Vitamin D and its role during pregnancy in attaining optimal health of mother and fetus

Carol L Wagner, Sarah N Taylor, Adekunle Dawodu, Donna D Johnson, Bruce W Hollis, Carol L Wagner, Sarah N Taylor, Adekunle Dawodu, Donna D Johnson, Bruce W Hollis

Abstract

Despite its discovery a hundred years ago, vitamin D has emerged as one of the most controversial nutrients and prohormones of the 21st century. Its role in calcium metabolism and bone health is undisputed but its role in immune function and long-term health is debated. There are clear indicators from in vitro and animal in vivo studies that point to vitamin D's indisputable role in both innate and adaptive immunity; however, the translation of these findings to clinical practice, including the care of the pregnant woman, has not occurred. Until recently, there has been a paucity of data from randomized controlled trials to establish clear cut beneficial effects of vitamin D supplementation during pregnancy. An overview of vitamin metabolism, states of deficiency, and the results of recent clinical trials conducted in the U.S. are presented with an emphasis on what is known and what questions remain to be answered.

Keywords: calcitriol; cholecalciferol; neonate; pregnancy; vitamin D.

Figures

Figure 1
Figure 1
Human vitamin D synthesis pathways. Reproduced with permission from [7].
Figure 2
Figure 2
Relationship of circulating 25(OH)D on circulating 1,25(OH)D during pregnancy.

References

    1. Drake A., Walker B. The intergenerational effects of fetal programming: Non-genomic mechanisms for the inheritance of low birth weight and cardiovascular risk. J. Endocrinol. 2004;180:1–16.
    1. Whitelaw E. Epigenetics: Sins of the fathers, and their fathers. Eur. J. Hum. Genet. 2006;14:131–132.
    1. Burris H.H., Collins J.W., Jr. Race and preterm birth—The case for epigenetic inquiry. Ethn. Dis. 2010;20:296–299.
    1. Bjorn L.O., Wang T. Is provitamin D a UV-B receptor in plants? Plant Ecol. 2001;154:1–8.
    1. Bjorn L.O., Wang T. Vitamin D in an ecological context. Int. J. Circumpolar. Health. 2000;59:26–32.
    1. Hollis B.W., Johnson D., Hulsey T.C., Ebeling M., Wagner C.L. Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. J. Bone Miner. Res. 2011;26:2341–2357.
    1. Wagner C.L., Taylor S.N., Hollis B.W. Does vitamin D make the world go ‘round’? Breastfeed. Med. 2008;3:239–250.
    1. Armas L., Hollis B.W., Heaney R.P. Vitamin D2 is much less effective than vitamin D3 in humans. J. Clin. Endocrinol. Metab. 2004;89:5387–5391.
    1. Lambert P.W., Stern P.H., Avioli R.C., Brackett N.C., Turner R.T., Greene A., Fu I.Y., Bell N.H. Evidence for extrarenal production of 1α,25-dihydroxyvitamin D in man. J. Clin. Invest. 1982;69:722–725.
    1. Turner R.T., Avioli R.C., Bell N.H. Extrarenal metabolism of 25-hydroxycholecalciferol in the rat: Regulation by 1,25-dihydroxycholecalciferol. Calcif. Tissue Int. 1984;36:274–278.
    1. Zehnder D., Bland R., Williams M., McNinch R.W., Howie A.J., Stewart P., Hewison M. Extrarenal expression of 25-hydroxyvitamin D3-1a-hydroxylase. J. Clin. Endocrinol. Metab. 2001;86:888–894.
    1. Adams J.S., Chen H., Chun R., Ren S., Wu S., Gacad M., Nguyen L., Ride J., Liu P., Modlin R., et al. Substrate and enzyme trafficking as a means of regulating 1,25-dihydroxyvitamin D synthesis and action: The human innate immune response. J. Bone Miner. Res. 2007;22:V20–V24.
    1. Novakovic B., Sibson M., Ng H.K., Manuelpillai U., Rakyan V., Down T., Beck S., Fournier T., Evain-Brion D., Dimitriadis E., 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;284:14838–14848.
    1. Mellanby E. Experimental rickets. Med. Res. Counc. Spec. Rep. Ser. 1921;61:1–78.
    1. Mellanby E. An experimental investigation on rickets. Lancet. 1919;194:407–412.
    1. Narang N., Gupta R., Jain M., Aaronson K. Role of vitamin D in pulmonary tuberculosis. J. Assoc. Phys. India. 1984;32:185–186.
    1. Weick M.T. A history of rickets in the United States. Am. J. Clin. Nutr. 1967;20:1234–1241.
    1. Rehman P. Sub-clinical rickets and recurrent infection. J. Trop. Pediatr. 1994;40:58.
    1. Liu P.T., Stenger S., Li H., Wenzel L., Tan B.H., Krutzik S.R., Ochoa M.T., Schauber J., Wu K., Meinken C., et al. Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006;311:1770–1773.
    1. Liu P., Stenger S., Tang D., Modlin R. Cutting edge: Vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J. Immunol. 2007;179:2060–2063.
    1. Zheng Y., Niyonsaba F., Ushio H., Nagaoka I., Ikeda S., Okumura K., Ogawa H. Cathelicidin LL-37 induces the generation of reactive oxygen species and release of human α-defensins from neutrophils. Br. J. Dermatol. 2007;157:1124–1131.
    1. Bikle D., Adams J., Christakos S. Vitamin D: Production, Metabolism, Mechanism of Action, and Clinical Requirements. In: Rosen C., editor. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th. American Society for Bone and Mineral Research; Washington, DC, USA: 2008. pp. 141–149.
    1. Fabri M., Stenger S., Shin D.M., Yuk J.M., Liu P.T., Realegeno S., Lee H.M., Krutzik S.R., Schenk M., Sieling P.A., et al. Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Sci. Transl. Med. 2011;3 doi: 10.1126/scitranslmed.3003045.
    1. Bikle D. Nonclassic actions of vitamin D. J. Clin. Endocrinol. Metab. 2009;94:26–34.
    1. Kamen D.L., Cooper G.S., Bouali H., Shaftman S.R., Hollis B.W., Gilkeson G.S. Vitamin D deficiency in systemic lupus erythematosus. Autoimmun. Rev. 2006;5:114–117.
    1. Kieseier B., Giovannoni G., Hartung H. Immunological surrogate markers of disease activity in multiple sclerosis. Electroencephalogr. Clin. Neurophysiol. Suppl. 1999;50:570–583.
    1. Hayes C.E. Vitamin D: A natural inhibitor of multiple sclerosis. Proc. Nutr. Soc. 2000;59:531–535.
    1. Munger K., Zhang S., O’Reilly E., Hernan M., Olek M., Willett W., Ascherio A. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62:60–65.
    1. Willer C.J., Dyment D.A., Sadovnick A.D., Rothwell P.M., Murray T.J., Ebers G.C. Timing of birth and risk of multiple sclerosis: Population based study. BMJ. 2005;330 doi: 10.1136/bmj.38301.686030.63.
    1. Chaudhuri A. Why we should offer routine vitamin D supplementation in pregnancy and childhood to prevent multiple sclerosis. Med. Hypothesis. 2005;64:608–618.
    1. Ponsonby A., Lucas R., vanderMei I. UVR, vitamin D and three autoimmune diseases—multiple sclerosis, type 1 diabetes, rheumatoid arthritis. Photochem. Photobiol. 2005;81:1267–1275.
    1. Munger K.L., Levin L.I., Hollis B.W., Howard N.S., Ascherio A. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. J. Am. Med. Assoc. 2006;296:2832–2838.
    1. Arnson Y., Amital H., Shoenfeld Y. Vitamin D and autoimmunity: New aetiological and therapeutic considerations. 2007;66:1137–1142.
    1. Kimball S.M., Ursell M.R., O’Connor P., Vieth R. Safety of vitamin D3 in adults with multiple sclerosis. 2007;86:645–651.
    1. Arnson Y., Amital H., Shoenfeld Y. Vitamin D and autoimmunity: New aetiological and therapeutic considerations. 2007;66:1137–1142.
    1. Merlino L.A., Curtis J., Mikuls T.R., Cerhan J.R., Criswell L.A., Saag K.G. Vitamin D intake is inversely associated with rheumatoid arthritis: Results from the Iowa Women’s Health Study. Arthritis Rheum. 2004;50:72–77.
    1. Cutolo M., Otsa K., Uprus M., Paolino S., Seriolo B. Vitamin D in rheumatoid arthritis. Autoimmun. Rev. 2007;7:59–64.
    1. Boucher B.J. Strategies for reduction in the prevalence of NIDDM; the case for a population-based approach to the development of policies to deal with environmental factors in its aetiology. Diabetologia. 1995;38:1125–1129. doi: 10.1007/BF00402186.
    1. The EURODIAB Substudy 2 Study Group. Vitamin D supplement in early childhood and risk for Type 1 (insulin-dependent) diabetes mellitus. Diabetologia. 1999;42:51–54.
