Table 2.
Incidence rates and hazard ratios of neurodevelopmental disorders according to pre-existing maternal and paternal cardiovascular diseases: 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 | ||||||||||||
| Maternal CVD (n=2 699 675) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 153 355 | 4.1 | 1.00 (Ref.) | 1.00 (Ref.) | 63 974 | 1.7 | 1.00 (Ref.) | 1.00 (Ref.) | 22 626 | 0.6 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 1044 | 5.4 | 1.29 (1.21–1.37) | 1.17 (1.10–1.25) | 462 | 2.3 | 1.21 (1.10–1.32) | 1.12 (1.02–1.23) | 132 | 0.7 | 1.06 (0.90–1.26) | 0.99 (0.83–1.18) |
| Subtype of maternal CVDc | ||||||||||||
| Cerebrovascular disease | 204 | 6.0 | 1.40 (1.22–1.61) | 1.21 (1.06–1.39) | 99 | 2.9 | 1.54 (1.26–1.88) | 1.35 (1.11–1.65) | 28 | 0.8 | 1.30 (0.90–1.88) | 1.12 (0.77–1.62) |
| Arrhythmia | 565 | 5.2 | 1.24 (1.14–1.34) | 1.16 (1.07–1.26) | 242 | 2.2 | 1.11 (0.97–1.26) | 1.04 (0.91–1.18) | 57 | 0.5 | 0.81 (0.63–1.05) | 0.79 (0.61–1.03) |
| Heart failure | 26 | 6.4 | 2.04 (1.08–2.34) | 1.44 (0.98–2.12) | 18 | 4.4 | 2.12 (1.30–3.46) | 1.92 (1.18–3.14) | <5d | 0.9 | 1.54 (0.58–4.11) | 1.17 (0.44–3.10) |
| Valvular heart disease | 85 | 4.9 | 1.15 (0.93–1.43) | 1.12 (0.91–1.39) | 41 | 2.3 | 1.20 (0.88–1.65) | 1.15 (0.84–1.57) | 19 | 1.1 | 1.73 (1.10–2.71) | 1.49 (0.95–2.33) |
| Congenital heart disease | 239 | 5.4 | 1.35 (1.19–1.54) | 1.17 (1.03–1.33) | 108 | 2.4 | 1.24 (1.02–1.51) | 1.15 (0.94–1.39) | 35 | 0.8 | 1.26 (0.90–1.75) | 1.15 (0.83–1.61) |
| Paternal CVD (n=2 672 229) | ||||||||||||
| Composite paternal CVD | ||||||||||||
| No | 151 794 | 4.1 | 1.00 (Ref.) | 1.00 (Ref.) | 63 281 | 1.7 | 1.00 (Ref.) | 1.00 (Ref.) | 22 367 | 0.6 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 1212 | 4.7 | 1.10 (1.04–1.16) | 1.07 (1.01–1.13) | 572 | 2.2 | 1.13 (1.04–1.22) | 1.08 (1.00–1.17) | 185 | 0.7 | 1.13 (0.98–1.30) | 1.08 (0.94–1.25) |
| Subtype of paternal CVDc | ||||||||||||
| Cerebrovascular disease | 254 | 5.8 | 1.36 (1.20–1.54) | 1.29 (1.4–1.46) | 103 | 2.3 | 1.22 (1.00–1.48) | 1.13 (0.93–1.37) | 34 | 0.8 | 1.24 (0.88–1.74) | 1.09 (0.78–1.53) |
| Arrhythmia | 710 | 4.3 | 1.02 (0.94–1.09) | 1.00 (0.93–1.08) | 349 | 2.1 | 1.09 (0.98–1.21) | 1.06 (0.95–1.17) | 100 | 0.6 | 0.96 (0.80–1.18) | 0.96 (0.79–1.17) |
| Heart failure | 55 | 5.2 | 1.23 (0.94–1.60) | 1.12 (0.86–1.46) | 24 | 2.3 | 1.14 (0.77–1.70) | 0.99 (0.66–1.48) | 11 | 1.0 | 1.62 (0.90–2.93) | 1.24 (0.64–2.23) |
| Valvular heart disease | 121 | 4.2 | 0.98 (0.82–1.17) | 0.99 (0.83–1.19) | 58 | 2.0 | 1.03 (0.80–1.34) | 1.00 (0.77–1.30) | 24 | 0.8 | 1.33 (0.89–1.98) | 1.20 (0.81–1.80) |
| Congenital heart disease | 185 | 4.9 | 1.20 (1.04–1.39) | 1.10 (0.95–1.27) | 96 | 2.5 | 1.30 (1.06–1.58) | 1.24 (1.01–1.51) | 29 | 0.7 | 1.21 (0.84–1.74) | 1.17 (0.81–1.68) |
| British Columbia, Canada | ||||||||||||
| Maternal CVD (n=887 582) | ||||||||||||
| Composite maternal CVD | ||||||||||||
