Determinants of Placental Versus Maternal Preeclampsia - PubMed (original) (raw)
Comparative Study
Determinants of Placental Versus Maternal Preeclampsia
Omonigho Aisagbonhi et al. Hypertension. 2026 Apr.
Abstract
Background: The placenta is known to be critical in the etiology 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 (tumor necrosis factor alpha), glycolysis, unfolded protein response, estrogen response, ultraviolet response, p53, TGFβ (transforming growth factor beta), and mTORC1 (mammalian target of rapamycin complex 1) 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.
Keywords: birth weight; glycolysis; humans; hypoxia; infants; pre-eclampsia; pregnancy.
Conflict of interest statement
None.
Figures
Figure 1:
Comparisons of preeclampsia (PE) subclasses. 197 cases of PE were compared based on three PE categorizations: 1. PE associated with calculated birthweight <10th percentile (small) for gestational age (SGA PE) versus PE associated calculated birthweight ≥10th percentile (not small) for gestational age (NSGA PE). 2. PE associated with delivery <34 weeks gestation (EDPE) versus PE associated with delivery ≥ 34 weeks gestation (LDPE). 3. PE with severe features (PE with SF) versus PE without severe features (PE without SF). A. Forest plot of the likelihood ratio of finding 3 or more of 5 evaluated placental abnormalities in the PE subclasses. B. ROC curves of logistic regression analyses performed adjusting for maternal age, BMI, parity and diabetes mellitus (design = ≥3 of 5 placental pathologic findings ~ Intercept + SGA PE (or EDPE or PE with severe features) + P0 parity + DM + Maternal age + BMI. C. Clustered bar graph comparing disease severity and placental abnormality percentages in the PE subclasses.
Figure 2.
Comparisons of small for gestational age (SGA) and not small for gestational age (NSGA) preeclampsia (PE) to SGA and NSGA normotensive (Norm) parturitions. 197 cases of PE (63 SGA PE and 134 NSGA PE) were compared to 881 normotensive (143 SGA Norm and 738 NSGA Norm) parturitions. A. Forest plot of the likelihood ratio associated with 3 or more of the 5 evaluated placenta abnormalities in SGA PE and NSGA PE compared to SGA Normotensive and NSGA Normotensive placentas B. Forest plot of the relative risk associated with 3 of 3 evaluated maternal risk factors (BMI ≥ 30, P0 parity and diabetes mellitus) in SGA PE and NSGA PE compared to SGA Normotensive and NSGA Normotensive patients. C. ROC curves of SGA PE compared to NSGA normotensive: design = SGA PE ~ Intercept + P0 parity + DM + ≥3 of 5 placental pathologic findings + Maternal age + BMI + BMI≥30 + 3 of 3 maternal risk factors. D. ROC curves of NSGA PE compared to NSGA normotensive: design = NSGA PE ~ Intercept + P0 parity + DM + ≥3 of 5 placental pathologic findings + Maternal age + BMI + BMI≥30 + 3 of 3 maternal risk factors.
Figure 3:
Molecular analysis and Model. RNA sequencing was performed on 203 placentas. A. Pathways significantly differentially expressed in placentas from normotensive patients with calculated birthweights <10th percentile (small) for gestational age (SGA Norm; N = 40) compared to placentas from normotensive patients with calculated birthweights ≥10th percentile (not small) for gestational age (NSGA Norm; N = 117). B. Pathways significantly differentially expressed in placentas from patients with preeclampsia and small for gestational age fetus/neonate (SGA PE; N = 46) compared to placentas from NSGA Norm. C. Shared pathways altered in SGA PE and SGA Norm in comparison to NSGA Norm. D. Model for the interplay between maternal, fetal and placenta factors in the pathophysiology of PE and SGA normotensive gestations.
References
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