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Table 2 Mediation analysis of the associations between maternal metabolic conditions and offspring NDCs: single- and multiple-component approaches

From: Associations between maternal metabolic conditions and neurodevelopmental conditions in offspring: the mediating effects of obstetric and neonatal complications

 

Any NDCs

Autism

ID

ADHD

Multiple mediatorsa

OR (95% CI)

P-value

OR (95% CI)

P-value

OR (95% CI)

P-value

OR (95% CI)

P-value

A PGDM

 NDE

1.26 (1.26–1.27)

NA

1.23 (1.22–1.25)

NA

1.38 (1.36–1.40)

NA

1.27 (1.26–1.28)

NA

 NIE

1.14 (1.09–1.20)

NA

1.17 (1.07–1.26)

NA

1.29 (1.18–1.41)

NA

1.12 (1.04–1.18)

NA

 TE

1.44 (1.38–1.51)

NA

1.44 (1.31–1.55)

NA

1.77 (1.63–1.96)

NA

1.42 (1.32–1.50)

NA

 Proportion mediated, %

36.4**

 

42.9**

 

44.4**

 

31.4**

 

Single mediatorsb

 Pregnancy hypertensive diseases

  NDE

1.38 (1.31–1.45)

 < 0.001

1.36 (1.25–1.49)

 < 0.001

1.76 (1.55–1.96)

 < 0.001

1.35 (1.27–1.43)

 < 0.001

  NIE

1.04 (1.02–1.05)

 < 0.001

1.04 (1.02–1.07)

0.001

1.03 (1.00–1.07)

0.038

1.03 (1.01–1.05)

0.001

  TE

1.43 (1.36–1.51)

 < 0.001

1.41 (1.31–1.55)

 < 0.001

1.83 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

9.97**

 

11.97**

 

5.70*

 

8.30**

 

 Placenta/membrane disorders

  NDE

1.42 (1.35–1.49)

 < 0.001

1.41 (1.31–1.53)

 < 0.001

1.79 (1.59–2.01)

 < 0.001

1.38 (1.31–1.46)

 < 0.001

  NIE

1.01 (1.01–1.02)

 < 0.001

1.01 (1.00–1.01)

0.155

1.02 (1.01–1.03)

0.004

1.01 (1.00–1.01)

0.034

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.32–1.55)

 < 0.001

1.83 (1.61–2.05)

 < 0.001

1.39 (1.32–1.47)

 < 0.001

  Proportion mediated, %

2.73**

 

1.50

 

2.90*

 

1.74*

 

 Gestational infection

  NDE

1.42 (1.35–1.49)

 < 0.001

1.40 (1.30–1.51)

 < 0.001

1.79 (1.57–1.98)

 < 0.001

1.39 (1.31–1.46)

 < 0.001

  NIE

1.01 (1.00–1.02)

0.008

1.01 (1.00–1.03)

0.047

1.02 (1.00–1.04)

0.044

1.01 (1.00–1.01)

0.143

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.31–1.54)

 < 0.001

1.82 (1.61–2.02)

 < 0.001

1.39 (1.32–1.47)

 < 0.001

  Proportion mediated, %b

2.78*

 

3.53*

 

2.85*

 

1.80

 

 Intrauterine hypoxia

  NDE

1.41 (1.34–1.49)

 < 0.001

1.40 (1.29–1.54)

 < 0.001

1.74 (1.54–1.93)

 < 0.001

1.38 (1.30–1.46)

 < 0.001

  NIE

1.01 (1.01–1.02)

0.003

1.01 (1.00–1.03)

0.163

1.05 (1.02–1.07)

 < 0.001

1.01 (1.00–1.02)

0.048

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.31–1.55)

 < 0.001

1.82 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

3.76**

 

2.85

 

8.07**

 

3.08*

 

 SGA

  NDE

1.42 (1.34–1.51)

 < 0.001

1.35 (1.22–1.46)

 < 0.001

1.82 (1.58–2.01)

 < 0.001

1.38 (1.29–1.48)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.104

1.00 (1.00–1.01)

0.236

1.00 (1.00–1.01)

0.138

1.00 (1.00–1.00)

0.399

  TE

1.42 (1.35–1.51)

 < 0.001

1.35 (1.22–1.46)

 < 0.001

1.83 (1.58–2.01)

 < 0.001

1.38 (1.29–1.48)

 < 0.001

  Proportion mediated, %

0.37

 

0.40

 

0.44

 

0.14

 

 LGA

  NDE

1.42 (1.35–1.50)

 < 0.001

1.36 (1.22–1.48)