| No | 76 290 | 7.0 | 1.00 (Ref.) | 1.00 (Ref.) | 18 404 | 1.6 | 1.00 (Ref.) | 1.00 (Ref.) | 4035 | 0.3 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 2043 | 9.5 | 1.29 (1.23–1.35) | 1.14 (1.09–1.20) | 614 | 2.7 | 1.28 (1.17–1.39) | 1.17 (1.07–1.27) | 97 | 0.4 | 1.18 (0.96–1.44) | 1.08 (0.89–1.32) |
| Subtype of maternal CVDc | ||||||||||||
| Cerebrovascular disease | 195 | 10.1 | 1.41 (1.21–1.64) | 1.19 (1.02–1.39) | 57 | 2.8 | 1.29 (0.95–1.74) | 1.10 (0.81–1.48) | 13 | 0.6 | 1.79 (1.04–3.09) | 1.57 (0.91–2.70) |
| Arrhythmia | 1274 | 9.4 | 1.25 (1.18–1.33) | 1.12 (1.06–1.19) | 407 | 2.9 | 1.29 (1.16–1.43) | 1.18 (1.06–1.31) | 63 | 0.4 | 1.21 (0.95–1.56) | 1.13 (0.88–1.45) |
| Heart failure | 68 | 10.9 | 1.47 (1.13–1.91) | 1.27 (0.97–1.65) | 19 | 2.9 | 1.22 (0.75–1.98) | 1.07 (0.66–1.74) | <5d | 0.6 | 1.65 (0.62–4.40) | 1.38 (0.52–3.68) |
| Valvular heart disease | 300 | 8.2 | 1.16 (1.03–1.31) | 1.12 (0.99–1.26) | 73 | 1.9 | 1.22 (0.95–1.56) | 1.14 (0.89–1.46) | 9 | 0.2 | 0.65 (0.34–1.25) | 0.65 (0.34–1.24) |
| Congenital heart disease | 390 | 10.5 | 1.44 (1.29–1.61) | 1.18 (1.06–1.32) | 117 | 3.0 | 1.30 (1.07–1.59) | 1.19 (0.98–1.45) | 18 | 0.5 | 1.28 (0.80–2.02) | 1.07 (0.68–1.70) |
| Paternal CVD (n=811 481) | ||||||||||||
| Composite paternal CVD | ||||||||||||
| No | 71 270 | 7.0 | 1.00 (Ref.) | 1.00 (Ref.) | 16 911 | 1.6 | 1.00 (Ref.) | 1.00 (Ref.) | 3778 | 0.4 | 1.00 (Ref.) | 1.00 (Ref.) |
| Yes | 1066 | 8.0 | 1.07 (1.01–1.14) | 0.99 (0.93–1.06) | 322 | 2.3 | 1.06 (0.94–1.19) | 1.00 (0.89–1.12) | 52 | 0.4 | 1.03 (0.78–1.36) | 0.99 (0.75–1.31) |
| Subtype of paternal CVDc | ||||||||||||
| Cerebrovascular disease | 150 | 9.5 | 1.29 (1.09–1.52) | 1.14 (0.96–1.35) | 57 | 3.4 | 1.58 (1.21–2.06) | 1.42 (1.09–1.86) | 9 | 0.5 | 1.51 (0.78–2.90) | 1.34 (0.70–2.57) |
| Arrhythmia | 677 | 7.4 | 0.99 (0.91–1.07) | 0.93 (0.86–1.01) | 219 | 2.3 | 1.05 (0.92–1.21) | 1.00 (0.87–1.16) | 27 | 0.3 | 0.78 (0.53–1.14) | 0.77 (0.53–1.12) |
| Heart failure | 61 | 9.3 | 1.31 (1.00–1.73) | 1.21 (0.92–1.58) | 16 | 2.3 | 1.11 (0.68–1.81) | 1.01 (0.62–1.64) | <5d | 0.3 | 0.83 (0.21–3.30) | 0.71 (0.18–2.84) |
| Valvular heart disease | 125 | 8.4 | 1.10 (0.91–1.33) | 1.02 (0.85–1.24) | 33 | 2.1 | 1.05 (0.73–1.50) | 0.98 (0.69–1.41) | 7 | 0.4 | 1.21 (0.58–2.53) | 1.15 (0.55–2.42) |
| Congenital heart disease | 196 | 9.0 | 1.23 (1.06–1.42) | 1.02 (0.88–1.19) | 47 | 2.0 | 0.84 (0.62–1.14) | 0.80 (0.59–1.08) | 10 | 0.4 | 1.24 (0.63–2.43) | 1.10 (0.56–2.15) |
ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CI, confidence interval; CVD, cardiovascular disease; HR, hazard ratio; ID, intellectual disability.
a
Incidence rate per 1000 child-years.
b
Model 1 was minimally adjusted for birth year and sex. 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.
c
All CVD subtypes were coded as binary: no (reference)/yes.
d
Exact count is suppressed for confidentiality reasons.