Skip to main content Accessibility help

Influence of daily 10–85 μg vitamin D supplements during pregnancy and lactation on maternal vitamin D status and mature milk antirachitic activity

  • Eline Stoutjesdijk (a1), Anne Schaafsma (a2), Ido P. Kema (a1), Jan van der Molen (a1), D. A. Janneke Dijck-Brouwer (a1) and Frits A. J. Muskiet (a1)...


Pregnant and lactating women and breastfed infants are at risk of vitamin D deficiency. The supplemental vitamin D dose that optimises maternal vitamin D status and breast milk antirachitic activity (ARA) is unclear. Healthy pregnant women were randomised to 10 (n 10), 35 (n 11), 60 (n 11) and 85 (n 11) µg vitamin D3/d from 20 gestational weeks (GW) to 4 weeks postpartum (PP). The participants also received increasing dosages of fish oil supplements and a multivitamin. Treatment allocation was not blinded. Parent vitamin D and 25-hydroxyvitamin D (25(OH)D) were measured in maternal plasma at 20 GW, 36 GW and 4 weeks PP, and in milk at 4 weeks PP. Median 25(OH)D and parent vitamin D at 20 GW were 85 (range 25–131) nmol/l and ‘not detectable (nd)’ (range nd–40) nmol/l. Both increased, seemingly dose dependent, from 20 to 36 GW and decreased from 36 GW to 4 weeks PP. In all, 35 µg vitamin D/d was needed to increase 25(OH)D to adequacy (80–249 nmol/l) in >97·5 % of participants at 36 GW, while >85 µg/d was needed to reach this criterion at 4 weeks PP. The 25(OH)D increments from 20 to 36 GW and from 20 GW to 4 weeks PP diminished with supplemental dose and related inversely to 25(OH)D at 20 GW. Milk ARA related to vitamin D3 dose, but the infant adequate intake of 513 IU/l was not reached. Vitamin D3 dosages of 35 and >85 µg/d were needed to reach adequate maternal vitamin D status at 36 GW and 4 weeks PP, respectively.


