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

Abstract

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 0.32-0.92), 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.*See Supplementary material (Table S1) Tweetable abstract There was no evidence that women treated with methyldopa versus labetalol had worse outcomes.

Can adverse maternal and perinatal outcomes be predicted when blood pressure becomes elevated? Secondary analyses from the CHIPS (Control of Hypertension In Pregnancy Study) randomized controlled trial

“…Very preterm delivery at <34 weeks was more common among women who were in hospital at enrolment or had higher BP, and less common among women were enrolled at later gestational ages, had preexisting (vs. gestational hypertension) or were taking methyldopa as their antihypertensive agent at enrolment (as previously reported) (Figure e). No significant interactions were identified.…”

Preventing deaths due to the hypertensive disorders of pregnancy

“…Following adjusted analyses, methyldopa (vs. labetalol) at randomisation was associated with fewer babies with a birthweight <10th centile. Methyldopa (vs. labetalol) post randomisation was associated with fewer CHIPS primary outcomes, birthweight <10th centile, severe hypertension, pre-eclampsia and delivery before both 34 and 37 weeks [92].…”

Labetalol Versus Nifedipine as Antihypertensive Treatment for Chronic Hypertension in Pregnancy

“…Recent evidence (although not from a randomized head-tohead comparison) suggested that this agent may be associated with benefit in maternal and perinatal outcome compared with labetalol, and it should be considered for inclusion in a definitive trial. 25 In the nonpregnant population, there is evidence that some antihypertensive agents have additional therapeutic benefits beyond reduction in arterial BP, including anti-inflammatory and oxidative stress-lowering properties. 26 Given the role of inflammation and oxidative stress in the pathophysiology of preeclampsia, 27 future research should further explore the mechanistic actions of each drug to establish if other therapeutic benefits exist in pregnancy.…”