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 (FGR) pregnancies. OBJECTIVE To explore the effectiveness of treatment using low molecular weight heparin (LMWH) at a prophylactic dose started at the time of diagnosis in prolonging gestation in pregnancies with early-onset fetal growth restriction (FGR). STUDY DESIGN This was a phase III, multicenter, triple-blind, parallel-arm randomized clinical trial conducted in two 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 (PI) of umbilical artery Doppler >95th percentile; or estimated fetal weight <10th percentile plus mean PI of uterine artery Doppler >95th) were randomized to receive either subcutaneous treatment with bemiparin 3500 IU/0.2 mL/day 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 49 patients were included (23 in the LMWH group and 26 in the placebo group). In the LMWH 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% CI -22.7 to 6.3] (p=0.667) and in the LMWH 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% CI -3.4 to 1.2] (p=0.639). CONCLUSION The use of prophylactic dose LMWH started at the time of diagnosis does not prolong pregnancy in individuals with early-onset fetal restriction.

中文翻译：

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用低分子肝素治疗早发性胎儿生长受限不会延长妊娠：一项随机临床试验。


背景 尽管有生物学依据，但很少有证据表明肝素在改善胎儿生长受限 （FGR） 妊娠的胎盘功能不全和最大限度地提高分娩时的胎龄。目的 探讨诊断时开始预防剂量使用低分子肝素 （LMWH） 治疗早发性胎儿生长受限 （FGR） 妊娠延长的有效性。研究设计 这是一项在西班牙两所大学医院进行的 III 期、多中心、三盲、平行臂随机临床试验。根据适应性 Delphi 共识（诊断时 20+0-31+6 周，脐动脉多普勒舒张血流缺失/反向;或估计胎儿体重 <第 10 个百分位数加上脐动脉搏动指数 （PI） 多普勒 >95 个百分位数;或估计胎儿体重 <第 10 个百分位数加上子宫动脉多普勒 >95th 的平均 PI）随机接受贝米肝素 3500 IU/0.2 皮下治疗mL/天或安慰剂从诊断时纳入到分娩时。主要结局是从纳入到活产的妊娠时间（天）和活产胎龄（天）。结果 共纳入 49 例患者 （LMWH 组 23 例，安慰剂组 26 例）。LMWH 组的中位妊娠延长时间为 42 天，而安慰剂组为 41.5 天（中位差异 0.5 天 [95% CI -22.7 至 6.3] （p=0.667），LMWH 组分娩时的中位胎龄为 35.1 周，而安慰剂组为 34.6 周（中位差异 0.5 周 [95% CI -3.4 至 1.2] （p=0.639）。 结论 诊断时开始使用预防剂量 LMWH 不会延长早发性胎儿限制个体的妊娠时间。