ED-CORTISOL-CBCL

Main results

Author

M. Rolland

Published

June 27, 2024

Note:

Ajouter toutes les tables de sortie des modeles et les N

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1 Main results

1.1 Flowchart

Figure 1: Study flowchart

1.2 Population description

Table 1: Population Description Stratified by Cohort
Characteristic Overall, N = 1,0241 BiSC, N = 6071 SEPAGES, N = 4171 p-value2
Season of birth


0.5
    Winter 202 (20%) 116 (19%) 86 (21%)
    Other 822 (80%) 491 (81%) 331 (79%)
Maternal BMI


<0.001
    Normal 687 (71%) 375 (67%) 312 (75%)
    Underweight 48 (4.9%) 20 (3.6%) 28 (6.8%)
    Overweight 238 (24%) 164 (29%) 74 (18%)
Maternal age 33.9 (31.0, 36.8) 35.0 (32.0, 38.0) 32.3 (30.0, 35.3) <0.001
Maternal education


<0.001
    Below university 156 (15%) 134 (22%) 22 (5.3%)
    University, below master 323 (32%) 168 (28%) 155 (37%)
    University, master or above 543 (53%) 305 (50%) 238 (57%)
Ethnicity


<0.001
    caucasian 894 (88%) 495 (82%) 399 (97%)
    other 126 (12%) 112 (18%) 14 (3.4%)
Anxiety 0.00 (-0.70, 0.60) -0.18 (-0.70, 0.55) 0.00 (-0.70, 0.60) 0.9
Parity


<0.001
    multiparous 437 (43%) 214 (35%) 223 (53%)
    nulliparous 587 (57%) 393 (65%) 194 (47%)
Passive smoking 305 (31%) 229 (39%) 76 (19%) <0.001
Active smoking 68 (6.9%) 45 (7.5%) 23 (6.0%) 0.4
Child sex


0.075
    male 528 (52%) 299 (49%) 229 (55%)
    female 496 (48%) 308 (51%) 188 (45%)
Alcohol 262 (27%) 169 (29%) 93 (23%) 0.014
Folic acid 705 (82%) 338 (76%) 367 (88%) <0.001
Breasfeeding (N weeks) 35 (17, 48) 48 (26, 48) 26 (15, 42) <0.001
Child in kindergarten at 12m 378 (45%) 255 (51%) 123 (35%) <0.001
Sum(cortisol) 0.024 (0.016, 0.037) 0.027 (0.020, 0.037) 0.019 (0.010, 0.037) <0.001
Age at CBCL (weeks) 85 (81, 106) 81 (79, 84) 106 (105, 108) <0.001
1 n (%); Median (IQR)
2 Pearson’s Chi-squared test; Wilcoxon rank sum test
  • Populations differ between SEPAGES and BiSC

1.3 Exposure description

Table 2: Exposure Detection Rates and Description Stratified by Cohort and by Pool
BiSC (N = 607) SEPAGES (N = 417)
N %>LOD p5 p50 p95 N %>LOD p5 p50 p95
Trimester 2
Benzophenone-3 455 100% 0.68 3.54 81.91 415 100% 0.17 0.81 26.13
Bisphenol A 455 86% 0.02 1.00 11.53 415 100% 0.65 1.83 7.93
Bisphenol S 455 61% 0.03 0.33 2.83 415 82% 0.00 0.00 1.01
Ethylparaben 455 100% 0.90 2.20 40.21 415 100% 0.29 0.87 35.45
Methylparaben 455 100% 7.08 19.98 313.08 415 100% 2.15 10.77 212.00
Propylparaben 455 87% 0.02 0.52 37.27 415 78% 0.00 0.32 42.51
Triclosan 455 94% 0.03 0.59 88.67 415 98% 0.21 0.91 186.31
Trimester 3
Benzophenone-3 523 100% 0.51 3.39 71.23 409 100% 0.17 0.71 16.77
Bisphenol A 523 87% 0.02 1.16 10.46 409 99% 0.49 1.66 7.83
Bisphenol S 523 58% 0.02 0.30 2.76 407 78% 0.00 0.00 0.32
Ethylparaben 523 100% 0.98 2.54 23.86 409 100% 0.25 0.91 25.45
Methylparaben 523 100% 7.79 24.55 1,321.53 409 100% 2.10 11.06 1,993.47
Propylparaben 523 89% 0.02 0.69 149.33 409 77% 0.00 0.38 110.42
Triclosan 523 90% 0.02 0.50 61.85 409 98% 0.19 0.86 197.39
  • Exposure levels differ between SEPAGES and BiSC except for TRCS
Figure 2: Spearman correlation between exposures

