Citation
Lee, Siew Siew
(2019)
Maternal and neonatal vitamin D deficiency, vitamin D-related gene polymorphism and birth outcomes.
Doctoral thesis, Universiti Putra Malaysia.
Abstract
Epidemiology data have shown widespread vitamin D deficiency in several
populations. However, up to date, data on vitamin D status of women and neonates
living in Malaysia is scarce to inform the development of national recommendation
for vitamin D supplementation for pregnant women and newborns. In addition, the
associations between low maternal and cord 25-hydroxyvitamin D (25OHD) with size
at birth is inconsistent, and the plausible mechanisms of action of vitamin D on fetal
growth have remained unexplored. Therefore, this study aims to determine the
prevalence of vitamin D deficiency in pregnant women and newborns at delivery as
well as factors associated with the deficiency. At the same time, this study also sought
to investigate the associations between maternal and cord total vitamin D deficiency,
and vitamin D polymorphism with birth outcomes concomitantly.
Healthy pregnant women and neonates (217 dyads) were recruited from Hospital
Serdang, Selangor, Malaysia. Venous blood was collected from pregnant mothers
before delivery. Umbilical cord blood was collected from the severed umbilical cord
after the delivery of the baby but before the delivery of the placenta. Maternal and cord
total 25OHD levels were measured by using a validated ultra-high-performance liquid
chromatography (UHPLC) method. Vitamin D Receptor (VDR) polymorphism
(rs2228570) was determined using High-Resolution Melting (HRM), while Group-
Specific component (GC) polymorphisms (rs4588 and rs7041) were determined using
restriction fragment length polymorphism (RFLP).
The result showed that the median maternal total 25OHD was 29.8 nmol/L
(Interquartile Range [IQR] 18.8-43.5 nmol/L), with 50.2% of pregnant women had
vitamin D deficiency (25OHD <30 nmol/L). Multivariate analysis showed that the risk
factors of maternal vitamin D deficiency (25OHD <30nmol/L) were age, veiled
clothing, homozygous mutant for GC rs7041. On the other hands, the protective factors
for maternal vitamin D deficiency were vitamin D intake from food and supplements.
The median cord total 25OHD was 22.0 nmol/L (IQR 15.5-31.0 nmol/L), which 71.4%
of newborns had vitamin D deficiency (25OHD <30 nmol/L). Consistent with the
previous studies, maternal status was the best predictor of neonatal vitamin D
deficiency (25OHD < 30nmol/L). In the present study, neonates born from a mother
with vitamin D deficiency had eight times higher risk of deficiency. Moreover, factors
that independently associated with neonatal vitamin D deficiency were nulliparous,
vitamin D supplements, maternal vitamin D binding protein level, and maternal VDR
rs2228570.
In addition, the analysis showed that maternal but not cord vitamin D deficiency was
inversely associated with birth weight, head circumference, and length at birth. In
contrast, cord but not maternal VDR rs2228570 was significantly associated with birth
weight. Additionally, cord but not maternal GC rs4588 was significantly associated
with the head circumference. A potential interaction effect between maternal VDR
rs2228570 SNP and maternal vitamin D deficiency on head circumference was
observed.
In conclusion, a high prevalence of maternal and cord vitamin D deficiency was
observed in this study. The analysis of factors associated with vitamin D deficiency
supports supplementation as a potential strategy to decrease the risk of deficiency. The
current work also consistently showed that maternal but not cord vitamin D deficiency
was associated with the birth outcomes. In contrast, cord but not maternal SNPs were
associated with several of the birth outcomes.
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