Fetal pulmonary vascular volume is impaired in mothers with early onset preeclampsia – a proof of concept study

Objective: Children of mothers with (early-onset) preeclampsia (EOPE) face an increased risk of developing respiratory morbidity, which has been shown to result of multiple factors, including associated fetal growth restriction (FGR) and premature birth, but also by an impaired pulmonary vascular development. While animal models have demonstrated compromised fetal pulmonary vasculature in preeclampsia, evidence in human fetuses remains lacking. As a proof of concept, this study aimed to compare fetal pulmonary vascular volume in EOPE pregnancies to healthy controls.Methods: Healthy controls and pregnant women with EOPE were recruited prospectively. Ultrasound measurements were performed during three gestational age intervals: 19+0–24+0 weeks (US1), 24+1–29+6 weeks (US2), and 30+0–32+0 weeks (US3). Using 3D Power Doppler ultrasound, fetal right pulmonary vascular volume (R-PVV), right lung volume (R-LV), and the right pulmonary vascular volume-to-lung volume ratio (R-PVV/LV ratio) were collected. Perinatal parameters were compared between EOPE fetuses and controls.Results: Seventy-two healthy controls and 36 EOPE fetuses were included. Maternal BMI, gestational age at birth, and birth outcomes differed significantly between groups. EOPE fetuses showed significantly reduced R-PVV at US2 and US3 compared to controls, with impaired vascular growth evident during later gestational stages. When corrected for lung growth, the R-PVV/LV ratio remained significantly lower in EOPE fetuses at US2 and US3, indicating impaired vascular development independent of lung size.Conclusion: This is the first study that supports the hypothesis that pulmonary vascular growth is impaired in fetuses of mothers with EOPE. These findings provide valuable insights into the pathophysiological impact of preeclampsia on fetal pulmonary health.