1.4 EWAS

See Table 3 for detail on model Ns.

1.4.1 Direct association

1.4.1.1 Main model

Figure 3: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure
  • See model table here
  • See model residuals here

1.4.1.2 Sensitivity analysis

Figure 4: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, complete case analysis
  • See model table here
  • See model residuals here
Figure 5: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using unstandardised exposure data
Figure 6: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, without top and bottom 1%
Figure 7: Adjusted estimates and CIs for externalising and internalising CBCL, stratified by cohort for associations that were significant in the overall EWAS
  • MEPA association for pool 2 consistant across externalising and internalising score
  • MEPA association clearly only pool 2 (opposite direction for pool 1)
  • TRCS externalising => Pool 1
  • MEPA consistant across complete case
  • BPS bexomes signif when limited to mediation data
  • Observed associations consistant across cohort

1.4.1.3 Non linear (quartiles)

Figure 8: Adjusted estimates and CIs for BPA and PRPA coded as quartiles and for Pool 2 only (as determined in ADD REF)
  • not much for the compounds that showed signs of non linear association

1.4.2 Sex interaction

1.4.2.1 Main model

Figure 9: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1)
Figure 10: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), complete case data
Figure 11: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), on not standardised exposure data
Figure 12: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), without top and bottom 1%

(There are no outliers in categorical data)

  • effect of exposure systematically lower in girls than boys => Mostly interaction for categorical (BPS/BUPA) need to make sure this is not an artifact
  • some associations NS after limiting to individuals with cortisol measure

See Section 4.2 for pval table.

2 BKMR

NEED TO RERUN

3 Mediation

Nonparametric Bootstrap Confidence Intervals with the Percentile Method

3.1 Main model

Figure 13: Adjusted estimates and confidence intervals for the direct and indirect effects and proportion mediated of the mediation analysis examining the potential mediating role of cortisol in the associations between prenatal exposure to various phenols and internalising and externalising Child Behaviour Checklist (CBCL) scores.

3.2 By sex

Figure 14: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis for boys and girls when a sign of interaction was present in the direct association

No association mediated by cortisol.

4 Supplementary data

4.1 N for each model

Table 3: Final N by pool and combination type and by cohort
Characteristic Overall, N = 1,0241 BiSC, N = 6071 SEPAGES, N = 4171
pool1 870 (85%) 455 (75%) 415 (100%)
pool2 932 (91%) 523 (86%) 409 (98%)
1 n (%)

4.2 Interaction p values

Table 4: P-value for the interaction term between exposure and sex (Wald p)
internalizing externalizing
Pool 1
BP3 0.8 0.6
BPA 0.9 0.079
ETPA 0.2 0.8
MEPA 0.2 0.5
PRPA 0.2 0.070
TRCS 0.6 0.4
BPS 0.6 0.5
BUPA 0.025 0.8
Pool 2
BP3 >0.9 0.6
BPA 0.5 0.4
ETPA 0.2 0.13
MEPA 0.2 0.3
PRPA 0.2 0.8
TRCS 0.8 0.6
BPS 0.009 0.037
BUPA 0.3 0.4

