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Hypertensive Complications of Pregnancy


Key Points

  • Hypertensive disorders of pregnancy are classified as chronic hypertension, gestational hypertension, preeclampsia with and without severe features, and chronic hypertension with superimposed preeclampsia.

  • Pharmacologic management of chronic hypertension should be reserved for women with sustained elevations in blood pressure at or greater than 160 mm Hg systolic or 110 mm Hg diastolic.

  • Magnesium sulfate administration to prevent eclampsia is used for those preeclampsia cases with severe features.

  • Daily low-dose aspirin is recommended in women at high risk of preeclampsia, initiated between 12 and 16 weeks of gestation and continued until delivery.

  • When preeclampsia without severe features is diagnosed, delivery should be accomplished at or beyond 37 completed gestational weeks. When severe features are present, delivery should be accomplished expeditiously (regardless of gestational age) once maternal stabilization has been achieved.

Hypertension is the most common medical problem in pregnancy, affecting 10% to 15% of all pregnant women. As the third most common cause of maternal mortality after thromboembolic disease (15%) and hemorrhage (11%), hypertensive disorders account for almost 10% of maternal deaths in the United States. Complications arising from hypertensive disorders have profound effects on the fetus and neonate and thus are a major source of perinatal mortality and morbidity. Preeclampsia (PE) is a leading cause of perinatal morbidity and mortality, with an estimated 50,000 to 60,000 PE-related deaths per year worldwide. With the greatest morbidity and mortality, preeclampsia affects 5% to 7% of all pregnant women but is responsible for more than 70,000 maternal deaths and 500,000 fetal deaths worldwide every year. In the United States, it is a leading cause of maternal death, severe maternal morbidity, maternal intensive care admissions, cesarean section, and prematurity.

Unfortunately, the incidence of preeclampsia has increased by 25% in the United States during the past two decades. Furthermore, because preeclampsia has been shown to be a risk factor for future cardiovascular and metabolic disease in women, recognizing the importance of proper perinatal management and prevention is essential.

Classification of Hypertensive Disorders of Pregnancy

The diagnostic criteria for the hypertensive complications of pregnancy have undergone significant revision in the past several years. The American College of Obstetricians and Gynecologists (ACOG) has recently summarized the current consensus regarding the definitions of hypertensive disorders encountered in pregnancy. Hypertension during pregnancy is currently defined into four categories ( Table 10.1 ):

  • 1.

    Chronic hypertension which predates pregnancy or is present prior to 20 weeks of gestation

  • 2.

    Gestational hypertension which occurs after 20 weeks of pregnancy and resolves postpartum

  • 3.

    Preeclampsia

  • 4.

    Chronic hypertension (predating 20 weeks of gestation) with superimposed preeclampsia

Table 10.1
Classification of Hypertensive Disorders of Pregnancy
Data from American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics. ACOG practice bulletin No. 203: chronic hypertension in pregnancy. Obstet Gynecol . 2019 and Gestational hypertension and preeclampsia. ACOG Practice Bulletin No. 222. American College of Obstetricians and Gynecologists . Obstet Gynecol . 2020;135:e237–e260.
Category Definition
Hypertension in pregnancy Systolic blood pressure ≥140 mm Hg or diastolic BP ≥90 mm Hg, or both, measured on two occasions at least 4 hours apart
Chronic hypertension Hypertension diagnosed or present before pregnancy or before 20 weeks of gestation, or hypertension diagnosed for the first time during pregnancy and that does not resolve in the postpartum period
Gestational hypertension New-onset hypertension after 20 weeks of gestation in the absence of proteinuria that normalizes postpartum. Blood pressure elevation first noted after 20 weeks that does not resolve after delivery is defined as chronic hypertension.
Preeclampsia

  • New-onset hypertension with new-onset proteinuria (300 mg/24 hours or a protein/creatinine ratio of ≥0.3) or one or more of the following:

    • thrombocytopenia (<100 × 10 9 /L)

    • elevated liver transaminases (twice normal)

    • renal insufficiency (serum creatinine >1.1 mg/dL or doubling creatinine level without preexisting renal disease)

    • pulmonary edema

    • new-onset headache or visual disturbances

Chronic hypertension with superimposed preeclampsia Preeclampsia occurring in a woman with hypertension predating 20 weeks of pregnancy

Importantly, proteinuria is no longer required for the diagnosis of preeclampsia if other abnormal findings are present. Preeclampsia is now defined as hypertension plus proteinuria or hypertension plus other systemic abnormalities noted as follows.

