33 Placental maturation analysis in cases of term intra-uterine growth restriction revealed decreased villous angiogenesis and increased trophoblast turnover

Abstract

Introduction Intra-uterine growth restriction (IUGR), failure of the fetus to reach normal birth weight, represents an important health hazard among neonates, and is associated with increased mortality and morbidity later in life. It is postulated that IUGR is associated with an inefficient blood and gas-supply at the feto-maternal interface of the placenta resulting in fetal hypoxia and under nutrition. Objectives The aim of the present study is to analyze, placental maturation assuring adequate increase of gas exchange efficiency by histo-morphological analyses of placentas comparing control term placentas to those of term growth restricted fetuses. This includes analyses of the degree of terminal villi vascularization, the diffusion distance between fetal capillary and maternal blood and the syncytial trophoblast turnover. Methods Paraffin sections of placental samples from term IUGR ( n = 10) and healthy term pregnancies ( n = 11) were stained immunohistochemically for endothelial cells (CD31). This is followed by stereological evaluation by light microscopy and an Image Analyzer. Surface areas, distances and numbers from terminal villi (TV), numbers and area of fetal capillaries (FC), diffusion distances (DD), vascular-syncytial membranes (VSM) and apoptotic knots (AK), were recorded. Non-parametric analyses were applied and statistical significance was set at P Results The mean birth weight for the IUGR group (2353±285g) in accordance to the group definitions differed significantly ( p p = 0.049). No significant differences were found in maternal age ( p = 0.28), BMI ( p = 0.24) gravidity or parity. We observed less TV per field ( p = 0.058), VSM’s ( p = 0.31) and FC’s per TV (0.64) less area of FC per TV ( p = 0.27) and shorter diffusion distances in IUGR compared to controls, however these differences are not statistically significant. VSM lengths were significantly shorter per TV ( p = 0.04) in IUGR. Analysis of AK showed a significant increase ( p = 0.002) in IUGR compared to controls. Conclusion TV’s are sites specialized in gas exchange. They comprise of VSM’s characterized by fusions of the basal membranes of the capillary endothelium and the syncytiotrophoblast layer making the diffusion distance shortest and thus gas exchange most efficient. There are less TV’s and shorter VSM’s in the IUGR samples. This diffusion deficit may be compensated, by decreasing the mean diffusion distance of all fetal capillaries. In addition the trophoblast turnover as measured by the presence of AK seems to be increased in IUGR. The preceding is supported by the theory of post-placental hypoxia. According to this theory both mother and placenta are normoxic whereas the fetus is hypoxic from fetoplacental malperfusion. This results in a reduced oxygen extraction from the placenta resulting in intra-placental hyperoxia. These high pO2 values inhibit villous growth resulting in decreased TV and shorter VSM’s, and accordingly cause IUGR. The high intra-placental pO2 leads to increased oxidative stress in the placenta and might also be the cause of the increased trophoblast turn over observed in IUGR.