ESPE Abstracts (2021) 94 FC7.2

ESPE2021 Free Communications Fetal Endocrinology and Multisystem Disorders (6 abstracts)

Maternal, rather than fetal, genetic variation in vitamin D metabolism is associated with umbilical cord blood 25-hydroxyvitamin D in pregnancies supplemented with cholecalciferol: findings from the MAVIDOS randomized controlled trial

Rebecca Moon 1,2 , Stefania D’Angelo 1 , Elizabeth Curtis 1 , Laura Cooke 3 , Justin Davies 2 , Sarah Crozier 1 , Keith Godfrey 1,4 , Nikki Graham 3 , John Holloway 3 , Rohan Lewis 3 , Jane Cleal 3 , Hazel Inskip 1,4 & Cyrus Cooper 1,4,5

1MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, United Kingdom.;2Paediatric Endocrinology, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.;3Human Health and Development, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.;4NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.;5NIHR Biomedical Research Centre, University of Oxford, Oxford, United Kingdom

Background: Neonatal vitamin D deficiency (VDD) can result in symptomatic hypocalcemia, seizures and cardiomyopathy and has been associated with reduced bone mineralization in childhood, but is potentially preventable with antenatal cholecalciferol supplementation. Single nucleotide polymorphisms (SNP) in the vitamin D metabolism pathway are associated with serum 25-hydroxyvitamin D [25(OH)D] in adulthood. We assessed whether maternal and/or offspring SNPs in DHCR7 (7-dehydrocholesterol reductase), CYP2R1 (25-hydroxylase), CYP24A1 (24-hydroxylase), and GC (vitamin D binding protein [DBP]) are associated with umbilical cord blood (UCB) 25(OH)D, and if antenatal vitamin D supplementation modifies the relationships.

Methods: MAVIDOS is a randomized placebo-controlled trial of 1000 IU/day cholecalciferol from 14 weeks gestation until delivery. UCB 25(OH)D was measured by tandem mass spectrometry. Maternal and offspring SNPs at rs12785878 (DHCR7), rs10741657 (CYP2R1), rs6013897 (CYP24A1), and rs2282679 (GC) were genotyped. Associations between de-seasonalized UCB 25(OH)D (generated by Fourier analysis) and the SNPs were assessed by linear regression for each treatment group using an additive model. β is the change in 25(OH)D per additional common allele. Models were adjusted for maternal age, triceps skinfold thickness and smoking in late pregnancy to increase precision as these were identified as associated with UCB 25(OH)D.

Results: 329 mother-offspring pairs were included (185 placebo; 165 cholecalciferol). UCB 25(OH)D was higher in the intervention group (mean 42.3 nmol/l; SD 13.1) than the placebo group (mean 28.6 nmol/l; SD 12.1), P < 0.001. In the cholecalciferol group, the maternal SNP at rs2282679 (GC) was associated with UCB 25(OH)D (β=4.2 nmol/l per allele; 95%CI 1.0, 7.3). The effect size of this SNP in the placebo group was smaller (β=1.9 nmol/l per allele; 95%CI -0.6, 4.4). The other maternal SNPs and offspring SNPs were not associated with UCB 25(OH)D in either group.

Conclusion: Maternal, rather than offspring, genetic variation in GC, encoding DBP, is associated with fetal 25(OH)D. The effect was larger in pregnancies supplemented with cholecalciferol, suggesting the SNP modifies vitamin D status when 25(OH)D is more readily available. This could be due to an effect of the SNP on DBP concentration or binding affinity. Future work needs to establish the effect variation at rs2282679 on DBP levels in pregnancy and the role of maternal DBP in the transport of 25(OH)D to and across the placenta.

Volume 94

59th Annual ESPE (ESPE 2021 Online)

22 Sep 2021 - 26 Sep 2021

European Society for Paediatric Endocrinology 

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