Diverse Effects of Combinations of Maternal-Neonatal VDR Polymorphisms and 25-Hydroxyvitamin D Concentrations on Neonatal Birth Anthropometry: Functional Phenocopy Variability Dependence, Highlights the Need for Targeted Maternal 25-Hydroxyvitamin D Cut-Offs during Pregnancy.

Vitamin D receptor (VDR) polymorphisms have been associated with a plethora of adverse pregnancy and offspring outcomes. The aim of this study was to evaluate the combined effect of maternal and neonatal VDR polymorphisms (ApaI, TaqI, BsmI, FokI, Tru9I) and different maternal and neonatal 25(OH)D cut-offs on neonatal birth anthropometry. This cross-sectional study included data and samples from a cohort of mother-child pairs at birth. A detailed neonatal anthropometry analysis at birth was also conducted. Different 25(OH)D cut-offs for neonates and mothers were included, according to their vitamin D status at birth: for neonates, cut-offs of [25(OH)D ≤ 25 and > 25 nmol/L] and [25(OH)D ≤ 50 nmol/L] were adopted, whereas for mothers, a 25(OH)D cut-off of [25(OH)D ≤ 50 and > 50 nmol/L)] was investigated. Following this classification, maternal and neonatal VDR polymorphisms were evaluated to investigate the potential different effects of different neonatal and maternal 25(OH)D cut-offs on neonatal birth anthropometry. A total of 69 maternal-neonatal dyads were included in final analysis. Weight, neck rump length, chest circumference, abdominal circumference, abdominal circumference (iliac), high thigh circumference, middle thigh circumference, lower arm radial circumference, and lower leg calf circumference of neonates who had the TAQl SNP TT genotype and maternal 25(OH)D < 50 nmol/L were significantly higher than that of neonates who had the Tt or tt genotypes (p = 0.001, Hg = 1.341, p = 0.036, Hg = 0.976, p = 0.004, Hg = 1.381, p = 0.001, Hg = 1.554, p = 0.001, Hg = 1.351, p = 0.028, Hg = 0.918, p = 0.008, Hg = 1.090, p = 0.002, Hg = 1.217, and p = 0.020, Hg = 1.263, respectively). Skin fold high anterior was significantly lower in neonates who had the BSMI SNP BB genotype compared to that of neonates with Bb or bb genotypes (p = 0.041, Hg = 0.950), whereas neck rump length was significantly higher in neonates who had the FOKI SNP FF genotype compared to that of neonates who had Ff or ff genotypes (p = 0.042, Hg = 1.228). Regarding neonatal VDR polymorphisms and cut-offs, the abdominal circumference (cm) of neonates who had the TAQI SNP TT genotype and 25(OH)D < 25 nmol/L were significantly higher than that of neonates who had the Tt or tt genotypes (p = 0.038, Hg = 1.138). In conclusion, these results indicate that the maternal TAQI VDR polymorphism significantly affected neonatal birth anthropometry when maternal 25(OH) concentrations were <50 nmol/L, but not for a higher cut-off of >50 nmol/L, whereas this effect is minimally evident in the presence of neonatal TAQI polymorphism with neonatal 25(OH)D values <25 nmol/L. The implication of these findings could be incorporated in daily clinical practice by targeting a maternal 25(OH)D cut-off >50 nmol/L, which could be protective against any effect of genetic VDR variance polymorphism on birth anthropometry.