Do labetalol and methyldopa have different effects on pregnancy outcome? Analysis of data from the Control of Hypertension In Pregnancy Study (CHIPS) trial

Objective To compare pregnancy outcomes, accounting for allocated group, between methyldopa-treated and labetalol-treated women in the CHIPS Trial (ISRCTN 71416914) of 'less tight' versus 'tight' control of pregnancy hypertension. Design Secondary analysis of CHIPS Trial cohort. Setting International randomised controlled trial (94 sites, 15 countries). Population or sample Of 987 CHIPS recruits, 481/566 (85.0%) women treated with antihypertensive therapy at randomisation. Of 981 (99.4%) women followed to delivery, 656/745 (88.1%) treated postrandomisation. Methods Logistic regression to compare outcomes among women who took methyldopa or labetalol, adjusted for the influence of baseline factors. Main outcome measures CHIPS primary (perinatal loss or high level neonatal care for >48 hours) and secondary (serious maternal complications) outcomes, birthweight <10th centile, severe maternal hypertension, pre-eclampsia and delivery at <34 or <37 weeks. Results Methyldopa and labetalol were used commonly at randomisation (243/987, 24.6% and 238/987, 24.6%, respectively) and post-randomisation (224/981, 22.8% and 433/981, 44.1%, respectively). Following adjusted analyses, methyldopa (versus labetalol) at randomisation was associated with fewer babies with birthweight <10th centile [adjusted odds ratio (aOR) 0.48; 95% CI 0.20-0.87]. Methyldopa (versus labetalol) postrandomisation was associated with fewer CHIPS primary outcomes (aOR 0.64; 95% CI 0.40-1.00), birthweight <10th centile (aOR 0.54; 95% CI 0.320.92), severe hypertension (aOR 0.51; 95% CI 0.31-0.83), preeclampsia (aOR 0.55; 95% CI 0.36-0.85), and delivery at <34 weeks (aOR 0.53; 95% CI 0.29-0.96) or <37 weeks (aOR 0.55; 95% CI 0.35-0.85). Conclusion These nonrandomised comparisons are subject to residual confounding, but women treated with methyldopa (versus labetalol), particularly those with pre-existing hypertension, may have had better outcomes.