Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Pregnancy and Childbirth
Published in: BMC Pregnancy and Childbirth 1/2020

Open Access 01-12-2020 | Vitamin D Deficiency | Research article

Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women

Authors: Siew-Siew Lee, King-Hwa Ling, Maiza Tusimin, Raman Subramaniam, Kartini Farah Rahim, Su-Peng Loh

Published in: BMC Pregnancy and Childbirth | Issue 1/2020

Login to get access

Abstract

Background

Vitamin D deficiency (VDD) has been related to vitamin D binding protein (GC) gene polymorphism, demographics and lifestyle factors in different populations. However, previous studies only focused on demographic and lifestyle factors or genetic factors alone. Therefore, this cross-sectional study aimed to assess the association between GC gene polymorphism, demographics and lifestyle factors with VDD among Malaysian pregnant women.

Method

Information on demographic characteristics, dietary vitamin D intake from supplement and food, time spent outdoors, skin type and clothing were collected using a questionnaire. Plasma total 25-hydroxyvitamin D (25OHD) levels were measured using an Ultra-High-Performance Liquid Chromatography (UHPLC). Maternal GC single nucleotide polymorphisms (SNPs) (rs4588 and rs7041) were determined using restriction fragment length polymorphism (RFLP) technique.

Results

Results showed that 50.2% of pregnant women were vitamin D deficient (25OHD < 30 nmol/L). VDD (25OHD < 30 nmol/L) was significantly associated with age, veiled clothing, maternal vitamin D intakes from both food and supplements, and GC rs7041(and GC diplotypes). In contrast to previous studies that reported for non-pregnant population, a significant positive association was found between CC genotype for SNP GC rs7041, GC 1s–1s and GC If-2 with risk of VDD (25OHD < 30 nmol/L).

