Abstract
We studied bone mineral content (BMC), bone mineral density (BMD), and body composition in offspring of women supplemented with vitamin D during pregnancy. Pregnant women were randomized to receive oral cholecalciferol 60,000 units 4 weekly (group 1), 8 weekly (group 2), or placebo (group 3). All received 1 g calcium daily (groups 1 and 2 without, and group 3 with 400 units vitamin D). Offspring at 12–16 months underwent dual-energy X-ray absorptiometry. Maternal hypovitaminosis D at recruitment was common (serum 25OHD <50 nmol/L in 88 %) and severe (25OHD <25 nmol/L in 46 %). Groups 1 and 2 (n = 23 and 13, median age 14 months) had higher cord blood 25OHD (47.8 ± 13.8 and 31.0 ± 14.0 nmol/L) versus group 3 (n = 16, median age 16 months, 17.8 ± 13.5 nmol/L, p < 0.001). Babies in group 3 had higher whole-body BMC (250.8 ± 42.5 gm) and BMD (0.335 ± 0.033 gm/cm2) compared to group 1 (213.1 ± 46.2 gm and 0.295 ± 0.041 gm/cm2) and group 2 (202.9 ± 29.9 gm and 0.287 ± 0.023 gm/cm2) (p = 0.006 and 0.001, respectively). In multivariate analysis, age, weight z score, and lean body mass remained significant contributors to BMC. Parameters of body composition were comparable among the groups. Vitamin D supplementation to pregnant women with severe deficiency in doses that improved cord blood 25OHD did not result in improved bone health or body composition in offspring at 12–16 months, compared to a dose too small to improve 25OHD levels.
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References
Harvey N, Dennison E, Cooper C (2014) Osteoporosis: a lifecourse approach. J Bone Miner Res 29:1917–1925
Viljakainen HT, Saarnio E, Hytinantti T, Miettinen M, Surcel H, Makitie O, Andersson S, Laitinen K, Lamberg-Allardt C (2010) Maternal vitamin D status determines bone variables in the newborn. J Clin Endocrinol Metab 95:1749–1757
Javaid MK, Crozier SR, Harvey NC, Gale CR, Dennison EM, Boucher BJ, Arden NK, Godfrey KM, Cooper C (2006) Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet 367:36–43
Zhu K, Whitehouse AJ, Hart PH, Kusel M, Mountain J, Lye S, Pennell C, Walsh JP (2014) Maternal vitamin D status during pregnancy and bone mass in offspring at 20 years of age: a prospective cohort study. J Bone Miner Res 29:1088–1095
Dror DK, King JC, Durand DJ, Fung EB, Allen LH (2012) Feto-maternal vitamin D status and infant whole-body bone mineral content in the first weeks of life. Eur J Clin Nutr 66:1016–1019
Ioannou C, Javaid MK, Mahon P, Yaqub MK, Harvey NC, Godfrey KM, Noble JA, Cooper C, Papageorghiou AT (2012) The effect of maternal vitamin D concentration on fetal bone. J Clin Endocrinol Metab 97:E2070–E2077
Viljakainen HT, Korhonen T, Hytinantti T, Laitinen EKA, Andersson S, Makitie O, Lamberg-Allardt C (2011) Maternal vitamin D status affects bone growth in early childhood—a prospective cohort study. Osteoporos Int 22:883–891
Lawlor DA, Wills AK, Fraser A, Sayers A, Fraser WD, Tobias JH (2013) Association of maternal vitamin D status during pregnancy with bone-mineral content in offspring: a prospective cohort study. Lancet 381:2176–2183
Weiler H, Fitzpatrick-Wong S, Veitch R, Kovacs H, Schellenberg J, McCloy U, Yuen KC (2005) Vitamin D deficiency and whole-body and femur bone mass relative to weight in healthy newborns. CMAJ 172:757–761
Petersen SB, Olsen SF, Molgaard C, Granstrom C, Cohen A, Vestergaard P, Strom M (2014) Maternal vitamin D status and offspring bone fractures: prospective study over two decades in Aarhus city, Denmark. PLoS One 9:e114334
Congdon P, Horsman A, Kirby PA, Dibble J, Bashir T (1983) Mineral content of the forearms of babies born to Asian and white mothers. Br Med J (Clin Res Ed) 286:1233–1235
Diogenes MEL, Bezerra FF, Rezende EP, Donangelo CM (2015) Calcium plus vitamin D supplementation during the third trimester of pregnancy in adolescents accustomed to low calcium diets does not affect infant bone mass at early lactation in a randomized controlled trial. J Nutr 145:1515–1523
Committee to review dietary reference intakes for vitamin D and calcium, Institute of Medicine (2011) In: Ross AC, Taylor CL, Yaktine AL, Valle HBD (eds) Dietary reference intakes for calcium and vitamin D. The National Academies Press, USA
Cooper C, Harvey NC, Bishop NJ, Kennedy S, Papageorghiou AT, Schoenmakers I, Fraser R, Gandhi SV, Carr A, D’Angelo S, Crozier SR, Moon RJ, Arden NK, Dennison EM, Godfrey KM, Inskip HM, Prentice A, Mughal MZ, Eastell R et al (2016) Maternal gestational vitamin D supplementation and offspring bone health (MAVIDOS): a multicentre, double-blind, randomised placebo-controlled trial. Lancet Diabetes Endocrinol 4:393–402
