Search

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.

This study evaluated the damage to the endothelial tight junctions (TJs) in pregnancies complicated by fetal growth restriction (FGR) and investigated whether FGR is related to blood–brain barrier disintegration and, subsequently, to the appearance of proteins indicative of neuronal injury in maternal blood. The studied group included 90 pregnant women diagnosed with FGR. The control group consisted of 70 women with an uncomplicated pregnancy. The biochemical measurements included serum neuronal proteins (subunit of the N-methyl-D-aspartate receptor—NR1, nucleoside diphosphate kinase A—NME1, and S100 calcium-binding protein B—S100B), serum TJ proteins (occludin—OCLN, claudin-5—CLN5, zonula occludens—zo-1, and OCLN/zo-1 and CLN5/zo-1 ratios), and placental expression of TJ proteins (OCLN, claudin-4 CLN4, CLN5, zo-1). The significantly higher serum S100B and CLN5 levels and serum CLN5/zo-1 ratio were observed in FGR compared to healthy pregnancies. Moreover, FGR was characterized by increased placental CLN5 expression. Both serum NME1 levels and placental CLN4 expression in FGR pregnancies were significantly related to the incidence of neurological disorders in newborns. Mothers of FGR neonates who developed neurological complications and intraventricular hemorrhage (IVH) had statistically higher NME1 concentrations during pregnancy and significantly lower placental CLN4 expression than mothers of FGR neonates without neurological abnormalities. The serum NME1 levels and placental CLN4 expression were predictive markers of IVH in the FGR group. The blood–brain barrier is destabilized in pregnancies complicated by FGR. Neurological disorders, including IVH, are associated with higher serum concentrations of NME1 and the decreased placental expression of CLN4. The serum NME1 levels and placental CLN4 expression may serve as biomarkers, helpful in predicting IVH in FGR. It may allow for more precise monitoring and influence decision-making on the optimal delivery time to avoid developing neurological complications.

The endothelial cells of the blood-brain barrier adhere closely, which is provided by tight junctions (TJs). The aim of the study was to assess the damage to the endothelial TJs in pregnancy, complicated by fetal growth restriction (FGR) and circulatory centralization (brain-sparing effect, BS). The serum concentrations of 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), and zonula occludens protein – 1 (zo-1), and the placental expressions of OCLN, claudin-4 (CLN4), CLN5, and zo-1 were assessed with ELISA. The significantly higher serum NME1 concentrations and the serum CLN5/zo-1 index were observed in FGR pregnancy with BS, as compared to the FGR group without BS. The FGR newborns with BS were about 20 times more likely to develop an intraventricular hemorrhage (IVH) than the FGR infants without BS. The cerebroplacental ratio (CPR) allowed to predict the IVH in growth-restricted fetuses. The significantly lower placental CLN4 expression was observed in the FGR group with BS and who postnatally developed an IVH, as compared to the growth-restricted infants with BS without IVH signs. Pregnancy complicated by FGR and BS is associated with the destabilization of the fetal blood-brain barrier. The IVH in newborns is reflected in the inhibition of the placental CLN4 expression, which may be a useful marker in the prediction of an IVH among growth-restricted fetuses.

Fetal growth restriction (FGR) is mainly caused by failure of the uteroplacental unit. The exact pathogenesis remains unclear. The cause is thought to be related to abnormal platelet activation, which may result in microthrombus formation in the small vessels of the placenta. Reactive oxygen species (ROS) may initiate the pathological process of platelet activation. This study aimed to evaluate selected platelet parameters in pregnancy complicated by FGR and relate them to the severity of hemodynamic abnormalities. A total of 135 women (pregnant with FGR, with an uncomplicated pregnancy, and non-pregnant) were enrolled to study different platelet parameters: count (PLT), mean volume (MPV), ROS levels, intracellular oxygen level, oxygen consumption, and aggregation indices. No abnormalities in PLT and MPV were found in the FGR group, although it revealed increased ROS levels in platelets, lower platelet oxygen consumption, and intraplatelet deprivation. Aggregation parameters were similar as in uncomplicated pregnancy. No significant relationships were observed between hemodynamic abnormalities and the studied parameters. Platelets in pregnancies complicated by FGR may reveal an impaired oxidative metabolism, which may, in turn, lead to oxidative stress and, consequently, to an impaired platelet function. This study adds to the understanding of the role of platelets in the etiology of FGR.