Current view of vitamin D in pregnant women: a review
Keywords:deficiency, pregnancy, insufficiency, vitamin D
Hypovitaminosis D is a global health problem that affects all age groups. Pregnant women are considered a high-risk group and the condition has potentially associated maternal and fetal complications. The goal of the present review is to analyze the magnitude and consequences of hypovitaminosis D in pregnant women and the safety of vitamin D supplementation. Prevalence of hypovitaminosis D during pregnancy is very high, even in sunny countries. Maternal vitamin D deficiency has been associated with increased risk of specific hypertensive disease of pregnancy, bacterial vaginosis, prematurity, gestational diabetes mellitus, osteomalacia, and muscle weakness. It has also been linked to prematurity, low birth weight, and fetal infectious complications.
Due to potential maternal and fetal complications, it is extremely important to achieve adequate vitamin D levels prior to pregnancy. During pregnancy, it would be prudent to monitor serum vitamin D levels and implement preventive measures to reduce maternal and fetal morbidity.
No consensus exists in the medical literature regarding vitamin D supplementation in pregnant women.
- Mulligan ML, Felton SK, Riek AE, Bernal-Mizrachi C. Implications of vitamin D deficiency in pregnancy and lactation. Am J Obstet Gynecol. 2010; 202 (5):429.e 1-9.
- Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences. Am J Clin Nutr. 2008; 87 (4):1080S-6S.
- Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr. 2004; 80 (6 Suppl):1678S-88S.
- Wagner CL, Greer FR. American Academy of Pediatrics Section on Breastfeeding, American Academy of Pediatrics Committee on Nutrition. Prevention of rickets and vitamin d deficiency in infants, children, and adolescents. Pediatrics. 2008;122 (5):1142-52.
- Theodoropoulos C, Demers C, Delvin E, Ménard D, Gascon-Barré M. Calcitriol regulates the expression of the genes encoding the three key vitamin D3 hydroxylases and the drug-metabolizing enzyme CYP3A4 in the human fetal intestine. Clin Endocrinol (Oxf). 2003;58 (4):489-99.
- Clifton-Bligh RJ, McElduff P, McElduff A. Maternal vitamin D deficiency, ethnicity and gestational diabetes. Diabet Med. 2008; 25(6):678-84.
- 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 (1):27-32.
- Palomer X, Gonzalez-Clemente JM, Blanco-Vaca F. Role of vitamin D in the pathogenesis of type 2 diabetes mellitus. Diabetes Obes Metab. 2008;10(3):185-97.
- Xuan Y, Zhao H, Liu J-M. Vitamin D and Type 2 diabetes mellitus. J Diabetes. 2013;5 (3):261-7.
- Novakovic B, Sibson M, Ng HK, Manuelpillai U, Rakyan V, Down T, et al. Placenta-specific methylation of the vitamin D 24-hydroxylase gene: implications for feedback autoregulation of active vitamin D levels at the fetomaternal interface. J Biol Chem. 2009; 284: 14838-48.
- Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: An endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2011; 96(7):1911-30.
- Holick MF. Vitamin D Deficiency. N Engl J Med. 2007;357(3):266-81.
- Palacios C, Gonzalez L. Is vitamin D deficiency a major global public health problem? J Steroid Biochem Mol Biol. 2014;144 (PART A):138-45.
-Nicolaidou P, Hatzistamatiou Z, Papadopoulou A, Kaleyias J, Floropoulou E, Lagona E, et al. Low vitamin D status in mother-newborn pairs in Greece. Calcif Tissue Int. 2006;78 (6):337-42.
-O’Riordan MN, Kiely M, Higgins JR, Cashman KD. Prevalence of suboptimal vitamin D status during pregnancy. Ir Med J. 2008; 101(8):240, 242-3.
- 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(4):313-21.