 < 0.001

1.87 (1.65–2.09)

 < 0.001

1.39 (1.30–1.47)

 < 0.001

  NIE

1.01 (0.99–1.03)

0.398

1.05 (1.01–1.09)

0.022

1.01 (0.97–1.06)

0.636

1.01 (0.99–1.04)

0.489

  TE

1.44 (1.37–1.51)

 < 0.001

1.42 (1.30–1.53)

 < 0.001

1.89 (1.68–2.10)

 < 0.001

1.40 (1.32–1.49)

 < 0.001

  Proportion mediated, %

2.47

 

12.90*

 

1.73

 

2.49

 

 Labour complications

  NDE

1.43 (1.35–1.50)

 < 0.001

1.41 (1.30–1.53)

 < 0.001

1.82 (1.60–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.163

1.01 (1.00–1.02)

0.144

1.00 (0.99–1.01)

0.764

1.00 (1.00–1.01)

0.389

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.32–1.55)

 < 0.001

1.82 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

1.10

 

2.05

 

0.29

 

0.82

 

 Preterm birth

  NDE

1.37 (1.30–1.44)

 < 0.001

1.38 (1.27–1.51)

 < 0.001

1.66 (1.49–1.88)

 < 0.001

1.34 (1.26–1.42)

 < 0.001

  NIE

1.05 (1.03–1.07)

 < 0.001

1.05 (1.03–1.08)

 < 0.001

1.12 (1.07–1.17)

 < 0.001

1.04 (1.02–1.06)

 < 0.001

  TE

1.44 (1.37–1.52)

 < 0.001

1.45 (1.33–1.58)

 < 0.001

1.86 (1.68–2.08)

 < 0.001

1.40 (1.31–1.47)

 < 0.001

  Proportion mediated, %

13.51**

 

13.50**

 

17.78**

 

11.68**

 

 Neonatal asphyxia comorbidities

  NDE

1.38 (1.31–1.45)

 < 0.001

1.38 (1.27–1.52)

 < 0.001

1.63 (1.43–1.85)

 < 0.001

1.35 (1.27–1.43)

 < 0.001

  NIE

1.04 (1.02–1.05)

 < 0.001

1.03 (1.00–1.05)

0.013

1.12 (1.08–1.16)

 < 0.001

1.03 (1.01–1.05)

 < 0.001

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.31–1.54)

 < 0.001

1.82 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

10.45**

 

7.30*

 

18.56**

 

8.34**

 

 Neonatal hematological comorbidities

  NDE

1.39 (1.32–1.47)

 < 0.001

1.38 (1.27–1.50)

 < 0.001

1.71 (1.52–1.92)

 < 0.001

1.37 (1.28–1.44)

 < 0.001

  NIE

1.03 (1.01–1.04)

 < 0.001

1.03 (1.01–1.05)

0.008

1.07 (1.03–1.10)

 < 0.001

1.02 (1.00–1.03)

0.021

  TE

1.43 (1.36–1.51)

 < 0.001

1.41 (1.31–1.54)

 < 0.001

1.82 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

7.24**

 

7.90*

 

10.90**

 

4.77*

 

 Neonatal hypoglycemia

  NDE

1.39 (1.32–1.47)

 < 0.001

1.37 (1.26–1.52)

 < 0.001

1.77 (1.57–2.01)

 < 0.001

1.36 (1.27–1.44)

 < 0.001

  NIE

1.03 (1.01–1.05)

0.008

1.03 (1.00–1.06)

0.064

1.03 (1.00–1.08)

0.129

1.02 (1.00–1.05)

0.036

  TE

1.43 (1.36–1.50)

 < 0.001

1.41 (1.31–1.55)

 < 0.001

1.83 (1.61–2.03)

 < 0.001

1.39 (1.31–1.47)

 < 0.001

  Proportion mediated, %

6.99*

 

8.30

 

5.24

 

6.81*

 

 Neonatal infection

  NDE

1.41 (1.34–1.48)

 < 0.001

1.40 (1.30–1.53)

 < 0.001

1.77 (1.57–1.97)

 < 0.001

1.37 (1.29–1.45)

 < 0.001

  NIE

1.02 (1.01–1.03)

 < 0.001

1.01 (1.00–1.02)

0.012

1.03 (1.02–1.05)

 < 0.001

1.01 (1.01–1.02)

 < 0.001

  TE

1.43 (1.36–1.51)

 < 0.001

1.42 (1.32–1.55)

 < 0.001

1.83 (1.61–2.04)

 < 0.001

1.39 (1.32–1.47)

