Nutritional Modulation of Associations between Prenatal Exposure to Persistent Organic Pollutants and Childhood Obesity: A Prospective Cohort Study

Background: Prenatal exposure to persistent organic pollutants (POPs) may contribute to the development of childhood obesity and metabolic disorders. However, little is known about whether the maternal nutritional status during pregnancy can modulate these associations.

Objectives: The main objective was to characterize the joint associations and interactions between prenatal levels of POPs and nutrients on childhood obesity.

Methods: We used data from to the Spanish INfancia y Medio Ambiente-Environment and Childhood (INMA) birth cohort, on POPs and nutritional biomarkers measured in maternal blood collected at the first trimester of pregnancy and child anthropometric measurements at 7 years of age. Six organochlorine compounds (OCs) [dichlorodiphenyldichloroethylene, hexachlorobenzene (HCB), $\beta -\text{hexachlorocyclohexane}$ ($\beta -\text{HCH}$) and polychlorinated biphenyls 138, 153, 180] and four per- and polyfluoroalkyl substances (PFAS) were measured. Nutrients included vitamins (D, B12, and folate), polyunsaturated fatty acids (PUFAs), and dietary carotenoids. Two POPs-nutrients mixtures data sets were established: a) OCs, PFAS, vitamins, and carotenoids ($n=660$), and b) OCs, PUFAs, and vitamins ($n=558$). Joint associations of mixtures on obesity were characterized using Bayesian kernel machine regression (BKMR). Relative importance of biomarkers and two-way interactions were identified using gradient boosting machine, hierarchical group lasso regularization, and BKMR. Interactions were further characterized using multivariate regression models in the multiplicative and additive scale.

Results: Forty percent of children had overweight or obesity. We observed a positive overall joint association of both POPs-nutrients mixtures on overweight/obesity risk, with HCB and vitamin B12 the biomarkers contributing the most. Recurrent interactions were found between HCB and vitamin B12 across screening models. Relative risk for a natural log increase of HCB was 1.31 (95% CI: 1.11, 1.54, $p_{\text{Interaction}}=0.02$) in the tertile 2 of vitamin B12 and in the additive scale a relative excess risk due to interaction of 0.11 (95% CI: 0.02, 0.20) was found. Interaction between perfluorooctane sulfonate and $\beta -\text{cryptoxanthin}$ suggested a protective effect of the antioxidant on overweight/obesity risk.

Conclusion: These results support that maternal nutritional status may modulate the effect of prenatal exposure to POPs on childhood overweight/obesity. These findings may help to develop a biological hypothesis for future toxicological studies and to better interpret inconsistent findings in epidemiological studies. https://doi.org/10.1289/EHP11258.