Association between overall cannabis exposure and risk of attention deficit with or without hyperactivity disorder in children
| Total infants, N=2408 | Infants with ADHD, N=241 | ADHD Follow-up no. of person-years | Unadjusted HR (95% CI) | Model 1—adjusted HR* (95% CI) | Model 2—adjusted HR† (95% CI) | Model 3—adjusted HR‡ (95 % CI) | |
| Exposure patterns | |||||||
| No exposure | 2322 | 224 | 1502 | Reference | Reference | Reference | Reference |
| Overall exposure | 86 | 17 | 120 | 1.36 (0.80 to 2.16) | 1.24 (0.73 to 1.98) | 1.05 (0.61 to 1.70) | 1.22 (0.70 to 2.02) |
| Maternal age at 1DG, years, mean (SD) | 27.6 (5.5) | 26.3 (6.0) | 1622 | 0.97 (0.95 to 0.99) | 0.97 (0.95 to 0.99) | 0.97 (0.95 to 0.99) | 0.98 (0.95 to 1.00) |
| Gestational age at delivery, weeks, mean (SD) | 39.2 (1.1) | 39.0 (1.2) | 1622 | 0.90 (0.81 to 1.01) | – | – | 0.89 (0.80 to 0.99) |
| Education | |||||||
| Secondary school | 1134 | 166 | 1167 | Reference | Reference | Reference | Reference |
| CEGEP or University | 948 | 45 | 258 | 0.60 (0.42 to 0.83) | – | 0.86 (0.59 to 1.22) | 0.79 (0.54 to 1.13) |
| Others | 326 | 30 | 197 | 0.98 (0.65 to 1.43) | – | 1.05 (0.70 to 1.53) | 1.05 (0.69 to 1.54) |
| Household annual income, $C | |||||||
| ≤18 000 | 810 | 169 | 1223 | Reference | Reference | Reference | Reference |
| 18 001–30 000 000 | 679 | 40 | 242 | 0.60 (0.42 to 0.85) | – | 0.69 (0.48 to 0.98) | 0.70 (0.48 to 1.01) |
| 30 001–46 000 000 | 483 | 21 | 107 | 0.58 (0.35 to 0.90) | – | 0.87 (0.52 to 1.39) | 0.87 (0.52 to 1.41) |
| >46 000 | 436 | 11 | 50 | 0.35 (0.18 to 0.62) | – | 0.51 (0.25 to 0.93) | 0.49 (0.24 to 0.92) |
| Marital status—living alone | 380 | 82 | 614 | 1.26 (0.96 to 1.65) | – | – | 0.91 (0.67 to 1.24) |
| Area of residence—rural | 620 | 44 | 298 | 1.46 (1.06 to 2.05) | – | – | 1.43 (1.03 to 2.04) |
| Race—caucasian | 2263 | 224 | 1495 | 1.08 (0.68 to 1.84) | – | – | 1.25 (0.76 to 2.20) |
| Previous pregnancies ending with a live birth | 98 | 16 | 100 | 2.00 (1.15 to 3.20) | – | 1.67 (0.95 to 2.75) | 1.71 (0.96 to 2.85) |
| Prepregnancy body mass index, kg/m2, mean (SD) | 23.5 (5.2) | 24.2 (6.8) | 1622 | 1.02 (1.00 to 1.04) | – | – | 1.02 (1.00 to 1.05) |
| Maternal lifestyle during pregnancy | |||||||
| Smoking | 869 | 110 | 794 | 1.03 (0.80 to 1.33) | – | – | 0.83 (0.63 to 1.11) |
| Alcohol | 546 | 48 | 319 | 0.95 (0.69 to 1.30) | – | – | 1.00 (0.71 to 1.38) |
| Cocaine use | 14 | 3 | 15 | 1.37 (0.34 to 3.58) | – | – | 1.11 (0,26 to 3.13) |
| Coffee | 1745 | 179 | 1205 | 0.91 (0.69 to 1.23) | – | – | 0.90 (0.66 to 1.24) |
| Multivitamins use | 2091 | 216 | 1452 | 1.32 (0.89 to 2.04) | – | – | 1.40 (0.93 to 2.19) |
| Physical activity | 1953 | 205 | 1381 | 1.11 (0.79 to 1.62) | – | – | 1.03 (0.72 to 1.50) |
| Maternal comorbidities in the year prior to or during pregnancy | |||||||
| Chronic/gestational diabetes§ | 252 | 28 | 194 | 1.05 (0.69 to 1.53) | – | – | 0.98 (0.64 to 1.46) |
| Chronic/gestational hypertension§ | 226 | 26 | 174 | 1.12 (0.73 to 1.65) | – | – | 1.03 (0.66 to 1.53) |
| Asthma§ | 535 | 101 | 709 | 2.07 (1.60 to 2.67) | – | 1.83 (1.39 to 2.39) | 1.76 (1.34 to 2.32) |
| Thyroid disorders§ | 127 | 8 | 43 | 0.74 (0.34 to 1.40) | – | – | 0.70 (0.31 to 1.34) |
| Maternal psychiatric disorders in the year prior to or during pregnancy | |||||||
| Depression/anxiety/bipolar disorder¶ | 1109 | 144 | 997 | 1.46 (1.13 to 1.90) | – | 1.11 (0.82 to 1.51) | 1.12 (0.82 to 1.52) |
| Other psychiatric disorders** | 550 | 84 | 605 | 1.40 (1.07 to 1.83) | – | 1.16 (0.84 to 1.59) | 1.19 (0.86 to 1.65) |
| Maternal ADHD | 6 | 3 | 22 | 5.24 (1.29 to 13.88) | – | 2.17 (0.52 to 6.06) | 3.01 (0.69 to 9.04) |
| Maternal pain†† | 716 | 90 | 637 | 1.34 (1.03 to 1.73) | – | 1.11 (0.85 to 1.46) | 1.08 (0.82 to 1.42) |
| Infant sex—male | 1305 | 148 | 958 | 1.61 (1.24 to 2.09) | 1.62 (1.25 to 2.10) | 1.68 (1.29 to 2.20) | 1.84 (1.41 to 2.43) |
| Calendar year of delivery | – | – | – | 1.15 (1.05 to 1.25) | – | 1.05 (0.96 to 1.16) | 1.04 (0.95 to 1.15) |
Italic characters represent reference category of each characteristic.
All bold numbers have a significant difference (p<0.05).
*Adjusted for only maternal age and infant sex.
†Adjusted for variables that have an unadjusted HR significant (p<0.05).
‡Adjusted for all variables included in the table.
§Based on ICD-9 and ICD-10 diagnostic codes and prescription filled for diabetes/hypertension/asthma/thyroid disorder medications.
¶Based on ICD-9 and ICD-10 diagnostic codes for affective disorders (unipolar depressive disorder), anxiety or bipolar disorder and data on filled prescription of antidepressants.
**Schizophrenia, schizotypal and delusional disorders; disorders of adult personality and behaviour; dissociative and conversion disorders; phobic disorders; obsessive–compulsive disorder; dysthemic disorder; neurasthenia; depersonalisation disorder; somatoform disorder; unspecified non-psychotic mental disorder; and drug dependence except for cannabis dependence, based on ICD-9 diagnostic codes and prescription filled for antipsychotic and other psychotropic medications.
††Based on ICD-9 diagnostic codes of chronic pain, cancer, epilepsy/seizures, glaucoma, muscles spasm, arthritis, nausea and vomiting.
ADHD, attention deficit with or without hyperactivity; CEGEP, Collège d'Enseignement Général et Professionnel; 1DG, first day of gestation.