Clinical nutrition

Vitamin D during pregnancy and its association with birth outcomes: a Brazilian cohort study



Evidence is lacking on how variation in vitamin D concentrations during gestation affects perinatal outcomes. Therefore, we evaluated the association between vitamin D serum concentrations during pregnancy and neonatal outcomes.


A prospective cohort of 180 healthy Brazilian pregnant women was followed and plasma 25-hydroxyvitamin [25(OH)D, nmol/L] was measured at 5–13 (baseline), 20–26 and 30–36 gestational weeks. Birth weight (BW), birth length (BL), BW z-scores, BL z-scores, first minute Apgar, small for gestational age (SGA), large for gestational age (LGA) and preterm birth were the outcomes. Multiple linear and Poisson regression models were estimated. Best linear unbiased prediction of random coefficients model was used to determine the association between the mean rate of change in vitamin D during pregnancy concentrations and neonatal outcomes.


Mean (SD) BW was 3300 (600) g, BW z-score 0.34 (1.11), BL 49.3 (3.3) cm, BL z-score 0.44 (1.5), and first minute Apgar score 8.2 (1.4). Prevalence of SGA, LGA and preterm birth were 6%, 18% and 13%, respectively. 25(OH)D was directly associated with the risk of preterm birth at all trimesters. Incidence-rate ratios were 1.02, 1.05 and 1.04 for the 1st, 2nd and 3rd trimester, respectively. Mean rate of change during pregnancy in 25(OH)D was directly associated with BW z-score (β: 0.36, 95% CI 0.07; 0.65), LGA risk (IRR: 1.97, 95% CI 1.07; 3.63) and preterm birth (IRR: 7.35, 95% CI 2.99; 18.07).


Mean 25(OH)D rate of change during pregnancy was directly associated with BW z-scores, and increased LGA and preterm birth risk.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Flowchart.
Fig. 2: Maternal 25(OH)D concentration comparison between birth outcomes.
Fig. 3: Relationship between mean 25(OH)D rate of change during pregnancy and birth outcomes.


  1. 1.

    Barker DJ. The origins of the developmental origins theory. J Intern Med. 2007;261:412–7.

    CAS  PubMed  Google Scholar 

  2. 2.

    Savchev S, Sanz-Cortes M, Cruz-Martinez R, Arranz A, Botet F, Gratacos E, et al. Neurodevelopmental outcome of full-term small-for-gestational-age infants with normal placental function. Ultrasound Obstet Gynecol. 2013;42:201–6.

    CAS  PubMed  Google Scholar 

  3. 3.

    Platt MJ. Outcomes in preterm infants. Public Health. 2014;128:399–403.

    CAS  PubMed  Google Scholar 

  4. 4.

    Kleiser C, Schaffrath Rosario A, Mensink GB, Prinz-Langenohl R, Kurth BM. Potential determinants of obesity among children and adolescents in Germany: results from the cross-sectional KiGGS Study. BMC Public Health. 2009;9:46.

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    de Jong F, Monuteaux MC, van Elburg RM, Gillman MW, Belfort MB. Systematic review and meta-analysis of preterm birth and later systolic blood pressure. Hypertension. 2012;59:226–34.

    PubMed  Google Scholar 

  6. 6.

    Nam HK, Lee KH. Small for gestational age and obesity: epidemiology and general risks. Ann Pediatr Endocrinol Metab. 2018;23:9–13.

    PubMed  PubMed Central  Google Scholar 

  7. 7.

    Chawanpaiboon S, Vogel JP, Moller AB, Lumbiganon P, Petzold M, Hogan D, et al. Global, regional, and national estimates of levels of preterm birth in 2014: a systematic review and modelling analysis. Lancet Glob Health. 2019;7:e37–46.

    PubMed  Google Scholar 

  8. 8.

    Blencowe H, Krasevec J, de Onis M, Black RE, An X, Stevens GA, et al. National, regional, and worldwide estimates of low birthweight in 2015, with trends from 2000: a systematic analysis. Lancet Glob Health. 2019;7:e849–60.

    PubMed  PubMed Central  Google Scholar 

  9. 9.

    Lee AC, Katz J, Blencowe H, Cousens S, Kozuki N, Vogel JP, et al. National and regional estimates of term and preterm babies born small for gestational age in 138 low-income and middle-income countries in 2010. Lancet Glob Health. 2013;1:e26–36.

    PubMed  PubMed Central  Google Scholar 

  10. 10.

    Frey HA, Klebanoff MA. The epidemiology, etiology, and costs of preterm birth. Semin Fetal Neonatal Med. 2016;21:68–73.

    PubMed  Google Scholar 

  11. 11.

    McCowan L, Horgan RP. Risk factors for small for gestational age infants. Best Pr Res Clin Obstet Gynaecol. 2009;23:779–93.

