Markers in umbilical cord blood in early-onset fetal growth restricted fetuses.

INTRODUCTION

Early-onset fetal growth restriction (FGR) is a severe form of placental insufficiency associated with high perinatal morbidity. Its pathophysiology involves angiogenic imbalance, endothelial dysfunction, and inflammation. Low-molecular-weight heparin (LMWH) has anti-inflammatory and pro-angiogenic properties, but its effects on fetal molecular pathways remain unclear.

METHODS

This phase III, multicenter, triple-blind randomized trial was conducted in two Spanish university hospitals between January 1, 2019 and January 31, 2023. Singleton pregnancies with early-onset FGR (20+0-31 + 6 weeks) defined by adapted Delphi criteria were randomized to receive bemiparin (3500 IU/day) or placebo from diagnosis until delivery. Umbilical cord blood biomarkers were measured at birth and compared with gestational age-matched preterm controls (±2 weeks).

RESULTS

Seventy-seven neonates (30 FGR, 47 controls) were analyzed. FGR fetuses showed higher leptin receptor, endoglin (CD105), and E-selectin, and lower VEGF-A compared with controls (p ≤ 0.05). No differences were observed between LMWH and placebo within the FGR group. A significant linear trend (control → LMWH → placebo) was found for all biomarkers except IL-6.

DISCUSSION: Early-onset FGR is associated with a distinct fetal profile characterized by endothelial activation and angiogenic imbalance, independent of prematurity. Prophylactic LMWH initiated at diagnosis did not modify these pathways, suggesting that fetal alterations are already established and not responsive to treatment at this stage. These findings support the need for earlier or alternative therapeutic strategies targeting placental dysfunction.