Placental programming, perinatal inflammation, and neurodevelopment impairment among those born extremely preterm

Abstract

Individuals born extremely preterm are at significant risk for impaired neurodevelopment. After discharge from the neonatal intensive care, associations between the child's well-being and factors in the home and social environment become increasingly apparent. Mothers' prenatal health and socioeconomic status are associated with neurodevelopmental outcomes, and emotional and behavioral problems. Research on early life risk factors and on mechanisms underlying inter-individual differences in neurodevelopment later in life can inform the design of personalized approaches to prevention. Here, we review early life predictors of inter-individual differences in later life neurodevelopment among those born extremely preterm. Among biological mechanisms that mediate relationships between early life predictors and later neurodevelopmental outcomes, we highlight evidence for disrupted placental processes and regulated at least in part via epigenetic mechanisms, as well as perinatal inflammation. In relation to these mechanisms, we focus on four prenatal antecedents of impaired neurodevelopment, namely, (1) fetal growth restriction, (2) maternal obesity, (3) placental microorganisms, and (4) socioeconomic adversity. In the future, this knowledge may inform efforts to detect and prevent adverse outcomes in infants born extremely preterm. IMPACT: This review highlights early life risk factors and mechanisms underlying inter-individual differences in neurodevelopment later in life. The review emphasizes research on early life risk factors (fetal growth restriction, maternal obesity, placental microorganisms, and socioeconomic adversity) and on mechanisms (disrupted placental processes and perinatal inflammation) underlying inter-individual differences in neurodevelopment later in life. The findings highlighted here may inform efforts to detect and prevent adverse outcomes in infants born extremely preterm.

Fig. 1. Early life risk factors and mechanisms underlying inter-individual differences in neurodevelopment later in life.

Arrows represent associations between pre- or perinatal risk factors, early in life health outcomes (birth–4 months), and later in life health outcomes (middle childhood–early childhood) as observed in the literature. Solid arrows represent associations between risk factors and outcomes that are topics of discussion in this review. Dashed arrows represent links that are not addressed in the current review.