Chapter 11: Hypertensive disorders of pregnancy

Hypertensive disorders affect approximately 10% of pregnancies worldwide and are a leading cause of maternal, fetal and neonatal morbidity and mortality. Maternal risks include placental abruption, stroke, pulmonary oedema, thromboembolism, multiple-organ failure and disseminated intravascular coagulation. Fetal risks include fetal-growth restriction, reported in about 25% of pre-eclampsia, prematurity in about 27% and intrauterine death in about 4%. Newborns may require prolonged high-level neonatal care and are at risk of low birth weight and postnatal death.

Classification

Chronic or pre-existing hypertension: hypertension present before pregnancy or developing before 20 weeks, usually continuing beyond 42 days postpartum; it may be primary, secondary, white-coat or masked hypertension and may coexist with proteinuria.

Gestational hypertension: hypertension developing after 20 weeks and usually resolving within 42 days after delivery. Transient gestational hypertension is detected in clinic but normalises on repeated measurements over several hours. It carries an approximately 40% risk of progressing to persistent gestational hypertension or pre-eclampsia and requires close follow-up.

Pre-eclampsia: new hypertension at or after 20 weeks with one or more new features of maternal or uteroplacental dysfunction. These include proteinuria, defined as urinary albumin above 0.3 g/day or an albumin-to-creatinine ratio above 30 mg/mmol (0.3 mg/mg); acute kidney injury with creatinine at least 90 µmol/L or 1 mg/dL; liver injury with ALT or AST above 40 IU/L, with or without right-upper-quadrant or epigastric pain; neurological complications such as altered mental status, stroke, seizures, severe headache or persistent visual scotomata; haematological complications such as platelets below 150,000/µL, disseminated intravascular coagulation or haemolysis; and uteroplacental dysfunction such as fetal-growth restriction, abnormal umbilical-artery Doppler or intrauterine death.

Chronic hypertension with superimposed pre-eclampsia: pre-existing hypertension followed by new proteinuria or any of the maternal or uteroplacental abnormalities listed above, usually with a sudden or progressive additional rise in pressure.

Unclassifiable hypertension: when hypertension is first recorded after 20 weeks, reassess at or after 42 days postpartum. If it resolves, classify it as gestational hypertension; if it persists, classify it as pre-existing hypertension.

Definition and classification of blood pressure

In pregnancy, clinic or hospital hypertension is defined as systolic pressure above 140 mmHg and/or diastolic pressure above 90 mmHg. It is classified as mild at 140–159/90–109 mmHg and severe at or above 160/110 mmHg, rather than by the general adult grades.

Blood pressure documented before pregnancy or in the first trimester is important to avoid misclassification. Early second-trimester values should be interpreted cautiously in women without earlier measurements because of physiological mid-pregnancy lowering. A woman first found to have hypertension after 20 weeks with an unknown earlier baseline should be managed as having gestational hypertension until clarified. Reassessment around six weeks postpartum helps distinguish chronic from gestational hypertension.

The broader International Society for the Study of Hypertension in Pregnancy definition of pre-eclampsia is preferred. HELLP syndrome—haemolysis, elevated liver enzymes and low platelets—should prompt assessment for additional features of pre-eclampsia. Clinicians should regard pre-eclampsia as potentially serious and unpredictable; older labels such as mild and severe pre-eclampsia are no longer sufficient on their own.

Approximately 25% of women with pre-existing hypertension develop superimposed pre-eclampsia. The diagnosis is based on new proteinuria or new maternal-organ dysfunction after 20 weeks, often with an additional rise in blood pressure.

Measuring blood pressure in pregnancy

Measure pressure seated, or in the left lateral position during labour, with an appropriately sized upper-arm cuff at heart level. Manual auscultation using Korotkoff phase V remains the reference standard because automated devices may underestimate pressure and can be unreliable in severe pre-eclampsia. Use devices validated specifically for pregnancy.

Ambulatory monitoring predicts pregnancy outcomes better than a single clinic measurement, helps avoid unnecessary treatment in white-coat hypertension and is useful in high-risk women, including those with diabetic nephropathy or chronic hypertension. In BUMP-1, home monitoring did not detect pre-eclampsia earlier than clinic measurement in high-risk pregnant people, but home and clinic measurements could be used as alternative or complementary approaches. In BUMP-2, home monitoring did not produce better blood-pressure control than scheduled clinic measurements in pre-existing or gestational hypertension; both approaches achieved similar control.

Laboratory assessment

Baseline and follow-up testing should include urinalysis, full blood count and haematocrit, liver enzymes, serum creatinine and serum uric acid, which tends to rise in clinically evident pre-eclampsia. All pregnant women should be assessed for proteinuria early to identify pre-existing kidney disease and again in the second half of pregnancy to assess for pre-eclampsia. Proteinuria is no longer essential for diagnosis. A dipstick result of at least +1 should be followed by a spot UACR; a value below 30 mg/g reliably argues against significant proteinuria.

