Table 2. Association of Mean Daily Dispensed Prescription Acetaminophen Dose During Pregnancy and Children’s Risk of Autism, ADHD, and Intellectual Disabilitya.
| Model 1b | Model 2c | Model 3d | Sibling analysise | |||||
|---|---|---|---|---|---|---|---|---|
| HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | HR (95% CI) | P value | |
| Autism | ||||||||
| No use | 1.00 | 1.00 | 1.00 | 1.00 | ||||
| Low dose (<166 mg/d) | 1.33 (1.20-1.48) | <.001 | 1.14 (1.02-1.26) | .017 | 1.01 (0.91-1.12) | .89 | 0.85 (0.67-1.07) | .17 |
| Medium dose (166-429 mg/d) | 1.52 (1.41-1.64) | <.001 | 1.29 (1.19-1.39) | <.001 | 1.11 (1.03-1.20) | .007 | 0.96 (0.79-1.16) | .64 |
| High dose (≥430 mg/d) | 1.87 (1.71-2.06) | <.001 | 1.45 (1.32-1.60) | <.001 | 1.10 (1.00-1.22) | .06 | 0.88 (0.68-1.14) | .33 |
| ADHD | ||||||||
| No use | 1.00 | 1.00 | 1.00 | 1.00 | ||||
| Low dose (<166 mg/d) | 1.46 (1.36-1.57) | <.001 | 1.17 (1.09-1.26) | <.001 | 1.14 (1.06-1.23) | <.001 | 1.01 (0.84-1.21) | .94 |
| Medium dose (166-429 mg/d) | 1.75 (1.65-1.85) | <.001 | 1.39 (1.31-1.47) | <.001 | 1.25 (1.18-1.33) | <.001 | 1.02 (0.88-1.18) | .81 |
| High dose (≥430 mg/d) | 1.97 (1.83-2.11) | <.001 | 1.41 (1.31-1.52) | <.001 | 1.17 (1.08-1.27) | <.001 | 0.98 (0.79-1.21) | .83 |
| Intellectual disability | ||||||||
| No use | 1.00 | 1.00 | 1.00 | 1.00 | ||||
| Low dose (<166 mg/d) | 1.34 (1.14-1.58) | .001 | 1.27 (1.07-1.50) | .006 | 0.98 (0.83-1.16) | .84 | 0.87 (0.60-1.24) | .43 |
| Medium dose (166-429 mg/d) | 1.47 (1.30-1.66) | <.001 | 1.38 (1.22-1.57) | <.001 | 1.06 (0.93-1.20) | .40 | 0.97 (0.74-1.27) | .82 |
| High dose (≥430 mg/d) | 1.92 (1.65-2.22) | <.001 | 1.75 (1.50-2.05) | <.001 | 1.12 (0.96-1.31) | .17 | 0.93 (0.63-1.38) | .73 |
Abbreviation: ADHD, attention-deficit/hyperactivity disorder; HR, hazard ratio; NSAID, nonsteroidal anti-inflammatory drugs.
Daily mean dose categories defined low (<25th percentile; <166 mg/d), medium (25th-75th percentile; 166-429 mg/d), and high (>75th percentile; ≥430 mg/d).
Model 1: Adjusted for birth cohort and child sex.
Model 2: Model 1 plus birthing parent’s diagnosis of migraine, chronic pain, infections, fevers, rheumatoid arthritis, and headaches, and any other analgesics (aspirin, nonaspirin NSAIDs, opioids, or anti-migraine medications).
Model 3: Model 2 plus calendar period of delivery, parity, birthing parent’s age at delivery, country of birth, residential region, cohabitation at delivery, early pregnancy body mass index, smoking status, and birthing parent’s autism, ADHD, intellectual disability, history of psychiatric conditions, and birthing parent’s prescription use of psycholeptic medications, antidepressants, and antiseizure medication, and health care visits in the year before pregnancy, and an inadequate number of antenatal visits, and the highest household education and disposable income.
Sibling analysis: Model 3 covariates, excluding those with perfect balance between full siblings (ie, birthing parent’s birth country, psychiatric history, and diagnosis of autism, ADHD, and intellectual disability).