    Google Scholar 

  12. 12.

    Triunfo S, Lanzone A, Lindqvist PG. Low maternal circulating levels of vitamin D as potential determinant in the development of gestational diabetes mellitus. J Endocrinol Investig. 2017;40:1049–59.

    CAS  Google Scholar 

  13. 13.

    Mannion CA, Gray-Donald K, Koski KG. Association of low intake of milk and vitamin D during pregnancy with decreased birth weight. CMAJ. 2006;174:1273–7.

    PubMed  PubMed Central  Google Scholar 

  14. 14.

    Francis EC, Hinkle SN, Song Y, Rawal S, Donnelly SR, Zhu Y, et al. Longitudinal maternal vitamin D status during pregnancy is associated with neonatal anthropometric measures. Nutrients. 2018;10:1631.

    PubMed Central  Google Scholar 

  15. 15.

    Bilic M, Qamar H, Onoyovwi A, Korsiak J, Papp E, Al Mahmud A, et al. Prenatal vitamin D and cord blood insulin-like growth factors in Dhaka, Bangladesh. Endocr Connect. 2019;8:745–53.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. 16.

    Wagner CL, Taylor SN, Johnson DD, Hollis BW. The role of vitamin D in pregnancy and lactation: emerging concepts. Women’s Health. 2012;8:323–40.

    CAS  PubMed  Google Scholar 

  17. 17.

    Agudelo-Zapata Y, Maldonado-Acosta LM, Sandoval-Alzate HF, Poveda NE, Garcés MF, Cortés-Vásquez JA, et al. Serum 25-hydroxyvitamin D levels throughout pregnancy: a longitudinal study in healthy and preeclamptic pregnant women. Endocr Connect. 2018;7:698–707.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18.

    Figueiredo AC, Cocate PG, Adegboye AR, Franco-Sena AB, Farias DR, de Castro MB, et al. Changes in plasma concentrations of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D during pregnancy: a Brazilian cohort. Eur J Nutr. 2017;57:1059–72.

    PubMed  Google Scholar 

  19. 19.

    Brannon PM, Picciano MF. Vitamin D in pregnancy and lactation in humans. Annu Rev Nutr. 2011;31:89–115.

    CAS  PubMed  Google Scholar 

  20. 20.

    Tous M, Villalobos M, Iglesias L, Fernández-Barrés S, Arija V. Vitamin D status during pregnancy and offspring outcomes: a systematic review and meta-analysis of observational studies. Eur J Clin Nutr. 2019;74:36–53.

    PubMed  Google Scholar 

  21. 21.

    Amegah AK, Klevor MK, Wagner CL. Maternal vitamin D insufficiency and risk of adverse pregnancy and birth outcomes: a systematic review and meta-analysis of longitudinal studies. PLoS ONE. 2017;12:e0173605.

    PubMed  PubMed Central  Google Scholar 

  22. 22.

    van der Pligt P, Willcox J, Szymlek-Gay EA, Murray E, Worsley A, Daly RM. Associations of maternal vitamin D deficiency with pregnancy and neonatal complications in developing countries: a systematic review. Nutrients. 2018;10:640.

    PubMed Central  Google Scholar 

  23. 23.

    Kelishadi R, Sharifi-Ghazvini F, Poursafa P, Mehrabian F, Farajian S, Yousefy H, et al. Determinants of hypovitaminosis D in pregnant women and their newborns in a sunny region. Int J Endocrinol. 2013;2013:460970.

    PubMed  PubMed Central  Google Scholar 

  24. 24.

    Pereira-Santos M, Carvalho GQ, Couto RD, Dos Santos DB, Oliveira AM. Vitamin D deficiency and associated factors among pregnant women of a sunny city in Northeast of Brazil. Clin Nutr Espen. 2018;23:240–4.

    PubMed  Google Scholar 

  25. 25.

    Bouillon R. Comparative analysis of nutritional guidelines for vitamin D. Nat Rev Endocrinol. 2017;13:466–79.

    CAS  PubMed  Google Scholar 

  26. 26.

    Karras SN, Fakhoury H, Muscogiuri G, Grant WB, van den Ouweland JM, Colao AM, et al. Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications. Ther Adv Musculoskelet Dis. 2016;8:124–35.

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Wagner CL, Hollis BW. The implications of vitamin D dtatus during pregnancy on mother and her developing child. Front Endocrinol. 2018;9:500.

    Google Scholar 

  28. 28.

    Chan SY, Susarla R, Canovas D, Vasilopoulou E, Ohizua O, McCabe CJ, et al. Vitamin D promotes human extravillous trophoblast invasion in vitro. Placenta. 2015;36:403–9.

    CAS  PubMed  Google Scholar 

  29. 29.

    Liu NQ, Larner DP, Yao Q, Chun RF, Ouyang Y, Zhou R, et al. Vitamin D-deficiency and sex-specific dysregulation of placental inflammation. J Steroid Biochem Mol Biol. 2018;177:223–30.