    1. Hypponen E., Laara E., Reunanen A., Jarvelin M.R., Virtanen S.M. Intake of vitamin D and risk of type 1 diabetes: A birth-cohort study. Lancet. 2001;358:1500–1503.
    1. Hypponen E. Micronutrients and the risk of type 1 diabetes: Vitamin D, vitamin E, and nicotinamide. Nutr. Rev. 2004;62:340–347.
    1. Harris S.S. Vitamin D in type 1 diabetes prevention. J. Nutr. 2005;135:323–325.
    1. Pittas A.G., Lau J., Hu F.B., Dawson-Hughes B. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J. Clin. Endocrinol. Metab. 2007;92:2017–2029. doi: 10.1210/jc.2007-0298.
    1. Liu S., Song Y., Ford E.S., Manson J.E., Buring J.E., Ridker P.M. Dietary calcium, vitamin D, and the prevalence of metabolic syndrome in middle-aged and older U.S. women. Diabetes Care. 2005;28:2926–2932. doi: 10.2337/diacare.28.12.2926.
    1. Ford E.S., Ajani U.A., McGuire L.C., Liu S. Concentrations of serum vitamin D and the metabolic syndrome among U.S. adults. Diabetes Care. 2005;28:1228–1230.
    1. Garland C., Comstock G., Garland F., Helsing K., Shaw E., Gorham E. Serum 25(OH)D and colon cancer: Eight-year prospective study. Lancet. 1989;334:1176–1178.
    1. Tseng M., Breslow R.A., Graubard B.I., Ziegler R.G. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am. J. Clin. Nutr. 2005;81:1147–1154.
    1. Wu K., Feskanich D., Fuchs C.S., Willett W.C., Hollis B.W., Giovannucci E.L. A nested case control study of plasma 25-hydroxyvitamin D concentrations and risk of colorectal cancer. J. Natl. Cancer Inst. 2007;99:1120–1129.
    1. Hu J., Morrison H., Mery L., DesMeules M., Macleod M. Canadian Cancer Registries Epidemiology Research Group. Diet and vitamin or mineral supplementation and risk of colon cancer by subsite in Canada. Eur. J. Cancer Prev. 2007;16:275–291. doi: 10.1097/01.cej.0000228411.21719.25.
    1. Eisman J.A., Suva L.J., Sher E., Pearce P.J., Funder J.W., Martin T.J. Frequency of 1,25-dihydroxyvitamin D3 receptor in human breast cancer. Cancer Res. 1981;41:5121–5124.
    1. Sher E., Eisman J.A., Moseley J.M., Martin T.J. Whole-cell uptake and nuclear localization of 1,25-dihydroxycholecalciferol by breast cancer cells (T47 D) in culture. Biochem. J. 1981;200:315–320.
    1. Garland F., Garland C., Gorham E., Young J. Geographic variation in breast cancer mortality in the United States: A hypothesis involving exposure to solar radiation. Prev. Med. 1990;19:614–622.
    1. Mordan-McCombs S., Valrance M., Zinser G., Tenniswood M., Welsh J. Calcium, vitamin D and the vitamin D receptor: Impact on prostate and breast cancer in preclinical models. Nutr. Rev. 2007;65:S131–S133.
    1. Garland C., Gorham E., Mohr S., Grant W., Giovannucci E., Lipkin M. Vitamin D and prevention of breast cancer: Pooled analysis. J. Steroids Biochem. 2007;103:708–711.
    1. Freedman D.M., Chang S.C., Falk R.T., Purdue M.P., Huang W.Y., McCarty C.A., Hollis B.W., Graubard B.I., Berg C.D., Ziegler R.G. Serum levels of vitamin D metabolites and breast cancer risk in the prostate, lung, colorectal, and ovarian cancer screening trial. Cancer Epidemiol. Biomark. Prev. 2008;17:889–894.
    1. Platz E.A., Leitzmann M.F., Hollis B.W., Willett W.C., Giovannucci E. Plasma 1,25-dihydroxy- and 25-hydroxyvitamin D and subsequent risk of prostate cancer. Cancer Causes Control. 2004;15:255–265.
    1. Giovannucci E., Liu Y., Rimm E.B., Hollis B.W., Fuchs C.S., Stampfer M.J., Willett W.C. Prospective study of predictors of vitamin D status and cancer incidence and mortality in men. J. Natl. Cancer Inst. 2006;98:451–459.
    1. Giovannucci E. Strengths and limitations of current epidemiologic studies: Vitamin D as a modifier of colon and prostate cancer risk. Nutr. Rev. 2007;65:S77–S79.