Corresponding author

*Corresponding author: E. Stoutjesdijk, email


Hide All
1. Brender, E, Burke, A & Glass, RM (2005) JAMA patient page. Vitamin D. JAMA 294, 2386.
2. Saraf, R, Morton, SM, Camargo, CA Jr, et al. (2016) Global summary of maternal and newborn vitamin D status – a systematic review. Matern Child Nutr 12, 647668.
3. Camargo, CA Jr, Ingham, T, Wickens, K, et al. (2011) Cord-blood 25-hydroxyvitamin D levels and risk of respiratory infection, wheezing, and asthma. Pediatrics 127, e180e187.
4. De-Regil, LM, Palacios, C, Lombardo, LK, et al. (2016) Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev, issue 1, CD008873.
5. Roth, DE, Leung, M, Mesfin, E, et al. (2017) Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ 359, j5237.
6. Kiely, ME, Zhang, JY, Kinsella, M, et al. (2016) Vitamin D status is associated with uteroplacental dysfunction indicated by pre-eclampsia and small-for-gestational-age birth in a large prospective pregnancy cohort in Ireland with low vitamin D status. Am J Clin Nutr 104, 354361.
7. Aghajafari, F, Nagulesapillai, T, Ronksley, PE, 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 346, f1169.
8. Miliku, K, Vinkhuyzen, A, Blanken, LM, et al. (2016) Maternal vitamin D concentrations during pregnancy, fetal growth patterns, and risks of adverse birth outcomes. Am J Clin Nutr 103, 15141522.
9. Wagner, CL, Baggerly, C, McDonnell, S, et al. (2016) Post-hoc analysis of vitamin D status and reduced risk of preterm birth in two vitamin D pregnancy cohorts compared with South Carolina March of Dimes 2009–2011 rates. J Steroid Biochem Mol Biol 155, 245251.
10. Wagner, CL, Hollis, BW, Kotsa, K, et al. (2017) Vitamin D administration during pregnancy as prevention for pregnancy, neonatal and postnatal complications. Rev Endocr Metab Disord 18, 307322.
11. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium, Ross AC, Taylor CL, et al. (editors) (2011) Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: National Academies Press (US). (accessed January 2016).
12. Vinkhuyzen, AA, Eyles, DW, Burne, TH, et al. (2016) Prevalence and predictors of vitamin D deficiency based on maternal mid-gestation and neonatal cord bloods: the Generation R Study. J Steroid Biochem Mol Biol 164, 161167.
13. Dawson-Hughes, B, Heaney, RP, Holick, MF, et al. (2005) Estimates of optimal vitamin D status. Osteoporos Int 16, 713716.
14. Zittermann, A (2003) Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutr 89, 552572.
15. Vieth, R (2006) What is the optimal vitamin D status for health? Prog Biophys Mol Biol 92, 2632.
16. Hossein-nezhad, A & Holick, MF (2013) Vitamin D for health: a global perspective. Mayo Clin Proc 88, 720755.
17. Evaluation of Dietary Reference Values for Vitamin D. The Hague: Health Council of the Netherlands, publication no. 2012/15E. (accessed March 2016).
18. Rossum CTM, Fransen HP, Verkaik-Kloosterman J, et al. (2011) Dutch National Food Consumption Survey 2007–2010: Diet of children and adults aged 7 to 69 years. (accessed March 2014).
19. Grant, CC, Stewart, AW, Scragg, R, et al. (2014) Vitamin D during pregnancy and infancy and infant serum 25-hydroxyvitamin D concentration. Pediatrics 133, e143e153.
20. March, KM, Chen, NN, Karakochuk, CD, et al. (2015) Maternal vitamin D(3) supplementation at 50 mug/d protects against low serum 25-hydroxyvitamin D in infants at 8 wk of age: a randomized controlled trial of 3 doses of vitamin D beginning in gestation and continued in lactation. Am J Clin Nutr 102, 402410.
21. Hollis, BW, Roos, BA, Draper, HH, et al. (1981) Vitamin D and its metabolites in human and bovine milk. J Nutr 111, 12401248.
22. Reeve, LE, Chesney, RW & DeLuca, HF (1982) Vitamin D of human milk: identification of biologically active forms. Am J Clin Nutr 36, 122126.
23. Neville, MC, Keller, R, Seacat, J, et al. (1988) Studies in human lactation: milk volumes in lactating women during the onset of lactation and full lactation. Am J Clin Nutr 48, 13751386.
24. Dawodu, A & Tsang, RC (2012) Maternal vitamin D status: effect on milk vitamin D content and vitamin D status of breastfeeding infants. Adv Nutr 3, 353361.