- Chrisostomo KR. Concentrações séricas de vitamina D em gestantes de Curitiba durante o verão e o inverno. Master degree thesis. Universidade Federal do Paraná, 2017. Avaiable at http://acervodigital.ufpr.br/handle/1884/48531
- Harvey NC, Holroyd C, Ntani G, et al. Vitamin D supplementation in pregnancy: A systematic review. Health Technol Assess (Rockv). 2014; 18(45):1-189.
- Bener A, Alsaied A, Al-Ali M, et al. High prevalence of vitamin D deficiency in type 1 diabetes mellitus and healthy children. Acta Diabetol. 2009;46(3):183-9.
- Pierrot-Deseilligny C, Souberbielle J-C. Is hypovitaminosis D one of the environmental risk factors for multiple sclerosis? Brain. 2010;133(7):1869-88.
- Tabesh M, Salehi-Abargouei A, Tabesh-Bodnar LM, Catov JM, Simhan HN, Holick MF, et al. Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab. 2007; 92(9):3517-22.
- 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(9):3517-22.
- Li D-K, Wi S. Maternal pre-eclampsia/eclampsia and the risk of sudden infant death syndrome in offspring. Paediatr Perinat Epidemiol. 2000;14(2):141-4.
- Mackay AP, Berg CJ, Atrash HK. Pregnancy-related mortality from preeclampsia and eclampsia. Obstet Gynecol. 2001; 97(4):533-8.
- Xiong X, Mayes D, Demianczuk N, et al. Impact of pregnancy-induced hypertension on fetal growth. Am J Obstet Gynecol. 1999;180(1 I):207-213.M, Esmaillzadeh A.
-August P, Marcaccio B, Gertner JM, Druzin ML, Resnick LM, Laragh JH. Abnormal 1,25-dihydroxyvitamin D metabolism in preeclampsia. Am J Obstet Gynecol. 1992;166(4):1295-9.
-Halhali A, Bourges H, Carrillo A, Garabedian M. Lower circulating insulin-like growth factor I and 1,25-dihydroxyvitamin D levels in preeclampsia. Rev Invest Clin. 1995;47(4):259-66.
-Farrant HJW, Krishnaveni G V, 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(5):646-52.
- Zhang C, Qiu C, Hu FB, David RM, van Dam RM, Bralley A, et al. Maternal plasma 25-hydroxyvitamin D concentrations and the risk for gestational diabetes mellitus. PLoS One. 2008;3(11):e3753.
- 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 meta-analysis of observational studies. BMJ. 2013;346 (March):f1169.
- Wei S-Q, Qi H-P, Luo Z-C, Fraser WD. Maternal vitamin D status and adverse pregnancy outcomes: a systematic review and meta-analysis. J Matern Fetal Neonatal Med. 2013;26 (9):889-99.
- Shahgheibi S, Farhadifar F, Pouya B.The effect of vitamin D supplementation on gestational diabetes in high-risk women: Results from a randomized placebo-controlled trial. J Res Med Sci. 2016 Jan 28;21:2. eCollection 2016.
-Hillier S, Marrazzo JM, Holmes KK. Bacterial vaginosis. In: Holmes, KK.; Sparling, PF.; Mårdh, P., et al., editors. Sexually transmitted diseases. 4th ed.. McGraw-Hill; New York: 2008.
- Oleen-Burkey MA, Hillier SL. Pregnancy complications associated with bacterial vaginosis and their estimated costs. Infect Dis Obstet Gynecol. 1995; 3(4):149–57.
- Cohen CR, Lingappa JR, Baeten JM, Ngayo MO, Spiegel CA, Hong T et al. Bacterial vaginosis associated with increased risk of female-to-male HIV-1 transmission: a prospective cohort analysis among African couples. PLoS Med. 2012; 9(6):e1001251.
- Van Oostrum N, De Sutter P, Meys J, Verstraelen H. Risks associated with bacterial vaginosis in infertility patients: a systematic review and meta-analysis. Hum Reprod. 2013; 28(7):1809–15.