Conclusions

The high prevalence of maternal VDD found in this study suggests the need for urgent development and implementation of vitamin D supplementation or fortification strategies to reduce VDD among pregnant women. The discrepancy in the association between GC rs7041 gene polymorphism and VDD reflects the variation in the factors associated with VDD in pregnancy compared to non-pregnant state.
Appendix
Available only for authorised users
Literature
1.
2.
Ankana G, Jennifer AT, Sarah F-S, Shiao YC, Melissa W, Janesh G, Mark DK, Stephane RG, Martin H. Vitamin D, the placenta and early pregnancy: effects on trophoblast function. J Endocrinol. 2018;236(2):R93–R103.CrossRef
3.
Karras SN, Wagner CL, Castracane VD. Understanding vitamin D metabolism in pregnancy: from physiology to pathophysiology and clinical outcomes. Metab Clin Exp. 2018;86:112–23.PubMedCrossRef
4.
Hypponen E, Cavadino A, Williams D, Fraser A, Vereczkey A, Fraser WD, Banhidy F, Lawlor D, Czeizel AE. Vitamin D and pre-eclampsia: original data, systematic review and meta-analysis. Ann Nutr Metab. 2013;63(4):331–40.PubMedCrossRef
5.
Kiely ME, Zhang JY, Kinsella M, Khashan AS, Kenny LC. Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status. Am J Clin Nutr. 2016;104(2):354–61.PubMedCrossRef
6.
Wilson RL, Leviton AJ, Leemaqz SY, Anderson PH, Grieger JA, Grzeskowiak LE, Verburg PE, McCowan L, Dekker GA, Bianco-Miotto T, et al. Vitamin D levels in an Australian and New Zealand cohort and the association with pregnancy outcome. BMC Pregnancy Childbirth. 2018;18(1):251.PubMedPubMedCentralCrossRef
7.
Chen Y-H, Fu L, Hao J-H, Yu Z, Zhu P, Wang H, Xu Y-Y, Zhang C, Tao F-B, Xu D-X. Maternal vitamin D deficiency during pregnancy elevates the risks of small for gestational age and low birth weight infants in Chinese population. J Clin Endocrinol Metab. 2015;100(5):1912–9.PubMedCrossRef
8.
Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, Marazita ML, Simhan HN. Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr. 2010;140(5):999–1006.PubMedPubMedCentralCrossRef
9.
Qin LL, Lu FG, Yang SH, Xu HL, Luo BA. Does maternal vitamin D deficiency increase the risk of preterm birth: a meta-analysis of observational studies. Nutrients. 2016;8(5):301.PubMedCentralCrossRef
10.
Saraf R, Morton SMB, Camargo CA, Grant CC. Global summary of maternal and newborn vitamin D status – a systematic review. Maternal Child Nutr. 2016;12(4):647–68.CrossRef
11.
Rodriguez A, Santa Marina L, Jimenez AM, Esplugues A, Ballester F, Espada M, Sunyer J, Morales E. Vitamin D status in pregnancy and determinants in a southern European cohort study. Paediatr Perinat Epidemiol. 2016;30(3):217–28.PubMedCrossRef
12.
Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, Osmond C, Veena SR, Fall CH. Vitamin D insufficiency is common in Indian mothers but is not associated with gestational diabetes or variation in newborn size. Eur J Clin Nutr. 2009;63(5):646–52.PubMedCrossRef
13.
Ariyawatkul K, Lersbuasin P. Prevalence of vitamin D deficiency in cord blood of newborns and the association with maternal vitamin D status. Eur J Pediatr. 2018;177(10):1541–5.PubMedCrossRef
14.
Pratumvinit B, Wongkrajang P, Wataganara T, Hanyongyuth S, Nimmannit A, Chatsiricharoenkul S, Manonukul K, Reesukumal K. Maternal vitamin D status and its related factors in pregnant women in Bangkok, Thailand. PloS One. 2015;10(7):e0131126.PubMedPubMedCentralCrossRef
15.
Bukhary NBI, Isa ZM, Shamsuddin K, Lin KG, Mahdy ZA, Hassan H, Yeop NSH. Risk factors for antenatal hypovitaminosis D in an urban district in Malaysia. BMC Pregnancy Childbirth. 2016;16(1):156.PubMedPubMedCentralCrossRef
16.
Public Health England: PHE publishes new advice on vitamin D. 2016.
