Korean J Perinatol.  2015 Sep;26(3):174-182. 10.14734/kjp.2015.26.3.174.

The Association between Vitamin D Deficiency and Perinatal Outcomes of Pregnancy

• Ji HM
• Cho GJ

• KMID: 2281220
• DOI: http://doi.org/10.14734/kjp.2015.26.3.174

Abstract

Vitamin D deficiency is a global health problem that increases risk for metabolic bone diseases in children and adults as well as many chronic illnesses including autoimmune diseases, type 2 diabetes, cardiovascular disease, infectious disease, and cancer. This has raised important questions concerning the physiological and clinical impact of low vitamin D levels during pregnancy, with implications for functions of vitamin D. The review describes the pathways that are required for metabolism and function of vitamin D, the various clinical complications that have been linked to impaired vitamin D status during pregnancy, and effects of vitamin D supplementation on maternal and neonatal outcomes.

Keyword

Vitamin D deficiency; Preeclampsia; Gestational diabetes; Perinatal outcome; Vitamin D supplementation

MeSH Terms

Adult
Autoimmune Diseases
Bone Diseases, Metabolic
Cardiovascular Diseases
Child
Chronic Disease
Communicable Diseases
Diabetes, Gestational
Female
Humans
Metabolism
Pre-Eclampsia
Pregnancy*
Vitamin D Deficiency*
Vitamin D*
Vitamins*
Vitamin D
Vitamins

Reference

References

1. Looker AC, Pfeiffer CM, Lacher DA, Schleicher RL, Picciano MF, Yetley EA. Serum 25-hydroxyvitamin D status of the US population: 1988–1994 compared with 2000–2004. Am J Clin Nutr. 2008; 88:1519–27.

2. van der Mei IA, Ponsonby AL, Engelsen O, Pasco JA, McGrath JJ, Eyles DW, et al. The high prevalence of vitamin D insufficiency across Australian populations is only partly explained by season and latitude. Environ Health Perspect. 2007; 115:1132–9.

3. Na BM, No SJ, Kim MJ, Han HS, Jeong EH, Han YH, et al. Nutritional Status of Vitamin D in Korean Mothers and their Newborn Infants. Korean J perinatol. 2007; 18:399–406.

4. Holick MF. Vitamin D deficiency. N Engl J Med. 2007; 357:266–81.

5. Liu NQ, Hewison M. Vitamin D, the placenta and pregnancy. Arch Biochem Biophys. 2012; 523:37–47.

6. Holick MF, Binkley NC, Bischoff-Ferrari HA, Gordon CM, Hanley DA, Heaney RP, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96:1911–30.

7. Ginde AA, Sullivan AF, Mansbach JM, Camargo CA Jr. Vitamin D insufficiency in pregnant and nonpregnant women of childbearing age in the United States. Am J Obstet Gynecol. 2010; 202:436. e1–8.

8. Johnson DD, Wagner CL, Hulsey TC, McNeil RB, Ebeling M, Hollis BW. Vitamin D deficiency and insufficiency is common during pregnancy. Am J Perinatol. 2011; 28:7–12.

9. Sloka S, Stokes J, Randell E, Newhook LA. Seasonal variation of maternal serum vitamin D in Newfoundland and Labrador. J Obstet Gynaecol Can. 2009; 31:313–21.

10. Holmes VA, Barnes MS, Alexander HD, McFaul P, Wallace JM. Vitamin D deficiency and insufficiency in pregnant women: a longitudinal study. Br J Nutr. 2009; 102:876–81.

11. Bowyer L, Catling-Paull C, Diamond T, Homer C, Davis G, Craig ME. Vitamin D, PTH and calcium levels in pregnant women and their neonates. Clin Endocrinol (Oxf). 2009; 70:372–7.

12. Madar AA, Stene LC, Meyer HE. Vitamin D status among immigrant mothers from Pakistan, Turkey and Somalia and their infants attending child health clinics in Norway. Br J Nutr. 2009; 101:1052–8.

13. Hofmeyr GJ, Lawrie TA, Atallah AN, Duley L, Torloni MR. Calcium supplementation during pregnancy for preventing hypertensive disorders and related problems. Cochrane Database Syst Rev. 2014; 6:CD001059.

14. Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007; 92:3517–22.

15. Baker AM, Haeri S, Camargo CA Jr, Espinola JA, Stuebe AM. A nested case-control study of midgestation vitamin D deficiency and risk of severe preeclampsia. J Clin Endocrinol Metab. 2010; 95:5105–9.

16. Bodnar LM, Simhan HN, Catov JM, Roberts JM, Platt RW, Diesel JC, et al. Maternal vitamin D status and the risk of mild and severe preeclampsia. Epidemiology. 2014; 25:207–14.