- Buve A, Jespers V, Crucitti T, Fichorova RN. The vaginal microbiota and susceptibility to HIV. AIDS. 2014; 28(16): 2333–44.
- Akoh CC, Pressman EK, Cooper E, Queenan RA, Pillittere J, O'Brien O. Low vitamin D is associated with infections and proinflammatory cytokines during pregnancy. Reprod Sci. 2017 Jan 1:1933719117715124. doi: 10.1177/1933719117715124. [Epub ahead of print]
- Klebanoff MA, Turner AN. Bacterial vaginosis and season, a proxy for vitamin D status. Sex Transm Dis. 2014;41(5):295-9.
- Turner AN, Carr Reese P, Chen PL, Kwok C, Jackson RD, Klebanoff MA, et al. Serum vitamin D status and bacterial vaginosis prevalence and incidence in Zimbabwean women. Am J Obstet Gynecol. 2016;215(3):332.e1-332.e10.
- Mathias E, Tangpricha V, Sarnaik A, Farooqi A, Sethuraman U. Association of vitamin D with cathelicidin and vitamin D binding protein in pediatric sepsis. J Clin Transl Endocrinol. 2017;10:36-38. eCollection 2017 Dec.
- Lips P. Vitamin D physiology. Prog Biophys Mol Biol. 2006; 92(1):4-8.
- Bouillon R, Carmeliet G, Verlinden L, van Etten E, Verstuyf A, Luderer HF, et al. Vitamin D and human health: Lessons from vitamin D receptor null mice. Endocr Rev. 2008; 29(6):726-76.
- Englund M, Persson J, Bergström I. Lower pain and higher muscular strength in immigrant women with vitamin D deficiency following vitamin D treatment. Int J Circumpolar Health. 2017; 76(1):1340547.
- Ghannam NN, Hammami MM, Bakheet SM, Khan BA. Bone mineral density of the spine and femur in healthy Saudi females: relation to vitamin D status, pregnancy, and lactation. Calcif Tissue Int. 1999; 65(1):23-8.
- Bergström I, Palmér M, Persson J, Blanck A. Observational study of vitamin D levels and pain in pregnant immigrant women living in Sweden. Gynecol Endocrinol. 2014; 30(1):74-7.
- Weinert LS, Reichelt AJ, Schmitt LR, Boff R, Oppermann ML, Camargo JL, Silveiro P. Vitamin D deficiency increases the risk of adverse neonatal outcomes in gestational diabetes. PLoS One. 2016 20;11(10):e0164999. eCollection 2016.
- Theodoratou E, Tzoulaki I, Zgaga L, Ioannidis JPA. Vitamin D and multiple health outcomes: umbrella review of systematic reviews and meta-analyses of observational studies and randomised trials. BMJ. 2014;348 (apr01 2):g2035-g2035.
- Leffelaar ER, Vrijkotte TG, van Eijsden M. 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. Br J Nutr 2010; 104: 108–17.
- De-Regil LM, Palacios C, Lombardo LK, Pena-Rosas JP Vitamin D supplementation for women during pregnancy. The Cochrane database of systematic reviews 1: CD008873. 2016; doi: 10.1002/ 14651858.CD008873.pub3
-- Barrera D, Avila E, Hernandez G, Halhali A, Biruete B, et al. Estradiol and progesterone synthesis in human placenta is stimulated by calcitriol. J Steroid Biochem Mol Biol 2007; 103: 529–32.
- Katz J, Lee AC, Kozuki N, Lawn JE, Cousens S, Blencowe H et al. Mortality risk in preterm and small-forgestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet 2013; 83(9890) : 417–25.
- Kaijser M, Bonamy AK, Akre O, Cnattingius S, Granath F, et al. Perinatal risk factors for ischemic heart disease: disentangling the roles of birth weight and preterm birth. Circulation 2008; 117: 405–10.
