Preeclampsia and Fetal Growth Restriction: Intervillous Space Flow

A major theory explaining both fetal growth restriction and preeclampsia is that defective spiral artery remodeling reduces the flow rate of maternal blood through the intervillous spaces of the placenta. According to the theory, this reduced flow causes intervillous hypoxia which (1) makes the chorionic villi hypoxic, causing preeclampsia via the release of anti-angiogenic factors and (2) makes the fetus hypoxic, causing fetal growth restriction. The key to this model is reduced intervillous space perfusion. Despite its elegance and a large amount of supportive evidence, this simple model is problematic since many cases of preeclampsia are not accompanied by fetal growth restriction and vice versa—many cases of fetal growth restriction arise in the absence of preeclampsia. But if we accept the model as it is, we could predict that obstruction of uterine venous return might cause preeclampsia and fetal growth restriction in the same way as defective spiral artery remodeling causes it—namely by a reduction of intervillous space perfusion. Obstruction of uterine venous return could impair chorionic villus and fetal oxygenation either by itself or by exacerbating the effects of other maternal conditions that restrict intervillous perfusion from the arterial side, such as diabetes, chronic hypertension, or defective spiral artery remodeling. Nitroglycerin therapy combined with volume loading may prevent or mitigate preeclampsia and fetal growth restriction, but further research needs to take the possible effects of concurrent obstruction of uterine venous return into account. Also, generalized intervillous hypoxia due to obstruction of uterine venous return may trigger generalized hypoxic fetoplacental vasoconstriction and nitroglycerin may prevent this response, among its many other hemodynamic effects.