25. Ala-Houhala, M, Koskinen, T, Parviainen, MT, et al. (1988) 25-Hydroxyvitamin D and vitamin D in human milk: effects of supplementation and season. Am J Clin Nutr 48, 10571060.
26. við Streym, S, Hojskov, CS, Moller, UK, et al. (2016) Vitamin D content in human breast milk: a 9-mo follow-up study. Am J Clin Nutr 103, 107114.
27. Stoutjesdijk, E, Schaafsma, A, Nhien, NV, et al. (2017) Milk vitamin D in relation to the ‘adequate intake’ for 0–6-month-old infants: a study in lactating women with different cultural backgrounds, living at different latitudes. Br J Nutr 118, 804812.
28. Braegger, C, Campoy, C, Colomb, V, et al. (2013) Vitamin D in the healthy European paediatric population. J Pediatr Gastroenterol Nutr 56, 692701.
29. Wagner, CL, Greer, FR, American Academy of Pediatrics Section on Breastfeeding, et al. (2008) Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics 122, 11421152.
30. Wall, CR, Stewart, AW, Camargo, CA Jr, et al. (2015) Vitamin D activity of breast milk in women randomly assigned to vitamin D3 supplementation during pregnancy. Am J Clin Nutr 103, 382388.
31. Wagner, CL, Hulsey, TC, Fanning, D, et al. (2006) High-dose vitamin D3 supplementation in a cohort of breastfeeding mothers and their infants: a 6-month follow-up pilot study. Breastfeed Med 1, 5970.
32. Hollis, BW, Wagner, CL, Howard, CR, et al. (2015) Maternal versus infant vitamin D supplementation during lactation: a randomized controlled trial. Pediatrics 136, 625634.
33. EFSA (2012) Scientific Opinion of the NDA Panel: Tolerable Upper Intake Level of vitamin D. (accessed May 2014).
34. Mbugua, S, Ogeda, J, Muthui, I, et al. (2014) Reflections on Africa’s Indigenous Knowledge on Parenting. Indigenous Parenting Practices of Different Communities in Africa. Nairobi: Parenting in Africa Network.
35. Scheper-Hughes, N (1987) Child Survival. Anthropological Perspectives on the Treatment and Maltreatment of Children. Dordrecht: D. Reidel Publishing Company.
36. Stoutjesdijk, E, Schaafsma, A, Dijck-Brouwer, DAJ, et al. (2018) Fish oil supplemental dose needed to reach 1 g% DHA+EPA in mature milk. Prostaglandins Leukot Essent Fatty Acids 128, 5361.
37. van Grootheest, G, Milaneschi, Y, Lips, PT, et al. (2014) Determinants of plasma 25-hydroxyvitamin D levels in healthy adults in the Netherlands. Neth J Med 72, 533540.
38. Luxwolda, MF, Kuipers, RS, Kema, IP, et al. (2013) Vitamin D status indicators in indigenous populations in East Africa. Eur J Nutr 52, 11151125.
39. van Goor, SA, Dijck-Brouwer, DA, Hadders-Algra, M, et al. (2009) Human milk arachidonic acid and docosahexaenoic acid contents increase following supplementation during pregnancy and lactation. Prostaglandins Leukot Essent Fatty Acids 80, 6569.
40. Corso, G, Rossi, M, De, BD, et al. (2002) Effects of sample storage on 7- and 8-dehydrocholesterol levels analysed on whole blood spots by gas chromatography–mass spectrometry-selected ion monitoring. J Chromatogr B Analyt Technol Biomed Life Sci 766, 365370.
41. Kamao, M, Tsugawa, N, Suhara, Y, et al. (2007) Quantification of fat-soluble vitamins in human breast milk by liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 859, 192200.
42. Dirks, NF, Vesper, HW, van Herwaarden, AE, et al. (2016) Various calibration procedures result in optimal standardization of routinely used 25(OH)D ID-LC–MS/MS methods. Clin Chim Acta 462, 4954.
43. Basha, B, Rao, DS, Han, ZH, et al. (2000) Osteomalacia due to vitamin D depletion: a neglected consequence of intestinal malabsorption. Am J Med 108, 296300.
44. Heaney, RP (2005) The vitamin D requirement in health and disease. J Steroid Biochem Mol Biol 97, 1319.
45. Steegers, EAP, Thomas, CMG, de Boo, TM, et al. (1999) Klinisch-Chemische Referentiewaarden in De Zwangerschap (Clinical-Chemical Reference Values During Pregnancy). Maarssen: Elsevier/Bunge.
46. Cremers, E, Thijs, C, Penders, J, et al. (2011) Maternal and child’s vitamin D supplement use and vitamin D level in relation to childhood lung function: the KOALA Birth Cohort Study. Thorax 66, 474480.
