Editorial: Maternal Inflammation During Pregnancy: A Modifiable Pathway Toward Improving Offspring Socioemotional Outcomes in Childhood and Adolescence.

Childhood psychopathology is a well-established predictor of poor adult life-course outcomes including lower rates of educational attainment and reduced family income, with a total economic loss of $2.1 trillion in the United States. Given this high level of individual and societal burden, much effort has been devoted to identifying the modifiable risk factors that confer risk for psychiatric disorders during early childhood. Indeed, numerous aspects of early life adversity, such as socioeconomic disadvantage, stressful/traumatic life events, and disrupted parent-child relationships, demonstrate strong associations with socioemotional problems and psychiatric disorders into adolescence. However, the underlying biological mechanisms that also contribute to this risk trajectory remain less well understood. One proposed biological mechanism that is rapidly gaining momentum in the field of developmental psychopathology concerns excessive immune system activation and/or proinflammatory responses in the origins of health and disease. Of particular interest is the prenatal period, representing a window of vulnerability in which prenatal exposures prepare or program the fetus for the expected postnatal environment. More specifically, fetal programming posits that the effects of maternal adversity during pregnancy are, at least in part, transmitted to the fetus via multiple related pathways including chronic maternal inflammation and/or overactivation of the hypothalamic-pituitary-adrenal axis, resulting in aberrant maternal-fetal immune/glucocorticoid systems and downstream epigenetic alterations in the developing fetus. Together, these factors work to increase the susceptibility of offspring to adversity in the postnatal environment and, in turn, enhance risk for psychiatric disorders. However, much of the existing literature is based on preclinical animal models with comparatively fewer clinical studies. As such, there remains a paucity of large, prospectively designed clinical studies examining maternal proinflammatory conditions during pregnancy in relation to psychopathology in offspring. As part of the landmark National Institutes of Health-funded ECHO (Environmental influences on Child Health Outcomes) consortium, the study by Frazier et al. represents one of the largest investigations linking perinatal maternal proinflammatory conditions with co-occurring psychiatric symptoms in children and adolescents.