Archives of Women's Mental Health

, Volume 21, Issue 6, pp 745–755 | Cite as

Vitamin D deficiency and depressive symptoms in the perinatal period

  • Amy R. Lamb
  • Melanie Lutenbacher
  • Kenneth A. Wallston
  • Samuel H. Pepkowitz
  • Brett Holmquist
  • Calvin J. Hobel
Original Article


Depression affects 1 in 7 women during the perinatal period. Women with vitamin D deficiency may be at an increased risk for depression. This study investigated the relationship between maternal and cord blood 25-hydroxyvitamin D (25OHD) and maternal depressive symptoms over the perinatal period. Study objectives were to examine variations and relationships between maternal and cord blood vitamin D levels and maternal depressive symptoms over the perinatal period. At a large medical center in southern California, pregnant women (N = 126) were recruited for this longitudinal cohort study. Depressive symptoms (Edinburgh Postnatal Depression Screen, EPDS) and vitamin D status (25OHD) were measured at three time points in the perinatal period: time 1 (T1; N = 125) EPDS and 25OHD were collected in early pregnancy; time 2 (T2; N = 96) EPDS was conducted in the third trimester with blood collected at time of delivery; and time 3 (T3; N = 88) was collected postpartum. A significant inverse relationship between vitamin D status and depressive symptoms was observed between 25OHD and EPDS scores at all time points in this sample (T1 = − 0.18, P = 0.024; T2 = − 0.27, P = 0.009; T3 = − 0.22, P = 0.019). This association remained after controlling for confounders. Low cord blood 25OHD levels were inversely associated with higher EPDS scores in the third trimester (r = − 0.22, P = 0.02). Clinicians may want to consider screening women diagnosed with vitamin D deficiency for depression and vice versa. Vitamin D may represent an important biomarker for pregnant and postpartum women diagnosed with depression. Further studies examining underlying mechanisms and supplementation are needed.


Depression Vitamin D 25OHD Maternal mental health Pregnancy and postpartum complications 



Great thanks to all the women and infants who consented to participating in this trial. The authors would also like to thank Steven Ropers, M.D., and Quy Tran, M.D., for their help in abstracting the electronic medical records and David Shifrin, Ph.D., for his assistance with manuscript preparation and editing. No payment was given for their assistance.

Funding information

This project was supported by UL1 TR000445 from NCATS/NIH and a CTSA award No. UL1TR000445 from the National Center for Advancing Translational Sciences. The funding source was not involved in the study. Additional support came from the Miriam Jacobs Endowed Chair, Maternal Fetal Medicine, held by Dr. Hobel.

