The Effect of Vitamin D Consumption During Pregnancy on Maternal Thyroid Function and Depression: A Randomized, Placebo-Controlled, Clinical Trial


Mohammad Hossein Dabbaghmanesh 1 , Farideh Vaziri 1 , * , Fatemeh Najib 2 , Samira Nasiri 3 , Saeedeh Pourahmad 4

1 Shiraz Endocrinology and Metabolism Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

2 Department of Obstetrics and Gynecology, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

3 Student Research Committee, School of Nursing and Midwifery, Shiraz University of Medical Sciences, Shiraz, Iran

4 Department of Biostatistics, Medical School, Shiraz University of Medical Sciences, Shiraz, Iran

How to Cite: Dabbaghmanesh M H, Vaziri F, Najib F, Nasiri S, Pourahmad S. The Effect of Vitamin D Consumption During Pregnancy on Maternal Thyroid Function and Depression: A Randomized, Placebo-Controlled, Clinical Trial, Jundishapur J Nat Pharm Prod. Online ahead of Print ; 14(2):e65328. doi: 10.5812/jjnpp.65328.


Jundishapur Journal of Natural Pharmaceutical Products: 14 (2); e65328
Published Online: January 12, 2019
Article Type: Brief Report
Received: April 10, 2017
Revised: December 19, 2017
Accepted: March 11, 2018


Background: Beyond the vital function of vitamin D in the homeostasis of calcium balance, possible widespread effects of vitamin D are shown in numerous studies.

Objectives: The current study aimed at evaluating the effects of vitamin D supplement on thyroid function and postnatal depression.

Methods: In the current randomized experimental study, the vitamin D group presented with two 1000 IU vitamin D3 pills (2000 IU) daily from 26th to 28th week of gestation until birth; however, the control group received placebo. Inter- and intra-group comparisons were performed in terms of maternal serum level of 25-hydroxyvitamin D, thyroid-stimulating hormone (TSH), free thyroxine (FT4), and thyroid peroxidase (TPO), and 4th week postnatal depression score.

Results: At birth, changes in maternal serum level of 25-hydroxyvitamin D was significantly different between the two groups (P = 0.004). The two study groups were not different significantly in terms of TSH, FT4, and TPO levels at birth (P > 0.05). While, at 4th week postnatal, depression score was significantly different between the two groups (P = 0.002).

Conclusions: Vitamin D, 2000 IU /day in late pregnancy could induce a significant difference in the 4th week postnatal depression score independent of thyroid function.

1. Background

Vitamin D has a vital function in the homeostasis of calcium balance and bone fitness, although the expression of the receptor of vitamin D in different human body cells and tissue indicates that vitamin D probably acts like a steroid hormone in the organs (1, 2).

The relationship between vitamin D and thyroid function was observed in previous studies. Postnatal depression (PND) is a frequent disorder after childbirth in females. A study showed that the prevalence rate of PND varied from 0.5% to 60.8% across the countries. PND is considered as a public health issue that can cause serious complications for mothers, newborns, and families (3). In nonpregnant adults, a possible association between serum 25-hydroxyvitamin D level and emotional symptoms such as nervousness, depressive disorder, and cognitive function is observed in numerous studies (4, 5). Subsequent studies evaluated the relationship between low vitamin D and PND (6).

On the other hand, a relationship between the thyroid hormones imbalance and mood disorder has been hypothesized for many years (7).

It seems interesting to explore the effectiveness of vitamin D supplements during pregnancy on maternal thyroid function and depression.

2. Objectives

Therefore, the current study aimed at assessing the effects of 2000 IU vitamin D supplementation on such variables in pregnant mothers.

3. Methods

3.1. Setting and Participants

The current randomized clinical trial was conducted from January 2014 to early December 2015 among nulliparous as well as multiparous females experiencing antenatal care in a teaching hospital in Shiraz, Iran. The inclusion criteria were: age ≥ 18 years, no history of medical problems, no dependence on any types of narcotic substances or alcohol, no gestational complications, a singleton pregnancy with live fetus, and being at the week 26 - 28 of gestation. Less than eight weeks consumption of vitamin D3 supplement led to participant exclusion.

3.2. PND Assessment Instrument

The Edinburgh postnatal depression scale (EPDS) was used to evaluate depression intensity. This scale consists of 10 multiple-choice tests, the lowest possible score is 0 and the highest possible score is 30 (8). The EPDS can be used throughout the antenatal and postnatal period (9). At baseline, the mothers with the EPDS scores of > 13 were rejected and referred to a psychologist for clinical assessment. Depression score was evaluated twice for the two study groups; at baseline and four weeks postpartum.

3.3. Lab Data

25-hydroxyvitamin D [25(OH) D], thyroid stimulating hormone (TSH), free thyroxin (FT4), and anti-thyroid peroxidase antibody (TPOAb) were measured twice; at baseline and at birth.

