Table 3.
Sex-stratified incidence rates and hazard ratios of neurodevelopmental disorders according to pre-existing maternal and paternal cardiovascular disease: singleton offspring live-born without major malformations in Sweden 1990 to 2019 and in British Columbia, Canada, 1992 to 2019
| ADHD |
ASD |
ID |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| No. of events | Rate a | Model 1 HR (95% CI) b | Model 2 HR (95% CI) b | No. of events | Rate a | Model 1 HR (95% CI) b | Model 2 HR (95% CI) b | No. of events | Rate a | Model 1 HR (95% CI) b | Model 2 HR (95% CI) b | |
| Sweden | ||||||||||||
| Male (n=1 380 710) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 95 035 | 4.9 | 1.00 (Ref.) | 1.00 (Ref.) | 42 413 | 2.2 | 1.00 (Ref.) | 1.00 (Ref.) | 13 987 | 0.7 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 705 | 7.1 | 1.32 (1.22–1.42) | 1.21 (1.12–1.30) | 326 | 3.2 | 1.21 (1.08–1.35) | 1.14 (1.02–1.27) | 80 | 0.8 | 1.00 (0.80–1.24) | 0.93 (0.75–1.16) |
| Composite paternal CVD | ||||||||||||
| No | 94 015 | 4.9 | 1.00 (Ref.) | 1.00 (Ref.) | 41 638 | 2.2 | 1.00 (Ref.) | 1.00 (Ref.) | 13 718 | 0.7 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 820 | 6.2 | 1.13 (1.05–1.21) | 1.10 (1.03–1.18) | 403 | 3.0 | 1.14 (1.03–1.26) | 1.09 (0.99–1.21) | 123 | 0.9 | 1.16 (0.97–1.39) | 1.12 (0.94–1.34) |
| Female (n=1 318 891) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 58 320 | 3.1 | 1.00 (Ref.) | 1.00 (Ref.) | 21 561 | 1.1 | 1.00 (Ref.) | 1.00 (Ref.) | 8639 | 0.5 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 339 | 3.5 | 1.23 (1.11–1.37) | 1.10 (0.99–1.23) | 136 | 1.4 | 1.19 (1.00–1.40) | 1.08 (0.91–1.28) | 52 | 0.5 | 1.19 (0.90–1.56) | 1.09 (0.83–1.44) |
| Composite paternal CVD | ||||||||||||
| No | 57 779 | 3.1 | 1.00 (Ref.) | 1.00 (Ref.) | 21 206 | 1.1 | 1.00 (Ref.) | 1.00 (Ref.) | 8490 | 0.5 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 392 | 3.1 | 1.04 (0.94–1.15) | 1.00 (0.91–1.11) | 173 | 1.3 | 1.12 (0.97–1.31) | 1.07 (0.92–1.25) | 63 | 0.5 | 1.08 (0.84–1.39) | 1.02 (0.80–1.31) |
| P for interaction between maternal CVD and offspring sex | 0.001 | 0.001 | 0.048 | 0.045 | 0.783 | 0.761 | ||||||
| P for interaction between paternal CVD and offspring sex | 0.001 | 0.001 | 0.060 | 0.065 | 0.236 | 0.240 | ||||||
| British Columbia, Canada | ||||||||||||
| Male (n=451 770) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 53 231 | 9.9 | 1.00 (Ref.) | 1.00 (Ref.) | 14 223 | 2.5 | 1.00 (Ref.) | 1.00 (Ref.) | 2606 | 0.4 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 1434 | 13.3 | 1.28 (1.21–1.35) | 1.14 (1.08–1.21) | 449 | 3.9 | 1.20 (1.09–1.33) | 1.12 (1.01–1.23) | 57 | 0.5 | 1.05 (0.81–1.36) | 0.97 (0.75–1.26) |
| Composite paternal CVD | ||||||||||||
| No | 49 667 | 9.8 | 1.00 (Ref.) | 1.00 (Ref.) | 13 053 | 2.4 | 1.00 (Ref.) | 1.00 (Ref.) | 2418 | 0.4 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 749 | 11.3 | 1.07 (0.99–1.15) | 0.99 (0.92–1.07) | 245 | 3.5 | 1.04 (0.92–1.19) | 1.00 (0.88–1.14) | 43 | 0.6 | 1.31 (0.96–1.78) | 1.26 (0.92–1.71) |
| Female (n=435 812) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 23 048 | 4.2 | 1.00 (Ref.) | 1.00 (Ref.) | 4181 | 0.7 | 1.00 (Ref.) | 1.00 (Ref.) | 1429 | 0.2 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 610 | 5.6 | 1.31 (1.21–1.42) | 1.14 (1.05–1.24) | 165 | 1.5 | 1.54 (1.31–1.81) | 1.34 (1.14–1.57) | 40 | 0.3 | 1.43 (1.05–1.96) | 1.30 (0.95–1.78) |
| Composite paternal CVD | ||||||||||||
| No | 21 594 | 4.2 | 1.00 (Ref.) | 1.00 (Ref.) | 3858 | 0.7 | 1.00 (Ref.) | 1.00 (Ref.) | 1360 | 0.2 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 316 | 4.7 | 1.08 (0.97–1.21) | 0.99 (0.88–1.11) | 77 | 1.1 | 1.10 (0.87–1.39) | 1.00 (0.79–1.27) | 9 | 0.1 | 0.51 (0.27–0.99) | 0.50 (0.26–0.96) |
| P for interaction between maternal CVD and offspring sex | 0.706 | 0.772 | 0.010 | 0.010 | 0.215 | 0.187 | ||||||
| P for interaction between paternal CVD and offspring sex | 0.558 | 0.581 | 0.748 | 0.776 | 0.007 | 0.007 | ||||||
ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; ID, intellectual disability.
Incidence rate per 1000 child-years.
Model 1 was minimally adjusted for birth year. Model 2 was further adjusted for mother’s age at delivery, parity, education (Sweden only), region of birth, marital status/cohabitation with partner, smoking during early pregnancy (Sweden only), pre-gestational diabetes, pre-gestational hypertension and parental history of any neurodevelopmental or psychiatric disorders. The estimates for paternal CVD in Model 2 were additionally adjusted for maternal CVD.