Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis.
OBJECTIVE
To conduct a systematic review and meta-analysis of pregnancy outcome after metformin use for polycystic ovary syndrome (PCOS), because the efficacy of metformin has been demonstrated in the treatment of infertility caused by PCOS, whereas the fetal safety of metformin has received very little attention, and the few studies addressing this issue are limited by small sample sizes.


METHODS
Meta-analytic review.


METHODS
All pertinent studies in MEDLINE and EMBASE from 1966 to September 2004.


METHODS
Women with PCOS or diabetes.


METHODS
Exposure to metformin in the first trimester of pregnancy.


METHODS
Major malformations.


RESULTS
Eight studies were included in the meta-analysis, with an odds ratio of 0.50 (95% confidence interval, 0.15, 1.60). After adjustment for publication bias, metformin treatment in the first trimester was associated with a statistically significant 57% protective effect. After pooling the studies, the malformation rate in the disease-matched control group was approximately 7.2%, statistically significantly higher than the rate found in the metformin group (1.7%).


CONCLUSIONS
On the basis of the limited data available today, there is no evidence of an increased risk for major malformations when metformin is taken during the first trimester of pregnancy. Large studies are needed to corroborate these preliminary results.
Gilbert
Cameron
C
Motherisk Program, Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, Canada.
Valois
Maria
M
Koren
Gideon
G
D000014:Abnormalities, Drug-Induced / Q000453:epidemiology*; D002170:Canada; D015897:Comorbidity; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D015994:Incidence; D008687:Metformin / Q000008:administration & dosage*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000453:epidemiology*; D011247:Pregnancy; D011256:Pregnancy Outcome / Q000453:epidemiology*; D011261:Pregnancy Trimester, First / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology*; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors
D007004:Hypoglycemic Agents; D008687:Metformin