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
Maternal and Child Health Journal
Published in: Maternal and Child Health Journal 1/2015

01-01-2015

Maternal–Fetal Impact of Vitamin D Deficiency: A Critical Review

Authors: Letícia Schwerz Weinert, Sandra Pinho Silveiro

Published in: Maternal and Child Health Journal | Issue 1/2015

Login to get access

Abstract

Research into the extra-skeletal functions of vitamin D has been expanding in recent years. During pregnancy, maternal vitamin D status may be of concern because of the key role of this vitamin in fetal skeletal development and due to the association between hypovitaminosis D and adverse maternal–fetal outcomes. Therefore, the objective of this manuscript was to review the maternal–fetal impact of gestational vitamin D deficiency and the benefits of vitamin D supplementation during pregnancy. A literature search was performed in PubMed and Embase employing the following keywords: vitamin D deficiency, pregnancy, 25-hydroxyvitamin D, and hypovitaminosis D. All relevant articles in English language published since 1980 were analysed by the two authors. Neonatal complications derived from vitamin D deficiency include low birth weight, growth restriction, and respiratory tract infection. In the mother, vitamin D deficiency has been associated with altered glucose homeostasis and increased incidence of gestational diabetes mellitus, pre-eclampsia, and bacterial vaginosis. However, the current state of the evidence is controversial for some other endpoints and the actual benefit of vitamin D supplementation in pregnancy remains unclear. Additional longitudinal studies may clarify the actual impact of vitamin D deficiency during pregnancy, and randomised trials are required to define the benefits of vitamin D supplementation in reducing the incidence of adverse outcomes in the mother and infant.
Literature
1.
Wolden-Kirk, H., Gysemans, C., Verstuyf, A., et al. (2012). Extraskeletal effects of vitamin D. Endocrinology and Metabolism Clinics of North America, 41(3), 571–594.PubMedCrossRef
2.
Holick, M. F. (2007). Vitamin D deficiency. The New England Journal of Medicine, 357(3), 266–281.PubMedCrossRef
3.
Principi, N., Bianchini, S., Baggi, E., et al. (2013). Implications of maternal vitamin D deficiency for the fetus, the neonate and the young infant. European Journal of Nutrition, 52(3), 859–867.PubMedCrossRef
4.
Walsh, J. M., Kilbane, M., McGowan, C. A., et al. (2013). Pregnancy in dark winters: Implications for fetal bone growth? Fertility and Sterility, 99(1), 206–211.PubMedCrossRef
5.
Aghajafari, F., Nagulesapillai, T., Ronksley, P. E., et al. (2013). Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: Systematic review and meta-analysis of observational studies. BMJ: British Medical Journal, 346, f1169.PubMedCrossRef
6.
Holick, M. F., Binkley, N. C., Bischoff-Ferrari, H. A., et al. (2011). Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline. The Journal of Clinical Endocrinology and Metabolism, 96(7), 1911–1930.PubMedCrossRef
7.
Jones, G., Strugnell, S. A., & DeLuca, H. F. (1998). Current understanding of the molecular actions of vitamin D. Physiological Reviews, 78(4), 1193–1231.PubMed
8.
9.
10.
Wortsman, J., Matsuoka, L. Y., Chen, T. C., et al. (2000). Decreased bioavailability of vitamin D in obesity. The American Journal of Clinical Nutrition, 72(3), 690–693.PubMed
11.
Premaor, M. O., Paludo, P., Manica, D., et al. (2008). Hypovitaminosis D and secondary hyperparathyroidism in resident physicians of a general hospital in southern Brazil. Journal of Endocrinological Investigation, 31(11), 991–995.PubMedCrossRef
12.