Compliance with ethical standards

Statement of human rights

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent was obtained from all individual participants included in the study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Accortt EE, Schetter CD, Peters RM, Cassidy-Bushrow AE (2016) Lower prenatal vitamin D status and postpartum depressive symptomatology in African American women: preliminary evidence for moderation by inflammatory cytokines. Arch Women’s Ment Health 19:373–383. CrossRefGoogle Scholar
  2. Amini S, Jafarirad S, Amani R (2018) Postpartum depression and vitamin D: a systematic review. Crit Rev Food Sci Nutr:1–7.
  3. Bansil P, Kuklina EV, Meikle SF, Posner SF, Kourtis AP, Ellington SR, Jamieson DJ (2010) Maternal and fetal outcomes among women with depression. J Women’s Health (Larchmt) 19:329–334. CrossRefGoogle Scholar
  4. Banti S, Mauri M, Oppo A, Borri C, Rambelli C, Ramacciotti D, Montagnani MS, Camilleri V, Cortopassi S, Rucci P, Cassano GB (2011) From the third month of pregnancy to 1 year postpartum. Prevalence, incidence, recurrence, and new onset of depression. Results from the perinatal depression-research & screening unit study. Compr Psychiatry 52:343–351. CrossRefGoogle Scholar
  5. Bashutski JD, Eber RM, Kinney JS, Benavides E, Maitra S, Braun TM, Giannobile WV, McCauley LK (2011) The impact of vitamin D status on periodontal surgery outcomes. J Dent Res 90:1007–1012. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Borella E, Nesher G, Israeli E, Shoenfeld Y (2014) Vitamin D: a new anti-infective agent? Ann N Y Acad Sci 1317:76–83. CrossRefGoogle Scholar
  7. Brandenbarg J, Vrijkotte TG, Goedhart G, van Eijsden M (2012) Maternal early-pregnancy vitamin D status is associated with maternal depressive symptoms in the Amsterdam Born Children and Their Development cohort. Psychosom Med 74:751–757. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Brannon PM, Picciano MF (2011) Vitamin D in pregnancy and lactation in humans. Annu Rev Nutr 31:89–115. CrossRefGoogle Scholar
  9. Bunevicius R, Kusminskas L, Bunevicius A, Nadisauskiene RJ, Jureniene K, Pop VJ (2009) Psychosocial risk factors for depression during pregnancy. Acta Obstet Gynecol Scand 88:599–605. CrossRefGoogle Scholar
  10. Cassidy-Bushrow AE, Peters RM, Johnson DA, Li J, Rao DS (2012) Vitamin D nutritional status and antenatal depressive symptoms in African American women. J Women's Health 21:1189–1195. CrossRefGoogle Scholar
  11. de Castro F, Place JM, Villalobos A, Rojas R, Barrientos T, Frongillo EA (2017) Poor early childhood outcomes attributable to maternal depression in Mexican women. Arch Womens Ment Health 20:561–568. CrossRefGoogle Scholar
  12. Chung TK, Lau TK, Yip AS, Chiu HF, Lee DT (2001) Antepartum depressive symptomatology is associated with adverse obstetric and neonatal outcomes. Psychosom Med 63:830–834CrossRefGoogle Scholar
  13. Cipolla MJ (2013) The adaptation of the cerebral circulation to pregnancy: mechanisms and consequences. J Cereb Blood Flow Metab 33:465–478. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Cox JL, Holden JM, Sagovsky R (1987) Detection of postnatal depression. Development of the 10-item Edinburgh Postnatal Depression Scale. Br J Psychiatry 150:782–786. CrossRefGoogle Scholar
  15. Cross NA, Hillman LS, Allen SH, Krause GF, Vieira NE (1995) Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. Am J Clin Nutr 61:514–523CrossRefGoogle Scholar
  16. Cypryk K, Szymczak W, Czupryniak L, Sobczak M, Lewinski A (2008) Gestational diabetes mellitus—an analysis of risk factors. Endokrynol Pol 59:393–397Google Scholar
  17. van Etten E, Mathieu C (2005) Immunoregulation by 1,25-dihydroxyvitamin D3: basic concepts. J Steroid Biochem Mol Biol 97:93–101. CrossRefGoogle Scholar
