The predictive utility of the in utero exposome for childhood adiposity in independent and integrated frameworks.

ABSTRACT

OBJECTIVES: To assess the predictive potential of the in utero exposome in relation to childhood adiposity as indicated by body mass index z-scores (BMIz) and the fourth versus first quartile of % fat mass (FM) at median age of 4.6 years. METHODS: We leveraged data on clinical risk factors for childhood obesity during the perinatal period, along with cord blood per/polyfluoroalkyl substances (PFAS) and cord blood DNA methylation, in 268 mother-offspring pairs. We used the sparsity ranked LASSO penalized regression framework for each outcome and assessed model performance based on % variability explained for BMIz and area under the receiver operating characteristic curve (AUC) for the fourth versus first quartile of %FM. We employed cross-validation for model tuning and split-sample validation for model evaluation. RESULTS: Mean ± SD BMIz was 0.01 ± 1.1, %FM was 19.8 ± 6.34%. The optimal model for predicting BMIz explained 19.1% of the variability in the validation set and included only clinical characteristics maternal pre-pregnancy BMI, paternal BMI, gestational weight gain, physical activity during pregnancy and child race/ethnicity. The optimal model for fourth versus first quartiles of %FM achieved an AUC of 0.82 ± 0.01 in the validation set, with the clinical features again emerging as the strongest predictors. CONCLUSION: In this study sample, perinatal chemical exposures and the epigenome have low utility in predicting childhood adiposity, beyond known clinical risk factors.