Hypertension in pregnancy is defined when blood pressure is:

  • ≥140 mm Hg systolic or ≥90 mm Hg diastolic on two occasions at least 4 hours apart after 20 weeks’ gestation in a woman with a previously normal blood pressure.

  • The requirement for documenting hypertension twice over an interval of at least 4 hours is shortened to minutes if systolic pressure is ≥160 mm Hg or diastolic pressure is ≥110 mm Hg.

Proteinuria is defined when urinary protein is:

  • ≥300 mg per 24-hour urine collection

    or

  • Protein/creatinine ratio ≥0.3

    or

  • Dipstick reading of 1+ in a voided urine specimen if more precise laboratory-based results are not readily available

    When the hypertension criteria above are present but proteinuria is absent or not tested, preeclampsia is diagnosed when any of the following are present:

  • Platelet count <100,000/μL.

  • Liver transaminase levels are twice normal values or higher

  • Newly elevated serum creatinine is >1.1 mg/dL or a doubling in the absence of other renal disease

  • Pulmonary edema

  • New-onset cerebral or visual disturbances

Because fetal growth restriction is managed similarly in pregnant women with and without preeclampsia, it has been deleted as a criterion for severe preeclampsia.

Chronic Hypertension

Up to 5% of pregnant women have chronic hypertension, which is diagnosed when hypertension is present before pregnancy or recorded before 20 weeks of gestation. However, when hypertension is first noted in a patient after 20 weeks’ gestation, it may be difficult to distinguish chronic hypertension from preeclampsia. In such cases, the precise diagnosis might not be made until after delivery and well into the postpartum period. Hypertension that is first diagnosed during the second half of pregnancy and persists postpartum is diagnosed as chronic hypertension.

Chronic hypertension has adverse effects on pregnancy outcome. A report of 55 studies of chronic hypertension comprising 795,221 pregnancies found that 26% of women entering pregnancy with chronic hypertension developed superimposed preeclampsia, 41% required cesarean section, and 28% had preterm delivery. Of the neonates, 17% had birth weight less than 2500 g, NICU admission occurred in 21%, and perinatal death occurred in 4.0%. The adverse fetal and maternal perinatal outcomes are related to the severity of the preexisting hypertension. When chronic hypertension is secondary to maternal chronic renal disease, a large (506,000 pregnancies) systematic review found significantly elevated odds for preeclampsia (odds ratio [OR] 10.36), premature delivery (OR 5.72), small for gestational age (OR 4.85), and pregnancy failure (OR 1.80). Women with untreated severe chronic hypertension are also at increased risk for cardio-vascular complications during pregnancy, including stroke.

The majority of cases of chronic hypertension seen in pregnancy are idiopathic (essential hypertension), but other causes should always be sought because pregnancy outcome is worse in women with secondary hypertension. Renal disease (e.g., chronic renal failure, glomerulonephritis, renal artery stenosis), cardiovascular causes (coarctation of the aorta, Takayasu arteritis), and, rarely, Cushing disease, Conn syndrome, and pheochromocytoma should be excluded through physical examination, history, and more detailed testing if needed.

Patients with chronic hypertension should be evaluated thoroughly early in pregnancy with serum urea, creatinine, and electrolyte measurements, urinalysis, and 24-hour urine collection for protein and creatinine clearance determinations. Reassessment of renal function should be performed in each trimester and more frequently if the patient’s condition deteriorates.