Holick, M. F., & Vitamin, D. (2013). Sunlight and cancer connection. Anti-Cancer Agents in Medicinal Chemistry, 13(1), 70–82.PubMedCrossRef
13.
Afzal, S., Bojesen, S. E., & Nordestgaard, B. G. (2013). Low 25-hydroxyvitamin D and risk of type 2 diabetes: A prospective cohort study and meta-analysis. Clinical Chemistry, 59(2), 381–391.PubMedCrossRef
14.
Dobnig, H., Pilz, S., Scharnagl, H., et al. (2008). Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Archives of Internal Medicine, 168(12), 1340–1349.PubMedCrossRef
15.
Bikle, D. D., Gee, E., Halloran, B., et al. (1984). Free 1,25-dihydroxyvitamin D levels in serum from normal subjects, pregnant subjects, and subjects with liver disease. The Journal of Clinical Investigation, 74(6), 1966–1971.PubMedCentralPubMedCrossRef
16.
Kovacs, C. S. (2005). Calcium and bone metabolism during pregnancy and lactation. Journal of Mammary Gland Biology and Neoplasia, 10(2), 105–118.PubMedCrossRef
17.
McAree, T., Jacobs, B., Manickavasagar, T., et al. (2013). Vitamin D deficiency in pregnancy—Still a public health issue. Maternal and Child Nutrition, 9(1), 23–30.PubMedCrossRef
18.
Gernand, A. D., Simhan, H. N., Klebanoff, M. A., et al. (2013). Maternal serum 25-hydroxyvitamin D and measures of newborn and placental weight in a U.S. multicenter cohort study. The Journal of Clinical Endocrinology and Metabolism, 98(1), 398–404.PubMedCentralPubMedCrossRef
19.
Waiters, B., Godel, J. C., & Basu, T. K. (1998). Perinatal vitamin D and calcium status of northern Canadian mothers and their newborn infants. Journal of the American College of Nutrition, 18(2), 122–126.CrossRef
20.
Brooke, O. G., Brown, I. R., Bone, C. D., et al. (1980). Vitamin D supplements in pregnant Asian women: Effects on calcium status and fetal growth. The British Medical Journal, 280(6216), 751–754.CrossRef
21.
Basile, L. A., Taylor, S. N., Wagner, C. L., et al. (2007). Neonatal vitamin D status at birth at latitude 32 degrees 72’: Evidence of deficiency. Journal of Perinatology: Official Journal of the California Perinatal Association, 27(9), 568–571.CrossRef
22.
Burris, H. H., Rifas-Shiman, S. L., Camargo, C. A, Jr, et al. (2012). Plasma 25-hydroxyvitamin D during pregnancy and small-for-gestational age in black and white infants. Annals of Epidemiology, 22(8), 581–586.PubMedCentralPubMedCrossRef
23.
Leffelaar, E. R., Vrijkotte, T. G., & van Eijsden, M. (2010). Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: Results of the multi-ethnic Amsterdam Born Children and their Development cohort. The British Journal of Nutrition, 104(1), 108–117.PubMedCrossRef
24.
Bodnar, L. M., Catov, J. M., Zmuda, J. M., et al. (2010). Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. The Journal of Nutrition, 140(5), 999–1006.PubMedCentralPubMedCrossRef
25.
Robinson, C. J., Wagner, C. L., Hollis, B. W., et al. (2011). Maternal vitamin D and fetal growth in early-onset severe preeclampsia. American Journal of Obstetrics and Gynecology, 204(6), 556 e1–556 e4.CrossRef
26.
Morley, R., Carlin, J. B., Pasco, J. A., et al. (2006). Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. The Journal of Clinical Endocrinology and Metabolism, 91(3), 906–912.PubMedCrossRef
27.
Gale, C. R., Robinson, S. M., Harvey, N. C., et al. (2008). Maternal vitamin D status during pregnancy and child outcomes. European Journal of Clinical Nutrition, 62(1), 68–77.PubMedCentralPubMedCrossRef
28.
Barker, D. J. (2004). The developmental origins of adult disease. Journal of the American College of Nutrition, 23(6 Suppl), 588S–595S.PubMedCrossRef
29.
30.
Ioannou, C., Javaid, M. K., Mahon, P., et al. (2012). The effect of maternal vitamin D concentration on fetal bone. The Journal of Clinical Endocrinology and Metabolism, 97(11), E2070–E2077.PubMedCentralPubMedCrossRef
