Table 2.
Hazard ratio models of the association between prenatal opioid exposure during pregnancy and neuropsychiatric disorders in children with the 1:5 propensity score matched cohort A from 2010 to 2017
| Outcome | No (%) | Neuropsychiatric disorder events (%) | Person years | Neuropsychiatric incidence rate, per 1000 years | Hazard ratio (95% CI) | ||
|---|---|---|---|---|---|---|---|
| Crude | Adjusted† | Fully adjusted‡ | |||||
| Opioid exposure during pregnancy: | |||||||
| No | 1 075 454 (83.3) | 36 648 (3.4) | 6 650 015 | 5.5 | 1 (reference) | 1 (reference) | 1 (reference) |
| Yes | 215 958 (16.7) | 7398 (3.4) | 1 271 953 | 5.8 | 1.07 (1.04 to 1.10)* | 1.08 (1.05 to 1.11)* | 1.07 (1.05 to 1.10)* |
| Timing of opioid exposure: | |||||||
| No opioid exposure | 1 075 454 (83.3) | 36 648 (3.4) | 6 650 015 | 5.5 | 1 (reference) | 1 (reference) | 1 (reference) |
| First trimester only | 87 567 (6.8) | 3327 (3.8) | 532 956 | 6.2 | 1.15 (1.11 to 1.19)* | 1.12 (1.08 to 1.16)* | 1.11 (1.07 to 1.15)* |
| Second trimester only | 50 765 (3.9) | 1599 (3.2) | 290 988 | 5.5 | 1.02 (0.97 to 1.07) | 1.03 (0.98 to 1.09) | 1.04 (0.98 to 1.09) |
| Third trimester only | 61 122 (4.7) | 1863 (3.1) | 354 590 | 5.3 | 0.96 (0.92 to 1.01) | 1.01 (0.96 to 1.05) | 1.01 (0.97 to 1.06) |
| More than one trimester | 16 504 (1.3) | 609 (3.7) | 93 419 | 6.5 | 1.21 (1.12 to 1.31)* | 1.25 (1.15 to 1.35)* | 1.21 (1.11 to 1.31)* |
| Dose-dependent association, MME: | |||||||
| None | 1 075 454 (83.3) | 36 648 (3.4) | 6 650 015 | 5.5 | 1 (reference) | 1 (reference) | 1 (reference) |
| Low dose user | 161 695 (12.5) | 5732 (3.5) | 1 000 524 | 5.7 | 1.04 (1.01 to 1.07)* | 1.05 (1.02 to 1.08)* | 1.06 (1.03 to 1.09)* |
| High dose user | 54 263 (4.2) | 1666 (3.1) | 271 429 | 6.1 | 1.18 (1.12 to 1.24)* | 1.18 (1.12 to 1.24)* | 1.15 (1.09 to 1.21)* |
| Opioid prescriptions, days: | |||||||
| 0 | 1 075 454 (83.3) | 36 648 (3.4) | 6 650 015 | 5.5 | 1 (reference) | 1 (reference) | 1 (reference) |
| 1-29 | 212 839 (16.5) | 7267 (3.4) | 1 255 284 | 5.8 | 1.07 (1.04 to 1.09)* | 1.07 (1.05 to 1.10)* | 1.07 (1.04 to 1.10)* |
| 30-59 | 2824 (0.2) | 112 (4.0) | 15 196 | 7.4 | 1.39 (1.15 to 1.67)* | 1.44 (1.20 to 1.73)* | 1.34 (1.12 to 1.62)* |
| ≥60 | 295 (0.0) | 19 (6.4) | 1,473 | 12.9 | 2.54 (1.62 to 3.97)* | 2.53 (1.62 to 3.96)* | 1.95 (1.24 to 3.06)* |
| No of opioid prescriptions: | |||||||
| 0-1 | 1 075 454 (83.3) | 36 648 (3.4) | 6 650 015 | 5.5 | 1 (reference) | 1 (reference) | 1 (reference) |
| 2 | 104 991 (8.1) | 3508 (3.3) | 626 586 | 5.6 | 1.03 (0.99 to 1.06) | 1.03 (0.99 to 1.06) | 1.03 (1.00 to 1.07) |
| ≥3 | 110 967 (8.6) | 3890 (3.5) | 645 367 | 6.0 | 1.11 (1.08 to 1.15)* | 1.13 (1.09 to 1.17)* | 1.12 (1.08 to 1.16)* |
CI=confidence interval; MME=morphine milligram equivalent.
Propensity score matched cohort A, derived from the full unmatched cohort, involves a 1:5 matching ratio and pairs the exposed and unexposed groups in a 1:5 ratio using propensity score (cohort 2 in fig 1 and table S8).
Significant differences (P<0.05).
The adjusted model was adjusted for the following variables: maternal age at delivery years (≤19, 20-24, 25-29, 30-34, and ≥35 years), infant sex, region of residence (urban and rural), household income level (1st, 2nd, 3rd, and 4th quartiles), birth season (spring, summer, autumn, and winter), parity (1 and ≥2), maternal mental illness, severe maternal morbidity score (0, 1, and ≥2), and hospital outpatient visit (0, 1, and ≥2), and admission contact (0, 1, and ≥2) in a year before pregnancy.
The fully adjusted model was adjusted for the following variables: covariates as in the adjusted model, history of maternal neuropsychiatric conditions (alcohol or drug misuse, mood disorders except those with psychotic symptoms, anxiety and stress-related disorders, sleep disorders, epilepsy, and other neuropsychiatry disorders), and use of non-steroidal anti-inflammatory drugs and acetaminophen during pregnancy.