Abstract
BACKGROUND: Vitamin D and weight status are key determinants for neurodevelopmental outcomes in children. However, their independent and interactive associations with neurodevelopmental outcomes represent a critical yet insufficiently explored issue in pediatric health. OBJECTIVE: This study aims to evaluate the independent associations of vitamin D status and weight status with neurodevelopmental outcomes in a large pediatric cohort and to explore how these relationships are stratified by age and sex. METHODS: This retrospective study analyzed the electronic health records of 19,283 healthy children who visited a health management center in a tertiary children's hospital. Neurodevelopmental outcomes were assessed using the Ages and Stages Questionnaire, Third Edition (ASQ-3) (<6 years) and Conners Parent Rating Scale (CPRS) (≥6 years). Logistic regression analyses were applied to assess the independent and interactive impacts of vitamin D and weight status on neurodevelopmental outcomes. RESULTS: The study included 19,283 children, 10,065 (52.2%) of whom were under 6 years old and 9218 (47.8%) who were between 6 and 18 years old. Among them, 1275 (12.67%) children under 6 were at risk for neurodevelopmental delay, and 1483 (16.09%) children aged between 6 and 18 years had behavioral challenges. Multivariable logistic regression revealed that vitamin D insufficiency/deficiency was significantly associated with suboptimal neurodevelopment in both the younger (odds ratio [OR] 1.48, 95% CI 1.23-1.79; P<.001) and older cohorts (OR 1.56, 95% CI 1.39-1.74; P<.001. A subgroup analysis revealed that vitamin D insufficiency/deficiency significantly increased the risk of neurodevelopmental delay among normal-weight girls under 6 years (OR 2.24, 95% CI 1.60-3.15; P<.001; q<.006) after the Benjamini-Hochberg false discovery rate correction. In the 6-to-18-year-old cohort, similar robust associations with behavioral challenges were observed in normal-weight girls (OR 1.61, 95% CI 1.30-2.00; P<.001; q<.006) and boys (OR 1.64, 95% CI 1.36-1.96; P<.001; q<.006). CONCLUSIONS: Vitamin D insufficiency/deficiency is associated with suboptimal neurodevelopmental outcomes in a sex-dependent manner modulated by weight status, challenging "one-size-fits-all" clinical models. We advocate for stratified, sex-specific screening and personalized pediatric care strategies.