    CAS  PubMed  Google Scholar 

  30. 30.

    El-Khoury JM, Reineks EZ, Wang S. Progress of liquid chromatography-mass spectrometry in measurement of vitamin D metabolites and analogues. Clin Biochem. 2011;44:66–76.

    CAS  PubMed  Google Scholar 

  31. 31.

    Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, et al. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005;90:3215–24.

    CAS  PubMed  Google Scholar 

  32. 32.

    Villar J, Cheikh Ismail L, Victora CG, Ohuma EO, Bertino E, Altman DG, et al. International standards for newborn weight, length, and head circumference by gestational age and sex: the Newborn Cross-Sectional Study of the INTERGROWTH-21st Project. Lancet. 2014;384:857–68.

    PubMed  Google Scholar 

  33. 33.

    Gordon CC, Chumlea WC, Roche AF. Stature, recumbent length, and weight. Anthropometric standardization reference manual. Champaign: Human kinetics Books; 1988. pp. 3–8.

  34. 34.

    Giacomello A, Schmidt MI, Nunes MAA, Duncan BB, Soares RM, Manzolli P, et al. Validation of a food frequency questionnaire conducted among pregnant women attended by the Brazilian National Health Service, in two municipalities of the State of Rio Grande do Sul, Brazil. Rev Brasileira de Saúde Matern Infant. 2008;8:445–54.

    Google Scholar 

  35. 35.

    Sichieri R, Everhart J. Validity of a Brazilian food frequency questionnaire against dietary recalls and estimated energy intake. Nutr Res. 1998;18:1649–59.

    CAS  Google Scholar 

  36. 36.

    (US) IoM. Committee to review dietary reference intakes for vitamin D and calcium: dietary reference intakes for calcium and vitamin D. In: Ross ACTC, Yaktine AL, Del Valle HB, editors. Washington (DC) US: National Academies Press; 2011.

  37. 37.

    Chen YH, Ferguson KK, Meeker JD, McElrath TF, Mukherjee B. Statistical methods for modeling repeated measures of maternal environmental exposure biomarkers during pregnancy in association with preterm birth. Environ Health. 2015;14:9.

    PubMed  PubMed Central  Google Scholar 

  38. 38.

    Glymor MM, Greenland S. Causal diagrams. In: TL RKGSL, editor. Modern epidemiology. Philadelphia: Lippincott Williams & Wilkins; 2008. pp. 183–209.

  39. 39.

    Textor J, Hardt J, Knüppel S. DAGitty: a graphical tool for analyzing causal diagrams. Epidemiology. 2011;22:745.

    PubMed  Google Scholar 

  40. 40.

    StataCorp. Stata Statistical Software: Release 15. College Station, TX: StataCorp LLC; 2017.

  41. 41.

    Kale PL, Lordelo CVM, Fonseca SC, Silva KS, Lobato JCP, Costa AJL, et al. Adequação do peso ao nascer para idade gestacional de acordo com a curva INTERGROWTH-21 st e fatores associados ao pequeno para idade gestacional. Cad Saúde Coletiva. 2018;26:391–9.

    Google Scholar 

  42. 42.

    Francis A, Hugh O, Gardosi J. Customized vs INTERGROWTH-21. Am J Obstet Gynecol. 2018;218:S692–9.

    PubMed  Google Scholar 

  43. 43.

    Pereira-Santos M, Carvalho GQ, Dos Santos DB, Oliveira AM. Influence of vitamin D serum concentration, prenatal care and social determinants on birth weight: a northeastern Brazilian cohort study. Br J Nutr. 2019;122:284–92.

    CAS  PubMed  Google Scholar 

  44. 44.

    Nobles CJ, Markenson G, Chasan-Taber L. Early pregnancy vitamin D status and risk for adverse maternal and infant outcomes in a bi-ethnic cohort: the Behaviors Affecting Baby and You (B.A.B.Y.) Study. Br J Nut.r 2015;114:2116–28.

    CAS  Google Scholar 

  45. 45.

    Lapillonne A. Vitamin D deficiency during pregnancy may impair maternal and fetal outcomes. Med Hypotheses. 2010;74:71–5.

    CAS  PubMed  Google Scholar 

  46. 46.

    Shin JS, Choi MY, Longtine MS, Nelson DM. Vitamin D effects on pregnancy and the placenta. Placenta. 2010;31:1027–34.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Møller UK, Streym S, Heickendorff L, Mosekilde L, Rejnmark L. Effects of 25OHD concentrations on chances of pregnancy and pregnancy outcomes: a cohort study in healthy Danish women. Eur J Clin Nutr. 2012;66:862–8.

    PubMed  Google Scholar 

  48. 48.

    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.