- McGrath JJ, Eyles DW, Pedersen CB, Anderson C, Ko P, Burne TH, et al. Neonatal vitamin D status and risk of schizophrenia: a population-based case-control study. Arch Gen Psychiatry. 2010 ;67(9):889-94.
- Jacobsen R, Thorsen SU, Cohen AS, Lundqvist M, Frederiksen P, Pipper CB, et al. Neonatal vitamin D status is not associated with later risk of type 1 diabetes: results from two large Danish population-based studies. Diabetologia. 2016; 59(9):1871-81.
- Miettinen ME, Smart MC, Kinnunen L, Harjutsalo V, Reinert-Hartwall L, Ylivinkka I, et al. Genetic determinants of serum 25-hydroxyvitamin D concentration during pregnancy and type 1 diabetes in the child. PLoS One. 2017; 12(10):e0184942. eCollection 2017.
Munger KL, Åivo J, Hongell K, Soilu-Hänninen M, Surcel HM, Ascherio A. Vitamin D Status During Pregnancy and Risk of Multiple Sclerosis in Offspring of Women in the Finnish Maternity Cohort. JAMA Neurol. 2016;73(5):515-9.
-Godel JC, Canadian Paediatrics Society First Nations, Inuit and Métis Health Committee. Vitamin D supplementation: Recommendations for Canadian mothers and infants. Paediatr Child Heal. 2007; 12(7):583-589.
- Gale CR, Robinson SM, Harvey NC, et al. Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr. 2008;62(1):68-77.
- Dawson-Hughes B, Heaney RP, Holick MF, Lips P, Meunier PJ, Vieth R. Estimates of optimal vitamin D status. Osteoporos Int. 2005;16 (7):713-6.
-Utiger RD. The need for more vitamin D. N Engl J Med. 1998;338 (12):828-9.
-Sahu M, Das V, Aggarwal A, Rawat V, Saxena P, Bhatia V. Vitamin D replacement in pregnant women in rural north India: a pilot study. Eur J Clin Nutr. 2009; 63(9):1157-9.
- Yu CKH, Sykes L, Sethi M, Teoh TG, Robinson S. Vitamin D deficiency and supplementation during pregnancy. Clin Endocrinol (Oxf). 2009;70(5):685-90.
- Maeda SS, Borba VZC, Camargo MBR, Silva DM, Borges J, Bandeira F et al. Recommendations of the Brazilian Society of Endocrinology and Metabology (SBEM) for the diagnosis and treatment of hypovitaminosis D. Arq Bras Endocrinol Metabol. 2014; 58(5):411-33.
-Roth DE. Vitamin D supplementation during pregnancy: safety considerations in the design and interpretation of clinical trials. J Perinatol. 2011;31(7):449-59.
-Lee JH, O’Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency. An important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2008; 52(24):1949-56.
- Gallagher JC. Vitamin D and aging. Endocrinol Metab Clin North Am. 2013; 42(2):319-32.
- Bell DA, Crooke MJ, Hay N, Glendenning P. Prolonged vitamin D intoxication: Presentation, pathogenesis and progress. Intern Med J. 2013; 43(10):1148-50.
- Ariyuki F. Growth retardation induced in rat fetuses by maternal fasting and massive doses of ergocalciferol. J Nutr. 1987;117(2):342-8.
- Chan GM, Buchino JJ, Mehlhorn D, Bove KE, Steichen JJ, Tsang RC. Effect of vitamin D on pregnant rabbits and their offspring. Pediatr Res. 1979;13(2):121-6.
- Friedman WF, Mills LF. The relationship between vitamin D and the craniofacial and dental anomalies of the supravalvular aortic stenosis syndrome. Pediatrics. 1969; 43 (1):12-8.
- Ornoy A, Menczel J, Nebel L. Alterations in the mineral composition and metabolism of rat fetuses and their placentas induced by maternal hypervitaminosis D2. Isr J Med Sci. 1968; 4(4):827-32.
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