An observational study reveals that neonatal vitamin D is primarily determined by maternal contributions: implications of a new assay on the roles of vitamin D forms

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.

Determinants of Neonatal Vitamin D Levels as Measured on Neonatal Dried Blood Spot Samples

“…Past studies have analysed neonatal 25OHD determinants [8,9]. A study of 60 mother-baby dyads in Greece generated a model predicting 56% of neonatal 25OHD [8].…”

“…A study of 60 mother-baby dyads in Greece generated a model predicting 56% of neonatal 25OHD [8]. Maternal characteristics, including UVB exposure, explained 12.2% of variance, while maternal 25OHD levels and vitamin D epimers accounted for 44%.…”

“…A strong association between circulating maternal and cord blood 25OHD levels is well established [7,8,9], with maternal 25OHD accounting for 70-90% of variation observed in cord blood. No studies have examined the relative contribution of maternal and infant factors, including infant genetic variants, to neonatal 25OHD status.…”

Vitamin D metabolism in the premature newborn: A randomized trial

“…In infants, a 3-epi isomer of 25(OH)D 3 has been identified to occur in concentrations that are significantly elevated as compared to older 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 children and adults [3e7]. This elevation complicates the interpretation of 25(OH)D 3 concentrations as it may be erroneously included in the total 25(OH)D 3 by Liquid Chromatography-Mass Spectrometry methods that are unable to distinguish between the chiral compounds [8,9]. The 3-epimer of 1a,25-(OH) 2 D 3 , the presumed active form of 3-epi-25(OH)D 3 , has been shown to have a lower affinity for the vitamin D receptor than 25(OH)D 3 , suggesting that it's biological activity may be lower [10].…”

Vitamin D epimer: a significant bioregulator or an inactive compound?

“…While previous data indicated that neonatal and infant vitamin D stores are reliant from maternal ones [3], routine accurate measurement of epimers could overcome the technical flaws provoked by the presence of a significant percentage of epimers as a fraction of total vitamin D levels.…”