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Background: Low socioeconomic status (SES) environments often co-occur with greater rates of childhood lead exposure (Muller et al., 2018). Early life exposures may be particularly detrimental for the development of biological pathways involved in stress responses, such as the hypothalamic-pituitary-adrenal (HPA) axis, and associated hormones which influence later health and developmental outcomes, as suggested by the biological embedding model (Shonkoff et al., 2009). Both low SES and lead exposure have been independently associated with dysregulation of the HPA axis and associated hormones. Though early life low SES and lead exposure often co-occur, it remains unclear how they synergistically influence stress response hormones, especially in adolescence when the HPA axis is maturing, and hormones are naturally in flux as adolescents age. Thus, the purpose of this study was to examine associations between early life lead exposure and adolescent stress response hormones and to test whether SES modifies the relationship based on adolescent age.
Methods: The analytic sample comprised 263 adolescents from the ELEMENT cohort which enrolled pregnant mothers in Mexico City beginning in 1997. Those included had blood lead levels (BLLs; Mean= 5.09 mcg/dl) and SES data, measured via the Mexico specific AMAI tool (AMAI, 2017), collected when they were 3 years old. Adolescent follow-up at mean age: 14.1 years, SD= 1.77 ( 49.43% female) included assessment of fasting serum cortisol and dehydroepiandrosterone sulfate (DHEAs), major steroid hormones of the HPA axis, and corticosterone and cortisone, secondary HPA axis hormones. Altered levels of these hormones may indicate a dysregulated HPA axis. Multivariable linear regression was used to model the association of BLLs with hormones. Two-way interactions (BLLxAge) were tested in SES stratified models and three-way interactions (BLLxAgexSES) were examined in full models for each outcome. We probed interactions by mean centering predictors and creating global macros at 1 and 2 SD ± the mean and plotting simple slopes. All models were adjusted for sex.
Results: There was a trend-level association for the BLLxAge interaction predicting corticosterone in the stratified low SES model (β= 0.95, 95%CI -17.12, 211.35) and for the BLLxAgexSES interaction predicting corticosterone in the full model (β= -186.07, 95%CI -403.41, 31.27) which suggested older adolescents of low SES had positive associations between BLLs and corticosterone (Figure 1). For models predicting DHEAs, there was a significant BLLxAge interaction in the low SES stratified model (β= 2.01, 95%CI 0.17, 3.84) which showed older adolescents had significant positive associations between BLLs and DHEAs (Figure 2). The BLLxAgexSES interaction predicting DHEAs was non-significant as were adjusted models and interactions for cortisol and cortisone.
Conclusion: BLLs appeared to be longitudinally associated with HPA axis hormones in older adolescents, and only for those from low SES backgrounds. These results may suggest the biological embedding of both early life toxicant and social exposures which alter functionality of biological stress regulatory systems such as the HPA axis. Adolescents with early childhood lead and low SES exposure may be at greater risk for HPA axis dysfunction as they age.