  18. Eyles DW, Smith S, Kinobe R, Hewison M, McGrath JJ (2005) Distribution of the vitamin D receptor and 1 alpha-hydroxylase in human brain. J Chem Neuroanat 29:21–30. CrossRefGoogle Scholar
  19. Eyles DW, Feron F, Cui X, Kesby JP, Harms LH, Ko P, McGrath JJ, Burne THJ (2009) Developmental vitamin D deficiency causes abnormal brain development. Psychoneuroendocrinology 34(Suppl 1):S247–S257. CrossRefGoogle Scholar
  20. Fu CW, Liu JT, Tu WJ, Yang JQ, Cao Y (2015) Association between serum 25-hydroxyvitamin D levels measured 24 hours after delivery and postpartum depression. BJOG 122:1688–1694. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Gould JF, Anderson AJ, Yelland LN, Smithers LG, Skeaff CM, Gibson RA, Makrides M (2015) Association of cord blood vitamin D at delivery with postpartum depression in Australian women. Aust N Z J Obstet Gynaecol 55:446–452CrossRefGoogle Scholar
  22. Grantz KL, Hinkle SN, Mendola P, Sjaarda LA, Leishear K, Albert PS (2015) Differences in risk factors for recurrent versus incident preterm delivery. Am J Epidemiol 182:157–167. CrossRefPubMedPubMedCentralGoogle Scholar
  23. Grigoleit JS, Kullmann JS, Wolf OT, Hammes F, Wegner A, Jablonowski S, Engler H, Gizewski E, Oberbeck R, Schedlowski M (2011) Dose-dependent effects of endotoxin on neurobehavioral functions in humans. PLoS One 6:e28330. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Grote NK, Bledsoe SE (2007) Predicting postpartum depressive symptoms in new mothers: the role of optimism and stress frequency during pregnancy. Health Soc Work 32:107–118CrossRefGoogle Scholar
  25. Gur EB, Gokduman A, Turan GA, Tatar S, Hepyilmaz I, Zengin EB, Eskicioglu F, Guclu S (2014) Mid-pregnancy vitamin D levels and postpartum depression. Eur J Obstet Gynecol Reprod Biol 179:110–116. CrossRefPubMedPubMedCentralGoogle Scholar
  26. Harms LR, Burne TH, Eyles DW, McGrath JJ (2011) Vitamin D and the brain. Best Pract Res Clin Endocrinol Metab 25:657–669. CrossRefPubMedPubMedCentralGoogle Scholar
  27. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG (2009) Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 42:377–381. CrossRefGoogle Scholar
  28. Heaney RP (2003) Long-latency deficiency disease: insights from calcium and vitamin D. Am J Clin Nutr 78:912–919. CrossRefPubMedPubMedCentralGoogle Scholar
  29. Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL (2011) Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res 26:2341–2357. CrossRefPubMedPubMedCentralGoogle Scholar
  30. Hu R, Li Y, Zhang Z, Yan W (2015) Antenatal depressive symptoms and the risk of preeclampsia or operative deliveries: a meta-analysis. PLoS One 10:e0119018. CrossRefPubMedPubMedCentralGoogle Scholar
  31. Husain N, Rahman A, Husain M, Khan SM, Vyas A, Tomenson B, Cruickshank KJ (2014) Detecting depression in pregnancy: validation of EPDS in British Pakistani mothers. J Immigr Minor Health 16:1085–1092. CrossRefGoogle Scholar
  32. Institute of Medicine (IOM) (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DCGoogle Scholar
  33. Kesby JP, Eyles DW, Burne TH, McGrath JJ (2011) The effects of vitamin D on brain development and adult brain function. Mol Cell Endocrinol 347:121–127. CrossRefPubMedPubMedCentralGoogle Scholar
  34. Kozhimannil KB, Pereira MA, Harlow BL (2009) Association between diabetes and perinatal depression among low-income mothers. JAMA 301:842–847. CrossRefGoogle Scholar
  35. Kroll MH, Bi C, Garber CC, Kaufman HW, Liu D, Caston-Balderrama A, Zhang K, Clarke N, Xie M, Reitz RE, Suffin SC, Holick MF (2015) Temporal relationship between vitamin D status and parathyroid hormone in the United States. PLoS One 10:e0118108. CrossRefPubMedPubMedCentralGoogle Scholar
  36. Lagerberg D, Magnusson M, Sundelin C (2011) Drawing the line in the Edinburgh Postnatal Depression Scale (EPDS): a vital decision. Int J Adolesc Med Health 23:27–32Google Scholar
