Adverse effects of hypertension treatment during pregnancy
Evidence SummariesLevel of Evidence = B
Treatment-induced falls in maternal blood pressure appear to adversely affect fetal growth.
A population-based retrospective cohort study 2 (911,685 births between 1995 and 2008), using the Danish Fertility Database assessed the association between exposure to beta-blockers during pregnancy and the risk of adverse pregnancy outcomes. Beta-blocker exposure during pregnancy (n=2459) was found to be associated with increased risk of small for gestational age (SGA) (adjusted OR 1.97, 95% CI 1.75 to 2.23), preterm birth (aOR 2.26, 95% CI 2.03 to 2.52) and perinatal mortality (aOR 1.89, 95% CI 1.25 to 2.84). Analyses were adjusted for socioeconomic and maternal variables. The authors found similar risk profiles for labetalol and other β-blockers.
A retrospective cohort study 3 in Canada compared infant outcomes between mothers with hypertension treated by beta-blockers alone (n = 416) and by methyldopa alone (n = 1000) during pregnancy (all eligible women, women with chronic hypertension and women with gestational hypertension or pre-eclampsia/eclampsia, separately). Multiple logistic regression analyses were performed to adjust for potential confounding. Adjusted odds ratios (aORs) and 95% CIs for infants born to mothers with chronic hypertension with beta-blockers only, as compared methyldopa only, during pregnancy were: SGA < 10th percentile 1.95, 95% CI 1.21 to 3.15.
A systematic review 1 including 45 studies with a total of 3,733 subjects was abstracted in DARE. Seven trials (6 publications) randomised women with chronic hypertension to therapy or either placebo or no therapy. A further 38 trials randomly allocated women with late-onset hypertension to antihypertensive therapy or either placebo or no therapy (15 trials; 15 publications) or other antihypertensive therapy (23 trials; 20 publications).
A greater mean difference in mean arterial pressure (MAP) with antihypertensive therapy was associated with the birth of a higher proportion of small-for-gestational age (SGA) infants (slope 0.09, standard deviation (SD)=0.03, r2=0.48) and lower mean birth weight (slope -14.49, SD=6.98, r2=0.16); this was found to be significant after exclusion of a paper regarded as an extreme statistical outlier. Over the range of the reported mean difference in MAP, a 10 mmHg fall in MAP was associated with a 145 g decrease in birth weight. Only 16% of the variation in mean birth weight between groups could be explained by the differential fall in MAP between treatment and control groups.
The authors conclude that given the small maternal benefits that are likely to be derived from therapy, new data are urgently needed to elucidate the relative maternal and fetal benefits, and the risks of oral antihypertensive drug treatment for mild-to-moderate pregnancy hypertension.
1. von Dadelszen P, Ornstein MP, Bull SB, Logan AG, Koren G, Magee LA. Fall in mean arterial pressure and fetal growth restriction in pregnancy hypertension: a meta-analysis. Lancet 2000 Jan 8;355(9198):87-92. [PMID:10675164]
2. Meidahl Petersen K, Jimenez-Solem E, Andersen JT et al. β-Blocker treatment during pregnancy and adverse pregnancy outcomes: a nationwide population-based cohort study. BMJ Open 2012;2(4). [PMID:22815467]
3. Xie RH, Guo Y, Krewski D et al. Beta-blockers increase the risk of being born small for gestational age or of being institutionalised during infancy. BJOG 2014;121(9):1090-6. [PMID:24628701]
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