3.4. Design and Data Collection

The Canadian Pediatric Association suggested 2000 IU of vitamin D in pregnancy and breast-feeding period (10). Therefore, the vitamin D group received 2000 IU vitamin D3 (two 1000 IU pills) daily from the week 26 to 28 of gestation until birth. The supplements were provided by the Jalinous Pharmaceutical Company in Tehran, Iran. The control group took two tablets as placebo daily. Block randomization technique was employed as the sampling method. The study was a double-blind. The participants were not aware of the pill contents. The lab technicians and research assistant were blind to group allocations. All participating mothers could take prescribed supplements outside the study protocol.

3.5. Sample Size and Statistical Analysis

Lastly, 98 participants (out of 120) finished the study. Numerical values were compared using t-test and the Mann-Whitney U test in its right approach.

The current study obtained the ethics code (No. IR. SUMS.REC.1394.87) and a registration code in the Iranian Registry of Clinical Trial’s website (No. IRCT201508091312N2).

4. Results

Maternal demographic characteristics, vitamin D serum levels, thyroid function data, and depression scores were compared between the two groups, as shown in Tables 1 - 3, respectively. Linear regression (backward method) did not show any significant correlation between antenatal depression score (26th - 28th week of gestation) and thyroid function parameters (TSH, FT4, and TPO). Also, no linear correlation was observed between depression score at 4th week postpartum and thyroid function parameters at birth. The correlation between vitamin D levels and thyroid function was investigated by Spearman’s coefficient. No correlation was detected between vitamin D levels and thyroid function: TSH (rho = 0.03, P = 0.65); FT4 (rho = -0.07, P = 0.31); TPO (rho = -0.08, P = 0.56).

Table 1. Comparison of Maternal Demographic Data and Vitamin D Level in the Study Groupsa
VariableVitamin D (N = 46)Control (N = 52)P Value
Age, y26.04 ± 5.0726.61 ± 4.010.46
BMI, kg/m2 (pre-pregnancy)24.17 ± 4.2023.41 ± 3.750.30
Gestational age, d273.26 ± 8.94275.28 ± 7.290.22
Baseline 25 (OH) D, ng/mL11.94 ± 5.4713.34 ± 8.820.34b
Birth 25(OH)D, ng/mL18.43 ± 10.2213.11 ± 6.260.005b,c
Change in 25(OH) D, ng/mL5.92 ± 12.05-1.10± 9.980.008b,c
Parity, No. (%)0.25
Nullipara23 (50)32 (61.5)
Multipara23 (50)20 (38.5)

aValues are expressed as mean ± SD unless otherwise indicated.

bThe Mann-Whitney U test.

cP < 0.05: Significantly different compared with the baseline.

Table 2. Baseline and Birth Serum Levels of TSH, TF4, and TPOAb in the Study Groupsa
VariableAt Baseline (N = 46)At Birth (N = 52)P Value
Vitamin D2.74 ± 3.063.78 ± 5.910.11
Control2.38 ± 2.423.69 ± 3.620.001c
P valueb0.490.15
Vitamin D10.37 ± 2.599.50 ± 2.780.04c
Control10.08 ± 2.239.81 ± 3.020.55
P valueb0.53 ± 0.690.62
Vitamin D38.26 ± 145.0223.42 ± 73.860.04c
Control29.50 ± 87.6324.65 ± 73.760.008c
P valueb1.000.38

aValues are expressed as mean ± SD.

bThe Mann-Whitney U test.

cP < 0.05: Significantly different compared with the baseline.

Table 3. Depression Scores at Baseline and 4th Week Postnatal in the Study Groupsa
VariableBaseline (N = 46)4th Week (N = 52)P Value
Vitamin D8.52 ± 3.614.48 ± 3.300.000b
Control8.00 ± 3.697.07 ± 4.520.15
P valuec0.470.002b

aValues are expressed as mean ± SD.

bP < 0.05: Significantly different compared with the baseline and control group.

cThe Mann-Whitney U test.

5. Discussion

Some studies detected an association between serum levels of vitamin D and thyroid disturbances (11). In contrast, in the current study, no correlation was observed between vitamin D level and thyroid function (TSH, FT4, and TPOAb levels) at baseline. Also, after intervention, no significant differences were observed between the subjects receiving vitamin D supplement and the ones receiving placebo concerning TSH, FT4, and TPO levels.

On the other hand, depression scores at 4th week postpartum were significantly lower in the vitamin D group than those of the placebo group. Therefore, vitamin D consumption during pregnancy may be effective to relive symptoms of PND. In line with the current study, previous clinical trials in nonpregnant females showed positive effects of vitamin D on mental status (12, 13). Recent studies considering the relationship between thyroid function and PND show contradictory results. For example, thyroid hormones and TPOAb at 48 hours after birth could not predict PND in a study in Spain (14); in a study by Kuijpens et al. mothers with positive TPOAb during pregnancy were at risk for depression at 4 and 12 weeks postpartum (15). The current study results suggested that the role of vitamin D in decreasing depression score was independent of thyroid function. However, there are other ways that vitamin D can influence brain function. The presence of 1,25(OH)2D (the active form of vitamin D) receptor in the brain provokes a direct effect (16). Also, vitamin D may take action as an anti-inflammatory mediator in the brain by reducing the production of risky pro-inflammatory cytokines (17).




