Table 3.
Use of macrolides during first trimester and specific major congenital malformations
| Total no. | Exposure to any macrolides in 1st trimester (N=204) a | Exposure to erythromycins in 1st trimester (N=81) a | Exposure to non-erythromycin macrolides in 1st trimester (N=124) a | ||||
|---|---|---|---|---|---|---|---|
| N (%) | OR (95% CI) | N (%) | OR (95% CI) | N (%) | OR (95% CI) | ||
| No malformations | 6952 | 70 (1.0) | 1.0 (Ref) | 28 (0.4) | 43 (0.6) | ||
| CHD | 4132 | 46 (1.1) | 0.9 (0.6–1.3) | 18 (0.4) | 1.3 (0.6–2.6) | 29 (0.7) | 0.7 (0.4–1.3) |
| Conotruncal | 903 | 5 (0.6) | 0.4 (0.2–1.2) | 1 (0.1) | 4 (0.4) | ||
| Septal defects | 2811 | 33 (1.2) | 0.9 (0.6–1.5) | 12 (0.4) | 1.3 (0.6–3.0) | 21 (0.7) | 0.8 (0.4–1.4) |
| RVOTO | 464 | 5 (1.1) | 0.8 (0.3–2.2) | 4(0.9) | 2 (0.4) | ||
| LVOTO | 652 | 8 (1.2) | 1.0 (0.4–2.3) | 2(0.3) | 6 (0.9) | 1.2 (0.4–3.3) | |
| Pyloric stenosis | 735 | 12 (1.6) | 1.3 (0.6–2.8) | 4(0.5) | 0.9 (0.3–3.0) | 8 (1.1) | 1.7 (0.6–4.6) |
| Oral clefts | 1348 | 22 (1.6) | 1.2 (0.7–2.2) | 8(0.6) | 1.6 (0.6–4.4) | 13 (1.0) | 1.0 (0.5–2.1) |
| CL/P | 877 | 16 (1.8) | 1.5 (0.8–3.0) | 7(0.8) | 2.0 (0.7–6.0) | 8 (0.9) | 1.1 (0.5–2.7) |
| CP | 471 | 6 (1.3) | 1.1 (0.4–2.8) | 1 (0.2) | 5 (1.1) | 1.2 (0.4–3.3) | |
| CNS defects | 1138 | 11 (1.0) | 0.8 (0.4–1.6) | 6 (0.5) | 1.2 (0.4–3.6) | 6 (0.5) | 0.7 (0.3–1.8) |
| NTD | 465 | 5 (1.1) | 0.8 (0.3–2.2) | 4 (0.9) | 2 (0.4) | ||
| CNS NOS | 599 | 6 (1.0) | 0.8 (0.3–2.1) | 2 (0.3) | 4 (0.7) | ||
| Respiratory system defects | 308 | 6 (1.9) | 0.9 (0.3–2.4) | 4 (1.3) | 2 (0.6) | ||
| Respiratory system defects NOS | 250 | 6 (2.4) | 1.0 (0.4–2.8) | 4 (1.6) | 2 (0.8) | ||
| GI defects | 1825 | 21 (1.2) | 1.0 (0.6–1.7) | 9 (0.5) | 1.0 (0.4–2.4) | 13 (0.7) | 1.0 (0.5–1.9) |
| Genital system defects | 1099 | 13 (1.2) | 0.8 (0.4–1.6) | 4 (0.4) | 9 (0.8) | 0.7 (0.3–1.6) | |
| Hypospadias & epispadias b | 557 | 5 (0.9) | 0.4 (0.1–1.2) | 2 (0.4) | 3 (0.5) | ||
| Genital system defects NOS | 208 | 6 (2.9) | 2.8 (1.0–7.7) | 2 (1.0) | 4 (1.9) | ||
| Urinary system defects | 1511 | 18 (1.2) | 1.0 (0.5–1.7) | 7 (0.5) | 1.2 (0.5–3.0) | 11 (0.7) | 0.8 (0.4–1.7) |
| Renal collecting system anomalies | 958 | 9 (0.9) | 0.7 (0.3–1.5) | 4 (0.4) | 5 (0.5) | 0.5 (0.2–1.4) | |
| Musculoskeletal system defects | 1948 | 16 (0.8) | 0.8 (0.4–1.4) | 6 (0.3) | 0.7 (0.3–1.9) | 9 (0.5) | 0.7 (0.3–1.5) |
| Clubfoot | 562 | 5 (0.9) | 0.6 (0.2–1.6) | 3 (0.5) | 2 (0.4) | ||
CHD: congenital heart defects, CNS: central nervous system defects, NTD: neural tube defects, GI: gastrointestinal system defects, LVOTO: left ventricular outflow tract obstruction, RVOTO: right ventricular outflow tract obstruction, CL/P: cleft lip with/ without cleft palate, CP: cleft palate alone, GI: gastrointestinal system Reference group: no exposure to the antibiotic of interest during pregnancy
ORs adjusted for region of participants’ residences and calendar year when they were ascertained, maternal age, race, education level, pre-pregnancy BMI, family history of congenital malformations, diabetes mellitus, first trimester cigarette smoking, peri-conceptional folic acid supplement, multiple pregnancy, urinary tract, respiratory, or vaginal/yeast infection, sexually transmitted disease, and other kinds of infection, and/or febrile events that occurred in the first trimester; ORs with less than 5 exposed cases or 100 total cases were not estimated.
Likely exposure in the first trimester based on our algorithm 14
Restricted to male infants