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Does the Blood-Brain Barrier Integrity Change in Regard to the Onset of Fetal Growth Restriction?
Natalia Misan1, Sławomir Michalak2,3, Katarzyna Kapska1
1Department of Perinatology and Gynecology, Poznan University of Medical Sciences, 60-535 Poznan, Poland.
Insights
Early-onset fetal growth restriction (FGR) impacts blood-brain barrier integrity, with specific protein changes potentially predicting outcomes. Late-onset FGR shows different protein markers linked to fetal distress and acidosis.
Area of Science:
- Perinatology
- Neonatology
- Neuroscience
- Biochemistry
Background:
- Fetal growth restriction (FGR) is a significant complication of pregnancy.
- The integrity of the blood-brain barrier (BBB) in newborns with FGR is not fully understood.
- Neurological disorders are a concern in FGR newborns, potentially linked to BBB dysfunction.
Purpose of the Study:
- To investigate differential effects of early-onset versus late-onset FGR on BBB integrity.
- To explore the relationship between BBB breakdown markers and neurological issues in FGR neonates.
- To identify potential biomarkers for predicting FGR complications.
Main Methods:
- Evaluation of serum and placental tight junction (TJ) proteins using ELISA.
- Comparison of TJ protein concentrations between early-onset FGR, late-onset FGR, and control groups.
- Correlation analysis between protein levels and clinical outcomes like intraventricular hemorrhage (IVH) and acidosis.
Main Results:
- Significant differences in serum occludin (OCLN) concentrations were observed in early-onset FGR concerning intraventricular hemorrhage (IVH).
- Early-onset FGR showed elevated maternal circulation nucleoside diphosphate kinase A (NME1) related to brain-sparing and premature delivery.
- Late-onset FGR exhibited increased maternal serum S100 calcium-binding protein B (S100B) linked to fetal distress and elevated zonula occludens-1 (zo-1) associated with moderate acidosis.
Conclusions:
- Blood-brain barrier integrity disruption in FGR is not dependent on the gestational age at diagnosis.
- NME1 may serve as a predictive biomarker for fetal circulatory centralization and extremely low birth weight in early-onset FGR.
- Serum zo-1 concentration shows prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.
Abstract:
The aim of the study was to determine whether early-onset and late-onset fetal growth restriction (FGR) differentially affects the blood-brain barrier integrity. Furthermore, the purpose of the study was to investigate the relationship between the blood-brain barrier breakdown and neurological disorders in FGR newborns. To evaluate the serum tight junction (TJ) proteins and the placental TJ proteins expression, an ELISA method was used. A significant difference in serum OCLN concentrations was noticed in pregnancies complicated by the early-onset FGR, in relation to the intraventricular hemorrhage (IVH) occurrence in newborns. No significant differences in concentrations of the NR1 subunit of the N-methyl-d-aspartate receptor (NR1), nucleoside diphosphate kinase A (NME1), S100 calcium-binding protein B (S100B), occludin (OCLN), claudin-5 (CLN5), zonula occludens-1 (zo-1), the CLN5/zo-1 ratio, and the placental expression of OCLN, CLN5, claudin-4 (CLN4), zo-1 were noticed between groups. The early-onset FGR was associated with a higher release of NME1 into the maternal circulation in relation to the brain-sparing effect and premature delivery. Additionally, in late-onset FGR, the higher release of the S100B into the maternal serum in regard to fetal distress was observed. Furthermore, there was a higher release of zo-1 into the maternal circulation in relation to newborns' moderate acidosis in late-onset FGR. Blood-brain barrier disintegration is not dependent on pregnancy advancement at the time of FGR diagnosis. NME1 may serve as a biomarker useful in the prediction of fetal circulatory centralization and extremely low birth weight in pregnancies complicated by the early-onset FGR. Moreover, the serum zo-1 concentration may have prognostic value for moderate neonatal acidosis in late-onset FGR pregnancies.
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