 < 0.001

  Proportion mediated, %

4.77**

 

3.43*

 

5.45**

 

4.44**

 

B GDM

 NDE

1.19 (1.18–1.19)

NA

1.25 (1.24–1.26)

NA

1.26 (1.25–1.28)

NA

1.14 (1.13–1.14)

NA

 NIE

1.00 (0.93–1.07)

NA

1.08 (0.98–1.19)

NA

1.07 (0.96–1.26)

NA

0.98 (0.90–1.10)

NA

 TE

1.19 (1.10–1.27)

NA

1.35 (1.22–1.48)

NA

1.35 (1.21–1.60)

NA

1.12 (1.03–1.25)

NA

 Proportion mediated, %

-0.1

 

25.7

 

22.8

 

-16.2

 

Single mediationb

 Pregnancy hypertensive diseases

  NDE

1.23 (1.16–1.28)

 < 0.001

1.31 (1.19–1.42)

 < 0.001

1.34 (1.20–1.51)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.345

1.00 (0.99–1.01)

0.845

1.01 (1.00–1.03)

0.110

1.00 (1.00–1.01)

0.604

  TE

1.23 (1.16–1.29)

 < 0.001

1.32 (1.19–1.42)

 < 0.001

1.36 (1.22–1.53)

 < 0.001

1.17 (1.09–1.24)

 < 0.001

  Proportion mediated, %

1.27

 

0.29

 

3.62

 

1.09

 

 Placenta/membrane disorders

  NDE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.35 (1.20–1.51)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.074

1.00 (1.00–1.00)

0.883

1.01 (1.00–1.02)

0.005

1.00 (1.00–1.00)

0.471

  TE

1.23 (1.16–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.37 (1.22–1.53)

 < 0.001

1.17 (1.08–1.24)

 < 0.001

  Proportion mediated, %

1.23

 

0.10

 

3.75*

 

0.74

 

 Maternal infection

  NDE

1.23 (1.26–1.29)

 < 0.001

1.32 (1.18–1.42)

 < 0.001

1.36 (1.21–1.52)

 < 0.001

1.17 (1.09–1.25)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.901

1.00 (1.00–1.00)

0.929

1.00 (1.00–1.01)

0.254

1.00 (1.00–1.00)

0.343

  TE

1.23 (1.15–1.29)

 < 0.001

1.32 (1.18–1.42)

 < 0.001

1.36 (1.22–1.52)

 < 0.001

1.17 (1.09–1.24)

 < 0.001

  Proportion mediated, %

-0.08

 

-0.07

 

1.25

 

-0.90

 

 Intrauterine hypoxia

  NDE

1.23 (1.15–1.28)

 < 0.001

1.32 (1.19–1.42)

 < 0.001

1.35 (1.21–1.52)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.157

1.00 (1.00–1.00)

0.523

1.00 (1.00–1.01)

0.101

1.00 (1.00–1.00)

0.173

  TE

1.23 (1.15–1.28)

 < 0.001

1.32 (1.19–1.42)

 < 0.001

1.36 (1.21–1.52)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  Proportion mediated, %

0.35

 

-0.07

 

1.40

 

0.53

 

 SGA

  NDE

1.20 (1.13–1.27)

 < 0.001

1.27 (1.16–1.39)

 < 0.001

1.35 (1.19–1.51)

 < 0.001

1.14 (1.06–1.22)

 < 0.001

  NIE

1.00 (0.99–1.00)

0.029

1.00 (0.99–1.00)

0.215

0.99 (0.98–1.00)

0.014

1.00 (0.99–1.00)

0.164

  TE

1.20 (1.13–1.27)

 < 0.001

1.27 (1.15–1.38)

 < 0.001

1.33 (1.17–1.50)

 < 0.001

1.14 (1.06–1.22)

 < 0.001

  Proportion mediated, %

-1.77

 

-0.98

 

-3.81

 

-1.67

 

 LGA

  NDE

1.21 (1.15–1.27)

 < 0.001

1.29 (1.17–1.42)

 < 0.001

1.35 (1.18–1.51)

 < 0.001

1.15 (1.08–1.23)

 < 0.001

  NIE

1.01 (1.00–1.02)

0.011

1.02 (1.00–1.04)

0.027

1.01 (0.99–1.04)

0.209

1.01 (1.00–1.02)

0.052

  TE

1.23 (1.17–1.29)

 < 0.001

1.31 (1.20–1.45)

 < 0.001

1.37 (1.20–1.53)

 < 0.001

1.16 (1.10–1.25)

