Review reports lower preeclampsia risk with some higher-dose vitamin D regimens
The analysis involved high-risk pregnancies, but its authors say the findings are exploratory and not evidence of clinical effectiveness.
Low evidenceReviewInterpret with caution
Medical disclaimer: This article summarizes research findings and is for informational purposes only. It is not medical advice.
Editorial illustration — not from the study.
Researchers compared different doses of vitamin D with statins and metformin for preeclampsia and related outcomes. The review included women considered high risk for reasons that varied across trials, including previous preeclampsia, obesity, metabolic conditions, or vitamin D deficiency.
The vitamin D regimens of 4,000 IU daily and 60,000 IU monthly had the strongest estimated positions in the analysis for preeclampsia. However, these results came from limited direct evidence and partly indirect comparisons. Findings for statins and metformin were inconsistent, and the authors described the overall results as hypothesis-generating rather than a basis for clinical decisions.
The question reviewed
The researchers conducted a systematic review and network meta-analysis of randomized controlled trials. They searched five databases for studies published or indexed from September 2020 through September 2025 and included eight trials with 4,078 high-risk pregnant women. Participants were assigned to statins, metformin, or different vitamin D regimens, generally compared with placebo. The main outcome was preeclampsia; other outcomes included gestational hypertension, preterm birth, low birth weight, neonatal intensive care admission, gestational diabetes, respiratory distress syndrome, and other perinatal outcomes.
Key conclusions
Compared with placebo, vitamin D at 4,000 IU daily was associated with an estimated risk ratio for preeclampsia of 0.21, with a 95% confidence interval of 0.06 to 0.72. Vitamin D at 60,000 IU monthly was associated with an estimated risk ratio of 0.36, with a 95% confidence interval of 0.19 to 0.70. Based on the baseline risks observed in these studies, these estimates corresponded to approximate absolute risk differences of 8% and 6%, respectively. These are associations from a limited network and do not establish that vitamin D caused the lower risk.
Higher-dose vitamin D was also associated with possible lower rates of preterm birth and low birth weight, but those estimates were imprecise. Evidence for statins and metformin was inconsistent and had wide confidence intervals. Rankings that placed vitamin D higher than other interventions were exploratory; they indicate relative positioning within this particular network, not proven comparative effectiveness. A possible numerical advantage for pravastatin 20 mg was reported for neonatal intensive care admission and respiratory distress syndrome, but it was not statistically significant.
Who this may apply to
The findings apply most directly to pregnant women considered high risk in the included trials, although that group was varied and not consistently defined. They may not apply to people at lower risk, to all forms of high-risk pregnancy, or to vitamin D doses and schedules not represented in the trials. The review does not establish whether the findings apply equally across different baseline vitamin D levels, medical conditions, gestational ages, or care settings. It also does not provide evidence that statins, metformin, or vitamin D are effective for the general pregnant population.
Why it matters
Preeclampsia and related pregnancy outcomes were the focus of this human research, so the topic is relevant to pregnancy health. The review suggests that certain vitamin D regimens merit further study, especially in carefully defined high-risk groups, but it does not establish clinical effectiveness or show that one intervention is superior. The results also highlight how differences in participants, timing, dose, and baseline vitamin D status can affect estimates.
Limitations & evidence assessment
Only eight trials were available, and the number of studies for individual interventions was small; some comparisons were based on a single trial. The high-risk groups were not defined consistently, and studies differed in baseline risk, obesity and metabolic conditions, vitamin D status, treatment timing, dose, duration, and background care. There were few direct comparisons between interventions, so several results depended heavily on indirect evidence, and the network may not have been sufficiently comparable for reliable indirect comparisons. Most contributing trials had some concerns or a high risk of bias, while some lacked control-group baseline data; small samples, unexplained attrition, and unequal allocation between intervention and control groups also reduced confidence. The search period was restricted, trials with aspirin comparators were excluded, and the available data did not allow reliable dose-response or subgroup analyses. The authors rated the certainty of evidence as low and said the findings should not guide current clinical decision-making.
Why this evidence level: This review combined eight randomized trials involving 4,078 high-risk pregnant women, but the authors rated the certainty of the evidence as low. The analysis used sparse and partly indirect comparisons, with substantial differences between the included studies.
Evidence levels are editorial estimates derived from study metadata — they are not clinical appraisals.
// Source
BMC Pregnancy and Childbirth · 2026 · DOI: 10.1186/s12884-026-09920-6
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