    1. Mikhak B., Hunter D.J., Spiegelman D., Platz E.A., Hollis B.W., Giovannucci E. Vitamin D receptor (VDR) gene polymorphisms and haplotypes, interactions with plasma 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and prostate cancer risk. Prostate. 2007;67:911–923.
    1. Haddow J.E., Neveux L.M., Palomaki G.E., Lambert-Messerlian G., Canick J.A., Grenache D.G., Lu J. The relationship between PTH and 25-hydroxy vitamin D early in pregnancy. Clin. Endocrinol. 2011;75:309–314.
    1. Vieth R., Ladak Y., Walfish P. Age-related changes in the 25-hydroxyvitamin D versus parathyroid hormone relationship suggest a different reason why older adults require more vitamin D. J. Clin. Endocrinol. Metab. 2003;88:185–191.
    1. Aloia J.F., Talwar S.A., Pollack S., Feuerman M., Yeh J.K. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am. J. Clin. Nutr. 2006;84:602–609.
    1. Okonofua F., Menon R.K., Houlder S., Thomas M., Robinson D., O’Brien S., Dandona P. Calcium, vitamin D and parathyroid hormone relationships in pregnant Caucasian and Asian women and their neonates. Ann. Clin. Biochem. 1987;24:22–28.
    1. Morley R., Carlin J.B., Pasco J.A., Wark J.D. Maternal 25-hydroxyvitamin D and parathyroid hormone concentrations and offspring birth size. J. Clin. Endocrinol. Metab. 2006;91:906–912.
    1. Hamilton S., McNeil R., Hollis B., Davis D., Winkler J., Cook C., Warner G., Bivens B., McShane P., Wagner C. Profound Vitamin D deficiency in a diverse group of women during pregnancy living in a sun-rich environment at latitude 32°N. Int. J. Endocrinol. 2010;2010 doi: 10.1155/2010/917428.
    1. Viljakainen H.T., Saarnio E., Hytinantti T., Miettinen M., Surcel H., Mäkitie O., Andersson S., Laitinen K., Lamberg-Allardt C. Maternal vitamin D status determines bone variables in the newborn. J. Clin. Endocrinol. Metab. 2010;95:1749–1757.
    1. Mahon P., Harvey N., Crozier S., Inskip H., Robinson S., Arden N., Swaminathan R., Cooper C., Godfrey K. Low maternal vitamin D status and fetal bone development: Cohort study. J. Bone Miner. Res. 2009;25:14–19.
    1. Pasco J.A., Wark J.D., Carlin J.B., Ponsonby A.L., Vuillermin P.J., Morley R. Maternal vitamin D in pregnancy may influence not only offspring bone mass but other aspects of musculoskeletal health and adiposity. Med. Hypotheses. 2008;71:266–269.
    1. Walker V., Zhang X., Rastegar I., Liu P., Hollis B., Adams J., Modlin R. Cord blood vitamin D status impacts innate immune responses. J. Clin. Endocrinol. Metab. 2010;96:1835–1843.
    1. Johnson D.D., Wagner C.L., Hulsey T.C., McNeil R.B., Ebeling M., Hollis B.W. Vitamin D Deficiency and Insufficiency is Common during Pregnancy. Am. J. Perinatol. 2011;28:7–12.
    1. Hollis B., Johnson D., Hulsey T., Ebeling M., Wagner C. Vitamin D supplementation during pregnancy: Double-blind, randomized clinical trial of safety and effectiveness. J. Bone Miner. Res. 2011;26:2341–2357.
    1. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes for Vitamin D and Calcium. National Academy Press; Washington, DC, USA: 2010.
    1. Hollis B., Roos B., Lambert P. Vitamin D in plasma: Quantitation by a nonequilbrium ligand binding assay. Steroids. 1981;37:609–619.
    1. Cockburn F., Belton N., Purvis R., Giles M., Brown J., Turner T., Wilkinson E., Forfar J., Barrie W., McKay G., et al. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. Br. Med. J. 1980;231:1–10.
    1. Maxwell J.D., Ang L., Brooke O.G., Brown I.R.F. Vitamin D supplements enhance weight gain and nutrional status in pregnant Asians. Br. J. Obstet. Gyneaecol. 1981;88:987–991.
    1. Brooke O.G., Brown I.R.F., Bone C.D.M., Carter N.D., Cleeve H.J.W., Maxwell J.D., Robinson V.P., Winder S.M. Vitamin D supplements in pregnant Asian women: Effects on calcium status and fetal growth. Br. Med. J. 1980;1:751–754.
