Table 2.
Risk of birth defects in pregnancies exposed to metformin during the first trimester compared to the matched unexposed reference group. Metformin study from European Teratology Information Services (TIS) 1993–2015
| Metformin group | Reference group | Odds ratio (OR) and 95% confidence interval (95 CI) | ||||||
|---|---|---|---|---|---|---|---|---|
| Overall | Indication diabetes | Indication other | Overall | ORcrude (95 CI) | ORadj c (95 CI) | ORcrude (95 CI) | ORcrude (95 CI) | |
| Birth defects | n = 392a, n (%) | n = 219, n (%) | n = 173, n (%) | n = 431b, n (%) | Metformin overall vs. reference | Metformin with diabetes vs. reference | Metformin without diabetes vs. reference | |
| All birth defects without chromosomal or genetic origin | 32 (8.1) | 24 (11.0) | 8 (4.6) | 18 (4.2) | 2.04 (1.14–3.77) | 1.86 (0.95–3.71) | 2.84 (1.50–5.39) | 1.11 (0.45–2.53) |
| Major birth defects | 20 (5.1) | 17 (7.8) | 3 (1.7) | 9 (2.1) | 2.52 (1.17–5.89) | 1.70 (0.70–4.38) | 3.95 (1.77–9.41) | 0.83 (0.18–2.81) |
| Minor birth defects | 12 (3.1) | 7 (3.2) | 5 (2.9) | 9 (2.1) | 1.48 (0.62–3.66) | 1.92 (0.72–5.21) | 1.55 (0.55–4.21) | 1.40 (0.42–4.10) |
| Cardiac birth defects | 9d (2.3) | 6 (2.7) | 3 (1.7) | 5e (1.2) | 2.00 (0.67–6.03) | 1.53 (0.43–5.72) | 2.40 (0.72–8.41) | 1.50 (0.31–6.20) |
Restricted to pregnancies with information on the presence or absence of a birth defect: 28 birth defects (16 major and 12 minor) identified among 378 live born infants and 4 defects (4 major and 0 minor) among 14 pregnancy losses with histopathological exam (16%; 14/79)
Restricted to pregnancies with information on the presence or absence of a birth defect; 16 birth defects (7 major and 9 minor) among 421 live born and 2 defects (2 major and 0 minor) among 10 pregnancy losses with histopathological exam (17%; 10/58)
Adjusted for maternal age (continuous), BMI categories (≤25; 26–30, >31, missing), maternal hypertension (yes/no), use of >1 medication (yes/no), centre 8 (yes/no)
Contains two minor birth defects (1 patent or persistent foramen ovale; 1 interventricular septal hypertrophy)
Contains two minor birth defects (1 patent or persistent foramen ovale; 1 patent ductus arteriosus)