4.3 Model outputs

4.3.1 EWAS

4.3.1.1 Main

Table 5: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure
Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Benzophenone-3 0.01 −0.03 0.06 0.6 0.01 −0.04 0.05 0.8
Bisphenol A −0.02 −0.07 0.02 0.3 −0.03 −0.08 0.02 0.2
Bisphenol S −0.12 −0.26 0.03 0.11 −0.06 −0.20 0.08 0.4
Butylparaben −0.11 −0.28 0.06 0.2 −0.06 −0.23 0.11 0.5
Ethylparaben −0.03 −0.08 0.02 0.3 0.00 −0.05 0.05 >0.9
Methylparaben −0.04 −0.10 0.01 0.088 −0.02 −0.07 0.03 0.4
Propylparaben −0.02 −0.05 0.01 0.12 −0.02 −0.04 0.01 0.2
Triclosan 0.03 0.00 0.06 0.065 0.01 −0.03 0.04 0.6
Trimester 3
Benzophenone-3 0.03 −0.01 0.07 0.2 −0.03 −0.08 0.01 0.11
Bisphenol A 0.00 −0.04 0.04 >0.9 −0.01 −0.05 0.03 0.6
Bisphenol S 0.04 −0.10 0.17 0.6 0.05 −0.08 0.19 0.4
Butylparaben 0.07 −0.10 0.24 0.4 −0.01 −0.18 0.16 >0.9
Ethylparaben 0.02 −0.03 0.08 0.4 −0.03 −0.08 0.03 0.3
Methylparaben 0.04 0.01 0.08 0.017 0.05 0.01 0.08 0.010
Propylparaben 0.01 −0.01 0.03 0.3 0.01 −0.01 0.03 0.5
Triclosan 0.02 −0.01 0.05 0.15 0.00 −0.03 0.03 >0.9

4.3.1.2 Sensitivity: complete case

Table 6: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Limited to Complete Cases
Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Benzophenone-3 0.01 −0.05 0.06 0.8 0.03 −0.02 0.09 0.2
Bisphenol A −0.02 −0.08 0.04 0.5 −0.03 −0.09 0.03 0.3
Bisphenol S −0.16 −0.34 0.02 0.089 −0.05 −0.23 0.12 0.5
Butylparaben −0.09 −0.30 0.12 0.4 0.01 −0.20 0.21 >0.9
Ethylparaben −0.01 −0.07 0.05 0.8 0.01 −0.05 0.07 0.7
Methylparaben −0.02 −0.08 0.04 0.6 −0.01 −0.07 0.05 0.8
Propylparaben −0.01 −0.04 0.02 0.7 −0.01 −0.04 0.02 0.4
Triclosan 0.02 −0.02 0.06 0.3 0.01 −0.03 0.05 0.7
Trimester 3
Benzophenone-3 0.03 −0.02 0.09 0.2 0.01 −0.04 0.06 0.7
Bisphenol A −0.02 −0.07 0.04 0.5 0.02 −0.04 0.07 0.6
Bisphenol S 0.07 −0.10 0.24 0.4 0.05 −0.11 0.21 0.5
Butylparaben 0.26 0.05 0.47 0.016 0.16 −0.05 0.36 0.13
Ethylparaben 0.05 −0.02 0.11 0.2 0.01 −0.05 0.07 0.8
Methylparaben 0.05 0.01 0.09 0.025 0.06 0.02 0.10 0.005
Propylparaben 0.01 −0.02 0.04 0.4 0.01 −0.01 0.04 0.3
Triclosan 0.04 0.00 0.08 0.046 0.00 −0.03 0.04 0.8

