Hodgkin's lymphoma: a review . J Family Med Prim Care   2020 ; 9 : 1834 – 40   PMID: 32670927; PMCID: PMC7346945 .

Google Scholar

Duncan   VE , Reddy   VVB , Jhala   NC , Chhieng   DC , Jhala   DN . Non-Hodgkin’s lymphoma of the breast: a review of 18 primary and secondary cases . Ann Diagn Pathol   2006 ; 10 : 144 – 8 .

Raj   SD , Shurafa   M , Shah   Z , Raj   KM , Fishman   MDC , Dialani   VM . Primary and secondary breast lymphoma: clinical, pathologic, and multimodality imaging review . Radiographics   2019 ; 39 : 610 – 25 .

Peng   F , Li   J , Mu   S , Cai   L , Fan   F , Qin   Y . et al.    Epidemiological features of primary breast lymphoma patients and development of a nomogram to predict survival . Breast   2021 ; 57 : 49 – 61   Epub 2021 Mar 17. PMID: 33774459; PMCID: PMC8027901 .

Sapkota   S , Shaikh   H . Non-Hodgkin Lymphoma. [Updated 2022 Dec 2] . In: Shumway S, (ed) StatPearls [Internet] . Treasure Island (FL) : StatPearls Publishing , 2022 . Available from:   https://www.ncbi.nlm.nih.gov/books/NBK559328/ .

Google Preview

Shim   E , Song   SE , Seo   BK , Kim   YS , Son   GS . Lymphoma affecting the breast: a pictorial review of multimodal imaging findings . J Breast Cancer   2013 ; 16 : 254 – 65 .

Wiseman   C , Liao   KT . Primary lymphoma of the breast . Cancer   1972 ; 29 : 1705 – 12 .

Wierda   WG , Brown   J , Abramson   JS , Awan   F , Bilgrami   SF , Bociek   G . et al.    NCCN guidelines® insights: chronic lymphocytic leukemia/small lymphocytic lymphoma, version 3.2022 . J Natl Compr Cancer Netw   2022 ; 20 : 622 – 34 .

Moura   C , Leite   MI , Parreira   R , Medeiros   A . Primary breast lymphoma . J Surg Case Rep   2020 ; 2020 : rjz405 .

Alyass   F , Ray   LA . Surgical excision versus medical Management of Primary Breast Lymphoma: a case report . Cureus   2022 ; 14 : e32802 .

Email alerts

Citing articles via, affiliations.

• Online ISSN 2053-8855
• Copyright © 2024 Oxford University Press
• About Oxford Academic
• Publish journals with us
• University press partners
• What we publish
• New features  
• Open access
• Institutional account management
• Rights and permissions
• Get help with access
• Accessibility
• Advertising
• Media enquiries
• Oxford University Press
• Oxford Languages
• University of Oxford

Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide

• Copyright © 2024 Oxford University Press
• Cookie settings
• Cookie policy
• Privacy policy
• Legal notice

This Feature Is Available To Subscribers Only

Sign In or Create an Account

This PDF is available to Subscribers Only

For full access to this pdf, sign in to an existing account, or purchase an annual subscription.

The Federal Register

The daily journal of the united states government, request access.

Due to aggressive automated scraping of FederalRegister.gov and eCFR.gov, programmatic access to these sites is limited to access to our extensive developer APIs.

If you are human user receiving this message, we can add your IP address to a set of IPs that can access FederalRegister.gov & eCFR.gov; complete the CAPTCHA (bot test) below and click "Request Access". This process will be necessary for each IP address you wish to access the site from, requests are valid for approximately one quarter (three months) after which the process may need to be repeated.

An official website of the United States government.

If you want to request a wider IP range, first request access for your current IP, and then use the "Site Feedback" button found in the lower left-hand side to make the request.