Placental histopathology and angiogenic biomarkers in two phenotypes of pre‐eclampsia, early and late onset–a prospective cohort study

OBJECTIVE: The placenta plays a central role in the development of pre-eclampsia (PE). It has been identified with two distinct types as early and late onset pre-eclampsia (EOPE and LOPE) with distinct pathophysiological profiles. This study aimed to compare angiogenic biomarkers, uterine artery Doppler indices and placental histopathology between EOPE and LOPE. METHODS: A prospective observational study was conducted at a tertiary care center involving 300 women (150 EOPE and 150 LOPE). Uterine artery Doppler, maternal serum biomarkers (soluble fms like tyrosine kinase [sFlt-1], placental growth factor [PlGF], sFlt-1/PlGF ratio) were measured within 2 weeks of delivery. Placentas were examined post-delivery and reported as per Amsterdam Placental Workshop Group Consensus. RESULTS: The mean uterine artery pulsatility index (PI) was higher in EOPE compared to LOPE. Median sFlt-1 and sFlt-PlGF ratios were elevated in EOPE while the PlGF values were significantly higher in LOPE. Histopathologic analysis revealed perivillous fibrin deposition, increased syncytial knots, and multiple infarctions as predominant lesions in EOPE. In LOPE, infarctions and calcifications were more common. In EOPE, all placental lesions correlated with PlGF, sFlt-1/PlGF ratio, and uterine artery PI. In LOPE, only infarctions and syncytial knots showed correlation with sFlt-1 and sFlt-1/PlGF ratio. CONCLUSION: EOPE is characterized by pronounced angiogenic imbalance, impaired uteroplacental perfusion, and severe placental pathology in terms of maternal vascular malperfusions. LOPE presents with milder biochemical and Doppler changes, with placental lesions suggestive of aging rather than maternal vascular malperfusions.