Safety of Metformin in Pregnancy

Study Overview
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Brief Summary
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This study aims to better characterize the risk linked to metformin use during pregnancy, using a prospective multicentric cohort design enabling a large sample size, in evaluating the rate of birth defects after first trimester exposure, as well as several other pregnancy related outcomes.

Official Title
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Pregnancy Outcome Following Maternal Exposure to Metformin: a Collaborative ENTIS Study

Conditions
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Pregnancy, Pregestational Diabetes, Polycystic Ovary Syndrom

Intervention / Treatment
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* Drug: metformin
* Drug: any drug not known as a major teratogen or major fetotoxicant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Exposed group: exposed to metformin (Anatomical Therapeutic Chemical A10BA02) any time during pregnancy (i. e. any time from conception to week 42 after last menstrual period (LMP)). Reference group: at no time during pregnancy were exposed to metformin, insulin or any other hypoglycaemic agent. Exclusion Criteria: exposed to any of the following known major teratogen or major fetotoxicant: acitretin, isotretinoin, mycophenolate, thalidomide, valproic acid, angiotensin-II receptor blockers (only when used in 2nd or 3rd trimester), ACE inhibitors (only when used in 2nd or 3rd trimester), or (b) following treatment indications coded: malignancies (MedDRA code: malignant or unspecified tumors (SMQ 20000091), ICD-10: C00-D09)) or malignancy related conditions (MedDRA: SMQ 20000092), ICD-10: C00-D09). lost to follow-up
Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pregnant patient exposed to metformin<br>Pregnant women seeking counseling by themselves or through their healthcare provider for exposure to metformin (Anatomical Therapeutic Chemical A10BA02) any time during pregnancy (i. e. any time from conception to week 42 after last menstrual period (LMP)). | Drug: metformin<br>* This is not an intervention but an observed exposure.<br>|
| Reference group<br>Pregnant women seeking counseling by themselves or through their healthcare provider for exposure to any drug not known as a major teratogen or fetotoxicant and different than metformin, insulin or any other hypoglycaemic agent. | Drug: any drug not known as a major teratogen or major fetotoxicant<br>* This is not an intervention but an observed exposure.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major birth defects |  | within two weeks after birth or at histopathological exam in case of late spontaneous abortion or stillbirth occuring in pregnancy | 
| Spontaneous abortion |  | until 20 weeks of pregnancy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minor birth defects |  | within two weeks after birth | 
| Preterm birth |  | after 24 weeks of pregnancy | 
| Pregnancy complications |  | after 12 weeks of pregnancy until delivery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metformin, pregnancy outcomes, birth defects, spontaneous abortion, pharmacoepidemiology