    CAS  PubMed  Google Scholar 

  49. 49.

    Fernández-Alonso AM, Dionis-Sánchez EC, Chedraui P, González-Salmerón MD, Pérez-López FR. Group SVDaWsHR. First-trimester maternal serum 25-hydroxyvitamin D3 status and pregnancy outcome. Int J Gynaecol Obstet. 2012;116:6–9.

    PubMed  Google Scholar 

  50. 50.

    Bärebring L, Bullarbo M, Glantz A, Leu Agelii M, Jagner Å, Ellis J, et al. Preeclampsia and blood pressure trajectory during pregnancy in relation to vitamin D status. PLoS ONE. 2016;11:e0152198.

    PubMed  PubMed Central  Google Scholar 

  51. 51.

    Kassai MS, Cafeo FR, Affonso-Kaufman FA, Suano-Souza FI, Sarni ROS. Vitamin D plasma concentrations in pregnant women and their preterm newborns. BMC Pregnancy Childbirth. 2018;18:412.

    CAS  PubMed  PubMed Central  Google Scholar 

  52. 52.

    Qin LL, Lu FG, Yang SH, Xu HL, Luo BA. Does maternal vitamin D deficiency increase the risk of preterm birth: a meta-analysis of observational studies. Nutrients. 2016;8:301.

    PubMed Central  Google Scholar 

  53. 53.

    McDonnell SL, Baggerly KA, Baggerly CA, Aliano JL, French CB, Baggerly LL, et al. Maternal 25(OH)D concentrations ≥40 ng/mL associated with 60% lower preterm birth risk among general obstetrical patients at an urban medical center. PLoS ONE. 2017;12:e0180483.

    PubMed  PubMed Central  Google Scholar 

  54. 54.

    Romero R, Espinoza J, Gonçalves LF, Kusanovic JP, Friel L, Hassan S. The role of inflammation and infection in preterm birth. Semin Reprod Med 2007;25:21–39.

    CAS  PubMed  Google Scholar 

  55. 55.

    Hewison M. Antibacterial effects of vitamin D. Nat Rev Endocrinol. 2011;7:337–45.

    CAS  PubMed  Google Scholar 

  56. 56.

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

    CAS  PubMed  Google Scholar 

  57. 57.

    Al-Shaikh GK, Ibrahim GH, Fayed AA, Al-Mandeel H. Impact of vitamin D deficiency on maternal and birth outcomes in the Saudi population: a cross-sectional study. BMC Pregnancy Childbirth. 2016;16:119.

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Viellas EF, Domingues RMSM, Dias MAB, et al. Assistência pré-natal no Brasil. Cad de Saúde Pública. 2014;30:S85–100.

    Google Scholar 

  59. 59.

    Moon RJ, Harvey NC, Cooper C, D’Angelo S, Curtis EM, Crozier SR, et al. Response to antenatal cholecalciferol supplementation is associated with common vitamin D-related genetic variants. J Clin Endocrinol Metab. 2017;102:2941–9.

    PubMed  PubMed Central  Google Scholar 

Download references


The authors are grateful to all the women who volunteered to participate in this cohort study, to the managers and professionals of the Municipal Health Centre Heitor Beltrão for providing us with the space and opportunities for the data collection and to the Quest Diagnostics Nichols Institute laboratory (San Juan Capistrano, CA, USA) for performing the vitamin D concentration analyses. Moreover, we thank the National Council for Scientific and Technological Development (CNPq in the Portuguese acronym; grant number: 471196/2010-0) and the Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ for the Portuguese acronym, grant number E-26/111.400/2010, E_14/2010) for the financial support. National Council for Scientific and Technological Development (CNPq in the Portuguese acronym; grant number: 471196/2010-0) and the Carlos Chagas Filho Foundation for Research Support of Rio de Janeiro State (FAPERJ in the Portuguese acronym, grant number E-26/111.400/2010, E_14/2010).

Author information




CB and GK developed the research question and designed the study. CB and TRBC conducted the statistical analyses. GK, TRBC and DF provided support for the statistical analyses. TRBC assisted with the literature review and with writing the manuscript. All of the authors have made substantial contributions to the manuscript and approved this final revision.

Corresponding author

Correspondence to Gilberto Kac.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The current study was performed in accordance with the guidelines of the Declaration of Helsinki. An informed consent for participation was thoroughly explained and signed by all participants. This study was approved by the Rio de Janeiro Federal University Maternity Teaching Hospital Ethics Committee (protocol number: 0023.0.361.000-08) and the Municipal Secretary of Rio de Janeiro Ethics Committee (protocol number: 0139.0.314.000-09).

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Benaim, C., Carrilho, T.R.B., Farias, D.R. et al. Vitamin D during pregnancy and its association with birth outcomes: a Brazilian cohort study. Eur J Clin Nutr (2020).

Download citation


Quick links