Treatment of early-onset fetal growth restriction with low molecular weight heparin does not prolong gestation: a randomized clinical trial

Abstract

Background: Although there is a biological basis for it, there is scarce evidence on the effect of heparin in ameliorating placental insufficiency and maximizing gestational age at delivery among fetal growth restriction pregnancies.

Objective: To explore the effectiveness of treatment using low molecular weight heparin at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction.

Study design: This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in 2 university hospitals in Spain. Singleton pregnancies qualifying for early-onset placental FGR according to the adapted Delphi consensus (20⁺⁰-31⁺⁶ weeks at diagnosis with umbilical artery Doppler with absent/reversed diastolic flow; or estimated fetal weight <10th percentile plus pulsatility index of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean pulsatility index of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/d or a placebo from inclusion at diagnosis to the time of delivery. The primary outcomes were prolongation of pregnancy from inclusion to live birth (days) and gestational age at live birth (days).

Results: Forty-nine patients were included (23 in the low molecular weight heparin group and 26 in the placebo group). In the low molecular weight heparin group, the median prolongation of pregnancy was 42 days, while in the placebo group it was 41.5 days (median difference 0.5 days [95% confidence interval -22.7 to 6.3] (P=.667)) and in the low molecular weight heparin group, the median gestational age at delivery was 35.1 weeks, while in the placebo group, it was 34.6 weeks (median difference 0.5 weeks [95% confidence interval -3.4 to 1.2] (P=.639)).

Conclusion: The use of prophylactic dose low molecular weight heparin started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction.

Keywords: clinical trial; fetal growth restriction; low molecular weight heparin; placenta; placental insufficiency; preeclampsia; prematurity.