The impact and mechanisms of preeclampsia on offspring neurodevelopment

Preeclampsia (PE) is a pregnancy-specific hypertensive disorder that has significant impact on offspring neurodevelopment. In this review, we first summarize the clinical and epidemiological evidence that PE disrupts fetal brain development while increasing the risk of neuropsychiatric diseases such as autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring. PE exposure is associated with altered brain growth and cortical morphology and white-matter microstructure in offspring, and with persistent deficits in cognition, emotion and social ability. We then propose the pathophysiological mechanisms underlying how PE exposure influences offspring neurodevelopment and thus increases the susceptibility of neuropsychiatric diseases in offspring from the studies of animal models. We pay attention to the heterogeneity across studies related to gestational age at delivery, fetal growth restriction (FGR) and postnatal exposures, highlighting the sex-specific mechanisms and translational therapeutic targets. Lastly, we discuss future directions including sexually dimorphic effects of PE and “two-hits” experimental paradigms to model prenatal-postnatal interactions.