Severe hypertension in pregnancy

Key points

• Severe hypertension in pregnancy is defined as a sustained systolic blood pressure of 160 mmHg or over or diastolic blood pressure of 110 mmHg or over.

• The most common cause of severe hypertension in pregnancy is pre-eclampsia, which presents after 20 weeks' gestation.

• Severe hypertension before 20 weeks' gestation is usually due to chronic hypertension, and requires assessment for target organ damage and exclusion of secondary causes of hypertension.

• Oral and intravenous labetalol and oral modified-release nifedipine are used for the control of severe hypertension in women with pre-eclampsia.

• Chronic hypertension and pre-eclampsia are vascular risk factors, therefore postnatal counselling is advocated, with management of modifiable risk.

Definitions

There is international consensus that a normal blood pressure in pregnancy is less than 140 mmHg systolic and 90 mmHg diastolic. This definition was originally derived from non-pregnant populations, with later assessment of the normal distribution of blood pressure values in pregnancy. More recent prospective cohort data have shown that the reference limit (97th percentile) for blood pressure has a nadir of 138/86 mmHg at gestational weeks 18–20, rising to 144/95 mmHg at term. When these data are restricted to women aged under 40 years, with body mass index less than 30 kg/m² and an absence of underlying conditions and pregnancy complications, the nadir is 132/83 mmHg, rising to 138/90 mmHg at 38 weeks’ and 140/92 mmHg at 40 weeks’ gestation.¹ These data support the long-standing threshold of 140/90 mmHg for the diagnosis of hypertension in pregnancy.

Severe hypertension in pregnancy is defined as a sustained systolic blood pressure of 160 mmHg or over, or diastolic blood pressure of 110 mmHg or over. This definition is also derived from long-standing consensus, supported by case series of maternal haemorrhagic stroke and aortic dissection in pregnant women with systolic blood pressures greater than 160 mmHg.^2,3

Aetiology

Hypertension affects up to 10% of pregnant women and is due to either pre-existing chronic hypertension or a new pregnancy-induced hypertensive disorder. Timing of disease may distinguish chronic hypertension from gestational hypertension, as chronic hypertension presents prior to 20 weeks’ gestation and persists after pregnancy. Endothelial dysfunction distinguishes pre-eclampsia from other pregnancy-induced hypertensive disorders and includes one or more of:

• proteinuria: new urinary protein:creatinine ratio over 30 mg/mmol

• acute kidney injury: new serum creatinine over 90 μmol/L

• liver involvement: alanine aminotransferase over 40 IU, right upper quadrant or epigastric pain

• haematological complications: thrombocytopenia less than 150 × 10⁹/L or haemolysis

• cerebral symptoms or signs in the absence of another cause: headache, visual scotomata or clonus

• uteroplacental insufficiency: fetal growth restriction, abnormal umbilical artery Doppler.⁴

Even transient and white-coat hypertension are not benign disorders in pregnancy, conferring a risk of progression to gestational hypertension and pre-eclampsia. Disease definitions are shown in Fig 1.⁵

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Fig 1.

Hypertensive disorders in pregnancy. AKI = acute kidney injury; BP = blood pressure; CKD = chronic kidney disease; CNS = central nervous system; CVD = cardiovascular disease.

Severe hypertension before 20 weeks’ gestation: chronic hypertension

Chronic hypertension affects 8% of women of childbearing age and 3% of pregnancies. In the absence of routine blood pressure checks outside pregnancy, chronic hypertension may be diagnosed for the first time during pregnancy as a sustained blood pressure ≥140/90 mmHg prior to 20 weeks’ gestation. Chronic hypertension can, however, be masked by the physiological changes of pregnancy, which include systemic and renal vasodilatation and a decrease in systemic vascular resistance. Chronic hypertension can therefore also manifest as persistent hypertension beyond the postpartum period.

Severe hypertension prior to 20 weeks’ gestation is most commonly asymptomatic, and accelerated hypertension is unlikely in the context of gestational physiology. However, all women with severe hypertension should be assessed in a hospital setting. Appropriate clinical care pathways should be agreed for women presenting with hypertension prior to 20 weeks’ gestation. In the UK, specialty referral is commonly determined by gestation, with referral to general medicine prior to 18–20 weeks and referral to obstetric services only at later gestations. This may not be appropriate for women with hypertension in early pregnancy, who should benefit from the expertise that obstetricians and obstetric physicians have in the pregnancy-specific management of hypertension, as well as established pathways for outpatient management and surveillance.

Due to the physiological changes of pregnancy, severe hypertension prior to 20 weeks’ gestation is rare. Where severe hypertension does occur before 20 weeks’ gestation, the possibility of secondary hypertension should be considered, particularly in the absence of a family history of hypertension and whenever there is treatment resistance (Table 1).⁶ Assessment for possible target organ damage is also required (Table 2).⁶

Treatment with hypertensive agents should be initiated, aiming for an initial target blood pressure below 160/110 mmHg, and an eventual target 110–135 / 70–85 mmHg for the remainder of the pregnancy.⁷ In the absence of accelerated hypertension and pre-eclampsia, severe hypertension in pregnancy can usually be treated with oral agents (see Table 3), with blood pressure control achieved over days, rather than hours. A sufficient response to oral treatment should, however, be confirmed with close clinical surveillance whenever outpatient management of hypertension in pregnancy is undertaken. Inpatient assessment and management of severe hypertension in the absence of pre-eclampsia is warranted for women with symptoms, atypical features, retinopathy, abnormal cardiovascular or neurological findings, acute kidney injury or if there is any other clinical concern.

