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• The study investigated maternal and neonatal determinants of neonatal vitamin D deificiency. • A total of 129 mother-neonates pairs from Northern Greece were classified according neonatal vitamin D status at birth. • Risk of neonatal deficiency was 6.89 increased for neonates of vitamin D deficient (<50 nmol/l) mothers. • Use of alcohol during pregnancy was associated with a 5.5-fold higher risk for neonatal hypovitaminosis D. Absence of adequate maternal vitamin D supplementation and decreased maternal ultraviolet exposure during pregnancy are key determinants for the manifestation of neonatal hypovitaminosis D at birth. These parameters may vary, according to country-specific dietary patterns, health policies and sunshine exposure. We aimed to investigate differences in calcium metabolism and anthropometric profiles according to neonatal vitamin D status at birth, in a sunny region of Northern Greece. A secondary aim was to identify maternal parameters as risk factors for developing neonatal vitamin D deficiency at birth. A total of 129 mother-neonate pairs were included in the study and classified into three groups, according to neonatal 25-hydroxy-D [25(OH)D)] concentrations at birth [deficiency (<30 nmol/l), insufficiency (30−50 nmol/l) and sufficiency (>50 nmol/l)]. Neonatal biochemical and anthropometric profiles and maternal demographic, social, dietary and biochemical profiles were comparatively evaluated between the three groups. Univariate and multivariate logistic regression was performed to identify independent associations of maternal factors with neonatal vitamin D status. Vitamin D deficient-neonates manifested higher parathyroid hormone (7.20 ± 2.60 vs 5.50 ± 1.50 pg/ml, p = 0.01) and lower corrected calcium (10.70 ± 0.70 vs 11.30 ± 1.30 mg/dl, p = 0.02) concentrations compared with vitamin d -insufficient neonates. Mothers of vitamin D deficient and insufficient neonates had a lower total of 25(OH)D (31.7 ± 19.2 and 36.5 ± 22.3 vs 53.3 ± 39.0 nmol/l, p < 0.01) and 25(OH)D 3 (27.4 ± 17.5 and 33.3 ± 19.9 vs 47.3 ± 36.7 nmol/l, p < 0.01 and p = 0.04, respectively) concentrations respectively, compared with those of vitamin D-sufficient neonates. Maternal use of alcohol during pregnancy was associated with a 5.57-fold higher risk for neonatal vitamin D deficiency at birth (OR 5.57, 95 % CI1.17–26.56, p = 0.03). Newborns with vitamin D deficiency presented a 6.89-fold higher risk of having been given birth by vitamin D deficient mothers (OR 6.89, 95 % CI 3.09–15.38, p < 0.01). In conclusion, neonatal vitamin D deficiency is associated with maternal 25(OH)D concentrations at birth and maternal alcohol use. Further studies are required to replicate these findings in other regions and populations. [ABSTRACT FROM AUTHOR]

Background: Vitamin D concentrations during pregnancy are measured to diagnose states of insufficiency or deficiency. The aim of this study is to apply accurate assays of vitamin D forms [single- hydroxylated [25(OH)D₂, 25(OH)D₃], double-hydroxylated [1α,25(OH)₂D₂, 1a25(OH)₂D₃], epimers [3-epi-25(OH)D₂, 3-epi-25(OH)D₃] in mothers (serum) and neonates (umbilical cord) to i) explore maternal and neonatal vitamin D biodynamics and ii) to identify maternal predictors of neonatal vitamin D concentrations., Methods: All vitamin D forms were quantified in 60 mother- neonate paired samples by a novel liquid chromatography -mass spectrometry (LC-MS/MS) assay. Maternal characteristics [age, ultraviolet B exposure, dietary vitamin D intake, calcium, phosphorus and parathyroid hormone] were recorded. Hierarchical linear regression was used to predict neonatal 25(OH)D concentrations., Results: Mothers had similar concentrations of 25(OH)D₂ and 25(OH)D₃ forms compared to neonates (17.9 ± 13.2 vs. 15.9 ± 13.6 ng/mL, p=0.289) with a ratio of 1:3. The epimer concentrations, which contribute approximately 25% to the total vitamin D levels, were similar in mothers and neonates (4.8 ± 7.8 vs. 4.5 ± 4.7 ng/mL, p=0.556). No correlation was observed in mothers between the levels of the circulating form (25OHD₃) and its active form. Neonatal 25(OH)D₂ was best predicted by maternal characteristics, whereas 25(OH)D₃ was strongly associated to maternal vitamin D forms (R²=0.253 vs. 0.076 and R2=0.109 vs. 0.478, respectively). Maternal characteristics explained 12.2% of the neonatal 25(OH)D, maternal 25(OH)D concentrations explained 32.1%, while epimers contributed an additional 11.9%., Conclusions: By applying a novel highly specific vitamin D assay, the present study is the first to quantify 3-epi-25(OH)D concentrations in mother-newborn pairs. This accurate assay highlights a considerable proportion of vitamin D exists as epimers and a lack of correlation between the circulating and active forms. These results highlight the need for accurate measurements to appraise vitamin D status. Maternal characteristics and circulating forms of vitamin D, along with their epimers explain 56% of neonate vitamin D concentrations. The roles of active and epimer forms in the maternal-neonatal vitamin D relationship warrant further investigation.