  • 1.

    Holick MF. The vitamin D epidemic and its health consequences. J Nutr. 2005;135(11):2739S-48S. doi: 10.1093/jn/135.11.2739S. [PubMed: 16251641].

  • 2.

    Medical Advisory Secretariat. Clinical utility of vitamin d testing: an evidence-based analysis. Ont Health Technol Assess Ser. 2010;10(2):1-93. [PubMed: 23074397]. [PubMed Central: PMC3377517].

  • 3.

    Halbreich U, Karkun S. Cross-cultural and social diversity of prevalence of postpartum depression and depressive symptoms. J Affect Disord. 2006;91(2-3):97-111. doi: 10.1016/j.jad.2005.12.051. [PubMed: 16466664].

  • 4.

    Ganji V, Milone C, Cody MM, McCarty F, Wang YT. Serum vitamin D concentrations are related to depression in young adult US population: The Third National Health and Nutrition Examination Survey. Int Arch Med. 2010;3:29. doi: 10.1186/1755-7682-3-29. [PubMed: 21067618]. [PubMed Central: PMC2996356].

  • 5.

    Hoang MT, Defina LF, Willis BL, Leonard DS, Weiner MF, Brown ES. Association between low serum 25-hydroxyvitamin D and depression in a large sample of healthy adults: The Cooper Center longitudinal study. Mayo Clin Proc. 2011;86(11):1050-5. doi: 10.4065/mcp.2011.0208. [PubMed: 22033249]. [PubMed Central: PMC3202994].

  • 6.

    Murphy PK, Mueller M, Hulsey TC, Ebeling MD, Wagner CL. An exploratory study of postpartum depression and vitamin D. J Am Psychiatr Nurses Assoc. 2010;16(3):170-7. doi: 10.1177/1078390310370476. [PubMed: 21659271].

  • 7.

    Hage MP, Azar ST. The Link between Thyroid Function and Depression. J Thyroid Res. 2012;2012:590648. doi: 10.1155/2012/590648. [PubMed: 22220285]. [PubMed Central: PMC3246784].

  • 8.

    Cox JL, Holden JM, Sagovsky R. Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry. 1987;150:782-6. doi: 10.1192/bjp.150.6.782. [PubMed: 3651732].

  • 9.

    Brancaglion MY, Gomide Vasconcellos A, Fernandes Malloy-Diniz L, Nicolato R, Corrêa H. Edinburgh postnatal depression scale for screening antepartum depression in the Brazilian public health system. Clin Neuropsychiatry. 2013;10(2):102-7.

  • 10.

    [No authors listed] . Vitamin D supplementation: Recommendations for Canadian mothers and infants. Paediatr Child Health. 2007;12(7):583-98. doi: 10.1093/pch/12.7.583. [PubMed: 19030432]. [PubMed Central: PMC2528771].

  • 11.

    Chailurkit LO, Aekplakorn W, Ongphiphadhanakul B. High vitamin D status in younger individuals is associated with low circulating thyrotropin. Thyroid. 2013;23(1):25-30. doi: 10.1089/thy.2012.0001. [PubMed: 22931506].

  • 12.

    Mozaffari-Khosravi H, Nabizade L, Yassini-Ardakani SM, Hadinedoushan H, Barzegar K. The effect of 2 different single injections of high dose of vitamin D on improving the depression in depressed patients with vitamin D deficiency: A randomized clinical trial. J Clin Psychopharmacol. 2013;33(3):378-85. doi: 10.1097/JCP.0b013e31828f619a. [PubMed: 23609390].

  • 13.

    Jorde R, Sneve M, Figenschau Y, Svartberg J, Waterloo K. Effects of vitamin D supplementation on symptoms of depression in overweight and obese subjects: Randomized double blind trial. J Intern Med. 2008;264(6):599-609. doi: 10.1111/j.1365-2796.2008.02008.x. [PubMed: 18793245].

  • 14.

    Albacar G, Sans T, Martin-Santos R, Garcia-Esteve L, Guillamat R, Sanjuan J, et al. Thyroid function 48h after delivery as a marker for subsequent postpartum depression. Psychoneuroendocrinology. 2010;35(5):738-42. doi: 10.1016/j.psyneuen.2009.10.015. [PubMed: 19939574].

  • 15.

    Kuijpens JL, Vader HL, Drexhage HA, Wiersinga WM, van Son MJ, Pop VJ. Thyroid peroxidase antibodies during gestation are a marker for subsequent depression postpartum. Eur J Endocrinol. 2001;145(5):579-84. doi: 10.1530/eje.0.1450579. [PubMed: 11720875].

  • 16.

    Eyles D, Brown J, Mackay-Sim A, McGrath J, Feron F. Vitamin D3 and brain development. Neuroscience. 2003;118(3):641-53. doi: 10.1016/S0306-4522(03)00040-X. [PubMed: 12710973].

  • 17.

    Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: When the immune system subjugates the brain. Nat Rev Neurosci. 2008;9(1):46-56. doi: 10.1038/nrn2297. [PubMed: 18073775]. [PubMed Central: PMC2919277].

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