Prepregnancy and prenatal risk factors for the neurodevelopmental delay of offspring: Machine learning analysis using national health insurance claims data

Abstract Neurodevelopmental disorders (NDD) in offspring are associated with a complex combination of pre-and postnatal factors. This study uses machine learning and population data to evaluate the association between prepregnancy or prenatal predictors and the NDD of offspring for as more reflective of the real world. Population-based retrospective cohort data were obtained from Korea National Health Insurance Service claims data for 209,424 singleton offspring and their mothers who gave birth for the first time in 2007. The dependent variables were motor development disorder (MDD), cognitive development disorder (CDD) and combined overall neurodevelopmental disorder (NDD) from offspring. Seventeen independent variables from 2002–2007 were included. Random forest variable importance and Shapley Additive Explanation (SHAP) values were calculated to analyze the directions of its associations with the predictors. The random forest with oversampling registered much higher areas under the receiver-operating-characteristic curves than the logistic regression, 72% vs. 50% (MDD), 76% vs. 51% (CDD) and 68% vs. 50% (NDD). Based on random forest variable importance, low socioeconomic status and age at birth were highly ranked. In SHAP values, there was a positive association between NDD and pre- or perinatal outcomes, especially, fetal male sex with growth restriction associated the development of NDD in offspring.