 < 0.001

  Proportion mediated, %

6.55*

 

7.05*

 

4.48

 

7.84

 

 Labour complications

  NDE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.17–1.40)

 < 0.001

1.36 (1.21–1.52)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.085

1.00 (1.00–1.01)

0.134

1.00 (1.00–1.01)

0.151

1.00 (1.00–1.00)

0.609

  TE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.18–1.40)

 < 0.001

1.36 (1.21–1.52)

 < 0.001

1.17 (1.09–1.24)

 < 0.001

  Proportion mediated, %

0.97

 

1.00

 

0.68

 

0.38

 

 Preterm birth

  NDE

1.23 (1.16–1.30)

 < 0.001

1.33 (1.20–1.45)

 < 0.001

1.39 (1.24–1.56)

 < 0.001

1.16 (1.08–1.23)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.120

1.00 (0.99–1.01)

0.833

1.02 (1.00–1.03)

0.045

1.00 (1.00–1.01)

0.204

  TE

1.23 (1.16–1.30)

 < 0.001

1.33 (1.20–1.45)

 < 0.001

1.41 (1.26–1.59)

 < 0.001

1.16 (1.09–1.24)

 < 0.001

  Proportion mediated, %

2.29

 

-0.32

 

4.41*

 

3.14

 

 Neonatal asphyxia comorbidities

  NDE

1.22 (1.15–1.28)

 < 0.001

1.30 (1.18–1.41)

 < 0.001

1.33 (1.19–1.50)

 < 0.001

1.15 (1.07–1.23)

 < 0.001

  NIE

1.01 (1.00–1.01)

 < 0.001

1.01 (1.00–1.01)

0.035

1.02 (1.01–1.03)

 < 0.001

1.01 (1.00–1.01)

0.012

  TE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.36 (1.22–1.53)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  Proportion mediated, %

3.95**

 

2.31*

 

6.88**

 

3.94*

 

 Neonatal hematological comorbidities

  NDE

1.22 (1.15–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.35 (1.20–1.52)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.053

1.00 (1.00–1.01)

0.201

1.01 (1.00–1.02)

0.059

1.00 (1.00–1.01)

0.136

  TE

1.23 (1.16–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.37 (1.22–1.53)

 < 0.001

1.17 (1.08–1.24)

 < 0.001

  Proportion mediated, %

2.27

 

1.75

 

3.46

 

2.82

 

 Neonatal hypoglycemia

  NDE

1.22 (1.15–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.34 (1.19–1.50)

 < 0.001

1.15 (1.06–1.23)

 < 0.001

  NIE

1.01 (1.00–1.02)

0.055

1.00 (0.99–1.02)

0.523

1.02 (1.00–1.05)

0.057

1.01 (1.00–1.02)

0.042

  TE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.18–1.41)

 < 0.001

1.36 (1.22–1.53)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  Proportion mediated, %

4.29

 

1.55

 

6.69

 

7.76*

 

 Neonatal infection

  NDE

1.22 (1.15–1.28)

 < 0.001

1.31 (1.18–1.40)

 < 0.001

1.34 (1.20–1.50)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  NIE

1.00 (1.00–1.01)

0.010

1.00 (1.00–1.01)

0.117

1.01 (1.00–1.02)

0.006

1.00 (1.00–1.01)

0.143

  TE

1.23 (1.15–1.28)

 < 0.001

1.31 (1.18–1.40)

 < 0.001

1.36 (1.21–1.52)

 < 0.001

1.16 (1.08–1.24)

 < 0.001

  Proportion mediated, %

1.79*

 

1.10

 

3.35*

 

1.36

 

C Adiposity

 NDE

1.34 (1.33–1.36)

NA

1.34 (1.32–1.36)

NA

1.52 (1.49–1.56)

NA

1.36 (1.34–1.37)

NA

 NIE

1.01 (1.00–1.02)

NA

1.02 (1.00–1.03)

NA

1.04 (1.01–1.07)

NA

1.00 (0.99–1.02)

NA

 TE

1.36 (1.34–1.38)

NA

1.36 (1.33–1.39)

NA

1.58 (1.53–1.62)

NA

1.37 (1.34–1.39)

NA

 Proportion mediated, %

3.6*

 

5.3*

 

8.1**

 

1.5

 

Single mediationb

 Pregnancy hypertensive diseases

  NDE

1.36 (1.34–1.38)

 < 0.001

1.36 (1.33–1.40)

 < 0.001

1.56 (1.50–1.61)

 < 0.001

1.37 (1.35–1.40)

