A perspective on pre‐eclampsia and neurodevelopmental outcomes in the offspring: Does maternal inflammation play a role?

Abstract

Pre‐eclampsia is a leading cause of maternal death and maternal and perinatal morbidity. Whilst the clinical manifestations of pre‐eclampsia often occur in late pregnancy, the molecular events leading into the onset of this disease are thought to originate in early pregnancy and result in insufficient placentation. Although the causative molecular basis of pre‐eclampsia remains poorly understood, maternal inflammation is recognised as a core clinical feature. While the adverse effects of pre‐eclampsia on maternal and fetal health in pregnancy is well‐recognised, the long‐term impact of pre‐eclampsia exposure on the risk of autism spectrum disorder (ASD) in exposed offspring is a topic of on‐going debate. In particular, a recent systematic review has reported an association between exposure to pre‐eclampsia and increased risk of ASD, however the molecular basis of this association is unknown. Here we review recent evidence for; 1) maternal inflammation in pre‐eclampsia; 2) epidemiological evidence for alterations in neurodevelopmental outcomes in offspring exposed to pre‐eclampsia; 3) long‐term changes in the brains of offspring exposed to pre‐eclampsia; and 4) how maternal inflammation may lead to altered neurodevelopmental outcomes in pre‐eclampsia exposed offspring. Finally, we discuss the implications of this for the development of future studies in this field.

Association between preeclampsia and attention‐deficit hyperactivity disorder: a population‐based and sibling‐matched cohort study

“…Animal models have shown that activation of interleukin‐17a (IL‐17a) in the foetal brain, in response to maternal immune activation, is associated with behavioural disturbances and an abnormal cortical phenotype in affected offspring . Therefore, we can speculate that maternal inflammation may be one such mechanism given the role of preeclampsia in chronic immune activation and elevated levels of inflammatory cytokines such as IL‐17a . In a separate study, maternal depressive symptoms throughout pregnancy were shown to be associated with ADHD in offspring .…”

Association between preeclampsia and autism spectrum disorder: a population‐based study

“…Such factors may include inflammatory cytokines given that preeclampsia is associated with chronic immune activation, leading to a significant increase in the circulation of proinflammatory cytokines. Thus, while uncomplicated pregnancies have a normal systemic inflammatory response (Redman, Sacks, & Sargent, 1999), preeclampsia results in a state of exaggerated maternal inflammation (Maher, McCarthy et al, 2018;Redman et al, 1999). Therefore, maternal inflammation, a recognised risk factor for poor neurodevelopmental outcome, could act as a mediator between preeclampsia and development of ASD, and the proinflammatory cytokine interleukin (IL)-6 may be a leading candidate in this regard (Jiang et al, 2018).…”

Mechanisms of Endothelial Dysfunction in Pre-eclampsia and Gestational Diabetes Mellitus: Windows Into Future Cardiometabolic Health?

“…Similar risks exist for the offspring, such as neurodevelopmental disorders in hypertensive pregnancies and type 1 diabetes mellitus in hyperglycemic pregnancies such as GDM (4,5). Population based studies have shown that the deleterious implications of obstetric complications on the fetus, such as an increased risk of endocrine, nutritional, and metabolic derangements, including T2DM, are present well into adolescence and early-adulthood (6,7).…”