Low-Molecular-Weight Heparin and Recurrent Placenta-Mediated Pregnancy Complications: A Meta-analysis of Individual Patient Data From Randomised Controlled Trials

Abstract

Placenta-mediated pregnancy complications include pre-eclampsia, birth of a small-for-gestational-age neonate, placental abruption, or late pregnancy loss and lead to maternal and fetal or neonatal morbidity and mortality. These complications have a high risk of recurring in subsequent pregnancies, and effective preventive measures are lacking. Findings from some randomized controlled trials suggest that low-molecular-weight heparin (LMWH) can be used to prevent recurrent placentamediated pregnancy complications, but these findings have not been universal. An individual patient data meta-analysis was done to evaluate the efficacy of LMWH to prevent recurrent placentamediated complications in subsequent pregnancies. The primary outcome was a composite of 4 pregnancy complications: early-onset or severe preeclampsia, birth of a small-for-gestational-age neonate (birth weight less than the fifth percentile), placental abruption, and late pregnancy loss. The data set included a total of 963 eligiblewomen from 8 randomized published trials. The primary outcome analysis showed that LMWH did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications (LMWH 62/444 [14%] vs no LMWH 95/443 [22%]; absolute difference, 8% [95% confidence interval, 17.3-1.4; P = 0.09]; relative risk, 0.64 [95% confidence interval, 0.36-1.11; P = 0.11]). Significant heterogeneity was noted between single-center and multicenter trials for the primary composite outcomes and also in the subgroup analyses. Low-molecular-weight heparin was found to be beneficial in women with previous placental abruption in both single-center and multicenter trials but not in any other subgroups of previous complications. No serious adverse reaction to LMWHwas observed. Inclusion of individual patient data set enabled a robust exploration of clinical, methodological, and statistical heterogeneity. In conclusion, this individual patient data meta-analysis showed that LMWH did not significantly reduce the risk of recurrent placenta-mediated pregnancy complications in women with previous complications