    1. Brooke O.G., Butters F., Wood C. Intrauterine vitamin D nutrition and postnatal growth in Asian infants. Br. Med. J. 1981;283:1024.
    1. Brooke O., Brown I., Cleeve H., Sood A. Observations on the vitamin D state of pregnant Asian women in London. Br. J. Obstet. Gynaecol. 1981;88:18–26.
    1. Marya R., Rathee S., Lata V., Mudgil S. Effects of vitamin D supplementation in pregnancy. Gynecol. Obstet. Invest. 1981;12:155–161.
    1. Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. Dietary Reference Intakes: Calcium, Phosphorus, Magnesium, Vitamin D and Fluoride. National Academy Press; Washington, DC, USA: 1997.
    1. Nesby-O’Dell S., Scanlon K., Cogswell M., Gillespie C., Hollis B., Looker A., Allen C., Doughertly C., Gunter E., Bowman B. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: Third National Health and Nutrition Examination Survey: 1988–1994. Am. J. Clin. Nutr. 2002;76:187–192.
    1. Hamilton S.A., McNeil R., Hollis B.W., Davis D.J., Winkler J., Cook C., Warner G., Bivens B., McShane P., Wagner C.L. Profound Vitamin D Deficiency in a Diverse Group of Women during Pregnancy Living in a Sun-Rich Environment at Latitude 32°N. Int. J. Endocrinol. 2010;2010 doi: 10.1155/2010/917428.
    1. Dawodu A., Wagner C.L. Mother-child vitamin D deficiency: An international perspective. Arch. Dis. Child. 2007;92:737–740.
    1. Javaid M., Crozier S., Harvey N., Gale C., Dennison E., Boucher B., Arden N., Godfrey K., Cooper C. Maternal vitamin D status during pregancy and childhood bone mass at 9 years: A longitudinal study. Lancet. 2006;367:36–43.
    1. Dawodu A., Agarwal M., Patel M., Ezimokhai M. Serum 25-hydroxyvitamin D and calcium homeostasis in the United Arab Emirates mothers and neonates: A preliminary report. Middle East Paediatr. 1997;2:9–12.
    1. Bassir M., Laborie S., Lapillonne A., Claris O., Chappuis M.C., Salle B.L. Vitamin D deficiency in Iranian mothers and their neonates: A pilot study. Acta Paediatr. 2001;90:577–579.
    1. Sachan A., Gupta R., Das V., Agarwal A., Awasth P., Bhatia V. High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. Am. J. Clin. Nutr. 2005;81:1060–1064.
    1. Judkins A., Eagleton C. Vitamin D deficiency in pregnant New Zealand women. N. Z. Med. J. 2006;119:U2144.
    1. Shibata M., Suzuki A., Sekiya T., Sekiguchi S., Asano S., Udagawa Y., Itoh M. High prevalence of hypovitaminosis D in pregnant Japanese women with threatened premature delivery. J. Bone Miner. Metab. 2011;29:615–620.
    1. Van der Meer I., Karamali N., Boeke A. High prevalence of vitamin D deficiency in pregnant non-Western women the The Hague, Netherlands. Am. J. Clin. Nutr. 2006;84:350–353.
    1. Milman N., Hvas A.M., Bergholt T. Vitamin D status during normal pregnancy and postpartum. A longitudinal study in 141 Danish women. J. Perinat. Med. 2011;40:57–61.
    1. Bouillon R., van Baelen H., DeMoor D. 25-Hydroxy-vitamin D and its binding protein in maternal and cord serum. J. Clin. Endocrinol. Metab. 1977;45:679–684.
    1. Bouillon R., Van Assche F.A., Van Baelen H., Heyns W., DeMoor P. Influence of the Vitamin D-binding protein on serum concentrations of 1,25(OH)2D. J. Clin. Invest. 1981;67:589–596.
    1. Markestad T., Aksnes L., Ulstein M., Aarskog D. 25-Hydroxyvitamin D and 1,25-dihydroxy vitamin D of D2 and D3 origin in maternal and umbilical cord serum after vitamin D2 supplementation in human pregnancy. Am. J. Clin. Nutr. 1984;40:1057–1063.
    1. Hollis B.W., Pittard W.B. Evaluation of the total fetomaternal vitamin D relationships at term: Evidence for racial differences. J. Clin. Endorcrinol. Metab. 1984;59:652–657.
    1. Hollis B.W., Wagner C.L. Assessment of dietary vitamin D requirements during pregnancy and lactation. Am. J. Clin. Nutr. 2004;79:717–726.
