Perinatal outcome and placental apoptosis in patients with late-onset pre-eclampsia and abnormal uterine artery Doppler at diagnosis

Objective: To determine the rate of placental apoptosis and adverse perinatal outcome in patients with late-onset pre-eclampsia (PE) and abnormal uterine artery (UtA) Doppler at diagnosis. Methods: This was a prospective cohort study of women with singleton pregnancy diagnosed with late PE, performed between August 2011 and January 2014 at the Maternal-Fetal Medicine Unit of Hospital Carlos Van Buren. Patients were stratified according to UtA Doppler status at diagnosis (pulsatility index (PI) ≤ or > 95^th percentile). Logistic regression analysis was performed to identify associations between abnormal UtA Doppler and adverse maternal and perinatal outcomes. In a subset of this cohort for whom placental samples were available, immunohistochemical analysis of the placenta was performed to identify the rate of apoptosis and its association with UtA Doppler by comparing samples from those with normal and those with abnormal UtA Doppler and normotensive controls. Non-parametric linear trend analysis was performed for assessment of the apoptotic index. Results: Eighty-six patients were included in the final analysis. Of these, UtA-PI was above the 95^th percentile in 33 (38.4%) patients. Gestational age at diagnosis and delivery were significantly lower in this group compared with patients with normal UtA Doppler. Abnormal UtA Doppler was associated with increased risk of severe PE (odds ratio (OR) = 7.5; 95% CI, 2.76–20.46; P < 0.001), late preterm delivery (OR = 13.7; 95% CI, 4.53–41.46; P < 0.001), small-for-gestational age at birth (OR = 12.3; 95% CI, 3.17–47.57; P < 0.001) and admission to the neonatal intensive care unit (OR = 12.8; 95% CI, 2.61–62.36; P = 0.002). Moreover, UtA Z-score demonstrated a significant inverse correlation with birth-weight Z-score (r = –0.34; P = 0.0013). Mean placental apoptotic index demonstrated an ascending linear trend according to UtA Doppler status (P = 0.04). Conclusions: In patients with late PE, UtA Doppler was useful for clinical classification and as an indicator of placental histological findings. Correlation between UtA Doppler and the apoptotic index provides new evidence of a subgroup of late PE with a placental origin.