Antihypertensive Treatment of Chronic Hypertension in Pregnancy

A 2014 Cochrane review of 49 trials found that treatment of mild-to-moderate hypertension reduced the risk of developing severe hypertension but had no effect on the incidence of preeclampsia, preterm birth, fetal death, fetal growth restriction, or any other measured outcome. However, a recent multicenter trial (chronic hypertension in pregnancy study [CHAP]; 2408 women before 23 weeks’ gestation with mild chronic hypertension randomized to receive antihypertensive medications if blood pressure was >140/90 mm Hg [active treatment] versus no treatment unless severe hypertension developed [SBP >160 or DBP >=105]) documented a reduction in composite outcome (severe preeclampsia, medically indicated delivery <35 weeks’ gestation, placental abruption, or fetal/neonatal death) with maternal antihypertensive medication treatment–30.2% versus 37.0%; adjusted risk ratio (RR), 0.82; 95% CI, 0.74–0.92; P<.001. Importantly, antihypertensive medication treatment had no effect on birth weight <10th percentile and other serious maternal and neonatal complications.The CHAP study demonstrated for pregnant women with chronic hypertension that a treatment threshold of 140/90 mm Hg yields improved outcomes compared to initiating medication only when blood pressure rises above 160/105 mm Hg, as previously recommended. One strength of the CHAP study includes the fact that the majority of enrolled patients had chronic hypertension on medication at the time of trial entry (56%) and 41% were enrolled prior to 14 weeks’ gestation. Thus, while antihypertensive medications were reserved in the past for patients whose blood pressures placed them at significant risk of maternal stroke (systolic blood pressure of ≥160 mm Hg or diastolic pressure of ≥110 mm Hg), the American College of Obstetricians and Gynecologists recently published a Practice Advisory recommending 140/90 as the threshold for initiation or adjustment of medical therapy for chronic hypertension in pregnancy, rather than the previous threshold of 160/110 mm Hg. Patients taking blood pressure medications at the start of pregnancy should be maintained on their medications, rather than discontinuing them and waiting to initiate treatment for blood pressures in the severe range.

Antihypertensive Medications in PregnancyThe choice of antihypertensive agent for use in pregnancy is governed by reducing risk of severe maternal sequelae (e.g., cerebral hemorrhage, myocardial infarction) while avoiding adverse effects on the fetus. Because lowering of maternal systolic blood pressure to <140 mm Hg or diastolic to <90 mm Hg can compromise uterine perfusion and fetal growth and oxygenation, maternal pressures should be maintained in the 120 to 155 mm Hg systolic and 90 to 105 mm Hg diastolic range.

The antihypertensive medications most commonly used in pregnancy are listed in Table 10.2 .

Table 10.2
Drugs Commonly Used to Treat Chronic Hypertension in Pregnancy and Their Modes of Action
Adapted from 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;122:1122–1131.
Drug Mode of Action Typical Dose
Methyldopa Centrally acting antihypertensive 0.5–3 g/day in 2–3 divided doses
Labetalol Mixed α- and β-adrenergic blockers 200–2400 mg/day in 2–3 divided doses
Nifedipine Calcium channel blocker 30–120 mg/day in slow-release form

α- and β-Adrenergic BlockersLabetalol is a mixed α 1 -adrenergic, β 1 -adrenergic, and β 2 -adrenergic blocker and is the most frequently used medication for chronic hypertension in pregnancy. Pure β-blockers have been associated with increased risk of IUGR (e.g., atenolol), and the mixed adrenergic blockade produced by labetalol is thought to mitigate this unwanted effect. Labetalol is also used intravenously to manage severe hypertension accompanying preeclampsia.

Calcium Channel BlockersNifedipine in extended-release forms is effective in managing chronic hypertension in pregnancy. In immediate-release form, nifedipine 10 to 20 mg orally or as a constant infusion of 0.5 to 10 mg/hr is recommended for urgent management of severe-range maternal blood pressures exceeding 160/110 mm Hg.

Methyldopaα-Methyldopa is a centrally acting antihypertensive agent, it has a slow onset of action with prolonged time to therapeutic effect (days), and compliance with methyldopa therapy may be impeded by side effects such as sedation in some patients.