    1. Hollis B.W., Wagner C.L. Nutritional vitamin D status during pregnancy: Reasons for concern. CMAJ. 2006;174:1287–1290.
    1. Medzhitov R., Janeway C. Innate immunity. N. Engl. J. Med. 2000;343:338–344.
    1. Neu J., Mackey A.D. Neonatal Gastrointestinal Innate Immunity. Neoreviews. 2003;4:e14–e19.
    1. Mannion C., Gray-Donald K., Koski K. Milk restriction and low maternal vitamin D intake during pregnancy are associated with decreased birth weight. CMAJ. 2006;174:1273–1277.
    1. Pawley N., Bishop N.J. Prenatal and infant predictors of bone health: The influence of vitamin D. Am. J. Clin. Nutr. 2004;80:1748S–1751S.
    1. Maghbooli Z., Hossein-Nezhad A., Shafaei A., Karimi F., Madani F., Larijani B. Vitamin D status in mothers and their newborns in Iran. BMC Pregnancy Childbirth. 2007;7 doi: 10.1186/1471-2393-7-1.
    1. Belderbos M.E., Houben M.L., Wilbrink B., Lentjes E., Bloemen E.M., Kimpen J.L., Rovers M., Bont L. Cord blood vitamin D deficiency is associated with respiratory syncytial virus bronchiolitis. Pediatrics. 2011;127:e1513–e1520.
    1. Houben M.L., Bont L., Wilbrink B., Belderbos M.E., Kimpen J.L., Visser G.H., Rovers M.M. Clinical prediction rule for RSV bronchiolitis in healthy newborns: Prognostic birth cohort study. Pediatrics. 2011;127:35–41.
    1. Hansdottir S., Monick M.M., Lovan N., Powers L., Gerke A., Hunninghake G.W. Vitamin D decreases respiratory syncytial virus induction of NF-kappaB-linked chemokines and cytokines in airway epithelium while maintaining the antiviral state. J. Immunol. 2010;184:965–974.
    1. McGrath J., Feton F., Eyles D. Does “imprinting” with low prenatal vitamin D contribute to the risk of various adult disorders? Med. Hypotheses. 2001;56:367–371. doi: 10.1054/mehy.2000.1226.
    1. Hathcock J.N., Shao A., Vieth R., Heaney R. Risk assessment for vitamin D. Am. J. Clin. Nutr. 2007;85:6–18.
    1. Hollick M. Vitamin D Deficiency. N. Engl. J. Med. 2007;357:266–281.
    1. Vieth R., Bischoff-Ferrari H., Boucher B.J., Dawson-Hughes B., Garland C.F., Heaney R.P., Holick M.F., Hollis B.W., Lamberg-Allardt C., McGrath J.J., et al. The urgent need to recommend an intake of vitamin D that is effective. Am. J. Clin. Nutr. 2007;85:649–650.
    1. Hollis B.W. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: Implications for establishing a new effective dietary intake recommendation for vitamin D. J. Nutr. 2005;135:317–322.
    1. Hollis B., Wagner C.L., Kratz A., Sluss P.M., Lewandrowski K.B. Normal serum vitamin D levels. N. Engl. J. Med. 2005;352:515–516.
    1. McGrath J. Hypothesis: Is low prenatal vitamin D a risk-modifying factor for schizophrenia? Schizophr. Res. 1999;49:173–177. doi: 10.1016/S0920-9964(99)00052-3.
    1. McGrath J., Selten J.P., Chant D. Long-term trends in sunshine duration and its association with schizophrenia birth rates and age at first registration-data from Australia and the Netherlands. Schizophr. Res. 2002;54:199–212.
    1. Eyles D., Brown J., MacKay-Sim A., McGrath J., Feron F. Vitamin D3 and brain development. Neuroscience. 2003;118:641–653.
    1. Brown J., Bianco J., McGrath J., Eyles D. 1,25-Dihydroxyvitamin D-3 induces nerve growth factor, promotes neurite outgrowth and inhibits mitosis in embryonic rat hippocampal neurons. Neurosci. Lett. 2003;343:139–143.
    1. Ko P., Burkert R., McGrath J., Eyles D. Maternal vitamin D3 deprivation and the regulation of apoptosis and cell cyle during rat brain development. Dev. Brain Res. 2004;153:61–68.
    1. Burne T., Becker A., Brown J., Eyles D., MacKay-Sim A., McGrath J. Transient prenatal vitamin D deficiency is associated with hyperlocomotion in adult rats. Behav. Brain Res. 2004;154:549–555.
