Vitamin D2026-07

Impact of vitamin D supplementation on preterm births and premature rupture of membranes: a study protocol for a double-blind randomised controlled trial.

Bhatnagar Gowri, Gowda Poornima, Michael John, Dias Mary et al. — BMJ open

Summary

This paper outlines the plan for a future study investigating whether higher vitamin D intake during pregnancy can reduce the risk of preterm birth and premature rupture of membranes. Researchers will compare two different daily doses of vitamin D in pregnant women with low vitamin D levels. The findings from this planned trial could offer insights into preventing serious birth complications, especially in regions where vitamin D deficiency is common.

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Key points

This paper describes the detailed plan for a future study on vitamin D and pregnancy outcomes.
The study aims to determine if higher daily vitamin D supplementation can lower the risk of preterm birth.
It will involve pregnant women with vitamin D deficiency, comparing a standard dose to a higher dose.
The research seeks to provide evidence for preventing serious birth complications.

What the study looked at

What question the study asked: This study protocol outlines a future research project designed to investigate if providing a higher daily dose of vitamin D to pregnant women can reduce the incidence of preterm birth and premature rupture of membranes. This question is particularly important in regions like India, where vitamin D deficiency is widespread among pregnant individuals. How it was studied (design/participants): This paper is a *protocol*, meaning it details the plan for a future double-blind randomized controlled trial, not the results of a completed study. The researchers intend to recruit over 900 pregnant women, all within their first 18 weeks of pregnancy and diagnosed with vitamin D deficiency. These participants will be randomly assigned to receive either 500 IU of vitamin D3 daily (considered standard care) or 2000 IU of vitamin D3 daily, along with calcium, until they give birth. Various health markers and birth outcomes will be carefully monitored. What it found: As this document is a study *protocol*, it describes the *plan* for the research rather than presenting any findings. The study itself has not yet been conducted, so there are no results to report at this stage. The protocol details the methods for collecting data on vitamin D levels, other biological markers, and infant health to assess the impact of the different supplementation levels.

Dietary takeaway

While this study is still in the planning stages, it underscores the ongoing scientific interest in vitamin D's potential role during pregnancy. For now, pregnant individuals should discuss their vitamin D status and any potential supplementation with their healthcare provider, as maintaining adequate vitamin D levels is important for overall health. Remember, this paper outlines a future study, and its findings, once available, will contribute to our understanding, but no single study provides definitive answers.

Abstract

INTRODUCTION: Preterm birth (PTB) is a major adverse outcome in developing countries, including India, with serious adverse consequences. Although the pathophysiology is not fully understood, maternal biomarkers influencing placental function may contribute to premature rupture of membranes and PTB. Vitamin D₃ supplementation during pregnancy may lower the risk of PTB, particularly in populations with a high prevalence of vitamin D deficiency (~90% in India). However, available biomarkers for PTB prediction are non-confirmatory, costly and not part of routine care. The aim of the study is to evaluate whether 2000 IU/day vitamin D₃ supplementation during pregnancy reduces PTB compared with 500 IU/day (standard care). METHODS AND ANALYSIS: Singleton pregnant women ≤18 weeks gestation with deficiency of 25-hydroxyvitamin D (<20 ng/mL) attending antenatal clinics will be randomised (n=902) in a double-blind trial to receive either 500 IU or 2000 IU/day of vitamin D₃ with 1000 mg elemental calcium until delivery. Women with chronic illness, infections (HIV, positive Venereal Disease Research Laboratory test and positive hepatitis B surface antigen test), assisted conception or planned relocation before study completion will be excluded. Baseline details such as socio-demographic data, diet, anthropometry, ultrasound findings and blood pressure will be collected. Monthly antenatal visits will include clinical monitoring, supplement distribution and compliance checks. Blood samples at baseline and second and third trimesters and cord blood will be collected to assess vitamin D-related markers, pregnancy-associated plasma protein A and haemoglobin. Urinary calcium-to-creatinine ratio will be measured mid-study. Birth outcomes and infant anthropometry will be recorded. Baseline and endline characteristics will be compared between study arms using the χ2 test or Fisher's exact test for categorical variables (depending on the expected frequencies) and the independent samples t-test or Mann-Whitney U test for continuous variables (following normality assessment). ETHICS AND DISSEMINATION: The study has been funded by the Department of Biotechnology, India (Grant Ref: BT/PR41941/MED/97/548/2021). Ethical clearance has been obtained from Institutional Ethics Committee (Ref No. IEC/344/2021), St. John's Medical College & Research Institute and Ethics Committee of Bangalore Medical College & Research Institute (BMCRI/EC/25/2024). Study data will be disseminated through peer-reviewed publications and conference presentations. TRIAL REGISTRATION: Trial has been prospectively registered with Clinical Trials Registry - India (CTRI/2021/10/037658).

View on PubMed →DOI: 10.1136/bmjopen-2026-116986