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.
- MeSH
- dospělí MeSH
- hypoglykemika aplikace a dávkování škodlivé účinky MeSH
- kohortové studie MeSH
- komplikace těhotenství farmakoterapie MeSH
- lidé MeSH
- metformin aplikace a dávkování škodlivé účinky MeSH
- narození mrtvého plodu epidemiologie MeSH
- prospektivní studie MeSH
- první trimestr těhotenství MeSH
- samovolný potrat epidemiologie MeSH
- těhotenství při diabetu farmakoterapie MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- práce podpořená grantem MeSH
This multicenter, observational prospective cohort study addresses the risk associated with exposure to mirtazapine during pregnancy. Pregnancy outcomes after exposure to mirtazapine were compared with 2 matched control groups: (1) exposure to any selective serotonin reuptake inhibitor (SSRI, control subjects with a psychiatric condition) and (2) no exposure to medication known to be teratogenic or any antidepressant (general control subjects). Data were collected by members of the European Network of Teratology Information Services between 1995 and 2011. Observations from 357 exposed pregnancies were compared with 357 pregnancies from each control group. The rate of major birth defects between the mirtazapine and the SSRI group did not differ significantly (4.5% vs 4.2%; odds ratio [OR], 1.1; 95% confidence interval [95% CI], 0.5-2.3; P = 0.9). A trend toward a higher rate of birth defects in the mirtazapine group compared with general control subjects (4.5% vs 1.9%; OR, 2.4; 95% CI, 0.9-6.3; P = 0.08) reached statistical significance after exclusion of chromosomal or genetic anomalies (4.1% vs 1.3%; OR, 3.3; 95% CI, 1.04-10.3; P = 0.03), but this difference became again nonsignificant if cases of exposure not comprising the first trimester were excluded from the analysis (3.4% vs 1.9%; OR, 1.8; 95% CI, 0.6-5.0; P = 0.26). The crude miscarriage rate did not differ significantly between the mirtazapine, the SSRI, and the general control groups (12.1% vs 12.0% vs 9.3%; P = 0.44). However, a higher rate of elective pregnancy termination was observed in the mirtazapine group compared with SSRI and general control subjects (7.8% vs 3.4% vs 5.6%; P = 0.03). This study did not observe a statistically significant difference in the rate of major birth defects after first-trimester exposure between mirtazapine, SSRI-exposed, and nonexposed pregnancies. A marginally higher rate of birth defects was, however, observed in the mirtazapine and SSRI groups compared with the low rate of birth defects in our general control subjects. Overall pregnancy outcome after mirtazapine exposure was similar to that of the SSRI-exposed control group.
- MeSH
- abnormality vyvolané léky epidemiologie etiologie MeSH
- antidepresiva škodlivé účinky MeSH
- depresivní poruchy komplikace farmakoterapie MeSH
- dospělí MeSH
- gestační stáří MeSH
- komplikace těhotenství farmakoterapie psychologie MeSH
- lidé MeSH
- mianserin škodlivé účinky analogy a deriváty MeSH
- porodní hmotnost účinky léků MeSH
- prospektivní studie MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- výsledek těhotenství epidemiologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- Klíčová slova
- Anatomický ústav 3. LF UK, Ústav histologie a embryologie 3. LF UK,
- MeSH
- anatomie * dějiny metody trendy MeSH
- antropologie * metody trendy výchova MeSH
- dějiny lékařství MeSH
- embryologie * dějiny organizace a řízení trendy MeSH
- histologie dějiny organizace a řízení trendy MeSH
- kardiovaskulární systém anatomie a histologie patofyziologie patologie MeSH
- lidé MeSH
- mozek anatomie a histologie patofyziologie patologie MeSH
- výchova a vzdělávání MeSH
- významné osobnosti MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- historické články MeSH
- MeSH
- lidé MeSH
- šíření informací * dějiny MeSH
- teratologie * dějiny organizace a řízení MeSH
- Check Tag
- lidé MeSH
- MeSH
- lidé MeSH
- teratologie * dějiny MeSH
- významné osobnosti * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