    1. Burne T., Feron F., Brown J., Eyles D., McGrath J., Mackay-Sim A. Combined prenatal and chronic postnatal vitamin D deficiency in rats impairs prepulse inhibition of acoustic startle. Physiol. Behav. 2004;81:651–655.
    1. Cui X., McGrath J.J., Burne T.H.J., Mackay-Sim A., Eyles D.W. Maternal vitamin D depletion alters neurogenesis in the developing rat brain. Int. J. Dev. Neurosci. 2007;25:227–232.
    1. O'Loan J., Eyles D.W., Kesby J., Ko P., McGrath J.J., Burne T.H.J. Vitamin D deficiency during various stages of pregnancy in the rat; its impact on development and behaviour in adult offspring. Psychoneuroendocrinology. 2007;32:227–234. doi: 10.1016/j.psyneuen.2006.12.006.
    1. Kesby J., Burne T., McGrath J., Eyles D. Developmental vitamin D deficiency alters MK 801-induced hyperlocomotion in the adult rat: An animal model of schizophrenia. Biol. Psychiat. 2006;60:591–596.
    1. Hatun S., Ozkan B., Orbak Z., Doneray H., Cizmecioglu F., Toprak D., Calikoglu A.S. Vitamin D Deficiency in Early Infancy. J. Nutr. 2005;135:279–282.
    1. Schnadower D., Agarwal C., Oberfield S., Fennoy I., Pusic M. Hypocalcemic seizures and secondary bilateral femoral fractures in an adolescent with primary vitamin D deficiency. Pediatrics. 2006;118:22226–22230.
    1. Cockburn F., Belton N.R., Purvis R.J., Giles M.M., Brown J.K., Turner T.L., Wilkinson E.M., Forfar J.O., Barrie W.J.M., McKay G.S., et al. Maternal vitamin D intake and mineral metabolism in mothers and their newborn infants. Br. Med. J. 1980;5:11–14.
    1. Chiu K., Chu A., Go V., Soad M. Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction. Am. J. Clin. Nutr. 2004;79:820–825.
    1. Forman J.P., Giovannucci E., Holmes M.D., Bischoff-Ferrari H.A., Tworoger S.S., Willett W.C., Curhan G.C. Plasma 25-hydroxyvitamin D levels and risk of incident hypertension. Hypertension. 2007;49:1063–1069.
    1. Zittermann A., Schleithoff S.S., Koerfer R. Putting cardiovascular disease and vitamin D insufficiency into perspective. Br. J. Nutr. 2005;94:483–492.
    1. Zittermann A., Schleithoff S.S., Koerfer R. Vitamin D insufficiency in congestive heart failure: Why and what to do about it? Heart Fail. Rev. 2006;11:25–33.
    1. Forman J.P., Giovannucci E., Holmes M.D., Bischoff-Ferrari H.A., Tworoger S.S., Willett W.C., Curhan G.C. Plasma 25-Hydroxyvitamin D Levels and Risk of Incident Hypertension. 2007;49:1063–1069.
    1. Giovannucci E., Liu Y., Hollis B.W., Rimm E.B. 25-hydroxyvitamin D and risk of myocardial infarction in men: A prospective study. Arch. Intern. Med. 2008;168:1174–1180.
    1. Rao R.K. Prospective study of colorectal cancer in the West of Scotland: 10-year follow-up. Br. J. Surg. 1990;77:280–282.
    1. Lefkowitz E., Garland C. Sunlight, vitamin D, and ovarian cancer mortality rates in US women. Int. J. Epidemiol. 1994;23:1133–1136.
    1. Grant W.B. An estimate of premature cancer mortality in the US due to inadequate doses of solar ultraviolet-B radiation. Cancer. 2002;94:1867–1875.
    1. Rao R.K. Prostate cancer. Trop. Doct. 2002;32:155–157.
    1. Holick M.F. Vitamin D: Importance in the prevention of cancers, type 1 diabetes, heart disease, and osteoporosis. Am. J. Clin. Nutr. 2004;79:362–371.
    1. Egan K.M., Signorello L.B., Munro H.M., Hargreaves M.K., Hollis B.W., Blot W.J. Vitamin D insufficiency among African-Americans in the southeastern United States: Implications for cancer disparities (United States). Cancer Causes Control. 2008;19:527–535.
    1. Morgan V., McGrath J., Hultman C., Zubrick S., Bower C., Valuri G., Jablensky A. The Offspring of Women with Severe Mental Disorder. In: Newnham J.P., Ross M.G., editors. Early Life Origins of Human Health and Disease. S. Karger; Basel, Switzerland: 2009. pp. 202–204.
