Blood-Brain Barrier Disintegration in Growth-Restricted Fetuses with Brain Sparing Effect

Area of Science:

• Neuroscience
• Obstetrics
• Perinatology

Background:

• The blood-brain barrier (BBB) integrity, maintained by tight junctions (TJs) between endothelial cells, is crucial for fetal brain development.
• Fetal growth restriction (FGR) and the associated brain-sparing effect (BS) can compromise BBB function.
• Intraventricular hemorrhage (IVH) is a serious complication in FGR neonates.

Purpose of the Study:

• To assess endothelial TJ damage in pregnancy complicated by FGR and BS.
• To investigate serum biomarkers and placental gene expression related to BBB integrity in FGR.
• To determine predictors of IVH in growth-restricted fetuses.

Main Methods:

• Serum concentrations of NR1, NME1, S100B, occludin (OCLN), claudin-5 (CLN5), and zonula occludens protein-1 (zo-1) were measured using ELISA.
• Placental expressions of OCLN, claudin-4 (CLN4), CLN5, and zo-1 were assessed.
• Correlation between biomarkers, placental expression, FGR, BS, and IVH development was analyzed.

Main Results:

• Elevated serum NME1 and a higher CLN5/zo-1 index were found in FGR pregnancies with BS compared to those without BS.
• FGR neonates with BS showed a significantly higher incidence of IVH (approximately 20 times).
• Lower placental CLN4 expression was observed in FGR infants with BS who developed IVH postnatally.

Conclusions:

• Pregnancy with FGR and BS is associated with fetal BBB destabilization.
• Reduced placental CLN4 expression may serve as a predictive marker for IVH in growth-restricted fetuses.
• Cerebroplacental ratio (CPR) can predict IVH in fetuses with growth restriction.