Do commonly used oral antihypertensives alter fetal or neonatal heart rate characteristics? A systematic review

Objective: To examine fetal (FHR) and neonatal heart rate patterns following use of common oral antihypertensives in pregnancy. Methods: A systematic review of randomized controlled trials (RCTs), observational studies (N greater than or equal to 6 women), and animal studies. Data were abstracted (two reviewers) to determine relative risk (RR) (or risk difference (RD) for low event rates) and 95% Cl. Results: Eighteen RCTs (1858 women), one controlled observational study (N = 22), and seven case series (N = 117) were reviewed. Most hypertension was pregnancy-induced (N = 14 studies). The FHR was assessed by cardiotocogram (CTG) (N = 17 studies (visual interpretation); I study (computerized CTG), or umbilical artery velocimetry (N = 4). Four studies examined neonatal heart rate. In placebo-controlled RCTs (N = 192 women), adverse FHR effects did not differ between groups [9/101 (drugs) vs. 7/91 (placebo); RD 0.02, 95% CI (-0.06, 0.11); chi(2) = 1.02]. In six drug vs. drug RCTs (295 women), adverse FHR effects did not differ between groups [29/144 (methyldopa) vs. 42/151 (other drugs); RR 0.72, 95% Cl (0.49, 1.07); chi(2) = 0.69]. In one labetalol vs. placebo trial, neonatal bradycardia did not differ between groups [4/70 (labetalol) vs. 4/74 (placebo); OR 1.06, 95% Cl (0.26, 4.39)], while in three drug vs. drug RCTs, neonatal bradycardia was not observed (0/24 vs. 0/26). Conclusions: Available data are inadequate to conclude whether oral methyldopa, labetalol, nifedipine, or hydralazine adversely affect fetal or neonatal heart rate and pattern. Until definitive data are available, FHR changes cannot be reliably attributed to drug effect, but may be due to progression of the underlying maternal or placental disease.