17.
Health Council of the Netherlands. Evaluation of dietary reference values for vitamin D. The Hague: Health Council of the Netherlands; 2012.
18.
Hossein-nezhad A, Holick MF. Vitamin D for health: a global perspective. Mayo Clin Proc. 2013;88(7):720–55.PubMedCrossRef
19.
Ahn J, Yu K, Stolzenberg-Solomon R, Simon KC, McCullough ML, Gallicchio L, Jacobs EJ, Ascherio A, Helzlsouer K, Jacobs KB, et al. Genome-wide association study of circulating vitamin D levels. Hum Mol Genet. 2010;19(13):2739–45.PubMedPubMedCentralCrossRef
20.
Wang TJ, Zhang F, Richards JB, Kestenbaum B, van Meurs JB, Berry D, Kiel DP, Streeten EA, Ohlsson C, Koller DL, et al. Common genetic determinants of vitamin D insufficiency: a genome-wide association study. Lancet. 2010;376(9736):180–8.PubMedPubMedCentralCrossRef
21.
Lucas RM, Ponsonby AL, Dear K, Valery PC, Taylor B, van der Mei I, McMichael AJ, Pender MP, Chapman C, Coulthard A, et al. Vitamin D status: multifactorial contribution of environment, genes and other factors in healthy Australian adults across a latitude gradient. J Steroid Biochem Mol Biol. 2013;136:300–8.PubMedCrossRef
22.
Suaini NHA, Koplin JJ, Ellis JA, Peters RL, Ponsonby A-L, Dharmage SC, Matheson MC, Wake M, Panjari M, Tan H-TT, et al. Environmental and genetic determinants of vitamin D insufficiency in 12-month-old infants. J Steroid Biochem Mol Biol. 2014;144:445–54.PubMedCrossRef
23.
Jan Mohamed HJ, Rowan A, Fong B, Loy S-L. Maternal serum and breast milk vitamin D levels: findings from the Universiti Sains Malaysia pregnancy cohort study. PLoS One. 2014;9(7):e100705.PubMedPubMedCentralCrossRef
24.
Lee CL, Ng BK, Wu LL, Cheah FC, Othman H, Ismail NAM. Vitamin D deficiency in pregnancy at term: risk factors and pregnancy outcomes. Horm Mol Biol Clin Invest. 2017;31(3): 20170005.
25.
Baca KM, Govil M, Zmuda JM, Simhan HN, Marazita ML, Bodnar LM. Vitamin D metabolic loci and vitamin D status in black and white pregnant women. Eur J Obstet Gynecol Reprod Biol. 2018;220:61–8.PubMedCrossRef
26.
Ganz AB, Park H, Malysheva OV, Caudill MA. Vitamin D binding protein rs7041 genotype alters vitamin D metabolism in pregnant women. FASEB J. 2018;32(4):2012–20.PubMedPubMedCentralCrossRef
27.
Tapia G, Mårild K, Stene LC, Haugen M, Størdal K, Cohen AS, Lie BA. Fetal and maternal genetic variants influencing neonatal vitamin D status. J Clin Endocrinol Metab. 2017;102(11):4072–9.PubMedPubMedCentralCrossRef
28.
Anwar S, Iqbal MP, Azam I, Habib A, Bhutta S, Soofi SB, Bhutta ZA. Urban and rural comparison of vitamin D status in Pakistani pregnant women and neonates. J Obstet Gynaecol. 2016;36(3):318–23.PubMedCrossRef
29.
Jolliffe DA, Walton RT, Griffiths CJ, Martineau AR. Single nucleotide polymorphisms in the vitamin D pathway associating with circulating concentrations of vitamin D metabolites and non-skeletal health outcomes: review of genetic association studies. J Steroid Biochem Mol Biol. 2016;164:18–29.PubMedCrossRef
30.
Gozdzik A, Zhu J, Wong BYL, Fu L, Cole DEC, Parra EJ. Association of vitamin D binding protein (VDBP) polymorphisms and serum 25(OH)D concentrations in a sample of young Canadian adults of different ancestry. J Steroid Biochem Mol Biol. 2011;127(3):405–12.PubMedCrossRef
31.
Arnaud J, Constans J. Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993;92(2):183–8.PubMedCrossRef
32.
Boutin B, Galbraith RM, Arnaud P. Comparative affinity of the major genetic variants of human group-specific component (vitamin D-binding protein) for 25-(OH) vitamin D. J Steroid Biochem. 1989;32(1a):59–63.PubMedCrossRef
33.