Krishnaveni GV, Veena SR, Winder NR, Hill JC, Noonan K, Boucher BJ, Karat SC, Fall CHD (2011) Maternal vitamin D status during pregnancy and body composition and cardiovascular risk markers in Indian children: the Mysore Parthenon study. Am J Clin Nutr 93:628–635
Crozier SR, Harvey NC, Inskip HM, Godfrey KM, Cooper C, Robinson SM, the SWS study group (2012) Maternal vitamin D status in pregnancy is associated with adiposity in the offspring: findings from the Southampton Women’s Survey. Am J Clin Nutr 96:57–63
Gale CR, Robinson SM, Harvey NC, Javaid MK, Jiang B, Martyn CN, Godfrey KM, Cooper C, the Princess Anne Hospital study group (2008) Maternal vitamin D status during pregnancy and child outcomes. Eur J Clin Nutr 62:68–77
Morales E, Romieu I, Guerra S, Ballester F, Rebagliato M, Vioque J, Tardon A, Rodriguez Delhi C, Arranz L, Torrent M, Espada M, Basterrechea M, Sunyer J (2012) Maternal vitamin D status in pregnancy and risk of lower respiratory tract infections, wheezing, and asthma in offspring. Epidemiology 23:64–71
Pike KC, Inskip HM, Robinson S, Lucas JS, Cooper C, Harvey NC, Godfrey KM, Roberts G, Southampton Women’s Survey study group (2012) Maternal late-pregnancy serum 25-hydroxyvitamin D in relation to childhood wheeze and atopic outcomes. Thorax 67:950–956
Baiz N, Dargent-Molina P, Wark JD, Souberbielle JC, Annesi-Maesano I, EDEN mother-child cohort study group (2014) Cord serum 25-hydroxyvitamin D and risk of early childhood transient wheezing and atopic dermatitis. J Allergy Clin Immunol 133:147–153
de Jongh RT, Crozier SR, D’Angelo S, Pike KC, Roberts G, Lucas JSA, Inskip H, Godfrey KM, Cooper C, Harvey NC, Southampton Women’s Survey study group (2014) Maternal 25-hydroxyvitamin D levels in relation to offspring respiratory symptoms and infections. Eur Respir J 43:1181–1183
Goldring ST, Griffiths CJ, Martineau AR, Robinson S, Yu C, Poulton S, Kirkby JC, Stocks J, Hooper R, Shaheen SO, Warner JO, Boyle RJ (2013) Prenatal vitamin D supplementation and child respiratory health: a randomised controlled trial. PLoS One 8:e66627
Kuppuswamy B (1981) Manual of socioeconomic status (urban), 1st edn. Manasayan, Delhi, pp 66–72
Indian Labour Journal (2012) Labour Bureau, Shimla. Government of India
Suri L, Gagari E, Vastardis H (2004) Delayed tooth eruption: pathogenesis, diagnosis, and treatment. A literature review. Am J Orthod Dentofacial Orthop 126:432–445
Williams HC, Burney PG, Pembroke AC, Hay RJ, atopic dermatitis diagnostic criteria working party (1994) The UK Working Party’s diagnostic criteria for atopic dermatitis. III. Independent hospital validation. Br J Dermatol 131:406–416
Gallo S, Vanstone CA, Weiler HA (2012) Normative data for bone mass in healthy term infants from birth to 1 year of age. J Osteoporos. doi: 10.1155/2012/672403
Kovacs CS, Woodland ML, Fudge NJ, Friel JK (2005) The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol Endocrinol Metab 289:E133–E144
Acknowledgments
SKS was responsible for planning, conduct of the study, offspring recruitment and assessment, and manuscript writing. KKK was responsible recruitment of mothers and their assessment. VD and AA were responsible for conception and design of the study, while VB was responsible for conception, design and planning of the study, data analysis and drafting, revision and final approval of the manuscript. We acknowledge the grant support from Department of Biotechnology (BT/PR/13985/SPD/11/1297/2010) to V. Bhatia, intramural grant to S. K. Sahoo and V. Bhatia from SGPGIMS, Indian Council for Medical Research grant (manpower development scheme) to S. K. Sahoo. We thank Dr Joshua Richman, UAB School of Medicine, Birmingham, USA and Dr Ashish Awasthi, Department of Biostatistics, SGPGIMS, Lucknow for helpful discussions in statistical analysis. We extend our thanks to Arjun Singh, Pallavi Tiwari, Manoj Dubey and Rajesh Srivastava for their technical support in this project.
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The study protocol can be found at http://www.icmr.nic.in/ and http://ctri.nic.in/Clinicaltrials/login.php.
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Sahoo, S.K., Katam, K.K., Das, V. et al. Maternal vitamin D supplementation in pregnancy and offspring outcomes: a double-blind randomized placebo-controlled trial. J Bone Miner Metab 35, 464–471 (2017). https://doi.org/10.1007/s00774-016-0777-4
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DOI: https://doi.org/10.1007/s00774-016-0777-4