Management of Chronic Hypertension During Pregnancy

Structured Abstract

Objectives

Of the nearly 4 million women giving birth in the United States each year, between 1 and 5 percent suffer from chronic hypertension. Chronic hypertension is associated with serious maternal and fetal complications, including superimposed preeclampsia, fetal growth restriction, premature delivery, placental abruption, and stillbirth. There is uncertainty and practice variability in monitoring and treatment strategies for chronic hypertension in pregnancy. This evidence report addresses several questions related to management of chronic hypertension. It summarizes research evidence concerning the magnitude of maternal and fetal risks associated with chronic hypertension, risks and benefits of antihypertensive agents before and during pregnancy, risks and benefits of aspirin and nonpharmacological therapies during pregnancy, and the role of various monitoring strategies in detecting fetal complications of chronic hypertension.

Search Strategy.

English and non-English research literature was identified from 16 electronic databases, references of pertinent articles and reviews, a primary text that routinely systematically reviews and categorizes teratogenicity risks, and technical experts. In general, electronic bibliographical sources were searched from 1947 or from their inception to February 1999. Four general search strategies were used to identify evidence relevant to: (1) efficacy, (2) harms, (3) blood pressure risks, and (4) monitoring techniques.

Selection Criteria.

Selection criteria varied according to the specific question addressed. For questions concerning treatment efficacy, the investigators of this evidence report selected randomized trials of antihypertensive agents or aspirin compared with either placebo or usual care that included a population of pregnant women with chronic hypertension and that reported clinical maternal and/or fetal outcomes. For the question regarding harm associated with antihypertensive therapy, we selected case reports, case-control and cohort studies, randomized trials, and surveillance studies that reported adverse maternal and/or fetal outcomes. To estimate the magnitude of risk associated with chronic hypertension, we examined case-control and cohort studies that compared maternal and fetal outcomes in women with chronic hypertension compared with those in either a general obstetrical population or pregnant women without chronic hypertension. For the question concerning monitoring techniques, we sought case series, cohort studies, and randomized trials that reported clinical perinatal morbidity or mortality outcomes.

Data Collection and Analysis.

Two or more persons independently screened the 5,558 titles and abstracts identified in the searches. Two reviewers abstracted articles meeting inclusion criteria except for articles addressing adverse effects, which were reviewed by only one person. Data were synthesized descriptively, emphasizing methodological characteristics of the studies such as populations enrolled, definitions of selection and outcome criteria, interventions and comparisons, and study designs. Because of concerns about heterogeneity in study populations and interventions, quantitative methods were not used to combine trial results. Random effects methods were used to estimate summary odds ratios or risk of perinatal mortality and abruption associated with chronic hypertension.

Main Results

• Benefits of treating chronic hypertension before conception. There was no evidence that addressed the effect of blood pressure control before conception on fetal outcomes. With regard to maternal outcomes, evidence from randomized trials involving nonpregnant women 30 to 54 years of age showed that approximately 250 (95 percent confidence interval 158 to 1,606) such women with mild to moderate hypertension need to be treated for 5 years to prevent one cardiovascular event such as stroke or myocardial infarction. Much larger numbers of women younger than age 30 (approximately 8,000) would need to be treated for 1 year to prevent a cardiovascular event.
• Benefit of treating chronic hypertension during pregnancy. There was insufficient evidence to prove or disprove moderate to large clinical effects of antihypertensive agents on perinatal outcomes.
• Adverse effects of antihypertensive drugs. The quality of evidence addressing this question was poor. The best-established adverse effect of antihypertensive agents in pregnancy was renal failure associated with use of the angiotensin-converting enzyme inhibitors. There was evidence suggesting that atenolol used early in pregnancy may be associated with small-for-gestational-age fetuses.
• Effects of nonpharmacological interventions. There was no evidence to address this question.
• Optimum levels for initiating therapy and risk of chronic hypertension in pregnancy. There was insufficient evidence to identify an optimum blood pressure at which treatment should be initiated and thereafter maintained. Chronic hypertension in pregnancy tripled the risk of perinatal mortality and doubled the risk of placental abruption. The risks of preeclampsia and small-for-gestational-age infants also were increased. Increased risk was evident even in the absence of superimposed preeclampsia.
• Effect of aspirin. A single trial showed low-dose aspirin begun before 26 weeks gestational age neither reduced perinatal morbidity and mortality nor increased maternal risks in women with chronic hypertension. Although the trial was of moderate size, small increases or reductions in benefits or risks could have been missed.
• Effectiveness of monitoring strategies. There was insufficient evidence to evaluate the effectiveness of any particular monitoring test or sequence of tests for women with chronic hypertension in pregnancy.

Conclusions.

Despite the burden of illness and costs imposed by chronic hypertension in pregnancy, evidence to date remains scant and provides little direction for clinicians. Epidemiological data demonstrate increased risks of perinatal morbidity and mortality in pregnant women with mild to moderate chronic hypertension. Treatment with antihypertensive agents has not been proven to lower those risks, though the evidence base is too small to rule out moderate to large effects on perinatal mortality, preeclampsia, and intrauterine growth retardation. Data on adverse effects of drug treatment is scant; the data on angiotensin-converting enzyme inhibitors suggest that their adverse effects are substantially greater than for other drugs. Moderate to large benefits of low dose aspirin begun early in pregnancy for women with chronic hypertension have been disproved. Nonpharmacological treatments remain unevaluated, as do monitoring strategies that are frequently used in pregnancies complicated by chronic hypertension.

Many important clinical issues faced by clinicians who care for pregnant women with chronic hypertension remain unresolved. Research in this area is critical. More pregnancies will be complicated by chronic hypertension as the trend continues for women to delay childbearing to older ages. Multicenter collaborative studies are needed with sufficient power to detect differences in outcomes such as perinatal mortality, preeclampsia, and small-for-gestational-age infants. Information from such trials can be augmented by well-designed surveillance systems to monitor outcomes and safety data from clinical practice. Finally, comparative studies with clinical outcomes are sorely needed to assess benefits, costs, and harms of various fetal monitoring strategies for the pregnant woman with chronic hypertension.