17. Wei SQ, Audibert F, Hidiroglou N, Sarafin K, Julien P, Wu Y, et al. Longitudinal vitamin D status in pregnancy and the risk of preeclampsia. BJOG. 2012; 119:832–9.

18. Robinson CJ, Alanis MC, Wagner CL, Hollis BW, Johnson DD. Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. Am J Obstet Gynecol. 2010; 203:366. e1–6.

19. Xu L, Lee M, Jeyabalan A, Roberts JM. The relationship of hypovitaminosis D and IL-6 in preeclampsia. Am J Obstet Gynecol. 2014; 210:149. e1–7.

20. Abedi P, Mohaghegh Z, Afshary P, Latifi M. The relationship of serum vitamin D with preeclampsia in the Iranian women. Matern Child Nutr. 2014; 10:206–12.

21. Haugen M, Brantsaeter AL, Trogstad L, Alexander J, Roth C, Magnus P, et al. Vitamin D supplementation and reduced risk of preeclampsia in nulliparous women. Epidemiology. 2009; 20:720–6.

22. Harvey NC, Holroyd C, Ntani G, Javaid K, Cooper P, Moon R, et al. Vitamin D supplementation in pregnancy: a systematic review. Health Technol Assess. 2014; 18:1–190.

23. Hyppönen E, Cavadino A, Williams D, Fraser A, Vereczkey A, Fraser WD, et al. Vitamin D and preeclampsia: original data, systematic review and metaanalysis. Ann Nutr Metab. 2013; 63:331–40.

24. Thorne-Lyman A, Fawzi WW. Vitamin D during pregnancy and maternal, neonatal and infant health outcomes: a systematic review and metaanalysis. Paediatr Perinat Epidemiol. 2012; 6(Suppl 1):75–90.

25. Aghajafari F, Nagulesapillai T, Ronksley PE, Tough SC, O'Beirne M, Rabi DM. Association between maternal serum 25-hydroxyvitamin D level and pregnancy and neonatal outcomes: systematic review and metaanalysis of observational studies. BMJ. 2013; 346:f1169.

26. Tabesh M, Salehi-Abargouei A, Tabesh M, Esmaillzadeh A. Maternal vitamin D status and risk of preeclampsia: a systematic review and metaanalysis. J Clin Endocrinol Metab. 2013; 98:3165–73.

27. Wei SQ, Qi HP, Luo ZC, Fraser WD. Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and metaanalysis. J Matern Fetal Neonatal Med. 2013; 26:889–99.

28. Schneuer FJ, Roberts CL, Guilbert C, Simpson JM, Algert CS, Khambalia AZ, et al. Effects of maternal serum 25-hydroxyvitamin D concentrations in the first trimester on subsequent pregnancy outcomes in an Australian population. Am J Clin Nutr. 2014; 99:287–95.

29. Maghbooli Z, Hossein-Nezhad A, Karimi F, Shafaei AR, Larijani B. Correlation between vitamin D3 deficiency and insulin resistance in pregnancy. Diabetes Metab Res Rev. 2008; 24:27–32.

30. Clifton-Bligh RJ, McElduff P, McElduff A. Maternal vitamin D deficiency, ethnicity and gestational diabetes. Diabet Med. 2008; 25:678–84.

31. Lacroix M, Battista MC, Doyon M, Houde G, Ménard J, Ardilouze JL, et al. Lower vitamin D levels at first trimester are associated with higher risk of developing gestational diabetes mellitus. Acta Diabetol. 2014; 51:609–16.

32. McManus R, Summers K, de Vrijer B, Cohen N, Thompson A, Giroux I. Maternal, umbilical arterial and umbilical venous 25-hydroxyvitamin D and adipocytokine concentrations in pregnancies with and without gestational diabetes. Clin Endocrinol (Oxf). 2014; 80:635–41.

33. Cho GJ, Hong SC, Oh MJ, Kim HJ. Vitamin D deficiency in gestational diabetes mellitus and the role of the placenta. Am J Obstet Gynecol. 2013; 209:560. e1–8.

34. Wang O, Nie M, Hu YY, Zhang K, Li W, Ping F, et al. Association between vitamin D insufficiency and the risk for gestational diabetes mellitus in pregnant Chinese women. Biomed Environ Sci. 2012; 25:399–406.

35. Farrant HJ, Krishnaveni GV, Hill JC, Boucher BJ, Fisher DJ, Noonan K, et al. 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; 63:646–52.

36. Whitelaw DC, Scally AJ, Tuffnell DJ, Davies TJ, Fraser WD, Bhopal RS, et al. Associations of circulating calcium and 25-hydroxyvitamin D with glucose metabolism in pregnancy: a cross-sectional study in European and South Asian women. J Clin Endocrinol Metab. 2014; 99:938–46.

