Association between antibiotic exposure and risk of attention-deficit/hyperactivity disorder in the overall cohort and the cohort matched on HDPS
| Variable | Overall cohort n = 187 605 | HDPS-matched cohort n = 129 674 | ||||
|---|---|---|---|---|---|---|
| No. of events | Person-years* | HR† (95% CI) | No. of events | Person-years* | HR‡ (95% CI) | |
| Main analysis | ||||||
| Prenatal antibiotic exposure | ||||||
| Unexposed | 8649 | 1 247 467 | 1.00 (Ref.) | 5500 | 690 186 | 1.00 (Ref.) |
| Exposed | 7641 | 742 985 | 1.22 (1.18–1.26) | 6599 | 684 298 | 1.20 (1.15–1.24) |
| Secondary analyses | ||||||
| Exposure by trimester§¶ | ||||||
| None | 8649 | 1 247 467 | 1.00 (Ref.) | 5500 | 690 186 | 1.00 (Ref.) |
| First | 3722 | 333 818 | 1.13 (1.09–1.17) | 3094 | 298 488 | 1.12 (1.05–1.19) |
| Second | 3919 | 352 091 | 1.17 (1.13–1.22) | 3270 | 317 862 | 1.19 (1.12–1.27) |
| Third | 3256 | 314 554 | 1.12 (1.07–1.16) | 2752 | 286 035 | 1.07 (1.00–1.14) |
| Antibiotic class¶ | ||||||
| None | 8649 | 1 247 467 | 1.00 (Ref.) | 5500 | 690 186 | 1.00 (Ref.) |
| Penicillin | 5150 | 500 082 | 1.15 (1.12–1.19) | 4419 | 458 112 | 1.12 (1.06–1.17) |
| Non-penicillin β-lactams | 1489 | 133 529 | 1.18 (1.12–1.25) | 1220 | 118 134 | 1.14 (1.04–1.25) |
| Macrolides and related antibiotics | 1675 | 131 987 | 1.17 (1.11–1.24) | 1336 | 116 915 | 1.30 (1.18–1.42) |
| Other | 2176 | 194 694 | 1.09 (1.04–1.14) | 1806 | 174 912 | 1.08 (1.00–1.17) |
| No. of antibiotic courses | ||||||
| 0 | 8649 | 1 247 467 | 1.00 (Ref.) | 5500 | 690 186 | 1.00 (Ref.) |
| 1 | 4317 | 467 362 | 1.16 (1.12–1.20) | 3938 | 444 343 | 1.18 (1.13–1.24) |
| 2 | 1898 | 168 403 | 1.26 (1.20–1.33) | 1623 | 153 050 | 1.22 (1.13–1.32) |
| ≥ 3 | 1426 | 107 221 | 1.39 (1.31–1.47) | 1038 | 86 904 | 1.22 (1.11–1.35) |
| Cumulative antibiotic duration, d | ||||||
| 0 | 8649 | 1 247 467 | 1.00 (Ref.) | 5500 | 690 186 | 1.00 (Ref.) |
| 1–7 | 2780 | 306 543 | 1.16 (1.11–1.21) | 2534 | 291 069 | 1.16 (1.10–1.24) |
| 8–14 | 2412 | 241 468 | 1.20 (1.14–1.25) | 2143 | 226 189 | 1.19 (1.11–1.27) |
| > 14 | 2449 | 194 975 | 1.33 (1.27–1.39) | 1922 | 167 040 | 1.26 (1.17–1.35) |
Note: CI = confidence interval, HDPS = high-dimensional propensity score, HR = hazard ratio, Ref. = reference.
↵* Values for person-years were rounded to the nearest integer.
↵† Adjusted for sex, mother’s age at delivery, region of residence, receipt of income assistance, year of child’s birth, birth order, mother’s medical conditions, prenatal exposure to antidepressants and number of physician visits by the mother in the year before pregnancy.
↵‡ Adjusted for maternal diagnosis of asthma.
↵§ First trimester = 0–13 weeks of pregnancy, second trimester = 14–27 weeks, third trimester = 28 weeks until date of birth.
↵¶ A child could be exposed to antibiotics during multiple trimesters and could be exposed to multiple antibiotic classes.