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Metformin for the Prevention of Hyperemesis Gravidarum: An Observational Cohort Study

Sillis L, Heinonen EW, Ceulemans M, Johnson D, Luo Y, Chambers CD

BJOG : an international journal of obstetrics and gynaecology, 2025

1,664 participants

Abstract

OBJECTIVE: To evaluate if metformin treatment prior to pregnancy reduces the likelihood of nausea and vomiting in pregnancy (NVP) and hyperemesis gravidarum (HG) compared to no exposure.

DESIGN: Observational cohort study.

SETTING: The MotherToBaby Pregnancy Studies in the United States and Canada.

SAMPLE: Live-born singleton pregnancies enrolled between 2012 and 2023, with HG diagnosis data available.

METHODS: Data were collected via maternal telephone interviews during pregnancy and medical records. Outcomes were compared between women with preconceptional metformin exposure and those unexposed to metformin before or during pregnancy.

MAIN OUTCOME MEASURES: Risk ratios (RR) and 95% confidence intervals (CI) for HG and NVP, and mean duration of NVP symptoms.

RESULTS: Data from 80 women exposed to metformin before conception and 4411 non-exposed women were analysed. In this cohort, the frequency of women with HG was lower among the exposed than the unexposed women (n = 1/80; 1.25% vs. n = 97/4411; 2.20%), but the study was not powered to detect statistical significance (adjusted RR 0.50, 95% CI 0.07-3.39). Rates of NVP were similar between groups (n = 32/80; 88.90% in the exposed and n = 1664/4111; 82.60% in the unexposed), with adjusted RR 1.06; 95% CI, 0.94-1.19. The mean duration of NVP symptoms was also similar between the groups.

CONCLUSIONS: This cohort study found a lower rate of HG in the preconceptional metformin-exposed group compared to unexposed, although the…

How strong is the evidence?

Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 1,664 participants or records.

How the five levels of evidence work. The level is assigned automatically from the abstract and can be wrong, so check the paper.

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