Intergenerational Transmission of Health Inequities: Early Life Socioeconomic Factors, Adult Cardiometabolic and Pregnancy Outcomes, and Potential Epigenetic Mechanisms in Young Adult Women.

Abstract

Parental socioeconomic status (SES) experienced by a woman in utero may directly affect her adult health, independent of her life course experiences. Developmental programming of gene expression through DNA methylation may be involved. However, investigations using prevailing regression methods have been impeded by complex causal structures and unmeasured confounding. Using a U.S.-national, longitudinal cohort, we investigated the effect of mother's education on (1) cardiometabolic risk and (2) pregnancy outcomes among women averaging 30 years of age. Using an Israeli birth cohort, we investigated associations between parental education and father's occupational class on (3) DNA methylation at cardiometabolic genes in 32-year old women. (1) Using marginal structural models estimated by inverse probability weighting, we found young adult women whose mothers had higher educational attainment (e.g. college versus high school) had 40% lower risk (Odds Ratio = 0.60, 95% Confidence Interval: 0.45, 0.80) of metabolic syndrome, independent of childhood maltreatment, adolescent overweight, adult SES, and behavioral risk. Additionally, there was evidence that women with more highly educated mothers were taller, thinner, and had a smaller waist, lower resting pulse rate, lower levels of inflammatory markers, and better blood sugar control. (2) Additionally, women born to more highly educated mothers who themselves bore children delivered newborns who were 90 grams heavier (95% CI: 20.8, 156.5), independent of childhood maltreatment, pre-pregnancy overweight, adult SES, and prenatal smoking. Moreover, results from (1) and (2) were robust to several sensitivity analyses including model alteration, data replacement, and quantitative bias analyses. (3) Finally, we found that lower SES at birth measured by father's occupational class was associated with reduced methylation at the ABCA1 cholesterol transporter gene and the NR3C1 glucocorticoid receptor genes in 32-year old women, after adjusting for numerous parental and offspring characteristics. Similarly, fewer years of mother's education was associated with reduced HSD11B2 glucocorticoid-inactivating enzyme gene methylation. However, such associations did not appear to mediate relationships between birth SES and young adult cardiometabolic risk. Overall, there appears to be substantial evidence that early life SES is independently related to adult women's health and DNA methylation, however the mechanisms relating them require further elucidation.