Placental pathology in early-onset fetal growth restriction: insights into fetal growth restriction mechanisms.

BACKGROUND: Early-onset fetal growth restriction (FGR), an identifiable variant of FGR, exhibits divergences in its severity, management, and placental pathologies when juxtaposed with late-onset FGR. The objective of this cross-sectional investigation was to scrutinize placental pathologies in pregnancies afflicted by early-onset FGR, emphasizing a comparative analysis between cohorts with and without preeclampsia (PE). PATIENTS, MATERIALS AND METHODS: The study encompassed a cohort of 85 expectant mothers who received a diagnosis of early-onset FGR. Rigorous histopathological (HP) and immunohistochemical (IHC) assessments were conducted on the placentas. Comparative analyses were performed, distinguishing between individuals diagnosed with both PE and early-onset FGR, and those presenting normotensive early-onset FGR. RESULTS: HP analysis unveiled a multitude of shared placental lesions, encompassing retroplacental hemorrhage, expedited villous maturation, infarctions, and calcification-associated fibrin deposits. IHC investigations displayed affirmative immunoreactivity for anti-hypoxia-inducible factor (HIF) and anti-vascular endothelial growth factor (VEGF) antibodies within the placental infarcted villitis. Moreover, noteworthy variances in placental measurements and distinctive lesions were discerned when comparing the PE and early-onset FGR cohort with the normotensive group. CONCLUSIONS: Maternal malperfusion emerged as a pivotal determinant linked to placental lesions in pregnancies affected by early-onset FGR. Remarkably, the occurrence of infarctions, specifically delayed infarctions, exhibited a noteworthy correlation with PE. These findings accentuate the significance of pursuing additional research endeavors aimed at unraveling the intricate mechanisms governing maternal malperfusion and its consequential influence on placental health in the context of early-onset FGR, with particular attention to the interplay with PE.

Appropriate Delivery Timing in Fetuses with Fetal Growth Restriction to Reduce Neonatal Complications: A Case-Control Study in Romania.

(1) Background: The main challenge in cases of early onset fetal growth restriction is management (i.e., timing of delivery), trying to determine the optimal balance between the opposing risks of stillbirth and prematurity. The aim of this study is to determine the likelihood of neonatal complications depending on the time of birth based on Doppler parameters in fetuses with early onset fetal growth restriction; (2) Methods: A case-control study of 205 consecutive pregnant women diagnosed with early onset FGR was conducted at the Obstetrics Clinic of the Municipal Emergency Hospital in Timisoara, Romania; The case group included newborns who were delivered at the onset of umbilical arteries absent/reversed end-diastolic flow, and the control included infants delivered at the onset of reversed/absent ductus venosus A-wave. (3) Results: The overall neonatal mortality rate was 2.0%, and there was no significant statistical difference between the two study groups. In infants delivered up to 30 gestational weeks, grades III/IV intraventricular hemorrhage and bronchopulmonary dysplasia were statistically significantly more frequent in the control group. Moreover, univariate binomial logistic regression analysis on fetuses born under 30 gestational weeks shows that those included in the control group are 30 times more likely to develop bronchopulmonary dysplasia and 14 times more likely to develop intraventricular hemorrhage grades III/IV; (4) Conclusions: Infants delivered according to the occurrence of umbilical arteries absent/reversed end-diastolic flow are less likely to develop intraventricular hemorrhage grades III/IV and bronchopulmonary dysplasia.

Analysis of the relationship between placental histopathological aspects of preterm and term birth.

OBJECTIVES: This study aims to establish a correlation between placental histopathological and immunohistochemical (IHC) changes and preterm birth with fetal growth restriction (FGR, formerly called intrauterine growth restriction - IUGR). PATIENTS, MATERIALS, AND METHODS: This prospective study was performed on a group of 30 parturients, with singleton gestation, of which 15 patients gave birth at term, and the other 15 patients gave birth prematurely. After the statistical correlation of the clinical and demographic data with premature birth (PB) and term birth (TB), we performed histological and IHC research on the respective placentae. To observe normal and pathological microscopic placental structures, we used the Hematoxylin-Eosin (HE) and Periodic Acid Schiff-Hematoxylin (PAS-H) classical stainings, but also special immunostaining with anti-cluster of differentiation 34 (CD34) and anti-vascular endothelial growth factor (VEGF) antibodies. RESULTS: We found a statistically significant difference between the TB∕PB categories and the age of the patients, their antepartum weight, the weight of the newborns, and the placenta according to the sex of the newborn. Histological analysis revealed in the case of TB, small areas of perivillous amyloid deposition, with the significant extension of these areas both intravillous and perivillous in the case of PB. Massive intravillous calcifications, syncytial knots, and intravillous vascular thrombosis were also frequently present in PB. With PAS-H staining were highlighted the intra∕extravillous vascular basement membranes, but especially the massive fibrin deposits rich in glycosaminoglycans. By the IHC technique with the anti-CD34 antibody, we noticed the numerical vascular density, higher in the case of TB, but in the case of PB, there were large areas of placental infarction, with a lack of immunostaining in these areas. Through the anti-VEGF antibody, we observed the presence of signal proteins that determined and stimulated the formation of neoformation vessels in the areas affected by the lack of post-infarction placental vascularization. We observed a highly significant difference between placental vascular density between TB∕PB and newborn weight, sex, or placental weight. CONCLUSIONS: Any direct proportional link between the clinical maternal-fetal and histological elements yet studied must be considered. Thus, establishing an antepartum risk group can prevent a poor pregnancy outcome.