37. Perez-Ferre N, Torrejon MJ, Fuentes M, Fernandez MD, Ramos A, Bordiu E, et al. Association of low serum 25-hydroxyvitamin D levels in pregnancy with glucose homeostasis and obstetric and newborn outcomes. Endocr Pract. 2012; 18:676–84.

38. Poel YH, Hummel P, Lips P, Stam F, van der Ploeg T, Simsek S. Vitamin D and gestational diabetes: a systematic review and metaanalysis. Eur J Intern Med. 2012; 23:465–9.

39. Zhou J, Su L, Liu M, Liu Y, Cao X, Wang Z, et al. Associations between 25-hydroxyvitamin D levels and pregnancy outcomes: a prospective observational study in southern China. Eur J Clin Nutr. 2014; 68:925–30.

40. Bodnar LM, Rouse DJ, Momirova V, Peaceman AM, Sciscione A, Spong CY, et al. Maternal 25-hydroxyvitamin d and preterm birth in twin gestations. Obstet Gynecol. 2013; 122:91–8.

41. Bodnar LM, Klebanoff MA, Gernand AD, Platt RW, Parks WT, Catov JM, et al. Maternal vitamin D status and spontaneous preterm birth by placental histology in the US Collaborative Perinatal Project. Am J Epidemiol. 2014; 179:168–76.

42. Shand AW, Nassar N, Von Dadelszen P, Innis SM, Green TJ. Maternal vitamin D status in pregnancy and adverse pregnancy outcomes in a group at high risk for preeclampsia. BJOG. 2010; 117:1593–8.

43. Fernández-Alonso AM, Dionis-Sánchez EC, Chedraui P, González-Salmerón MD, Pérez-López FR. Spanish Vitamin D and Women's Health Research Group. First-trimester maternal serum 25-hydroxyvitamin D(3) status and pregnancy outcome. Int J Gynaecol Obstet. 2012; 116:6–9.

44. Dunlop AL, Taylor RN, Tangpricha V, Fortunato S, Menon R. Maternal micronutrient status and preterm versus term birth for black and white US women. Reprod Sci. 2012; 19:939–48.

45. Mehta S, Hunter DJ, Mugusi FM, Spiegelman D, Manji KP, Giovannucci EL, et al. Perinatal outcomes, including mother-to-child transmission of HIV, and child mortality and their association with maternal vitamin D status in Tanzania. J Infect Dis. 2009; 200:1022–30.

46. Delmas PD, Glorieux FH, Delvin EE, Salle BL, Melki I. Perinatal serum bone Gla-protein and vitamin D metabolites in preterm and fullterm neonates. J Clin Endocrinol Metab. 1987; 65:588–91.

47. Thorp JM, Camargo CA, McGee PL, Harper M, Klebanoff MA, Sorokin Y, et al. Eunice Kennedy Shriver National Institute of Child Health and Human Development Ma-ternal-Fetal Medicine Units Network. Vitamin D status and recurrent preterm birth: a nested case-control study in high-risk women. BJOG. 2012; 119:1617–23.

48. Baker AM, Haeri S, Camargo CA Jr, Stuebe AM, Boggess KA. A nested case-control study of first-trimester maternal vitamin D status and risk for spontaneous preterm birth. Am J Perinatol. 2011; 28:667–72.

49. Hossain N, Khanani R, Hussain-Kanani F, Shah T, Arif S, Pal L. High prevalence of vitamin D deficiency in Pakistani mothers and their newborns. Int J Gynaecol Obstet. 2011; 112:229–33.

50. Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF. Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab. 2009; 94:940–5.

51. Scholl TO, Chen X, Stein P. Maternal vitamin D status and delivery by cesarean. Nutrients. 2012; 4:319–30.

52. Savvidou MD, Makgoba M, Castro PT, Akolekar R, Nicolaides KH. First-trimester maternal serum vitamin D and mode of delivery. Br J Nutr. 2012; 108:1972–5.

53. Folayan MO, Haire B, Harrison A, Fatusi O, Brown B. Beyond informed consent: ethical considerations in the design and implementation of sexual and reproductive health research among adolescents. Afr J Reprod Health. 2014; 18:118–26.

54. Innes AM, Seshia MM, Prasad C, Al Saif S, Friesen FR, Chudley AE, et al. Congenital rickets caused by maternal vitamin D deficiency. Paediatr Child Health. 2002; 7:455–8.

55. Anatoliotaki M, Tsilimigaki A, Tsekoura T, Schinaki A, Stefanaki S, Nicolaidou P. Congenital rickets due to maternal vitamin D deficiency in a sunny island of Greece. Acta Paediatr. 2003; 92:389–91.

56. Orbak Z, Karacan M, Doneray H, Karakelleoglu C. Congenital rickets presenting with hypocalcaemic seizures. West Indian Med J. 2007; 56:364–7.

