In 1914, James Young set out a detailed account of the placental findings in preeclampsia that included the incidence of infarction and villous over-crowding. His placental ischemia theory displaced the preceding mechanical distension theory as an explanation of preeclampsia. In 2014, Nelson et al conclude that “preeclampsia is a different disease depending on the gestational age at diagnosis.” In their large series, the placental findings at <34 weeks’ gestation include signs of placental ischemia, small placentae, and small-for-gestational-age fetuses; whereas at >34 weeks’ gestation, there are larger placentae with appropriate-for-gestational-age fetuses. They suggest there are 2 causes of the preeclamptic syndromes, although recent observations suggest the 2 placental phenotypes may both result from injuries to uterine nerves at different anatomic sites (the uterine reinnervation theory).
Injuries to uterine vasomotor nerves release cytokines that result in irregular hyperplasia of denervated blood vessel walls and reduced uteroplacental blood flow that may result in preeclampsia with a small-for-gestational age fetus ( Figure ; placental ischemia theory). Increased myometrial tension bearing on injured nerves in the extraplacental myometrium may result in preeclampsia with an appropriate-for-gestational-age fetus (eg, nulligravidity, multiple pregnancy, hydramnios, etc; the mechanical distension theory). In both settings, regenerated nerves act as simple mechanoreceptors that respond to stretch. Autonomic nerves conduct these signals to the renal cortex where vasoconstriction leads to hypertension, proteinuria, and widespread activation of autonomic nerves that results in the multisystem features of the syndrome. Variations in placental site and circulatory compliance alter clinical presentations in successive pregnancies.
