Impact of Chronic Hypertension and Antihypertensive Treatment on Adverse Perinatal Outcomes: Systematic Review and Meta-Analysis

Abstract

Background Maternal chronic hypertension is associated with adverse pregnancy outcomes. Previous studies examined the association between either chronic hypertension or antihypertensive treatment and adverse pregnancy outcomes. We aimed to synthesize the evidence on the effect of chronic hypertension/antihypertensive treatment on adverse pregnancy outcomes. Methods and Results Medline/PubMed, EMBASE, and Web of Science were searched; we included observational studies and assessed the effect of race/ethnicity, where possible, following a registered protocol (CRD42019120088). Random-effects meta-analyses were used. A total of 81 studies were identified on chronic hypertension, and a total of 16 studies were identified on antihypertensive treatment. Chronic hypertension was associated with higher odds of preeclampsia (adjusted odd ratio [aOR], 5.43; 95% CI, 3.85-7.65); cesarean section (aOR, 1.87; 95% CI, 1.6-2.16); maternal mortality (aOR, 4.80; 95% CI, 3.04-7.58); preterm birth (aOR, 2.23; 95% CI, 1.96-2.53); stillbirth (aOR, 2.32; 95% CI, 2.22-2.42); and small for gestational age (SGA) (aOR, 1.96; 95% CI, 1.6-2.40). Subgroup analyses indicated that maternal race/ethnicity does not influence the observed associations. Women with chronic hypertension on antihypertensive treatment (versus untreated) had higher odds of SGA (aOR, 1.86; 95% CI, 1.38-2.50). Conclusions Chronic hypertension is associated with adverse pregnancy outcomes, and these associations appear to be independent of maternal race/ethnicity. In women with chronic hypertension, those on treatment had a higher risk of SGA, although the number of studies was limited. This could result from a direct effect of the treatment or because severe hypertension during pregnancy is a risk factor for SGA and women with severe hypertension are more likely to be treated. The effect of antihypertensive treatment on SGA needs to be further tested with large randomized controlled trials.

Keywords: antihypertensive; chronic hypertension; fetal outcome; meta‐analysis; neonatal outcome; pregnancy; systematic review.

Figure 1. Preferred Reporting Items for Systematic Review and Meta‐Analysis flow diagram of studies of chronic hypertension in pregnancy.

Figure 2. Preferred Reporting Items for Systematic Review and Meta‐Analysis flow diagram of studies of antihypertensive treatment during pregnancy.

Figure 3. Forest plots of adjusted estimates of the association between chronic hypertension and maternal complications.

The red rectangles represent the odd ratio (OR) for each study, and the lateral black lines represent the 95% CI for each study. The diamond represents the overall OR, and the lateral tips of the diamond represent the 95% CI for the combined estimates. IV indicates inverse‐variance.

Figure 4. Forest plots of adjusted estimates of the association between chronic hypertension and fetal/neonatal complications.

The red rectangles represent the odd ratio (OR) for each study, and the lateral black lines represent the 95% CI for each study. The diamond represents the overall OR, and the lateral tips of the diamond represent the 95% CI for the combined estimates. IV indicates inverse‐variance.