4.3.1.3 Sensitivity: Non standardised

Table 7: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Using Non-Standardised Exposures Data
Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Benzophenone-3 0.01 −0.03 0.05 0.7 0.01 −0.04 0.05 0.7
Bisphenol A −0.02 −0.06 0.03 0.4 −0.02 −0.07 0.02 0.4
Bisphenol S −0.12 −0.26 0.03 0.11 −0.06 −0.20 0.08 0.4
Butylparaben −0.11 −0.28 0.06 0.2 −0.06 −0.23 0.11 0.5
Ethylparaben −0.03 −0.08 0.02 0.2 0.00 −0.05 0.05 0.9
Methylparaben −0.05 −0.10 0.00 0.039 −0.02 −0.07 0.03 0.5
Propylparaben −0.02 −0.05 0.01 0.11 −0.01 −0.04 0.01 0.4
Triclosan 0.03 0.00 0.06 0.082 0.01 −0.03 0.04 0.7
Trimester 3
Benzophenone-3 0.03 −0.01 0.07 0.2 −0.03 −0.07 0.01 0.13
Bisphenol A 0.00 −0.04 0.04 >0.9 −0.01 −0.05 0.03 0.8
Bisphenol S 0.04 −0.10 0.17 0.6 0.05 −0.08 0.19 0.4
Butylparaben 0.07 −0.10 0.24 0.4 −0.01 −0.18 0.16 >0.9
Ethylparaben 0.02 −0.03 0.07 0.5 −0.02 −0.07 0.03 0.4
Methylparaben 0.04 0.01 0.08 0.020 0.05 0.01 0.08 0.011
Propylparaben 0.02 −0.01 0.04 0.2 0.01 −0.01 0.03 0.4
Triclosan 0.02 −0.01 0.05 0.15 0.00 −0.03 0.03 >0.9

4.3.1.4 Sensitivity: Without top and bottom 1%

Table 8: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Excluding Top and Bottom 1% of Exposure and Outcome Values
Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Benzophenone-3 0.02 −0.03 0.06 0.5 0.02 −0.02 0.07 0.3
Bisphenol A −0.04 −0.08 0.01 0.13 −0.05 −0.10 −0.01 0.025
Ethylparaben −0.01 −0.06 0.04 0.6 0.02 −0.02 0.07 0.3
Methylparaben −0.02 −0.08 0.03 0.4 0.01 −0.04 0.06 0.8
Propylparaben −0.02 −0.05 0.01 0.13 −0.02 −0.04 0.01 0.2
Triclosan 0.03 −0.01 0.06 0.10 0.02 −0.01 0.05 0.2
Trimester 3
Benzophenone-3 0.02 −0.02 0.07 0.3 −0.02 −0.06 0.02 0.4
Bisphenol A 0.01 −0.03 0.06 0.6 0.00 −0.04 0.04 >0.9
Ethylparaben 0.02 −0.04 0.07 0.6 0.02 −0.03 0.07 0.4
Methylparaben 0.02 −0.02 0.06 0.3 0.03 0.00 0.06 0.066
Propylparaben 0.00 −0.02 0.03 0.7 0.01 −0.01 0.03 0.6
Triclosan 0.02 −0.01 0.05 0.2 0.00 −0.03 0.03 0.9

4.3.1.5 Sensitivity: By cohort

Table 9: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort
cohort Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Methylparaben BiSC −0.03 −0.12 0.05 0.5 — — — —
Methylparaben SEPAGES −0.04 −0.10 0.02 0.2 — — — —
Triclosan BiSC 0.02 −0.03 0.06 0.5 — — — —
Triclosan SEPAGES 0.05 0.00 0.09 0.043 — — — —
Trimester 3
Methylparaben BiSC 0.07 0.01 0.12 0.018 0.06 0.00 0.11 0.046
Methylparaben SEPAGES 0.03 −0.02 0.07 0.2 0.05 0.00 0.09 0.032

