UC Irvine

BACKGROUND: Empirical evidence suggests that the origins of obesity and metabolic dysfunction can be traced to stress-related exposures in prenatal life. The aim of the present study was to examine the prospective association of a composite, multi-system measure of maternal biological stress in pregnancy -- allostatic load (AL) -- with offspring adiposity and insulin resistance across infancy and early childhood. METHODS: In N = 55 mother-child dyads, maternal allostatic load was operationalized as a latent variable representing the following components: pre-pregnancy BMI, cortisol, interleukin-6, C-reactive protein, homeostasis model assessment of insulin resistance (HOMA-IR), free fatty acids, and systolic/diastolic blood pressure. Offspring percent total (%FM) and abdominal (%AbFM) fat were quantified with dual-energy X-ray absorptiometry at birth (newborn), 6-mo, and ∼5 yrs age, and HOMA-IR was quantified at ∼5 yrs age. Generalized estimating equation modeling was used to estimate effects of maternal AL on serial (repeated) measures of child adiposity, and linear regression was used to estimate effects on child HOMA-IR. A priori model covariates included maternal race and ethnicity, socioeconomic status, infant feeding practices, child age, and sex. RESULTS: Maternal AL was positively associated with child %FM and %AbFM before as well as after adjustment for key maternal and offspring covariates (%FM: adjusted β=0.38, p = 0.0074; %AbFM: adjusted β=0.37, p = 0.0013). Maternal AL also was positively associated with child insulin resistance (adjusted β= 0.011, p = 0.0324). CONCLUSION: Our findings suggest that exposure to a higher biological stress milieu during prenatal development predisposes towards elevated early life adiposity and insulin resistance in early childhood, a proximate cause of type 2 diabetes and cardiometabolic disease. Collectively, these results provide evidence that a multi-systems approach to quantify early life exposures is useful in prospectively predicting variation in childhood adiposity and metabolic function.