A randomized controlled trial of vitamin D supplementation on perinatal depression: in Iranian pregnant mothers

Randomized, placebo-controlled trial in pregnant women receiving prenatal care at Hafez hospital in Shiraz, Iran. Women were 18 years or older, had singleton pregnancies, and had no history of mental illness or major internal disease; enrollment occurred in the late second to early third trimester. The vitamin D3 arm included 74 randomized participants.

Vitamin D3 (cholecalciferol) was given orally at 2000 IU daily, as two 1000 IU pills, from 26 to 28 weeks of gestation until childbirth. The comparison group received placebo.

Vitamin D3 supplementation was associated with lower perinatal depression scores than placebo and was generally well tolerated. Baseline EPDS scores were similar between groups (8.44 ± 3.89 vs 8.64 ± 3.81; p=0.747), but at 38-40 weeks gestation the vitamin D group scored lower (6.17 ± 3.47 vs 7.77 ± 3.92; p=0.01). Benefits persisted postpartum at 4 weeks (4.59 ± 3.29 vs 7.36 ± 4.27; p<0.001) and 8 weeks (4.19 ± 3.76 vs 7.18 ± 3.99; p<0.001). Serum 25(OH)D at delivery was also higher with vitamin D3 (17.46 ± 10.09 ng/mL vs 12.07 ± 5.98 ng/mL; p=0.001).

Interpretation is limited by a single-center design, a relatively small sample, and incomplete outcome follow-up (136 participants completed EPDS assessments across both groups). Some participants also used supplements outside the protocol, including multivitamins containing vitamin D, which could dilute or confound the observed effect.