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The association between maternal vitamin D concentrations and birth weight is controversial. We conducted a large-scale retrospective cohort study in southern China to explore this relationship. From July 2017 to April 2019, we enrolled 10,586 pregnant women and measured serum vitamin D [ via  25-hydroxyvitamin D, 25(OH)D] in the second trimester using electrochemiluminescence immunoassays. The association between macrosomia and 25(OH)D was analyzed using logistic regression and ROC curve. Average vitamin D concentration was 61.1 ± 20.2 nmol/L. Additionally, 31.1% participants had 25(OH)D concentrations &lt;50.0 nmol/L, while 68.9% exhibited concentrations ≥50.0 nmol/L. Of the subjects, 3.2% of women delivered macrosomic infants (neonatal birth weight ≥4000 g) and 96.8% did not. The macrosomia group had lower vitamin D concentrations than the non-macrosomia group (59.5 ± 22.3  vs.  61.2 ± 20.1,  p  &lt; .05). Approximately a third of each group had vitamin  D  &lt; 50.0 nmol/L (non-macrosomia, 31.3%; macrosomia, 35.9%;  p  = .055). After adjusting for confounding variables, women with 25(OH) D  ≥ 50.0 nmol/L had 24.3% lower macrosomia risk than women with 25(OH) D  &lt; 50.0 nmol/L (adjusted OR = 0.757, 95% CI = 0.599–0.956,  p  = .0193). The predictive accuracy of vitamin D concentrations for evaluating macrosomia risk was 0.667 area under the ROC curve. Maternal vitamin D levels are negatively correlated with macrosomia. Elevating vitamin D above 50.0 nmol/L may reduce macrosomia incidence.

Second-trimester 25-hydroxyvitamin D status in pregnant women from southern China and risk of macrosomia: a large-scale retrospective cohort study