Table 4.
Mediation of effect from maternal T1D to offspring ID, mediated by preterm birth. Mediation analyses assessing risk by relative risks (RR) from log-binomial regression T1D → ID and for preterm → ID
| A: Any ID (mild, moderate or severe) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Model | Number of subjects | ID (%) | Direct effect£ RR (95% CI) | E-value | Mediation effect£ RR (95% CI) | E-value | Proportion mediation£ % (95% CI) | Total effect RR (95% CI) |
| Crude# | 1,406,441 | 8,523 (0.61%) | 1.45 (1.14–1.76) | 2.26 (1.54–2.92) | 1.30 (1.27–1.33) | 1.92 (1.86–1.99) | 49 (40–71) | 1.88 (1.48–2.31) |
| Adjusted## | 1,406,441 | 8,523 (0.61%) | 1.26 (1.01–1.57) | 1.83 (1.11–2.52) | 1.19 (1.17–1.21) | 1.66 (1.62–1.71) | 47 (33–95) | 1.50 (1.20–1.86) |
| Subgroups: | ||||||||
| Singletons## | 1,365,316 | 8,157 (0.60%) | 1.26 (0.98–1.54) | 1.83 (1.00–2.45) | 1.20 (1.18–1.23) | 1.70 (1.64–1.76) | 49 (36–102) | 1.52 (1.19–1.85) |
| Males## | 723,661 | 5,172 (0.71%) | 1.12 (0.82–1.46) | 1.49 (1.00–2.28) | 1.19 (1.17–1.22) | 1.67 (1.62–1.74) | 65 (31–526) | 1.33 (0.96–1.74) |
| Females## | 682,780 | 3,351 (0.49%) | 1.50 (1.07–2.00) | 2.37 (1.34–3.41) | 1.18 (1.15–1.21) | 1.64 (1.57–1.71) | 35 (24–75) | 1.76 (1.27–2.36) |
Abbreviations: CI, two-sided confidence interval from bootstrapping 1,000 samples; ID, intellectual disability; RR, relative risk from log-binomial regression.
Note: # Crude: Outcome and mediation model adjusted for birth year (1998–2002, 2003–2007, 2008–2012, 2013–2015). ## Adjusted: Outcome and mediation model additionally adjusted for maternal age (<20, 20–24, 24–29, 30–34, 34–39, 40–44, >45), paternal age (<20, 20–24, 24–29, 30–34, 34–39, 40–44, >45), maternal psychiatric history at delivery (yes/no), paternal psychiatric history at delivery (yes/no), Maternal and paternal education attainment at delivery (“Grundskola,” “Gymnasium” University), preeclampsia and hypertension. £: Direct effect often referred to as “Controlled Direct Effect” and Mediation usually referred to as “Natural Indirect Effect (NIE).” “Controlled Direct Effect” is the RR of ID comparing offspring to mothers with T1D diagnosis to offspring to mothers without T1D diagnosis, when the preterm covariates are assigned the same value, for example, term. “Natural Indirect Effect” is the RR of ID comparing offspring born preterm to offspring born term assuming all are born to mothers diagnosed with T1D. “Total Effect” is the RR of ID comparing preterm born offspring to mothers with T1D diagnosis to term born offspring to mothers without T1D diagnosis, that is, the RR comparing assumed highest risk group to lowest risk group.