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Br J Clin Pharmacol. 2018 Mar;84(3):568-578. doi: 10.1111/bcp.13481. Epub 2018 Jan 14.

Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services.

Author information

1
School of Pharmaceutical Sciences, University of Geneva and Lausanne, Geneva, Switzerland.
2
Swiss Teratogen Information Service (STIS) and Service of Clinical Pharmacology, University Hospital, Lausanne, Switzerland.
3
Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
4
Institute of Social and Preventive Medicine (IUMSP), Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
5
Pharmacovigilance Center of Lyon, Hospices Civils de Lyon, France.
6
Materno-Fetal and Obstetrics Research Unit, Departement "Femme-Mere-Enfant", University Hospital, Lausanne, Switzerland.
7
Registre des Malformations en Rhone Alpes (REMERA), Faculté Laennec, Lyon, France.
8
Telefono Rosso-Teratology Information Service, Department of Obstetrics and Gynecology, Catholic University of Sacred Heart, Rome, Italy.
9
Centro di Riferimento Regionale di Tossicologia Perinatale, SODc Tossicologia Medica, Azienda Ospedaliero Universitaria Careggi, Firenze, Italy.
10
Pharmacovigilance Center of Dijon, CHU, Dijon, France.
11
Pharmacovigilance Center of Tours, CHRU, Tours, France.
12
Teratology Information Service, Clinical Genetics Unit, Department of Women's and Children's Health, University of Padova, Padova, Italy.
13
UKTIS, Regional Drug and Therapeutics Centre, Newcastle upon Tyne, UK.
14
Teratology Information Service (TIS), Netherlands Pharmacovigilance Centre Lareb, The Netherlands.
15
Faculty of Medicine Department of Pharmacology Teratology Information Service, Izmir Katip Celebi University, Izmir, Turkey.
16
Faculty of Medicine, Department of Pharmacology, Karadeniz Technical University, Trabzon, Turkey.
17
CZTIS, 3rd Faculty of Medicine, Charles University, Prague, Czech Republic.
18
Poison Control Center, Bergamo, Italy.
19
BELTIS, Rabin Medical Center and NICU, Schneider Children's Medical Center of Israel, Petach Tikva, Israel and Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Abstract

AIMS:

Metformin is used to treat type 2 diabetes, polycystic ovary syndrome associated infertility, and gestational diabetes. This study aims to evaluate the safety of metformin in early pregnancy.

METHOD:

We evaluated the risk of major birth defects and pregnancy losses in a cohort of pregnant women exposed to metformin during the first trimester for different indications relative to a matched unexposed reference group.

RESULTS:

The risk of major birth defects was 5.1% (20/392) in pregnancies exposed to metformin during the first trimester and 2.1% (9/431) in the reference group [adjusted odds ratio (OR) 1.70; 95% CI 0.70-4.38]. Among metformin users, this risk was 7.8% (17/219) in patients with pre-gestational diabetes and 1.7% (3/173) in those without this diagnosis. Compared to the unexposed reference, the OR for metformin user with diabetes was 3.95 (95% CI 1.77-9.41) and for metformin with other indications it was 0.83 (95% CI 0.18-2.81). The risk of pregnancy losses (spontaneous abortions and stillbirths) was 20.8% in women on metformin during the first trimester and 10.8% in the reference group [adjusted hazard ratio (HR) 1.57; 95% CI 0.90-2.74]. The risks for women on metformin with and without pre-gestational diabetes were 24.0% and 16.8% respectively, with adjusted HR of 2.51 (95% CI 1.44-4.36) and 1.38 (95% CI 0.74-2.59) when compared to the reference.

CONCLUSION:

Pregnant women with pre-gestational diabetes on metformin are at a higher risk for adverse pregnancy outcomes than the general population. This appears to be due to the underlying diabetes since women on metformin for other indications do not present meaningfully increased risks.

KEYWORDS:

diabetes; metformin; observational study; pregnancy; spontaneous abortion; teratogen

PMID:
29215149
PMCID:
PMC5809340
[Available on 2019-03-01]
DOI:
10.1111/bcp.13481

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