Table 3.
Multiple mediation analysis of mediators at different stages
| Stage 1a | Stage 2b | Stage 3c | |
|---|---|---|---|
| OR (95% CI) | OR (95% CI) | OR (95% CI) | |
| A PGDM | |||
| Any NDCs | |||
| NDE | 1.37 (1.36–1.38) | 1.35 (1.34–1.36) | 1.28 (1.27–1.29) |
| NIE | 1.05 (1.01–1.11) | 1.07 (1.03–1.13) | 1.13 (1.08–1.19) |
| TE | 1.44 (1.38–1.51) | 1.44 (1.38–1.51) | 1.44 (1.38–1.51) |
| Proportion mediated, % | 14.1** | 18.8** | 33.1** |
| Autism | |||
| NDE | 1.36 (1.35–1.38) | 1.33 (1.31–1.34) | 1.27 (1.26–1.29) |
| NIE | 1.06 (0.97–1.14) | 1.09 (0.99–1.17) | 1.13 (1.03–1.22) |
| TE | 1.44 (1.31–1.55) | 1.44 (1.31–1.55) | 1.44 (1.31–1.55) |
| Proportion mediated, % | 15.1 | 22.4 | 34.0** |
| ID | |||
| NDE | 1.70 (1.68–1.72) | 1.60 (1.57–1.62) | 1.33 (1.32–1.35) |
| NIE | 1.05 (0.96–1.15) | 1.12 (1.02–1.22) | 1.34 (1.22–1.46) |
| TE | 1.77 (1.63–1.96) | 1.77 (1.63–1.96) | 1.77 (1.63–1.96) |
| Proportion mediated, % | 8.6 | 19.4* | 50.1** |
| ADHD | |||
| NDE | 1.34 (1.33–1.35) | 1.33 (1.32–1.34) | 1.29 (1.28–1.29) |
| NIE | 1.06 (0.99–1.12) | 1.06 (0.99–1.13) | 1.10 (1.03–1.17) |
| TE | 1.42 (1.32–1.50) | 1.42 (1.32–1.50) | 1.42 (1.32–1.50) |
| Proportion mediated, % | 15.6 | 17.7 | 28.1** |
| B GDM | |||
| Any NDCs | |||
| NDE | 1.21 (1.20–1.22) | 1.22 (1.21–1.22) | 1.18 (1.17–1.18) |
| NIE | 0.98 (0.91–1.05) | 0.97 (0.91–1.04) | 1.01 (0.94–1.08) |
| TE | 1.19 (1.10–1.27) | 1.19 (1.10–1.27) | 1.19 (1.10–1.27) |
| Proportion mediated, % | -11.8 | -15.6 | 3.6 |
| Autism | |||
| NDE | 1.29 (1.28–1.30) | 1.29 (1.28–1.30) | 1.26 (1.24–1.27) |
| NIE | 1.05 (0.95–1.15) | 1.05 (0.95–1.15) | 1.08 (0.97–1.18) |
| TE | 1.35 (1.22–1.48) | 1.35 (1.22–1.48) | 1.35 (1.22–1.48) |
| Proportion mediated, % | 15.8 | 15.8 | 24.1 |
| ID | |||
| NDE | 1.32 (1.30–1.34) | 1.34 (1.32–1.36) | 1.21 (1.19–1.23) |
| NIE | 1.02 (0.92–1.21) | 1.01 (0.91–1.19) | 1.12 (1.01–1.32) |
| TE | 1.35 (1.21–1.60) | 1.37 (1.21–1.60) | 1.35 (1.21–1.60) |
| Proportion mediated, % | 7.6 | 2.7 | 37.6* |
| ADHD | |||
| NDE | 1.15 (1.14–1.16) | 1.16 (1.15–1.17) | 1.13 (1.12–1.39) |
| NIE | 0.97 (0.89–1.09) | 0.96 (0.88–1.08) | 0.99 (0.91–1.11) |
| TE | 1.12 (1.03–1.25) | 1.12 (1.03–1.25) | 1.12 (1.03–1.25) |
| Proportion mediated, % | -26.5 | -34.5 | -11.6 |
| C Adiposity | |||
| Any NDCs | |||
| NDE | 1.36 (1.34–1.37) | 1.36 (1.35–1.37) | 1.35 (1.33–1.36) |
| NIE | 1.00 (0.99–1.01) | 1.00 (0.99–1.01) | 1.01 (1.00–1.02) |
| TE | 1.36 (1.34–1.38) | 1.36 (1.34–1.38) | 1.36 (1.34–1.38) |
| Proportion mediated, % | 0.8 | 0.1 | 2.9 |
| Autism | |||
| NDE | 1.38 (1.36–1.40) | 1.38 (1.36–1.40) | 1.37 (1.35–1.39) |
| NIE | 0.99 (0.97–1.01) | 0.99 (0.97–1.01) | 0.99 (0.97–1.01) |
| TE | 1.36 (1.33–1.39) | 1.36 (1.33–1.39) | 1.36 (1.33–1.39) |
| Proportion mediated, % | -4.1 | -4.5 | -2.5 |
| ID | |||
| NDE | 1.58 (1.55–1.62) | 1.59 (1.56–1.62) | 1.53 (1.50–1.57) |
| NIE | 0.99 (0.97–1.02) | 0.99 (0.97–1.01) | 1.03 (1.00–1.05) |
| TE | 1.57 (1.51–1.63) | 1.57 (1.51–1.63) | 1.57 (1.51–1.63) |
| Proportion mediated, % | -1.4 | -2.0 | 5.5* |
| ADHD | |||
| NDE | 1.37 (1.36–1.38) | 1.38 (1.36–1.39) | 1.37 (1.35–1.38) |
| NIE | 1.00 (0.98–1.01) | 0.99 (0.98–1.01) | 1.00 (0.99–1.01) |
| TE | 1.37 (1.34–1.39) | 1.37 (1.34–1.39) | 1.37 (1.34–1.39) |
| Proportion mediated, % | -1.3 | -2.0 | -0.1 |
All analyses were adjusted for the child’s sex, birthyear, maternal age, birth order, maternal birth country, disposable income at birth, and maternal psychiatric history. Analyses for GDM were additionally adjusted for maternal BMI. Mediated proportions were marked with “*” when the 95% CI for NIEs did not encompass a value of 1, and by “**” when the 99.6% CI for NIEs did not encompass a value of 1 (refer to Additional file 1: Table S4), with both NDE and NIE having the same direction
The rationale for including different mediators in each multiple mediation analysis was described in Additional file 1: Figure S1
aMediators in stage 1 for PGDM and GDM included: pregnancy hypertensive diseases, placenta/membrane disorders, and gestational infection
Mediators in stage 1 for adiposity include: pregnancy hypertensive diseases, placenta/membrane disorders, gestational infection, and GDM
bMediators in stage 2 included: SGA, and LGA, intrauterine hypoxia, labour complications, and preterm birth
cMediators in stage 3 included: neonatal asphyxia comorbidities, neonatal hematological comorbidities, neonatal hypoglycemia, and neonatal infection