Table 4.
Sex-stratified causal mediation analysis to estimate the impact of preterm delivery on the association between maternal pre-existing cardiovascular disease and offspring’s ADHD and ASD: singleton offspring live-born without major malformations in Sweden 1990 to 2019 and British Columbia, Canada, 1992 to 2019
| ADHD | ASD | |
|---|---|---|
| IRR (95% CI) | IRR (95% CI) | |
| Sweden | ||
| Male (n=1 380 710) | ||
| Total effect (TE) | 1.20 (1.11–1.29) | 1.13 (1.01–1.26) |
| Natural direct effect (NDE)a | 1.19 (1.10–1.28) | 1.12 (1.00–1.25) |
| Natural indirect effect (NIE) | 1.01 (1.00–1.01) | 1.01 (1.00–1.02) |
| Controlled direct effect (CDE)b | 1.46 (1.17–1.83) | 1.39 (1.00–1.92) |
| Mediated proportionc | 5% | 7% |
| Female (n=1 318 891) | ||
| Total effect (TE) | 1.09 (0.98–1.22) | 1.06 (0.89–1.25) |
| Natural direct effect (NDE)a | 1.09 (0.98–1.22) | 1.04 (0.87–1.23) |
| Natural indirect effect (NIE) | 1.00 (0.99–1.00) | 1.02 (1.00–1.03) |
| Controlled direct effect (CDE)b | 1.03 (0.70–1.50) | 1.71 (1.10–1.67) |
| Mediated proportionc | 0% | 34% |
| British Columbia, Canada | ||
| Male (n=451 770) | ||
| Total effect (TE) | 1.13 (1.08–1.20) | 1.12 (1.01–1.22) |
| Natural direct effect (NDE)a | 1.13 (1.07–1.19) | 1.12 (1.01–1.23) |
| Natural indirect effect (NIE) | 1.00 (1.00–1.00) | 1.00 (0.99–1.00) |
| Controlled direct effect (CDE)b | 1.13 (1.07–1.20) | 1.14 (1.03–1.25) |
| Mediated proportionc | 0% | 0% |
| Female (n=435 812) | ||
| Total effect (TE) | 1.14 (1.05–1.23) | 1.32 (1.12–1.53) |
| Natural direct effect (NDE)a | 1.14 (1.05–1.23) | 1.32 (1.11–1.53) |
| Natural indirect effect (NIE) | 1.00 (0.99–1.00) | 1.00 (1.00–1.01) |
| Controlled direct effect (CDE)b | 1.14 (1.04–1.23) | 1.33 (1.11–1.54) |
| Mediated proportionc | 0% | 0% |
ADHD, attention-deficit/hyperactivity disorder; ASD, autism spectrum disorder; CI, confidence interval; CVD, cardiovascular disease; IRR, incidence rate ratio.
All parameters were derived from Poisson regression models and were conditional on the following covariates: child’s birth year; 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 NDE represents the effect of maternal CVD in the absence of preterm birth.
The CDE represents the effect of maternal CVD obtained by setting the value of preterm birth to 1 (i.e. everyone is assumed to be preterm).
The proportion mediated was calculated using the formula: [IRRNDE (IRRNIE− 1)/(IRRNDE * IRRNIE− 1)]*100.