Lauridsen AL, Vestergaard P, Hermann AP, Brot C, Heickendorff L, Mosekilde L, Nexo E. Plasma concentrations of 25-hydroxy-vitamin D and 1,25-dihydroxy-vitamin D are related to the phenotype of Gc (vitamin D-binding protein): a cross-sectional study on 595 early postmenopausal women. Calcif Tissue Int. 2005;77(1):15–22.PubMedCrossRef
34.
Carpenter TO, Zhang JH, Parra E, Ellis BK, Simpson C, Lee WM, Balko J, Fu L, Wong BYL, Cole DEC. Vitamin D binding protein is a key determinant of 25-hydroxyvitamin D levels in infants and toddlers. J Bone Miner Res. 2013;28(1):213–21.PubMedCrossRef
35.
Bikle D, Gee E, Halloran B, Haddad JG. Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. J Clin Invest. 1984;74(6):1966–71.PubMedPubMedCentralCrossRef
36.
Daniel WW. Biostatistics: A Foundation for Analysis in The Health Sciences 7th edition. New York: John Wiley & Sons; 1999.
37.
Hall LM, Kimlin MG, Aronov PA, Hammock BD, Slusser JR, Woodhouse LR, Stephensen CB. Vitamin D intake needed to maintain target serum 25-hydroxyvitamin D concentrations in participants with low sun exposure and dark skin pigmentation is substantially higher than current recommendations. J Nutr. 2010;140(3):542–50.PubMedPubMedCentralCrossRef
38.
Jamil NA, Yew MH, Noor Hafizah Y, Gray SR, Poh BK, Macdonald HM. Estimated vitamin D synthesis and dietary vitamin D intake among Asians in two distinct geographical locations (Kuala Lumpur, 3°N v. Aberdeen, 57°N) and climates. Public Health Nutr. 2018; 21(17):3118-24.
39.
Fitzpatrick TB. The validity and practicality of sun-reactive skin types I through VI. Arch Dermatol. 1988;124(6):869–71.PubMedCrossRef
40.
Cabaset S, Krieger J-P, Richard A, Elgizouli M, Nieters A, Rohrmann S, Quack Lötscher KC. Vitamin D status and its determinants in healthy pregnant women living in Switzerland in the first trimester of pregnancy. BMC Pregnancy Childbirth. 2019;19(1):10.PubMedPubMedCentralCrossRef
41.
Zaleha MI, Khadijah S, Bukhary N, Khor GL, Zaleha AM, Haslinda H, Hana NS, Hasanain Faisal G. Development and validation of a food frequency Questionaire for vitamin D intake among urban pregnant women in Malaysia. Malaysia J Nutr. 2015;21(2):179–90.
42.
Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington: The National Academies Press; 2011.
43.
John W. Graham. Missing Data Analysis: Making It Work in the Real World. Annual Review of Psychology 2009;60(1):549-76.
44.
Lee S-S, Loh SP, Subramaniam R, Tusimin M, Ling K-H, Farah K. Association of maternal and cord plasma total, free and bioavailable 25-Hyrodroxyvitamin D with neonatal anthropometric measurements at birth: a preliminary study in a private hospital. Malaysian J Med Health Sci. 2020;16(1):24-31.
45.
Kiely M, O'Donovan SM, Kenny LC, Hourihane JO, Irvine AD, Murray DM. Vitamin D metabolite concentrations in umbilical cord blood serum and associations with clinical characteristics in a large prospective mother-infant cohort in Ireland. J Steroid Biochem Mol Biol. 2017;167:162–8.PubMedCrossRef
46.
Wuertz C, Gilbert P, Baier W, Kunz C. Cross-sectional study of factors that influence the 25-hydroxyvitamin D status in pregnant women and in cord blood in Germany. Br J Nutr. 2013;110(10):1895–902.PubMedCrossRef
47.
Yun C, Chen J, He Y, Mao D, Wang R, Zhang Y, Yang C, Piao J, Yang X. Vitamin D deficiency prevalence and risk factors among pregnant Chinese women. Public Health Nutr. 2015;20(10):1746–54.PubMedCrossRef
48.
Kanatani KT, Nakayama T, Adachi Y, Hamazaki K, Onishi K, Konishi Y, Kawanishi Y, Go T, Sato K, Kurozawa Y, et al. High frequency of vitamin D deficiency in current pregnant Japanese women associated with UV avoidance and hypo-vitamin D diet. PLoS One. 2019;14(3):e0213264.PubMedPubMedCentralCrossRef
49.
