Risk of spontaneous abortion associated with use of antibiotics during pregnancy, by drug class and type
| Drug exposure; class/type | No. (%) of spontaneous abortions n = 8702 | Crude OR (95% CI) | Adjusted OR* (95% CI) |
|---|---|---|---|
| No antibiotic use (ref) | 7274 (83.6) | 1.00 | 1.00 |
| Cephalosporins | 60 (0.7) | 1.01 (0.78–1.31) | 0.90 (0.69–1.18) |
| Cephalexin | 9 (0.1) | 1.13 (0.60–2.10) | 0.83 (0.33–2.11) |
| Other cephalosporins | 48 (0.6) | 0.97 (0.72–1.29) | 0.88 (0.66–1.18) |
| ≥ 2 drugs in class | 3 (0.03) | 1.93 (0.58–6.45) | 1.87 (0.57–6.19) |
| Macrolides | 264 (3.0) | 1.78 (1.56–2.03) | 1.61 (1.41–1.85) |
| Azithromycin | 110 (1.3) | 1.76 (1.44–2.14) | 1.65 (1.34–2.02) |
| Clarithromycin | 111 (1.3) | 2.66 (2.16–3.27) | 2.35 (1.90–2.91) |
| Erythromycin | 29 (0.3) | 0.76 (0.53–1.10) | 0.70 (0.49–1.01) |
| Other macrolides | 7 (0.1) | 2.30 (1.02–5.14) | 1.96 (0.86–4.47) |
| ≥ 2 drugs in class | 7 (0.1) | 2.30 (1.03–5.15) | 1.89 (0.85–4.23) |
| Penicillins | 500 (5.7) | 0.94 (0.86–1.03) | 0.86 (0.78–0.95) |
| Amoxicillin | 257 (3.0) | 0.75 (0.66–0.85) | 0.67 (0.59–0.77) |
| Amoxicillin–potassium clavulanate | 7 (0.1) | 1.99 (0.90–4.43) | 1.57 (0.71–3.50) |
| Phenoxymethylpenicillin (penicillin V) | 74 (0.9) | 1.33 (1.05–1.67) | 1.20 (0.92–1.57) |
| Other penicillins | 117 (1.3) | 1.22 (1.01–1.47) | 1.18 (0.98–1.43) |
| ≥ 2 drugs in class | 45 (0.5) | 1.44 (1.06–1.95) | 1.33 (0.98–1.81) |
| Quinolones | 160 (1.8) | 3.07 (2.57–3.65) | 2.72 (2.27–3.27) |
| Ciprofloxacin | 114 (1.3) | 2.74 (2.23–3.37) | 2.45 (1.98–3.03) |
| Norfloxacin | 8 (0.1) | 5.32 (2.30–12.27) | 4.81 (2.05–11.26) |
| Levofloxacin | 14 (0.2) | 3.90 (2.12–7.16) | 3.28 (1.73–6.24) |
| Other quinolone | 23 (0.3) | 4.88 (2.99–7.96) | 4.23 (2.60–6.87) |
| ≥ 2 drugs in class | 1 (0.01) | 1.29 (0.17–9.92) | 0.92 (0.11–7.90) |
| Sulfonamides† | 30 (0.3) | 2.20 (1.49–3.24) | 2.01 (1.36–2.97) |
| Tetracyclines | 67 (0.8) | 2.75 (2.11–3.60) | 2.59 (1.97–3.41) |
| Doxycycline | 36 (0.4) | 3.12 (2.16–4.51) | 2.81 (1.93–4.10) |
| Minocycline | 21 (0.2) | 2.47 (1.54–3.94) | 2.48 (1.54–4.00) |
| Other tetracyclines | 9 (0.1) | 2.10 (1.04–4.24) | 1.98 (0.95–4.10) |
| ≥ 2 drugs in class | 1 (0.01) | NA | NA |
| Other antibacterials | 34 (0.4) | 1.26 (0.89–1.65) | 1.25 (0.88–1.79) |
| Clindamycin | 34 (0.4) | 1.29 (0.90–1.83) | 1.27 ( 0.89–1.81) |
| Antiprotozoals | |||
| Metronidazole | 53 (0.6) | 1.86 (1.40–2.48) | 1.70 (1.27–2.26) |
| Urinary anti-infectives | 39 (0.4) | 0.73 (0.53–1.00) | 0.69 (0.50–0.95) |
| Nitrofurantoin | 39 (0.4) | 0.73 (0.53–1.00) | 0.70 (0.51–0.96) |
| ≥ 2 classes of antibiotics | 221 (2.5) | 1.82 (1.58–2.09) | 1.54 (1.33–1.78) |
Note: CI = confidence interval, NA = not applicable, OR = odds ratio, ref = reference category.
↵* Adjusted for variables (a) on first day of gestation (maternal age, area of residence [urban v. rural], receipt of social assistance during pregnancy, education level in years [≤ 12 v. > 12] and marital status [living alone v. cohabiting]); (b) in the year before and during pregnancy until the index date (physician-based diagnoses or filled prescriptions of related medications for maternal chronic comorbidities [depression, asthma, diabetes mellitus, chronic hypertension, thyroid disorder, epilepsy, endometriosis, uterine malformation, and rheumatoid polyarthritis and systemic lupus erythematosus]; physician-based diagnoses of maternal infections [urinary tract infection, respiratory tract infection, bacterial vaginosis and sexually transmitted infections]; and use of other anti-infective agents); and (c) and in the year before pregnancy (use of health services, and history of planned and spontaneous abortions).
↵† Analysis considered only sulfonamides class, not individual types of sulfonamides.