PLACENTAL DEFECTS UNDERLIE FETAL WATER DISEASE

Fetal water diseases, which include hydrops fetalis and polyhydramnios,
are an increasingly common cause of infant mortality and morbidity. Nearly
all fetuses with the non-immune form do not survive. Yet the mechanisms
that underlie the pathophysiology are unknown. This application is based
on the umbrella hypothesis that a number of primary fetal abnormalities
cause fetal water diseases through a common pathway-alterations in the
physicochemical properties of the placental barrier. The application is
designed to quantitate missing pieces of data that will allow us to
estimate the physical forces that regulate the movement of water across
the placenta in normal and diseased patients. Aim l of the study is to
measure the diffusion permeability of the tracer substances of different
molecular weights and charges in normal placentas from pregnancies with
water disease. Aim 2 is to estimate the hydraulic conductivity and
reflection coefficients of several important molecular species from the in
vitro perfused placentas of hydropic and polyhydramniotic patients and
from normal control patients. The data for these two specific aims will
provide the basis for predicting the roles of disturbances in the forces
that drive water across the placenta under normal and pathological
conditions.