31.
Weiler, H., Fitzpatrick-Wong, S., Veitch, R., et al. (2005). Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns. CMAJ: Canadian Medical Association Journal = journal de l’Association medicale canadienne, 172(6), 757–761.CrossRef
32.
Javaid, M. K., Crozier, S. R., Harvey, N. C., et al. (2006). Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: A longitudinal study. Lancet, 367(9504), 36–43.PubMedCrossRef
33.
34.
Shibata, M., Suzuki, A., Sekiya, T., et al. (2011). High prevalence of hypovitaminosis D in pregnant Japanese women with threatened premature delivery. Journal of Bone and Mineral Metabolism, 29(5), 615–620.PubMedCrossRef
35.
Fernandez-Alonso, A. M., Dionis-Sanchez, E. C., Chedraui, P., et al. (2012). First-trimester maternal serum 25-hydroxyvitamin D(3) status and pregnancy outcome. International Journal of Gynaecology and Obstetrics: The Official Organ of the International Federation of Gynaecology and Obstetrics, 116(1), 6–9.CrossRef
36.
Burris, H. H., Rifas-Shiman, S. L., Kleinman, K., et al. (2012). Vitamin D deficiency in pregnancy and gestational diabetes mellitus. American Journal of Obstetrics and Gynecology, 207(3), 182 e1–182 e8.CrossRef
37.
Belderbos, M. E., Houben, M. L., Wilbrink, B., et al. (2011). Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics, 127(6), e1513–e1520.PubMedCrossRef
38.
Camargo, C. A, Jr, Ingham, T., Wickens, K., et al. (2011). Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics, 127(1), e180–e187.PubMedCrossRef
39.
Camargo, C. A, Jr, Rifas-Shiman, S. L., Litonjua, A. A., et al. (2007). Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. The American Journal of Clinical Nutrition, 85(3), 788–795.PubMed
40.
Weisse, K., Winkler, S., Hirche, F., et al. (2013). Maternal and newborn vitamin D status and its impact on food allergy development in the German LINA cohort study. Allergy, 68(2), 220–228.PubMedCrossRef
41.
Jones, A. P., Palmer, D., Zhang, G., et al. (2012). Cord blood 25-hydroxyvitamin D3 and allergic disease during infancy. Pediatrics, 130(5), e1128–e1135.PubMedCrossRef
42.
Sorensen, I. M., Joner, G., Jenum, P. A., et al. (2012). Maternal serum levels of 25-hydroxy-vitamin D during pregnancy and risk of type 1 diabetes in the offspring. Diabetes, 61(1), 175–178.PubMedCentralPubMedCrossRef
43.
Miettinen, M. E., Reinert, L., Kinnunen, L., et al. (2012). Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring. Diabetologia, 55(5), 1291–1294.PubMedCrossRef
44.
Morales, E., Guxens, M., Llop, S., et al. (2012). Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics, 130(4), e913–e920.PubMedCrossRef
45.
Torkildsen, O., Grytten, N., Aarseth, J., et al. (2012). Month of birth as a risk factor for multiple sclerosis: An update. Acta Neurologica Scandinavica. Supplementum, 195, 58–62.PubMedCrossRef
46.
Mirzaei, F., Michels, K. B., Munger, K., et al. (2011). Gestational vitamin D and the risk of multiple sclerosis in offspring. Annals of Neurology, 70(1), 30–40.PubMedCentralPubMedCrossRef
47.
Salzer, J., Hallmans, G., Nystrom, M., et al. (2012). Vitamin D as a protective factor in multiple sclerosis. Neurology, 79(21), 2140–2145.PubMedCrossRef
48.
Baker, A. M., Haeri, S., Camargo, C. A, Jr, et al. (2010). A nested case–control study of midgestation vitamin D deficiency and risk of severe preeclampsia. The Journal of Clinical Endocrinology and Metabolism, 95(11), 5105–5109.PubMedCentralPubMedCrossRef
49.
Bodnar, L. M., Catov, J. M., Simhan, H. N., et al. (2007). Maternal vitamin D deficiency increases the risk of preeclampsia. The Journal of Clinical Endocrinology and Metabolism, 92(9), 3517–3522.PubMedCrossRef
50.
