Effect of low‐molecular‐weight heparin on placenta‐mediated fetal growth restriction in a tertiary referral hospital: A 7‐year retrospective cohort study

Abstract Objective To investigate the effect of low‐molecular‐weight heparin (LMWH) on placenta‐mediated fetal growth restriction (FGR). Methods A cohort of 570 pregnant women diagnosed with placenta‐mediated FGR were enrolled from January 1, 2015 through to December 31, 2021. A birth database, including demographic data, antenatal complications, and detailed delivery and newborn data, was created to collect variables from the Hospital Information System (HIS) Database. The unique personal registration number, assigned to each patient on first registration with HIS in the West China Second University Hospital, was used to link these patients. LMWH use was defined as at least 1‐week prescription from diagnosis of placenta‐mediated FGR. Pregnant women received LMWH (Enoxaparin 4000 IU/day) by self‐administered subcutaneous injection only when they agreed and signed informed consent. Primary outcome was intrauterine fetal death after 20 weeks of pregnancy. Secondary outcomes included preterm birth (PB), Apgar score less than 7 at 1 min, admission to neonatal intensive care unit (NICU), and birth weight. Logistic regression analysis was conducted to compute adjusted odds ratio (aOR) with 95% confidence intervals (CI) for outcomes. Results After controlling for confounders, LMWH use was associated with a decreased risk of intrauterine fetal death (aOR 2.49, 95% CI 1.35–4.57, P = 0.003), PB before 37 weeks of pregnancy (aOR 3.35, 95% CI 2.14–5.23, P < 0.001), PB before 34 weeks of pregnancy (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), Apgar score less than 7 at 1 min (aOR 2.25, 95% CI 1.36–3.74, P = 0.002), NICU admission (aOR 2.29, 95% CI 1.48–3.55, P < 0.001). Using LMWH increased the mean birth weight in PB before 32 weeks of pregnancy (mean ± standard deviation [SD] 1126.4 ± 520.0 g, P = 0.020), PB before 37 weeks of pregnancy (mean ± SD 1563.9 ± 502.7 g, P = 0.019), early‐onset FGR (mean ± SD 2125.2 ± 665.7 g, P < 0.001), late‐onset FGR (mean ± SD 2343.4 ± 507.9, P < 0.001), and non‐severe FGR (mean ± SD 2231.1 ± 607.2 g, P < 0.001). Conclusion Use of LMWH can significantly improve the fetal and neonatal outcomes among pregnant women with placenta‐mediated FGR, particularly reducing the risk of intrauterine fetal death.