Severe hypertension after 20 weeks’ gestation

Severe hypertension after 20 weeks’ gestation can occur due to gestational hypertension, pre-eclampsia, superimposed gestational hypertension/pre-eclampsia in women with chronic hypertension, or poor control of chronic hypertension (see Fig 1). Most severe hypertension in pregnancy occurs in the context of pre-eclampsia. However, clinicians should not be reassured by the absence of clinical features of pre-eclampsia (usually proteinuria), as severe hypertension is associated with an increased risk of adverse maternal and fetal outcomes even in the absence of pre-eclampsia (Table 4).^8–11

Management of severe hypertension in pregnancy

Historically, strict blood pressure control in pregnancy was avoided due to theoretical concern that treatment compromised the fetal circulation and contributed to adverse neonatal outcomes. A randomised controlled trial of ‘tight’ (target diastolic 85 mmHg) with ‘less tight’ (100 mmHg) blood pressure control in pregnancy was designed to address this. Although achieved blood pressure difference between groups was lower than intended (139/90 mmHg versus 133/85 mmHg), tighter control was associated with a reduction in the incidence of severe hypertension (28% versus 41%) and its associated adverse outcomes (Table 4).¹² A systematic review including 59 trials and 4,723 pregnant women with blood pressures between 140–169 / 90–109 mmHg demonstrated that antihypertensive treatment halved the risk of severe maternal hypertension, with no adverse effects on fetal outcomes.¹³ Evidence of a reduction in severe maternal hypertension, in the absence of adverse fetal and neonatal consequences, has been sufficient to reduce the threshold at which antihypertensive treatment is commenced in pregnancy in the UK from 150/100 mmHg to 140/90 mmHg.¹⁴

The choice of antihypertensive agent in pregnancy is determined by licensing, availability and clinician experience, with no high-level evidence to guide prescribing.¹⁴ Labetalol, modified-release nifedipine and methyldopa are considered safe for use in pregnancy and are the most commonly used drugs in the UK. Fewer safety data are available for amlodipine and doxazosin, although no adverse fetal effects are reported.¹⁵ Angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor antagonists are contraindicated due to fetotoxicity in the second and third trimesters. Enalapril is, however, recommended for postpartum hypertension, with demonstrated safety in lactation in small cohorts, and pilot data showing improved diastolic function and left ventricular modelling compared with placebo after pre-term pre-eclampsia.^16,17

Where severe hypertension is caused by pre-eclampsia, it confers a sevenfold chance of haemorrhagic stroke compared with severe hypertension in the absence of pre-eclampsia. In contrast, chronic hypertension has not been found to increase the risk of pregnancy-associated stroke.¹⁸ This difference is attributed to the disruption of cerebral autoregulation in pre-eclampsia, which leads to increased vulnerability to cerebrovascular injury, as well the progressive nature of endothelial dysfunction in pre-eclampsia. For this reason, in severe hypertension due to pre-eclampsia, the aim is to control blood pressure to 160/110 mmHg within hours, followed by a target blood pressure of 110–140 / 70–85 mmHg.^4,14 There are no data to guide the rate at which systolic blood pressures of 200 mmHg or more should be corrected in pre-eclampsia. Consensus practice in non-pregnant hypertensive emergencies is to reduce systolic blood pressure by no more than 25% in the first hour, aiming for a systolic blood pressure below 160 mmHg over the next 2–6 hours provided the patient remains stable. Intravenous labetalol can be used for precise, rapid titration and control. Intravenous hydralazine is also safe to use in pregnancy where labetalol is contraindicated or ineffective, with care to avoid rapid blood pressure changes and hypotension (<110/70 mmHg). If a delay in intravenous treatment is anticipated due to the need for admission and high-level monitoring, then oral labetalol (200 mg) or modified-release nifedipine (10–20 mg) can be given, with doses repeated hourly. In the UK, modified-release preparations of nifedipine are used due to the risks of hypotension with immediate-release and sublingual preparations. The treatment of severe hypertension is detailed in Table 3.

Additional aspects of care for women with pre-eclampsia and severe hypertension include intravenous magnesium sulphate for seizure prophylaxis, careful fluid balance with restriction of fluid to reduce the risk of pulmonary oedema, and assessment of fetal wellbeing. An inability to control maternal blood pressure may be an indication for preterm delivery, which remains the only cure for pre-eclampsia.

Postpartum

There is a postpartum rise in blood pressure, peaking on day 3–6 after delivery in both normotensive women and those with hypertension during pregnancy. Blood pressure and pre-eclampsia surveillance should therefore be continued in the first week postpartum. About one in five women with hypertension in pregnancy will have persistent chronic hypertension postpartum. A longer duration of antihypertensive treatment in pregnancy, higher maximum systolic and diastolic blood pressures, and preterm pre-eclampsia are all risk factors for sustained hypertension.¹⁹ Both chronic hypertension and pre-eclampsia are risk factors for cardiovascular disease, cerebrovascular disease and chronic kidney disease later in life, with endothelial dysfunction, angiogenic imbalance and chronic inflammatory changes hypothesised as potential pathophysiological mechanisms.^20,21 In the absence of long-term prospective intervention studies, counselling of women following hypertensive disorders in pregnancy is advocated, with management of modifiable risk factors.