Abstract

Vitamin D deficiency during pregnancy has been associated with poor foetal growth and neonatal birth anthropometry. However, the associations were inconsistent and could be confounded by neonatal vitamin D status and genetic factors. Until recently, limited studies have concomitantly examined the effect of maternal and neonatal vitamin D deficiency and vitamin D-related single nucleotide polymorphisms (SNPs) on neonatal birth anthropometry. This study aims to examine the independent and combined effects of maternal and neonatal vitamin D deficiency and vitamin-D-related SNPs on neonatal birth anthropometry. This cross-sectional study included 217 mother–neonate dyads recruited from Hospital Serdang, Selangor, Malaysia, between 2015 and 2017. Plasma 25-hydroxyvitamin D (25OHD) concentration was measured in maternal and umbilical cord blood using ultra-high-performance liquid chromatography (UHPLC). Maternal and neonatal vitamin D Receptor (VDR) SNP (rs2228570) genotypes were determined using high-resolution melting (HRM). Group-specific component (GC) SNPs (rs4588 and rs7041) genotypes were determined using restriction fragment length polymorphism. Our results showed that: (1) maternal vitamin D deficiency (25OHD < 30 nmol/L) was inversely associated with birth weight, head circumference and crown–heel length; (2) neonatal SNPs, VDR rs2228570 and GC rs4588, were significantly associated with birth weight and head circumference, respectively; and (3) a potential interaction was observed between maternal VDR rs2228570 with maternal vitamin D deficiency on head circumference. These findings suggest that the underlying mechanisms of vitamin D on foetal growth are likely to be localised in the maternal compartment, mediated through the placenta, rather than through cellular mechanisms within the foetus. Further large-scale studies are warranted to validate and extend these findings.

Highlights

  • Within the paradigm of developmental origins of health and disease, the intrauterine environment plays an important role in programming the risk of disease later in life [1,2]

  • This study showed a consistent pattern effect of vitamin D deficiency and single nucleotide polymorphisms (SNPs) on birth anthropometry: (1) maternal vitamin D deficiency (25OHD

  • We observed consistent maternal, but not neonatal, vitamin D deficiency associations with birth anthropometry. These findings suggest that the putative mechanism of vitamin D on foetal growth might not occur through the local role of vitamin D in the foetus in bone mineralisation

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Summary

Introduction

Within the paradigm of developmental origins of health and disease, the intrauterine environment plays an important role in programming the risk of disease later in life [1,2]. Head circumference and crown–heel length are measurements that are routinely measured and recorded soon after the birth of the newborn. These measurements, the indicators of size at birth, provide important information on the foetal intrauterine nutritional and developmental status [3] and have been associated with morbidity and development of disease later in life [1,2]. Vitamin D deficiency in pregnant women can affect foetal growth and anthropometric parameters at birth

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