Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes

Among individuals born very preterm, perinatal inflammation, particularly if sustained or recurring, is highly likely to contribute to adverse neurodevelopmental outcomes, including cerebral white matter damage, cerebral palsy, cognitive impairment, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Antecedents and correlates of perinatal inflammation include socioeconomic disadvantage, maternal obesity, maternal infections, fetal growth restriction, neonatal sepsis, necrotizing enterocolitis, and prolonged mechanical ventilation. Genetic factors can modify susceptibility to perinatal inflammation and to neurodevelopmental disorders. Preliminary evidence supports a role of epigenetic markers as potential mediators of the presumed effects of preterm birth and/or its consequences on neurodevelopment later in life. Further study is needed of factors such as sex, psychosocial stressors, and environmental exposures that could modify the relationship of early life inflammation to later neurodevelopmental impairments. Also needed are pharmacological and non-pharmacological interventions to attenuate inflammation towards the goal of improving the neurodevelopment of individuals born very preterm.

Keywords: Attention-deficit/hyperactivity disorder; Autism spectrum disorder; Cerebral palsy; Epigenetics; Epilepsy; Genetics; Inflammation; Intellectual deficit; Neurodevelopment; Preterm birth.