Thinning of the intervascular tissue layers of the human placenta is an adaptive response to passive diffusion in vivo and may help to predict the origins of fetal hypoxia

Abstract

Objectives: To test the hypothesis that thinning of the placental intervascular layers, and greater variability in thickness, are positive adaptations to facilitate passive diffusion and may help to resolve different categories of fetal hypoxia. Study Design: Placentas from 12–41 weeks of normal gestation and from pregnancies associated with fetal hypoxic stress (high altitude, diabetes mellitus) were sampled systematically, fixed in formalin, wax-embedded and quantified using stereological methods. Arithmetic and harmonic mean distances across villous trophoblast, stroma and fetal plasma were estimated by measuring randomly sampled intercept lengths. In each case, an index of variability of layer thickness was calculated by dividing the arithmetic by harmonic mean distance. This index has the value 1 when a tissue layer is uniformly thick but increases in value as local layer thickness becomes more variable. Comparisons between groups were drawn using variance and regression analysis. Results: During pregnancy, there were significant negative correlations between layer thickness (trophoblast, stroma) and gestational age and fetal weight, and significant positive correlations between thickness irregularity and age and weight. Compared with lowland controls, high-altitude placentas possessed thinner layers but only the trophoblast and stroma (and not fetal plasma) were more variably thick. In maternal diabetes, only fetal plasma distance was reduced but fetal and stromal layers appeared to be more irregular in thickness. Conclusions: Alterations in placental intervascular layer thicknesses occur in normal and abnormal pregnancies and represent real adaptions leading to improved diffusive conductances. Differences in the tissue location of the adaptive response may depend on the nature and origins of the fetal hypoxia.