 < 0.001

  NIE

1.01 (1.00–1.01)

 < 0.001

1.01 (1.00–1.01)

 < 0.001

1.02 (1.01–1.02)

 < 0.001

1.00 (1.00–1.01)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

2.04**

 

2.25**

 

3.52**

 

1.50**

 

 Placenta/membrane disorders

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.59 (1.54–1.65)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

-0.28

 

-0.21

 

-0.64

 

-0.21

 

 Gestational infection

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

0.51**

 

0.43**

 

0.45**

 

0.48**

 

 Intrauterine hypoxia

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.40)

 < 0.001

1.57 (1.52–1.63)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.01 (1.01–1.01)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

0.90**

 

0.76**

 

1.79**

 

0.57**

 

 SGA

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.33–1.39)

 < 0.001

1.61 (1.55–1.66)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.36 (1.33–1.39)

 < 0.001

1.60 (1.55–1.66)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

-0.31

 

-0.30

 

-0.63

 

-0.24

 

 LGA

  NDE

1.38 (1.36–1.40)

 < 0.001

1.37 (1.34–1.40)

 < 0.001

1.62 (1.56–1.68)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.146

1.00 (1.00–1.01)

0.001

1.00 (0.99–1.00)

0.365

1.00 (1.00–1.00)

0.332

  TE

1.38 (1.36–1.40)

 < 0.001

1.37 (1.35–1.41)

 < 0.001

1.62 (1.56–1.68)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

0.33

 

1.30**

 

-0.32

 

0.24

 

 Labour complications

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

0.316

1.00 (1.00–1.00)

0.673

1.00 (1.00–1.00)

0.001

1.00 (1.00–1.00)

0.712

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

0.07

 

0.05

 

0.43**

 

-0.03

 

 Preterm birth

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.33–1.40)

 < 0.001

1.57 (1.51–1.62)

 < 0.001

1.38 (1.36–1.41)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.01 (1.01–1.01)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.40)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.59 (1.53–1.64)

 < 0.001

1.38 (1.36–1.41)

 < 0.001

  Proportion mediated, %

0.97**

 

0.84**

 

2.12**

 

0.67**

 

 Neonatal asphyxia comorbidities

  NDE

1.37 (1.35–1.38)

 < 0.001

1.36 (1.33–1.40)

 < 0.001

1.55 (1.50–1.61)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.01 (1.01–1.01)

 < 0.001

1.01 (1.00–1.01)

 < 0.001

1.02 (1.02–1.03)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.59 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

1.83**

 

1.65**

 

5.08**

 

0.95**

 

 Neonatal hematological comorbidities

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.40)

 < 0.001

1.57 (1.52–1.63)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.01 (1.01–1.01)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.59 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

1.19**

 

1.18**

 

2.19**

 

0.84**

 

 Neonatal hypoglycemia

  NDE

1.37 (1.35–1.38)

 < 0.001

1.36 (1.33–1.40)

 < 0.001

1.56 (1.50–1.61)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.01)

 < 0.001

1.00 (1.00–1.01)

 < 0.001

1.02 (1.01–1.02)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

1.50**

 

1.54**

 

3.39**

 

1.09**

 

 Neonatal infection

  NDE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.52–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

1.01 (1.00–1.01)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.41)

 < 0.001

1.58 (1.53–1.64)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

 Proportion mediated, %

0.53**

 

0.55**

 

1.22**

 

0.34**

 

 GDM

  NDE

1.36 (1.34–1.38)

 < 0.001

1.36 (1.33–1.40)

 < 0.001

1.57 (1.52–1.62)

 < 0.001

1.37 (1.35–1.40)

 < 0.001

  NIE

1.00 (1.00–1.00)

 < 0.001

1.00 (1.00–1.01)

 < 0.001

1.00 (1.00–1.01)

 < 0.001

1.00 (1.00–1.00)

 < 0.001

  TE

1.37 (1.35–1.39)

 < 0.001

1.37 (1.34–1.40)

 < 0.001

1.57 (1.52–1.63)

 < 0.001

1.38 (1.36–1.40)

 < 0.001

  Proportion mediated, %

1.01**

 

1.16**

 

0.87**

 

0.86**

 
  1. Adjusted for 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
  2. aMultiple mediators included in the analysis were subsequently presented as individual mediators in the subsequent single mediation analyses for each exposure and outcome. 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
  3. bSingle mediation analysis. Proportions mediated were marked with “*” when P < 0.05 for NIE and with “**” when PBonferroni corrected < 0.004 for NIE, with both NDE and NIE having the same direction
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