  37. Leonard B, Maes M (2012) Mechanistic explanations how cell-mediated immune activation, inflammation and oxidative and nitrosative stress pathways and their sequels and concomitants play a role in the pathophysiology of unipolar depression. Neurosci Biobehav Rev 36:764–785. CrossRefGoogle Scholar
  38. Maes M, Ruckoanich P, Chang YS, Mahanonda N, Berk M (2011) Multiple aberrations in shared inflammatory and oxidative & nitrosative stress (IO&NS) pathways explain the co-association of depression and cardiovascular disorder (CVD), and the increased risk for CVD and due mortality in depressed patients. Prog Neuro-Psychopharmacol Biol Psychiatry 35:769–783. CrossRefGoogle Scholar
  39. Marwaha RK, Tandon N, Chopra S, Agarwal N, Garg MK, Sharma B, Kanwar RS, Bhadra K, Singh S, Mani K, Puri S (2011) Vitamin D status in pregnant Indian women across trimesters and different seasons and its correlation with neonatal serum 25-hydroxyvitamin D levels. Br J Nutr 106:1383–1389. CrossRefPubMedPubMedCentralGoogle Scholar
  40. Matthey S, Henshaw C, Elliott S, Barnett B (2006) Variability in use of cut-off scores and formats on the Edinburgh Postnatal Depression Scale—implications for clinical and research practice. Arch Womens Ment Health 9:309–315. CrossRefGoogle Scholar
  41. McKibben RA, Zhao D, Lutsey PL, Schneider ALC, Guallar E, Mosley TH, Michos ED (2016) Factors associated with change in 25-hydroxyvitamin D levels over longitudinal follow-up in the ARIC Study. J Clin Endocrinol Metab 101:33–43. CrossRefGoogle Scholar
  42. Meijer JL, Beijers C, van Pampus M, Verbeek T, Stolk RP, Milgrom J, Bockting CLH, Burger H (2014) Predictive accuracy of Edinburgh Postnatal Depression Scale assessment during pregnancy for the risk of developing postpartum depressive symptoms: a prospective cohort study. BJOG Int J Obstet Gynaecol 121:1604–1610. CrossRefGoogle Scholar
  43. Merewood A, Mehta SD, Chen TC, Bauchner H, Holick MF (2009) Association between vitamin D deficiency and primary cesarean section. J Clin Endocrinol Metab 94:940–945. CrossRefGoogle Scholar
  44. Milgrom J, Gemmill AW, Bilszta JL, Hayes B, Barnett B, Brooks J, Ericksen J, Ellwood D, Buist A (2008) Antenatal risk factors for postnatal depression: a large prospective study. J Affect Disord 108:147–157. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Miyake Y, Tanaka K, Okubo H, Sasaki S, Arakawa M (2015) Dietary vitamin D intake and prevalence of depressive symptoms during pregnancy in Japan. Nutrition 31:160–165. CrossRefPubMedPubMedCentralGoogle Scholar
  46. Murphy PK, Mueller M, Hulsey TC, Ebeling MD, Wagner CL (2010) An exploratory study of postpartum depression and vitamin d. J Am Psychiatric Nurses Assoc 16:170–177. CrossRefGoogle Scholar
  47. Murray L, Carothers AD (1990) The validation of the Edinburgh Post-natal Depression Scale on a community sample. Br J Psychiatry 157:288–290. CrossRefGoogle Scholar
  48. National Center for Health Statistics, Centers for Disease Control and Prevention (2004–2006) National Health Interview Survey (NHIS)Google Scholar
  49. Nielsen NO, Strøm M, Boyd HA, Andersen EW, Wohlfahrt J, Lundqvist M, Cohen A, Hougaard DM, Melbye M (2013) Vitamin D status during pregnancy and the risk of subsequent postpartum depression: a case-control study. PLoS One 8:e80686. CrossRefPubMedPubMedCentralGoogle Scholar
  50. Pearlstein T (2015) Depression during pregnancy. Best Pract Res Clin Obstet Gynaecol 29:754–764. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Raedler TJ (2011) Inflammatory mechanisms in major depressive disorder. Curr Opin Psychiatry 24:519–525. CrossRefPubMedPubMedCentralGoogle Scholar
  52. Rai D, Lee BK, Dalman C, Golding J, Lewis G, Magnusson C (2013) Parental depression, maternal antidepressant use during pregnancy, and risk of autism spectrum disorders: population based case-control study. BMJ 346:f2059. CrossRefPubMedPubMedCentralGoogle Scholar
