Heparin Fails to Alter Cord Blood Markers in Growth-Restricted Preterm Babies
Cord blood from babies with early-onset growth restriction shows vessel activation and low VEGF-A. Heparin started at diagnosis did not change these markers.
Resumen
Early-onset fetal growth restriction (FGR) is a serious pregnancy complication in which a poorly functioning placenta limits fetal growth and raises the risk of problems around birth. Researchers in Spain analyzed umbilical cord blood from 77 preterm babies, 30 with FGR and 47 gestational-age-matched controls, to see how the fetal environment differs. Babies with FGR had higher levels of leptin receptor, endoglin and E-selectin, markers of blood vessel (endothelial) activation, and lower VEGF-A, a key growth signal for blood vessels. These differences appeared even when compared with similarly premature babies. The FGR babies were part of a randomized trial of low-molecular-weight heparin (bemiparin) versus placebo started at diagnosis. Heparin did not significantly change any marker compared with placebo. The findings suggest the vessel-related changes are already established by diagnosis, and that earlier or different treatments may be needed.
Resumen detallado
Early-onset fetal growth restriction (FGR), diagnosed before 32 weeks, is a severe form of placental insufficiency linked to high rates of perinatal illness. Its biology is thought to involve an imbalance in blood vessel growth signals, endothelial dysfunction, and inflammation. Low-molecular-weight heparin (LMWH) has anti-inflammatory and pro-angiogenic properties, but whether it affects molecular pathways in the fetus has been unclear.
This analysis comes from a phase III, multicenter, triple-blind randomized trial run in two Spanish university hospitals between 2019 and 2023. Women with singleton pregnancies and early-onset FGR (20+0 to 31+6 weeks, defined by adapted Delphi criteria) received bemiparin 3500 IU/day or placebo from diagnosis until delivery. Umbilical cord blood biomarkers were measured at birth and compared with those of preterm controls matched within two weeks of gestational age.
Seventy-seven neonates were analyzed: 30 with FGR and 47 controls. FGR fetuses had higher leptin receptor, endoglin (CD105), and E-selectin, and lower VEGF-A, than controls (p ≤ 0.05). No differences were found between LMWH and placebo within the FGR group. A significant linear trend from control to LMWH to placebo was reported for all biomarkers except IL-6.
The authors conclude that early-onset FGR carries a distinct fetal profile of endothelial activation and angiogenic imbalance, independent of prematurity. Because LMWH started at diagnosis did not shift these markers, they suggest the alterations are already established and not responsive to treatment at that stage. This supports exploring earlier or alternative approaches aimed at placental dysfunction.
Caveats apply. Only the abstract was available, and the FGR group was small once split into treatment arms, so the study may have been underpowered to detect modest LMWH effects. Controls were not randomized. The trend across groups should be read cautiously, since the abstract reports no significant difference between the two FGR arms. Cord blood markers were also not linked here to clinical outcomes.
Hallazgos clave
- Cord blood from early-onset FGR fetuses had higher leptin receptor, endoglin (CD105), and E-selectin than gestational-age-matched preterm controls.
- VEGF-A, a key angiogenic signal, was lower in FGR fetuses than in controls, indicating angiogenic imbalance independent of prematurity.
- Bemiparin 3500 IU/day started at diagnosis produced no detectable difference in biomarkers versus placebo within the FGR group.
- A linear trend (control, then LMWH, then placebo) was significant for all biomarkers except IL-6.
- The analysis included 77 neonates: 30 with FGR and 47 preterm controls.
Metodología
Phase III, multicenter, triple-blind randomized trial in two Spanish university hospitals (2019–2023). Singleton early-onset FGR pregnancies (20+0–31+6 weeks) received bemiparin 3500 IU/day or placebo until delivery. Cord blood biomarkers at birth were compared with gestational-age-matched preterm controls (±2 weeks).
Limitaciones del estudio
The sample was small (30 FGR, 47 controls), and the FGR group was split further by treatment, which limits power to detect modest LMWH effects. Controls were not randomized, and the abstract does not link markers to clinical outcomes. This summary is based only on the abstract, so details on statistics, adjustment and per-arm numbers are unavailable.
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