TY - JOUR
T1 - Pregnancy outcomes in women on metformin for diabetes or other indications among those seeking teratology information services
AU - Panchaud, Alice
AU - Rousson, Valentin
AU - Vial, Thierry
AU - Bernard, Nathalie
AU - Baud, David
AU - Amar, Emmanuelle
AU - De Santis, Marco
AU - Pistelli, Alessandra
AU - Dautriche, Anne
AU - Beau-Salinas, Frederique
AU - Cassina, Matteo
AU - Dunstan, Hannah
AU - Passier, Anneke
AU - Kaplan, Yusuf Cem
AU - Duman, Mine Kadioglu
AU - Maňáková, Eva
AU - Eleftheriou, Georgios
AU - Klinger, Gil
AU - Winterfeld, Ursula
AU - Rothuizen, Laura E.
AU - Buclin, Thierry
AU - Csajka, Chantal
AU - Hernandez-Diaz, Sonia
N1 - Publisher Copyright:
© 2017 The British Pharmacological Society
PY - 2018/3
Y1 - 2018/3
N2 - 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.
AB - 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.
KW - diabetes
KW - metformin
KW - observational study
KW - pregnancy
KW - spontaneous abortion
KW - teratogen
UR - http://www.scopus.com/inward/record.url?scp=85041952645&partnerID=8YFLogxK
U2 - 10.1111/bcp.13481
DO - 10.1111/bcp.13481
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C2 - 29215149
AN - SCOPUS:85041952645
VL - 84
SP - 568
EP - 578
JO - British Journal of Clinical Pharmacology
JF - British Journal of Clinical Pharmacology
SN - 0306-5251
IS - 3
ER -