  53. Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmacher T (2001) Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 58:445–452CrossRefGoogle Scholar
  54. Robinson M, Whitehouse AJO, Newnham JP, Gorman S, Jacoby P, Holt BJ, Serralha M, Tearne JE, Holt PG, Hart PH, Kusel MMH (2014) Low maternal serum vitamin D during pregnancy and the risk for postpartum depression symptoms. Arch Womens Ment Health 17:213–219. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Sanchez PA, Idrisa A, Bobzom DN, Airede A, Hollis BW, Liston DE, Jones DD, Dasgupta A, Glew RH (1997) Calcium and vitamin D status of pregnant teenagers in Maiduguri, Nigeria. J Natl Med Assoc 89:805–811PubMedPubMedCentralGoogle Scholar
  56. Schneid-Kofman N, Sheiner E, Levy A (2008) Psychiatric illness and adverse pregnancy outcome. Int J Gynaecol Obstet 101:53–56. CrossRefGoogle Scholar
  57. Shaffer JA, Edmondson D, Wasson LT, Falzon L, Homma K, Ezeokoli N, Li P, Davidson KW (2014) Vitamin D supplementation for depressive symptoms: a systematic review and meta-analysis of randomized controlled trials. Psychosom Med 76:190–196. CrossRefPubMedPubMedCentralGoogle Scholar
  58. Shakeel N, Eberhard-Gran M, Sletner L, Slinning K, Martinsen EW, Holme I, Jenum AK (2015) A prospective cohort study of depression in pregnancy, prevalence and risk factors in a multi-ethnic population. BMC Pregnancy Childbirth 15:5. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sinha A, Hollingsworth KG, Ball S, Cheetham T (2013) Improving the vitamin D status of vitamin D deficient adults is associated with improved mitochondrial oxidative function in skeletal muscle. J Clin Endocrinol Metab 98:E509–E513. CrossRefGoogle Scholar
  60. Sohr-Preston SL, Scaramella LV (2006) Implications of timing of maternal depressive symptoms for early cognitive and language development. Clin Child Fam Psychol Rev 9:65–83. CrossRefPubMedPubMedCentralGoogle Scholar
  61. Straub H, Adams M, Kim JJ, Silver RK (2012) Antenatal depressive symptoms increase the likelihood of preterm birth. Am J Obstet Gynecol 207:329. e321–329. e324CrossRefGoogle Scholar
  62. Strom M et al (2014) Vitamin D measured in maternal serum and offspring neurodevelopmental outcomes: a prospective study with long-term follow-up. Ann Nutr Metab 64:254–261. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Tendais I, Costa R, Conde A, Figueiredo B (2014) Screening for Depression and Anxiety Disorders from Pregnancy to Postpartum with the EPDS and STAI. Span J Psychol 17:E7. CrossRefPubMedPubMedCentralGoogle Scholar
  64. Vaziri F, Nasiri S, Tavana Z, Dabbaghmanesh MH, Sharif F, Jafari P (2016) A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers. BMC Pregnancy Childbirth 16:239. CrossRefPubMedPubMedCentralGoogle Scholar
  65. Villegas L, McKay K, Dennis CL, Ross LE (2011) Postpartum depression among rural women from developed and developing countries: a systematic review. J Rural Health 27:278–288. CrossRefPubMedPubMedCentralGoogle Scholar
  66. Williams D (2003) Pregnancy: a stress test for life. Curr Opin Obstet Gynecol 15:465–471. CrossRefPubMedPubMedCentralGoogle Scholar
  67. Williams JA, Romero VC, Clinton CM, Vazquez DM, Marcus SM, Chilimigras JL, Hamilton SE, Allbaugh LJ, Vahratian AM, Schrader RM, Mozurkewich EL (2016) Vitamin D levels and perinatal depressive symptoms in women at risk: a secondary analysis of the mothers, omega-3, and mental health study. BMC Pregnancy Childbirth 16:203. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Obstetrics and GynecologyCedars-Sinai Medical CenterLos AngelesUSA
  2. 2.The Schools of Nursing and Medicine (Pediatrics)Vanderbilt UniversityNashvilleUSA
  3. 3.The School of NursingVanderbilt UniversityNashvilleUSA
  4. 4.The Anatomic and Clinical Pathology DepartmentCedars-Sinai Medical CenterLos AngelesUSA
  5. 5.Esoterix, IncLabCorp CompanyCalabasasUSA

Personalised recommendations