    1. Martineau A.R., Wilkinson R.J., Wilkinson K.A., Newton S.M., Kampmann B., Hall B.M., Packe G.E., Davidson R.N., Eldridge S.M., Maunsell Z.J., et al. A single dose of vitamin D enhances immunity to mycobacteria. Am. J. Respir. Crit. Care Med. 2007;176:208–213.
    1. Hollis B.W. Circulating 25-hydroxyvitamin D levels indicative of vitamin sufficiency: Implications for establishing a new effective DRI for vitamin D. J. Nutr. 2005;135:317–322.
    1. Holick M.F. Vitamin D deficiency. N. Engl. J. Med. 2007;357:266–281.
    1. Luxwolda M.F., Kuipers R.S., Kema I.P., Janneke Dijck-Brouwer D.A., Muskiet F.A. Traditionally living populations in East Africa have a mean serum 25-hydroxyvitamin D concentration of 115 nmol/L. Br. J. Nutr. 2012 doi: 10.1017/S0007114511007161.
    1. Vieth R., Chan P.C., MacFarlane G.D. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am. J. Clin. Nutr. 2001;73:288–294.
    1. Heaney R., Davies K., Chen T., Holick M., Barger-Lux M. Human serum 25-hydroxycholecalciferol response to extended oral dosing with cholecalciferol. Am. J. Clin. Nutr. 2003;77:204–210.
    1. National Coalition for Skin Cancer Prevention. The National Forum for Skin Cancer Prevention in Health, Physical Education, Recreation and Youth Sports. American Association for Health Education; Reston, VA, USA: 1998.
    1. Reichrath J. The challenge resulting from positive and negative effects of sunlight: How much solar UV exposure is appropriate to balance between risks of vitamin D deficiency and skin cancer? Prog. Biophys. Mol. Biol. 2006;92:9–16. doi: 10.1016/j.pbiomolbio.2006.02.010.
    1. Greer F.R. Issues in establishing vitamin D recommendations for infants and children. Am. J. Clin. Nutr. 2004;80:1759S–1762S.
    1. Mahomed K., Gulmezoglu A.M. Cochrane Database of Systematic Reviews. John Wiley & Sons; Chicester, UK: 1999. Vitamin D Supplementation in Pregnancy (Cochrane Review)
    1. Wagner C., McNeil R., Hamilton S., Davis D., Prudgen C., Winkler J., Warner G., Bivens B., Cook C., McShane P., et al. Vitamin D (vitD) Supplementation during Pregnancy: Thrasher Research Fund RCT in SC Community Health Center Networks. Pediatric Academic Societies Annual Meeting; Vancouver, Canada. May 2010; Abstract 3737.375.
    1. Wagner C., Johnson D., Hulsey T., Ebeling M., Shary J., Smith P., Bivens B., Hollis B. Vitamin D Supplementation during Pregnancy Part 2 NICHD/CTSA Randomized Clinical Trial (RCT): Outcomes. Pediatric Academic Societies Annual Meeting; Vancouver, Canada. May 2010; Abstract 1665.6.
    1. Wagner C., McNeil R., Ebeling M., Hulsey T., Johnson D., Hollis B. Analysis of Two Randomized Vitamin D3 Supplementation Trials during Pregnancy: Health Characteristics and Outcomes. 2012. Medical University of South Carolina, Charleston, SC, USA. Unpublished work.
    1. Vieth R., Bischoff-Ferrari H., Boucher B., Dawson-Hughes B., Garland C., Heaney R., Holick M., Hollis B., Lamberg-Allardt C., McGrath J., et al. The urgent need to recommend an intake of vitamin D that is effective. Am. J. Clin. Nutr. 2007;85:649–650.
    1. Bodnar L.M., Simhan H.N. Vitamin D may be a link to black-white disparities in adverse birth outcomes. Obstet. Gynecol. Surv. 2010;65:273–284.
    1. Robinson C.J., Alanis M.C., Wagner C.L., Hollis B.W., Johnson D.D. Plasma 25-hydroxyvitamin D levels in early-onset severe preeclampsia. Am. J. Obstet. Gynecol. 2010;203:e361–e366.
    1. Robinson C.J., Wagner C.L., Hollis B.W., Baatz J.E., Johnson D.D. Maternal vitamin D and fetal growth in early-onset severe preeclampsia. Am. J. Obstet. Gynecol. 2011;204:e551–e554.

Source: PubMed

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