Sensitive periods to social adversity in immune and metabolic development: A systematic review

Childhood exposure to social adversity - including experiences such as poverty, discrimination, violence, family separation, household dysfunction, and maltreatment - is associated with cardiometabolic health problems across the life course. A key question in the field is whether the timing of social adversity matters. To better understand the developmental origins of cardiometabolic disease and the emergence of health disparities, we conducted a systematic review of human observational studies to synthesize the evidence for sensitive periods to social adversity in immune and metabolic development. To be included in the study, some form of social adversity had to be independently reported at two or more non-overlapping time points during the prenatal period or childhood (<21 years old) and studies were required to include an outcome relevant to immune and/or metabolic biomarkers measured at some time after the social adversity exposure. Of the 2440 unique records screened, 25 met criteria for inclusion. Twenty studies investigated sensitive periods in immune development and six in metabolic development. For immune development, studies identified sensitive periods to social adversity inconsistently from the prenatal period through age 18. However, the proportion of studies confirming sensitive periods was highest at the youngest stages of development and gradually decreased across the life course. 50 % of studies found significant sensitive period effects in the prenatal period, while only 20 % found significant effects in late adolescence. For metabolic development, studies identified sensitive periods more consistently from birth through age 12. The proportion of studies reporting sensitive periods peaked at 50 % in infancy and decreased to zero after preadolescence. Overall, we found insufficient evidence to identify precise periods during which specific social adversity exposures have been consistently associated with altered immune and metabolic development. More birth cohorts with repeated measures of both social exposures and immune and metabolic biomarkers are needed, as are studies leveraging causal inference methods to more robustly account for time-varying confounding. However, these limitations notwithstanding, our review finds evidence that early experiences matter for immune and metabolic functioning. Improving the social and economic circumstances of young children may benefit lifelong cardiometabolic health.