Abstract
BackgroundVitamin 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, 1α,25(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.MethodsAll 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.ResultsMothers 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%.ConclusionsBy 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.
Highlights
Vitamin D insufficiency and deficiency has been associated with a wide spectrum of diseases, ranging from neurological disorders to chronic inflammatory conditions [1]
Thirty-six women were on Ca supplementation and none were on vitamin D supplementation
Maternal predictors of neonatal vitamin D concentrations Based on our primary results, regarding the accurate proportions of vitamin D metabolites in maternal circulation, we further investigated if there is an ability to predict neonatal 25(OH)D concentrations from maternal parameters
Summary
Vitamin D insufficiency and deficiency has been associated with a wide spectrum of diseases, ranging from neurological disorders to chronic inflammatory conditions [1]. The resurgence of rickets in some Western countries highlights the potential risks of not gaining sufficient vitamin D through diet, supplementation or exposure to sunlight [2,3]. Vitamin D deficiency is frequently defined as serum concentrations less than 20 ng/mL with concentrations between 21–29 ng/mL treated as insufficiency and greater than 30 ng/mL as sufficient [4,5,6,7]. Recent studies attest to widespread insufficiency of vitamin D in many Western nations, namely the UK, USA and other European countries, including Greece [5,6,8]. Vitamin D deficiency during pregnancy has been associated with maternal morbidity, including gestational diabetes [9] and an increased rate of caesarean section [10]. 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, 1α,25(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
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