Neurosonographic Insights into Maternal Vitamin D Deficiency: Early Markers of Fetal Cortical Development

The aim of this study was to investigate the association between maternal vitamin D status and fetal cortical maturation using detailed neurosonographic assessment at 28-30 weeks of gestation.

This prospective observational study included 422 singleton pregnancies evaluated between 28 and 30 gestational weeks. Maternal serum 25-hydroxyvitamin D [25(OH)D] was measured by chemiluminescence immunoassay and categorized as deficient (<20 ng/mL), insufficient (20-30 ng/mL), or sufficient (>30 ng/mL). Fetal neurosonography was performed with a GE Voluson E8 system to quantify sulcal depths (insula, Sylvian, parieto-occipital, calcarine, and cingulate fissures), corpus callosum thickness, cavum septum pellucidum length, operculization, and cortical maturation grades. Interobserver reliability, correlation, regression, and receiver operating characteristic (ROC) analyses were conducted.

Of 422 women, 280 (66.4%) were vitamin D deficient, 110 (26.1%) insufficient, and 32 (7.6%) sufficient. Deficient participants showed significantly lower mean insula, parieto-occipital, and calcarine fissure depths and thinner corpus callosum (p < 0.05). Operculization and cortical maturation grades were also reduced (p = 0.02 and p = 0.01, respectively). Maternal 25(OH)D levels positively correlated with calcarine fissure depth (r = 0.42, p < 0.001) and cortical maturation grade (r = 0.45, p < 0.001). After adjustment for gestational age, vitamin D deficiency independently predicted low cortical maturation (≤ grade 3) (adjusted OR 2.56, 95% CI: 1.34-4.89, p = 0.004). ROC analysis demonstrated good discriminatory ability (AUC = 0.74, p < 0.001), with an optimal vitamin D threshold of ≈ 21 ng/mL yielding 78% sensitivity and 65% specificity.

Maternal vitamin D deficiency during the late second to early third trimester is associated with delayed fetal cortical sulcation and reduced operculization grades. Quantitative neurosonography can noninvasively identify early neurodevelopmental vulnerability related to suboptimal maternal vitamin D status, supporting the role of adequate vitamin D as a modifiable determinant of fetal brain development. Given the high prevalence of hypovitaminosis D observed in this cohort, assessment of maternal 25(OH)D levels may be justified in high-risk or high-prevalence populations. Based on commonly applied clinical thresholds, supplementation of approximately 600 IU/day for vitamin D-sufficient women, 1,000 IU/day for those with insufficiency, and 1,500-2,000 IU/day for deficient women may be considered.