Metformin and small for gestational age babies: findings of a randomised placebo-controlled clinical trial of metformin in gestational diabetes (EMERGE).

Autor: Dunne F; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland. Fidelma.dunne@universityofgalway.ie.; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland. Fidelma.dunne@universityofgalway.ie.; Galway University Hospital, Newcastle Road, Galway, Ireland. Fidelma.dunne@universityofgalway.ie., Newman C; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland.; Galway University Hospital, Newcastle Road, Galway, Ireland., Alvarez-Iglesias A; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland., O'Shea P; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland., Devane D; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland.; School of Nursing and Midwifery, University of Galway, Galway, Ireland., Gillespie P; School of Business and Economics, University of Galway, Galway, Ireland., Egan A; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.; Mayo Clinic, Rochester, MN, USA., O'Donnell M; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland.; Galway University Hospital, Newcastle Road, Galway, Ireland., Smyth A; College of Medicine, Nursing and Health Sciences, University of Galway, Galway, Ireland.; HRB Clinical Research Facility Galway, University of Galway, Galway, Ireland.; Galway University Hospital, Newcastle Road, Galway, Ireland.
Jazyk: angličtina
Zdroj: Diabetologia [Diabetologia] 2024 Dec; Vol. 67 (12), pp. 2660-2666. Date of Electronic Publication: 2024 Aug 31.
DOI: 10.1007/s00125-024-06252-y
Abstrakt: Aims/hypothesis: Gestational diabetes mellitus (GDM) is associated with adverse perinatal outcomes because of suboptimal glucose management and glucose control and excessive weight gain. Metformin can offset these factors but is associated with small for gestational age (SGA) infants. We sought to identify risk factors for SGA infants, including the effect of metformin exposure on SGA status.
Methods: In this prespecified secondary analysis of the EMERGE trial, which evaluated the effectiveness of metformin vs placebo in treating GDM and found reduced gestational weight gain and longer time to insulin initiation with metformin use, we included women with a live-born infant and known infant birthweight and gestational age at delivery. We compared the numbers of SGA infants in both groups and explored baseline predictive factors to help identify those at highest risk of delivering an SGA infant.
Results: Baseline maternal characteristics were similar between SGA and non-SGA pregnancies. On multivariable-adjusted regression, no baseline maternal variables were associated with SGA status. Mothers of SGA infants were more likely to develop pre-eclampsia or gestational hypertension (18.2% vs 2.0%, p=0.001; 22.7% vs 5.4%, p=0.005, respectively); after multivariable adjustment, pre-eclampsia was positively associated with SGA status). Among SGA pregnancies, important perinatal outcomes including preterm birth, Caesarean delivery and neonatal care unit admission did not differ between the metformin and placebo groups (20.0% vs 14.3%, p=1.00; 50.0% vs 28.6%, p=0.25; 13.3% vs 42.9%, p=0.27, respectively).
Conclusions/interpretation: Pre-eclampsia was strongly associated with SGA infants. Metformin-exposed SGA infants did not display a more severe SGA phenotype than infants treated with placebo.
Trial Registration: Clinical Trials.gov NCT02980276; EudraCT number: 2016-001644-19.
Competing Interests: Data availability: Data are not available as ongoing and long-term follow-up is underway. Funding: Open Access funding provided by the IReL Consortium. The trial was funded by the Health Research Board of Ireland (HRB), coordinated by the HRB-Clinical Research Facility Galway. The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Authors’ relationships and activities: The authors received non-financial support from Merck Healthcare KGaA and Ascensia, which contributed metformin and matched placebo and blood glucose monitoring strips, respectively. Contribution statement: FD, AE, AS, DD and MOD devised the concept for this trial and FD, AE, CN, AS, DD, PO’S and MO’D wrote the protocol. AA-I and PG performed the statistical analysis. All authors drafted and revised the manuscript and approved the final version to be published. FD and CN are accountable for the integrity of the work as a whole.
(© 2024. The Author(s).)
Databáze: MEDLINE
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