Renal ultrasound should be considered when creatinine or urine tests are abnormal. Uterine- and umbilical-artery Doppler after 20 weeks can help identify people at increased risk of gestational hypertension, pre-eclampsia and fetal-growth restriction.

Prediction and prevention of pre-eclampsia

Women at high or moderate risk should generally be advised to take aspirin 100–150 mg daily at bedtime, preferably before 16 weeks and ideally from 11–14 weeks through 36 weeks, according to obstetric guidance.

High-risk factors include a hypertensive disorder in a previous pregnancy, chronic hypertension, CKD, type 1 or type 2 diabetes, autoimmune disease such as systemic lupus or antiphospholipid syndrome, and assisted reproductive therapy in the current pregnancy. Moderate risk includes two or more of nulliparity, age 40 years or older, an interpregnancy interval over 10 years, BMI at least 35 kg/m² at the first visit, family history of pre-eclampsia and multiple pregnancy.

Angiogenic markers such as endoglin, PlGF, sFlt-1 and the sFlt-1/PlGF ratio, and pregnancy-associated plasma protein A combined with clinical and uterine-Doppler features, have been studied for early prediction. Further validation is needed. When pre-eclampsia is clinically suspected, an sFlt-1/PlGF ratio of 38 or lower may help rule out short-term progression, but this should be interpreted within local pathways.

Lifestyle

Unless contraindicated, aerobic exercise three to four times weekly for 30–60 minutes until delivery can help maintain healthy weight and reduce adverse pregnancy outcomes, including hypertensive disorders. Calcium supplementation of at least 1 g/day may be considered in women with low dietary calcium intake, below approximately 600 mg/day. Salt restriction is not recommended solely to prevent hypertensive disorders of pregnancy, but women with pre-existing hypertension may reasonably continue a salt-limited diet.

Clinical management

Mild pre-existing hypertension

During the first trimester, ACE inhibitors, ARBs and direct renin inhibitors must be stopped. Whether to continue other antihypertensive treatment during organogenesis, up to about 16 weeks, should be individualised by weighing untreated pre-pregnancy pressure, first-trimester values, HMOD and a short supervised withdrawal in selected cases. If pressure is below 130/80 mmHg early in pregnancy, treatment may sometimes be reduced or paused with close monitoring. Restart treatment for pressure above 140/90 mmHg at any gestational age.

Large CHIPS and CHAP trials found that tighter control or active treatment of pre-existing hypertension was beneficial and did not cause overall harm. Pregnancy-related composite outcomes fell by 35% in CHIPS and 18% in CHAP, with fewer severe pre-eclampsia outcomes. CHIPS reported more small-for-gestational-age outcomes, whereas CHAP did not, so the safety margin of very low pressure remains important. Given treated pressures around 133/85 and 129/79 mmHg in the trials, a general threshold to start or intensify treatment of 140/90 mmHg is reasonable; intensive lowering below this should not be pursued at the expense of fetal perfusion.

Labetalol and alpha-methyldopa are traditional first-line options; extended-release nifedipine is an alternative. Labetalol is not available or preferred in some countries because of concerns about hepatotoxicity, which can also occur during pregnancy.

Mild gestational hypertension

Although CHIPS included relatively few women with gestational hypertension, secondary analyses did not suggest materially different outcomes from pre-existing hypertension. Starting treatment around 140/90 mmHg is reasonable, while reducing diastolic pressure below 80 mmHg is not generally recommended. The same medication options can be used as for pre-existing hypertension.

Pre-eclampsia

Women with pre-eclampsia should be admitted and carefully assessed at diagnosis. Diagnosis at or after 37 weeks supports blood-pressure control and prompt delivery. Clinically stable women before 37 weeks may sometimes be managed as outpatients, but delivery should be considered before 37 weeks if severe hypertension persists despite optimal treatment, if maternal neurological, haematological or cardiac symptoms develop, or if fetal status is non-reassuring.

Pre-eclampsia with severe features—severe hypertension with or without proteinuria, or any hypertension with neurological, haematological, cardiovascular, liver or kidney complications—should be treated with magnesium sulfate infusion and delivery planning to prevent eclampsia. Magnesium sulfate for 24 hours postpartum is reasonable for prophylaxis and remains the preferred treatment for eclamptic seizures. Blood pressure may be controlled with labetalol, if not contraindicated, alone or with extended-release nifedipine and/or alpha-methyldopa.

Severe hypertension

Severe hypertension requires hospital treatment to lower pressure gradually below 160/105 mmHg and exclude pre-eclampsia; continuous ECG monitoring is required. Choice and route depend on the initial diagnosis, expected delivery time, presence of pre-eclampsia and local expertise.

