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

Abstract

Background: Vitamin D deficiency is linked to adverse childhood health outcomes, yet data on the distribution and quantifiable determinants of neonatal 25-hydroxyvitamin D₃ (25OHD) concentration, a vitamin D biomarker, are limited. Objective: Our aim was to identify determinants of neonatal 25OHD concentration, measured using neonatal dried blood spots (DBS). Methods: A total of 259 ethnically diverse children aged 0-16 years born in Victoria, Australia, were recruited. Data included maternal sun exposure, skin type, 25OHD concentration on stored neonatal DBS, and genotypes at the target genes. Associations were investigated using multiple linear regression models. Results: The median 25OHD concentration was 29.2 nmol/l (IQR 18.0-47.4). Measured 25OHD was <50 nmol/l in almost half of the neonatal sample. Ambient ultraviolet radiation (UVR) 6 weeks before birth was the strongest predictor of neonatal 25OHD, accounting for 23% of its variation. A further 10% was explained by infant genetic variants at GC (rs2282679), the gene encoding the vitamin D binding protein, and DHCR7 (rs12785878), a gene required for synthesis of 7-dehydrocholesterol, a precursor to 25OHD. DBS age explained 7%, and patterns of maternal sun exposure and clothing choices accounted for 4%. A child's skin colour was strongly associated with GC gene variants and not independent of these variants in predicting 25OHD. The final model explained 43% of the total variance in neonatal 25OHD concentration. Conclusion: Maternal lifestyle factors and infant genetic variants predict neonatal 25OHD levels; the importance of maternal UVR exposure in late pregnancy is highlighted.

Environmental and individual predictors of 25-hydroxyvitamin D concentrations in Denmark measured from neonatal dried blood spots: the D-tect study

“…Previous prediction models of maternal or neonatal 25(OH)D concentrations found higher prediction than ours, explaining between 40 (20) and 43 % (25) of the total 25(OH)D variance. This difference might relate to the different variables included in the prediction models, distinct study population characteristics, differences in sample sizes and potentially different analytical methods used.…”

“…In the Danish population, the 25(OH)D risk loci in GC and 25-hydroxylase (CYP2R1) were associated with serum 25(OH) D concentrations (57) ; and in Hungary, selected SNP (NADSYN1, DHCR7, GC, CYP2R1 and CYP24A1) accounted for 13•1 % of the variance of total 25(OH)D levels (58) . In Australia, the study by Smith et al (25) reported that 5•2 % of the predicted variance in neonatal 25(OH)D from DBS could be explained by infant genetic variants GC (rs2282679) and DHCR7 (rs12785878). Therefore, including information on genetic variance would also have most likely improved our model.…”

“…However, currently there is poor understanding regarding the environmental factors or individual (maternal and offspring) characteristics that best contribute to determine neonatal 25(OH)D concentrations. Previous studies describing the determinants of neonatal 25(OH)D were based on either relative small samples <300 individuals or used cord blood 25(OH)D concentration (21,(25)(26)(27)(28)(29)(30) . Only one previous study used 25(OH)D from dried blood spots (DBS) obtained from 259 children (25) .…”

“…Previous studies describing the determinants of neonatal 25(OH)D were based on either relative small samples <300 individuals or used cord blood 25(OH)D concentration (21,(25)(26)(27)(28)(29)(30) . Only one previous study used 25(OH)D from dried blood spots (DBS) obtained from 259 children (25) . Hence, there is a need for large cohort studies based on representative samples of the population using objective measurements of neonatal 25(OH)D. Furthermore, no previous studies have included measured bright sunshine hours and temperature as environmental proxies of 25(OH)D status among neonates.…”

Neonatal vitamin D status in relation to autism spectrum disorder and developmental delay in the CHARGE case–control study

“…Mean neonatal vitamin D concentrations from DBSs in this Northern California population, at 80 nmol/L, were on average higher than mean concentrations previously reported in studies using DBS with similar methods in other populations, including other predominantly Caucasian populations that ranged from 29 to 53 nmol/L [Fernell et al, ; McGrath et al, ; Nielsen et al, ; Smith et al, ; Tornhammar et al, ] (Table S5). Additionally, the percentage that met criteria for vitamin D deficiency (23%) or insufficiency (27%) were much lower than in other populations where the majority met these criteria (Table S5).…”