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

Marc A. Rodger, Jean Christophe Gris, Johanna I.P. De Vries, Ida Martinelli, Évelyne Rey, Ekkehard Schleussner, Saskia Middeldorp, Risto Kaaja, Nicole J. Langlois, Timothy Ramsay, Ranjeeta Mallick, Shannon M. Bates, Carolien N.H. Abheiden, Annalisa Perna, David Petroff, Paulien De Jong, Marion E. Van Hoorn, P. Dick Bezemer, Alain D. Mayhew

Research output: Contribution to journalComment/Letter to the editorAcademic

1 Citation (Scopus)


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
Original languageEnglish
Pages (from-to)153-155
Number of pages3
JournalObstetrical and Gynecological Survey
Issue number3
Publication statusPublished - 1 Mar 2017

Cite this