Determinants of Placental Versus Maternal Preeclampsia

BACKGROUND: The placenta is known to be critical in the cause of preeclampsia. However, there is a subset of preeclampsia cases without identifiable placental pathology. We evaluated which clinical preeclampsia classification system best distinguishes preeclampsia with placental pathology from preeclampsia without placental pathology. METHODS: We evaluated 5 placental pathological features in 197 placentas from patients with preeclampsia grouped by 3 clinical preeclampsia subclasses: (1) preeclampsia with calculated infant birthweight <10th percentile for gestational age (small for gestational age [SGA] preeclampsia) versus preeclampsia with birthweight ≥10th percentile for gestational age (not SGA preeclampsia); (2) preeclampsia with delivery before 34 weeks of gestation (early delivery preeclampsia) versus preeclampsia with delivery at or after 34 weeks of gestation (late delivery preeclampsia); and (3) preeclampsia with severe features versus preeclampsia without severe features. Clinical, histological and molecular findings in patients with preeclampsia were compared with normotensive patients, with and without SGA infants (N=1078 total). RESULTS: The SGA versus not small for gestational age preeclampsia classification system performed best (likelihood ratios [95% CI] for ≥3 of 5 placental pathological findings: 15.7 [6.5–38.1] in SGA preeclampsia versus not small for gestational age preeclampsia; 6.8 [4.3–10.8] in early delivery preeclampsia versus late delivery preeclampsia; and 5.2 [1.95–14.1] in preeclampsia with severe features versus preeclampsia without severe features; all P <0.0001). SGA preeclampsia and SGA normotensive placentas were abnormal and shared alterations in hypoxia, TNFα, glycolysis, unfolded protein response, estrogen response, UV response, p53, TGFβ, and mTORC1 signaling pathways. CONCLUSIONS: Classifying preeclampsia based on birthweight percentile for gestational age is the most useful system for consistently identifying preeclampsia associated with placental pathology.