A recent meta-analysis supports nifedipine as an effective acute strategy; labetalol and hydralazine showed more limited effectiveness in that analysis. In severe-feature pre-eclampsia or persistent or recurrent severe pressure despite oral treatment, labetalol or urapidil may be used before, during and after delivery. Hydralazine is generally reserved for lack of availability or failure of labetalol/urapidil, second- or third-degree AV block, severe heart failure, asthma, bradycardia or severe postpartum hypertension. Sodium nitroprusside is a last resort because prolonged exposure increases fetal cyanide risk. With pulmonary oedema, intravenous nitroglycerin is preferred. Sublingual immediate-release nifedipine should not be used.

Pre-existing secondary hypertension

Women with pre-existing hypertension should receive pre-pregnancy counselling and evaluation for secondary causes. Renal-artery Doppler should be considered in women planning pregnancy. When fibromuscular dysplasia is known, the vascular tree should be assessed for additional arterial disease, blood pressure optimised and renal-artery disease treated when indicated before pregnancy.

Women with primary aldosteronism should be counselled about the risks of pregnancy because of progesterone–aldosterone receptor interactions. Close laboratory monitoring is needed if known disease or strong suspicion is present. After the second trimester, eplerenone may be considered for uncontrolled hypertension with or without hypokalaemia. Phaeochromocytoma is rare but potentially fatal; undiagnosed maternal and fetal mortality may approach 50%, whereas early diagnosis and treatment reduce maternal and fetal mortality to below 5% and 15%, respectively. Plasma or urinary metanephrines are preferred for biochemical diagnosis and MRI for localisation. Laparoscopic adrenalectomy is usually performed after 10–14 days of alpha-blockade, adding beta-blockade only after adequate alpha-blockade. A caesarean delivery with tumour removal at the same or a later operation is often preferred.

Hypertensive disorders occur in about half of pregnant women with CKD. Pre-pregnancy risk depends particularly on CKD stage, eGFR and proteinuria. Women with mild CKD, normal early pressure and no severe proteinuria may have a relatively uncomplicated course. Moderate or advanced CKD increases maternal, fetal and kidney risk. eGFR below 40 mL/min/1.73 m² with proteinuria above 1 g/day represents very high risk, including possible need for dialysis.

Postpartum blood pressure

Postpartum hypertension is common during the first week. Even after a normotensive pregnancy, day-one hypertension may reflect vasoactive uterotonic drugs such as oxytocin or methylergometrine, transfusion, physiological autotransfusion from the contracting uterus or excess fluid.

In pre-eclampsia, urine output may fall during the first 12–36 hours because fluid redistribution is delayed. In a small randomised study, furosemide 20 mg daily for five days postpartum prevented postpartum hypertension in one of 13 women with gestational hypertension, but routine use needs confirmation in larger studies.

Pressure usually returns to normal within six weeks after gestational hypertension or pre-eclampsia. It often persists beyond six weeks in pre-existing hypertension or superimposed pre-eclampsia. A less common delayed postpartum phenotype begins after six months and resolves over subsequent months; its cause is uncertain.

Most antihypertensive drugs used during pregnancy can be used postpartum. ACE inhibitors are particularly appropriate when cardiorenal disease is present; methyldopa should be used cautiously because of postpartum-depression risk.

Postpartum treatment and breastfeeding

Most antihypertensive drugs enter breast milk at very low concentrations. Nifedipine and verapamil are compatible with breastfeeding. Diuretics are not absolutely contraindicated but may reduce milk production. Alpha-methyldopa is compatible with breastfeeding but is not preferred postpartum because of depression risk. ACE inhibitors can be used in breastfeeding women with hypertensive disorders and cardiovascular or kidney disease. ARBs are generally avoided because safety data are limited.

Recurrence and long-term risk

Women with hypertension in a first pregnancy have increased risk of hypertension and hypertensive disorders in a later pregnancy. The earlier hypertension developed in the first pregnancy, the higher the recurrence risk.

Registries consistently show increased future cardiovascular events after hypertensive disorders of pregnancy, together with a higher risk of persistent hypertension. More severe pre-eclampsia is associated with a greater later disease burden than less severe pre-eclampsia. Genetic and Mendelian-randomisation analyses support an association with coronary disease and stroke, partly mediated by cardiometabolic factors. Women with a history of hypertensive pregnancy disorders should receive lifestyle counselling, annual primary-care review, repeated blood-pressure measurements and cardiovascular-risk assessment.

Evidence mentioned

• CHIPS and CHAP support active treatment of appropriate chronic or gestational hypertension around 140/90 mmHg, while avoiding excessive lowering that could compromise fetal perfusion.
• Magnesium sulfate remains central to prevention and treatment of eclampsia in severe-feature disease.
• Pregnancy evidence is population-specific; medication changes, delivery timing and breastfeeding decisions must follow obstetric guidance and local protocols.