Robinson, C. J., Alanis, M. C., Wagner, C. L., et al. (2010). Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. American Journal of Obstetrics and Gynecology, 203(4), 366 e1–366 e6.CrossRef
51.
Wei, S. Q., Audibert, F., Hidiroglou, N., et al. (2012). Longitudinal vitamin D status in pregnancy and the risk of pre-eclampsia. BJOG: An International Journal of Obstetrics and Gynaecology, 119(7), 832–839.CrossRef
52.
Azar, M., Basu, A., Jenkins, A. J., et al. (2011). Serum carotenoids and fat-soluble vitamins in women with type 1 diabetes and preeclampsia: A longitudinal study. Diabetes Care, 34(6), 1258–1264.PubMedCentralPubMedCrossRef
53.
Powe, C. E., Seely, E. W., Rana, S., et al. (2010). First trimester vitamin D, vitamin D binding protein, and subsequent preeclampsia. Hypertension, 56(4), 758–763.PubMedCentralPubMedCrossRef
54.
Shand, A. W., Nassar, N., Von Dadelszen, P., et al. (2010). Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for pre-eclampsia. BJOG: An International Journal of Obstetrics and Gynaecology, 117(13), 1593–1598.CrossRef
55.
Senti, J., Thiele, D. K., & Anderson, C. M. (2012). Maternal vitamin D status as a critical determinant in gestational diabetes. Journal of Obstetric, Gynecologic, and Neonatal Nursing: JOGNN/NAACOG, 41(3), 328–338.CrossRef
56.
Parlea, L., Bromberg, I. L., Feig, D. S., et al. (2012). Association between serum 25-hydroxyvitamin D in early pregnancy and risk of gestational diabetes mellitus. Diabetic Medicine: A Journal of the British Diabetic Association, 29(7), e25–e32.CrossRef
57.
Tomedi, L. E., Simhan, H. N., & Bodnar, L. M. (2013). Early-pregnancy maternal vitamin D status and maternal hyperglycaemia. Diabetic Medicine: A Journal of the British Diabetic Association, 30(9), 1033–1039. doi:10.​1111/​dme.​12229.
58.
Hensel, K. J., Randis, T. M., Gelber, S. E., et al. (2011). Pregnancy-specific association of vitamin D deficiency and bacterial vaginosis. American Journal of Obstetrics and Gynecology, 204(1), 41 e1–41 e9.CrossRef
59.
60.
van Oostrum, N., De Sutter, P., Meys, J., et al. (2013). Risks associated with bacterial vaginosis in infertility patients: A systematic review and meta-analysis. Human Reproduction, 28(7), 1809–1815. doi:10.​1093/​humrep/​det096.PubMedCrossRef
61.
Mirmonsef, P., Krass, L., Landay, A., et al. (2012). The role of bacterial vaginosis and trichomonas in HIV transmission across the female genital tract. Current HIV Research, 10(3), 202–210.PubMedCentralPubMedCrossRef
62.
63.
Merewood, A., Mehta, S. D., Chen, T. C., et al. (2009). Association between vitamin D deficiency and primary cesarean section. The Journal of Clinical Endocrinology and Metabolism, 94(3), 940–945.PubMedCentralPubMedCrossRef
64.
65.
66.
Simpson, E. L., Lawrenson, R. A., Nightingale, A. L., et al. (2001). Venous thromboembolism in pregnancy and the puerperium: Incidence and additional risk factors from a London perinatal database. BJOG: An International Journal of Obstetrics and Gynaecology, 108(1), 56–60.
67.
68.
Brandenbarg, J., Vrijkotte, T. G., Goedhart, G., et al. (2012). Maternal early-pregnancy vitamin D status is associated with maternal depressive symptoms in the Amsterdam Born Children and their Development cohort. Psychosomatic Medicine, 74(7), 751–757.PubMedCrossRef
69.
Cassidy-Bushrow, A. E., Peters, R. M., Johnson, D. A., et al. (2012). Vitamin D nutritional status and antenatal depressive symptoms in African American women. Journal of Women’s Health, 21(11), 1189–1195.PubMedCrossRef
70.
Hollis, B. W., Johnson, D., Hulsey, T. C., et al. (2011). Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. Journal of Bone and Mineral Research: The Official Journal of the American Society for Bone and Mineral Research, 26(10), 2341–2357.CrossRef
71.