47. Wacker, M & Holick, MF (2013) Sunlight and vitamin D: a global perspective for health. Dermatoendocrinol 5, 51108.
48. Holick, MF (2007) Vitamin D deficiency. N Engl J Med 357, 266281.
49. Jones, KS, Assar, S, Prentice, A, et al. (2016) Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations. Sci Rep 6, 26795.
50. Park, H, Brannon, PM, West, AA, et al. (2016) Vitamin D metabolism varies among women in different reproductive states consuming the same intakes of vitamin D and related nutrients. J Nutr 146, 15371545.
51. Sanchez, PA, Idrisa, A, Bobzom, DN, et al. (1997) Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria. J Natl Med Assoc 89, 805811.
52. Schleicher, RL, Encisco, SE, Chaudhary-Webb, M, et al. (2011) Isotope dilution ultra performance liquid chromatography–tandem mass spectrometry method for simultaneous measurement of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3 and 3-epi-25-hydroxyvitamin D3 in human serum. Clin Chim Acta 412, 15941599.
53. Dent, CE & Gupta, MM (1975) Plasma 25-hydroxyvitamin-D-levels during pregnancy in Caucasians and in vegetarian and non-vegetarian Asians. Lancet 2, 10571060.
54. Salle, BL, Delvin, EE, Lapillonne, A, et al. (2000) Perinatal metabolism of vitamin D. Am J Clin Nutr 71, Suppl. 5, 1317S1324S.
55. Brooke, OG, Brown, IR, Bone, CD, et al. (1980) Vitamin D supplements in pregnant Asian women: effects on calcium status and fetal growth. Br Med J 280, 751754.
56. Ardawi, MS, Nasrat, HA & BA’Aqueel, HS (1997) Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study. Eur J Endocrinol 137, 402409.
57. Hadden, DR & McLaughlin, C (2009) Normal and abnormal maternal metabolism during pregnancy. Semin Fetal Neonatal Med 14, 6671.
58. Gomme, PT & Bertolini, J (2004) Therapeutic potential of vitamin D-binding protein. Trends Biotechnol 22, 340345.
59. Hollis, BW & Wagner, CL (2013) Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. J Clin Endocrinol Metab 98, 46194628.
60. Abboud, M, Rybchyn, MS, Rizk, R, et al. (2017) Sunlight exposure is just one of the factors which influence vitamin D status. Photochem Photobiol Sci 16, 302313.
61. Heaney, RP, Horst, RL, Cullen, DM, et al. (2009) Vitamin D3 distribution and status in the body. J Am Coll Nutr 28, 252256.
62. Carberry, AE, Colditz, PB & Lingwood, BE (2010) Body composition from birth to 4·5 months in infants born to non-obese women. Pediatr Res 68, 8488.
63. Dawodu, A & Akinbi, H (2013) Vitamin D nutrition in pregnancy: current opinion. Int J Womens Health 5, 333343.
64. Gallagher, JC, Sai, A, Templin, T 2nd, et al. (2012) Dose response to vitamin D supplementation in postmenopausal women: a randomized trial. Ann Intern Med 156, 425437.
65. Vaes, AMM, Tieland, M, de Regt, MF, et al. (2017) Dose–response effects of supplementation with calcifediol on serum 25-hydroxyvitamin D status and its metabolites: a randomized controlled trial in older adults. Clin Nutr 37, 808814.
66. Schlingmann, KP, Kaufmann, M, Weber, S, et al. (2011) Mutations in CYP24A1 and idiopathic infantile hypercalcemia. N Engl J Med 365, 410421.
67. Borst, LCC, Duk, MJ, Tromp, EAM, et al. (2017) Vitamin D supplementation according to guidelines may be insufficient to correct preexisting deficiency in pregnancy. Ned Tijdschrift Klin Chem Labgeneesk 42, 8288.
68. Tamblyn, JA, Hewison, M, Wagner, CL, et al. (2015) Immunological role of vitamin D at the maternal-fetal interface. J Endocrinol 224, R107R121.


Type Description Title
Supplementary materials

Stoutjesdijk et al. supplementary material
Table S3

 Word (27 KB)
27 KB
Supplementary materials

Stoutjesdijk et al. supplementary material
Table S2

 Word (17 KB)
17 KB
Supplementary materials

Stoutjesdijk et al. supplementary material
Table S1

 Word (18 KB)
18 KB

Influence of daily 10–85 μg vitamin D supplements during pregnancy and lactation on maternal vitamin D status and mature milk antirachitic activity

  • Eline Stoutjesdijk (a1), Anne Schaafsma (a2), Ido P. Kema (a1), Jan van der Molen (a1), D. A. Janneke Dijck-Brouwer (a1) and Frits A. J. Muskiet (a1)...


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed