Evidence map›Paper›PMID 41398893›Full record

SynthesisMedicine2025

The effectiveness and safety of the active form of folate on biochemical parameters in women of childbearing age: A systematic review and meta-analysis.

Min Xie, Xuemei Qing, Hailong Huang, Jing Zhang

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors.

Min XieDepartment of Obstetrics and Gynecology, Chengdu Qingbaijiang District People's Hospital, Chengdu, China.ORCID 0009-0009-5582-1563
Xuemei QingDepartment of Obstetrics and Gynecology, Chengdu Qingbaijiang District People's Hospital, Chengdu, China.
Hailong HuangDepartment of Obstetrics and Gynecology, Chengdu Qingbaijiang District People's Hospital, Chengdu, China.
Jing ZhangDepartment of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLow folate levels in women of childbearing age can cause various health issues. Additionally, low perinatal folate concentrations are a significant cause of neural tube defects. Currently, folic acid supplements mainly consist of folic acid and the active form of folate. Therefore, this systematic review and meta-analysis aimed to evaluate the effectiveness and safety of the active form of folate in women of childbearing age.

methodsWe searched the published literature in PubMed, Medline, EMBASE, The Cochrane Library, China National Knowledge Infrastructure, and Wanfang. Randomized controlled trials (RCTs) were obtained to assess the effects of the active form of folate versus folic acid in women of childbearing age. The random or fixed effects model was used to analyze the data in meta-analysis. The results were expressed as standardized mean differences or risk ratios along with their corresponding 95% confidence intervals.

resultsEleven RCTs were identified in our systematic review. The results indicated that the active form of folate supplementation might significantly increase plasma folate (P = .04), increase erythrocyte folate (P = .01), and decrease unmetabolized folic acid (P < .0001). Supplementation with the active form of folate might increase the subsequent pregnancy rates (P = .0005) and might decrease the incidence of adverse pregnancy outcomes (P = .0003) in women with a history of adverse pregnancy outcomes. However, there were no significant differences in homocysteine, vitamin B12, and betaine. In addition, subgroup analyses showed a significant increase in plasma folate and erythrocyte folate in the active form of folate supplementation group, specifically in subgroups with dosage ≥0.4 mg, intervention of the active form of folate supplementation versus the equimolar mass of folic acid, and intervention duration ≥12 weeks.

conclusionActive form of folate supplementation might contribute to higher plasma folate, erythrocyte folate, and subsequent pregnancy rates, lower unmetabolized folic acid, and lower incidence of adverse pregnancy outcomes in women of childbearing age. Due to the limitation in the quality of involved studies and the short duration of treatment, more RCTs with high-quality, long-term duration and pregnancy outcomes are needed for further validation.

Indexed as

Dietary SupplementsFolic AcidAdultFemaleHumansPregnancyPregnancy OutcomeRandomized Controlled Trials as TopicFolic Acid5-methyltetrahydrofolateactive form of folateerythrocyte folatefolic acidhomocysteinemeta-analysisplasma folate

Identifiers

PMID41398893
PMCPMC12708167

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.