57. Curtis EM, Moon RJ, Dennison EM, Harvey NC. Prenatal calcium and vitamin D intake, and bone mass in later life. Curr Osteoporos Rep. 2014; 12:194–204.

58. Robinson CJ, Wagner CL, Hollis BW, Baatz JE, Johnson DD. Maternal vitamin D and fetal growth in early-onset severe preeclampsia. Am J Obstet Gynecol. 2011; 204:556. e1–4.

59. Leffelaar ER, Vrijkotte TG, van Eijsden M. Maternal early pregnancy vitamin D status in relation to fetal and neonatal growth: results of the multiethnic Amsterdam Born Children and their Development cohort. Br J Nutr. 2010; 104:108–17.

60. Bodnar LM, Catov JM, Zmuda JM, Cooper ME, Parrott MS, Roberts JM, et al. Maternal serum 25-hydroxyvitamin D concentrations are associated with small-for-gestational age births in white women. J Nutr. 2010; 140:999–1006.

61. Morley R, Carlin JB, Pasco JA, Wark JD. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J Clin Endocrinol Metab. 2006; 91:906–12.

62. Ioannou C, Javaid MK, Mahon P, Yaqub MK, Harvey NC, Godfrey KM, et al. The effect of maternal vitamin D concentration on fetal bone. J Clin Endocrinol Metab. 2012; 97:E2070–7.

63. Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N, et al. Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res. 2010; 25:14–9.

64. Namgung R, Tsang RC, Lee C, Han DG, Ho ML, Sierra RI. Low total body bone mineral content and high bone resorption in Korean winter-born versus summer-born newborn infants. J Pediatr. 1998; 132:421–5.

65. Namgung R, Tsang RC. Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization. Proc Nutr Soc. 2000; 59:55–63.

66. Weiler H, Fitzpatrick-Wong S, Veitch R, Kovacs H, Schellenberg J, McCloy U, et al. Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns. CMAJ. 2005; 172:757–61.

67. Mehrotra P, Marwaha RK, Aneja S, Seth A, Singla BM, Ashraf G, et al. Hypovitaminosis d and hypocalcemic seizures in infancy. Indian Pediatr. 2010; 47:581–6.

68. Salama MM, El-Sakka AS. Hypocalcemic seizures in breastfed infants with rickets secondary to severe maternal vitamin D deficiency. Pak J Biol Sci. 2010; 13:437–42.

69. Camargo CA Jr, Rifas-Shiman SL, Litonjua AA, Rich-Edwards JW, Weiss ST, Gold DR, et al. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Am J Clin Nutr. 2007; 85:788–95.

70. Belderbos ME, Houben ML, Wilbrink B, Lentjes E, Bloemen EM, Kimpen JL, et al. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011; 127:e1513–20.

71. Camargo CA Jr, Ingham T, Wickens K, Thadhani R, Silvers KM, Epton MJ, et al. Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics. 2011; 127:e180–7.

72. Walker VP, Zhang X, Rastegar I, Liu PT, Hollis BW, Adams JS, et al. Cord blood vitamin D status impacts innate immune responses. J Clin Endocrinol Metab. 2011; 96:1835–43.

73. Pérez-López FR, Pasupuleti V, Mezones-Holguin E, Benites-Zapata VA, Thota P, Deshpande A, et al. Effect of vitamin D supplementation during pregnancy on maternal and neonatal outcomes: a systematic review and metaanalysis of randomized controlled trials. Fertil Steril. 2015; 103:1278–88e4.

74. Marya RK, Rathee S, Manrow M. Effect of calcium and vitamin D supplementation on toxaemia of pregnancy. Gynecol Obstet Invest. 1987; 24:38–42.

75. Yap C, Cheung NW, Gunton JE, Athayde N, Munns CF, Duke A, et al. Vitamin D supplementation and the effects on glucose metabolism during pregnancy: a randomized controlled trial. Diabetes Care. 2014; 37:1837–44.

76. Soheilykhah S, Mojibian M, Moghadam MJ, Shojaoddiny-Ardekani A. The effect of different doses of vitamin D supplementation on insulin resistance during pregnancy. Gynecol Endocrinol. 2013; 29:396–9.

77. Asemi Z, Hashemi T, Karamali M, Samimi M, Esmaillzadeh A. Effects of vitamin D supplementation on glucose metabolism, lipid concentrations, inflammation, and oxidative stress in gestational diabetes: a double-blind randomized controlled clinical trial. Am J Clin Nutr. 2013; 98:1425–32.

78. ACOG Committee on Obstetric Practice. ACOG Committee Opinion No. 495: Vitamin D: Screening and supplementation during pregnancy. Obstet Gynecol. 2011; 118:197–8.

79. Royal College of Obstetricians & Gynaecologist. Scientific Impact Paper No. 43: Vitamin D in Pregnancy. 2014.