HydralazineHydralazine, a potent peripheral vasodilator, is used intravenously to treat acute hypertensive emergencies in pregnancy (blood pressure >160/110 mm Hg). Its role as an oral agent in the management of chronic hypertension is limited to a second- or third-line choice. Long-term use of hydralazine may be associated with a lupus-like syndrome in some patients.

DiureticsDiuretics are often used in hypertension in nonpregnant adults, but there is little role for their use in pregnant women with hypertension. Because diuretics can reduce the plasma volume expansion of normal pregnancy and thus impede fetal growth, use of diuretics in pregnant patients should be limited to those with cardiac dysfunction or frank pulmonary edema.

Angiotensin-Converting Enzyme (ACE) Inhibitors and Angiotensin Receptor Blockers (ARBs)ACE and ARBs should not be used during pregnancy because of their association with fetal renal failure, oligohydramnios, pulmonary hypoplasia, and intrauterine or neonatal death. Transitioning women taking these agents in the prepregnancy period is recommended. Patients who conceive while taking an ARB or ACE inhibitor should be switched to a safer alternative as soon as possible.

Low-Dose AspirinLow-dose aspirin prophylaxis (81 mg/day) after 12 weeks of gestation has been shown to modestly reduce the risk of preeclampsia in women at increased risk, without adverse fetal or maternal effects. The US Preventive Services Task Force and ACOG recommend daily low-dose aspirin for women with a history of early-onset preeclampsia requiring delivery <34 weeks of gestation, or with more than one prior pregnancy complicated by preeclampsia. The guidelines recommend initiating aspirin prophylaxis (81 to 162 mg daily) between 12 and 28 weeks of gestation (optimally before 16 weeks) and to continue until delivery.

Antenatal Fetal Surveillance in Chronic or Gestational Hypertension

Because women with chronic hypertension are at increased risk of slowing of fetal growth and of superimposed preeclampsia, antenatal surveillance in women with chronic hypertension is recommended. However, limited data exist regarding optimal timing and intervals of testing.

The procedures of providing antenatal fetal biophysical testing in chronic hypertension should also include maternal screening for signs of superimposed preeclampsia.

Detection of tapering fetal growth requires periodic sonographic fetal growth assessments, typically every 3 to 4 weeks from 24 weeks onward. Because arrest of fetal growth is an indication for delivery, tapering of growth on sonogram should prompt more frequent and intensive evaluations. If the sonographic estimated fetal weight tapers below the 20th percentile or the abdominal circumference is at a significantly smaller percentile than the head circumference, more intensive growth sonography and frequent fetal biophysical surveillance is indicated. In such cases, sonography is typically performed at 10- to 21-day intervals with attention to amniotic fluid volume, trending of each biometric parameter (especially abdominal circumference), and umbilical artery Doppler waveforms.

Weekly fetal biophysical testing in IUGR has been shown to reduce perinatal mortality while not increasing labor induction or cesarean delivery. Indications for delivery in the hypertensive patient with fetal IUGR include absence of growth of the head and abdomen over a 10-day interval, oligohydramnios, biophysical score of less than 6, or reversal of end-diastolic velocity on the umbilical Doppler waveform.

Women with renal impairment and chronic hypertension have a markedly higher risk of poor perinatal outcome than women without renal impairment. The incidence of impaired fetal growth is closely related to the degree of renal impairment, and women undergoing dialysis are at particular risk for fetal growth failure, preterm delivery, and fetal death, even with optimal management. Those who start dialysis during pregnancy are at the greatest risk, with only a 50% chance of a surviving infant.

Gestational Hypertension

Management of women with gestational hypertension and preeclampsia is summarized in Box 10.1 .

Box 10.1
Management of Pregnant Women With Chronic Hypertension
ACE , Angiotensin-converting enzyme; ARBs , angiotensin receptor blockers; BP , blood pressure.

Monitoring

  • Daily home BP monitoring with a validated cuff after 5 minutes in sitting position

  • Fetal growth sonography every 4 weeks

  • Fetal biophysical testing at least weekly from 32–34 weeks

Avoid

  • Low sodium diets

  • Weight loss prescriptions

  • Limitations of moderate exercise

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