Determinants of “placental” versus “maternal” preeclampsia

Background: The placenta is known to be critical in the etiology of preeclampsia (PE). However, there is a subset of PE cases without identifiable placental pathology. We evaluated which clinical PE classification system best distinguishes PE with placental pathology from PE without placental pathology. Methods: We evaluated five placental pathologic features in 197 placentas from PE patients grouped by three clinical PE subclasses. 1. PE with calculated infant birthweight <10th percentile (small) for gestational age (SGA PE) versus PE with birthweight ≥10th percentile for gestational age (NSGA PE). 2. PE with delivery before 34 weeks of gestation (EDPE) versus PE with delivery at or after 34 weeks of gestation (LDPE) and 3. PE with severe features versus PE without severe features. Clinical, histologic and molecular findings in patients with PE were compared to normotensive patients, with and without SGA infants (N = 1,078 total). Results: The SGA versus NSGA PE classification system performed best (likelihood ratios (95% CI) for ≥ 3 of 5 placenta pathologic findings: 15.7 (6.5, 38.1) in SGA PE vs. NSGA PE; 6.8 (4.3, 10.8) in EDPE vs. LDPE and 5.2 (1.95, 14.1) in PE with SF vs. PE without SF; all p <.0001). SGA PE and SGA normotensive placentas were abnormal and shared alterations in hypoxia, TNF alpha, glycolysis, unfolded protein response, estrogen response, UV response, p53, TGF beta and mTORC1 signaling pathways. Conclusions: Classifying PE based on birthweight percentile for gestational age is the most useful system for consistently identifying PE associated with placenta pathology.