De-Regil, L. M., Palacios, C., Ansary, A., et al. (2012). Vitamin D supplementation for women during pregnancy. Cochrane Database of Systematic Reviews, 2, CD008873.PubMedCentralPubMed
72.
Dawodu, A., Saadi, H. F., Bekdache, G., et al. (2013). Randomized controlled trial (RCT) of vitamin D supplementation in pregnancy in a population with endemic vitamin D deficiency. The Journal of Clinical Endocrinology and Metabolism, 98(6), 2337–2346.PubMedCrossRef
73.
Wagner, C. L., McNeil, R., Hamilton, S. A., et al. (2013). A randomized trial of vitamin D supplementation in 2 community health center networks in South Carolina. American Journal of Obstetrics and Gynecology, 208(2), 137 e1–137 e13.CrossRef
74.
Roth, D. E., Al Mahmud, A., Raqib, R., et al. (2013). Randomized placebo-controlled trial of high-dose prenatal third-trimester vitamin D3 supplementation in Bangladesh: The AViDD trial. Nutrition Journal, 12(1), 47.PubMedCentralPubMedCrossRef
75.
Hashemipour, S., Lalooha, F., Zahir Mirdamadi, S., et al. (2013). Effect of vitamin D administration in vitamin D-deficient pregnant women on maternal and neonatal serum calcium and vitamin D concentrations: A randomised clinical trial. The British Journal of Nutrition, 110(9), 1611–1616. doi:10.​1017/​S000711451300124​4.
76.
77.
Weinert, L. S., Reichelt, A. J., Schmitt, L. R., et al. (2014) Serum vitamin D insufficiency is related to blood pressure levels in diabetic pregnancy. American Journal of Hypertension. doi:10.​1093/​ajh/​hpu043.
78.
Aly, Y. F., El Koumi, M. A., & Abd El Rahman, R. N. (2013). Impact of maternal vitamin D status during pregnancy on the prevalence of neonatal vitamin D deficiency. Pediatric Reports, 5(1), 6. doi:10.​4081/​pr.​2013.​e6.CrossRef
79.
80.
Toher, C., Lindsay, K., McKenna, M., et al. (2013). Relationship between vitamin D knowledge and 25-hydroxyvitamin D levels amongst pregnant women. Journal of Human Nutrition and Dietetics: The Official Journal of the British Dietetic Association,. doi:10.​1111/​jhn.​12150.
81.
82.
Bartoszewicz, Z., Kondracka, A., Krasnodebska-Kiljanska, M., et al. (2013). Vitamin D insufficiency in healthy pregnant women living in Warsaw. Ginekologia Polska, 84(5), 363–367.PubMed
83.
84.
85.
86.
Bodnar, L. M., Simhan, H. N., Powers, R. W., et al. (2007). High prevalence of vitamin D insufficiency in black and white pregnant women residing in the northern United States and their neonates. The Journal of Nutrition, 137(2), 447–452.PubMed
87.
Metadata
Title
Maternal–Fetal Impact of Vitamin D Deficiency: A Critical Review
Authors
Letícia Schwerz Weinert
Sandra Pinho Silveiro
Publication date
01-01-2015
Publisher
Springer US
Published in
Maternal and Child Health Journal / Issue 1/2015
Print ISSN: 1092-7875
Electronic ISSN: 1573-6628
DOI
https://doi.org/10.1007/s10995-014-1499-7

Other articles of this Issue 1/2015

Maternal and Child Health Journal 1/2015 Go to the issue

OriginalPaper

Prevalence of Serious Psychological Distress and Mental Health Treatment in a National Sample of Pregnant and Postpartum Women

OriginalPaper

HIV Counseling and Testing for the Prevention of Mother-to-Child Transmission of HIV in Swaziland: A Multilevel Analysis

OriginalPaper

Skilled Birth Attendants in Tanzania: A Descriptive Study of Cadres and Emergency Obstetric Care Signal Functions Performed

Brief Report

Incidence of Low Birthweight in Central Nepal: A Community-Based Prospective Cohort Study

OriginalPaper

Gendered Effects of Siblings on Child Malnutrition in South Asia: Cross-sectional Analysis of Demographic and Health Surveys from Bangladesh, India, and Nepal

OriginalPaper

Knowledge and Attitudes of Adults towards Smoking in Pregnancy: Results from the HealthStyles© 2008 Survey