Karras S, Paschou SA, Kandaraki E, Anagnostis P, Annweiler C, Tarlatzis BC, Hollis BW, Grant WB, Goulis DG. Hypovitaminosis D in pregnancy in the Mediterranean region: a systematic review. Eur J Clin Nutr. 2016;70(9):979–86.PubMedCrossRef
50.
Al-Musharaf S, Fouda MA, Turkestani IZ, Al-Ajlan A, Sabico S, Alnaami AM, Wani K, Hussain SD, Alraqebah B, Al-Serehi A, et al. Vitamin D deficiency prevalence and predictors in early pregnancy among Arab women. Nutrients. 2018;10(4):489.PubMedCentralCrossRef
51.
Brembeck P, Winkvist A, Olausson H. Determinants of vitamin D status in pregnant fair-skinned women in Sweden. Br J Nutr. 2013;110(5):856–64.PubMedCrossRef
52.
Bärebring L, Schoenmakers I, Glantz A, Hulthén L, Jagner Å, Ellis J, Bärebring M, Bullarbo M, Augustin H. Vitamin D status during pregnancy in a multi-ethnic population-representative Swedish cohort. Nutrients. 2016;8(10):655.PubMedCentralCrossRef
53.
Wierzejska R, Jarosz M, Klemińska-Nowak M, Tomaszewska M, Sawicki W, Bachanek M, Siuba-Strzelińska M. Maternal and cord blood vitamin D status and anthropometric measurements in term newborns at birth. Front Endocrinol. 2018;9:9.CrossRef
54.
Vinkhuyzen AAE, Eyles DW, Burne TH, Blanken LME, Kruithof CJ, Verhulst F, Jaddoe VW, Tiemeier H, McGrath JJ. Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: the generation R study. J Steroid Biochem Mol Biol. 2016;164:161–7.PubMedCrossRef
55.
Krieger J-P, Cabaset S, Canonica C, Christoffel L, Richard A, Schröder T, von Wattenwyl BL, Rohrmann S, Lötscher KQ. Prevalence and determinants of vitamin D deficiency in the third trimester of pregnancy: a multicentre study in Switzerland. Br J Nutr. 2018;119(3):299–309.PubMedCrossRef
56.
Dovnik A, Mujezinovic F, Treiber M, Pecovnik Balon B, Gorenjak M, Maver U, Takac I. Determinants of maternal vitamin D concentrations in Slovenia : a prospective observational study. Wien Klin Wochenschr. 2017;129(1–2):21–8.PubMedCrossRef
57.
Barebring L, Bullarbo M, Glantz A, Hulthen L, Ellis J, Jagner A, Schoenmakers I, Winkvist A, Augustin H. Trajectory of vitamin D status during pregnancy in relation to neonatal birth size and fetal survival: a prospective cohort study. BMC Pregnancy Childbirth. 2018;18(1):51.PubMedPubMedCentralCrossRef
58.
Shao B, Jiang S, Muyiduli X, Wang S, Mo M, Li M, Wang Z, Yu Y. Vitamin D pathway gene polymorphisms influenced vitamin D level among pregnant women. Clin Nutr. 2018;37(6, Part A):2230–7.PubMedCrossRef
Metadata
Title
Influence of vitamin D binding protein polymorphism, demographics and lifestyle factors on vitamin D status of healthy Malaysian pregnant women
Authors
Siew-Siew Lee
King-Hwa Ling
Maiza Tusimin
Raman Subramaniam
Kartini Farah Rahim
Su-Peng Loh
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Pregnancy and Childbirth / Issue 1/2020
Electronic ISSN: 1471-2393
DOI
https://doi.org/10.1186/s12884-020-03397-7

Other articles of this Issue 1/2020

BMC Pregnancy and Childbirth 1/2020 Go to the issue

Research article

The joint effect of maternal smoking during pregnancy and maternal pre-pregnancy overweight on infants’ term birth weight

Research article

Facility readiness and counseling during antenatal care and the relationship with early breastfeeding in Haiti and Malawi

Research article

Adherence to iron-folic acid supplementation among pregnant women in Ethiopia: a systematic review and meta-analysis

Research article

Socioeconomic risk factors for labour induction in the United Kingdom

Research article

Cost-effectiveness evidence for strategies to promote or support breastfeeding: a systematic search and narrative literature review

Research article

Influence of pacifier use on the association between duration of breastfeeding and anterior open bite in primary dentition