4.3.2 Sex interaction

4.3.2.1 Main

Table 10: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores stratified by child sex, performed only when the p-value for interaction was less than 0.1
sex Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Bisphenol A Boys 0.02 −0.05 0.08 0.6 — — — —
Bisphenol A Girls −0.06 −0.13 0.00 0.056 — — — —
Butylparaben Boys — — — — 0.11 −0.12 0.34 0.3
Butylparaben Girls — — — — −0.28 −0.53 −0.03 0.031
Propylparaben Boys 0.00 −0.03 0.04 >0.9 −0.03 −0.06 0.01 0.094
Propylparaben Girls −0.05 −0.08 −0.01 0.016 0.00 −0.04 0.04 >0.9
Triclosan Boys 0.02 −0.03 0.06 0.4 — — — —
Triclosan Girls 0.05 0.00 0.10 0.061 — — — —
Trimester 3
Bisphenol S Boys 0.17 −0.01 0.35 0.068 0.22 0.04 0.40 0.018
Bisphenol S Girls −0.10 −0.29 0.08 0.3 −0.12 −0.30 0.07 0.2
Ethylparaben Boys −0.01 −0.08 0.06 0.7 — — — —
Ethylparaben Girls 0.06 −0.01 0.14 0.091 — — — —
Methylparaben Boys 0.02 −0.03 0.07 0.4 0.02 −0.03 0.07 0.4
Methylparaben Girls 0.06 0.01 0.11 0.012 0.07 0.02 0.12 0.004

4.3.2.2 Sensitivity: Complete case

Table 11: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, including sex interaction limited to complete case data
sex Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Bisphenol A Boys 0.03 −0.05 0.12 0.4 — — — —
Bisphenol A Girls −0.07 −0.15 0.01 0.088 — — — —
Butylparaben Boys — — — — 0.15 −0.13 0.42 0.3
Butylparaben Girls — — — — −0.17 −0.47 0.14 0.3
Propylparaben Boys 0.03 −0.01 0.07 0.2 −0.03 −0.07 0.01 0.2
Propylparaben Girls −0.05 −0.09 0.00 0.040 0.00 −0.04 0.04 >0.9
Triclosan Boys 0.02 −0.03 0.07 0.4 — — — —
Triclosan Girls 0.02 −0.04 0.08 0.4 — — — —
Trimester 3
Bisphenol S Boys 0.11 −0.12 0.34 0.4 0.11 −0.11 0.33 0.3
Bisphenol S Girls 0.03 −0.20 0.26 0.8 −0.01 −0.23 0.21 >0.9
Ethylparaben Boys 0.05 −0.05 0.14 0.3 — — — —
Ethylparaben Girls 0.04 −0.05 0.13 0.3 — — — —
Methylparaben Boys 0.05 −0.01 0.11 0.13 0.03 −0.03 0.09 0.3
Methylparaben Girls 0.05 −0.01 0.11 0.090 0.08 0.02 0.13 0.004

4.3.2.3 Sensitivity: Non standardised

Table 12: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using no standardised exposure data
sex Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Bisphenol A Boys 0.02 −0.04 0.08 0.6 — — — —
Bisphenol A Girls −0.05 −0.12 0.01 0.089 — — — —
Butylparaben Boys — — — — 0.11 −0.12 0.34 0.3
Butylparaben Girls — — — — −0.28 −0.53 −0.03 0.031
Propylparaben Boys 0.00 −0.03 0.04 0.9 −0.02 −0.06 0.01 0.2
Propylparaben Girls −0.05 −0.08 −0.01 0.015 0.00 −0.04 0.04 >0.9
Triclosan Boys 0.01 −0.03 0.06 0.6 — — — —
Triclosan Girls 0.05 0.00 0.10 0.056 — — — —
Trimester 3
Bisphenol S Boys 0.17 −0.01 0.35 0.068 0.22 0.04 0.40 0.018
Bisphenol S Girls −0.10 −0.29 0.08 0.3 −0.12 −0.30 0.07 0.2
Ethylparaben Boys 0.00 −0.07 0.06 0.9 — — — —
Ethylparaben Girls 0.05 −0.02 0.12 0.2 — — — —
Methylparaben Boys 0.02 −0.02 0.07 0.3 0.02 −0.03 0.07 0.5
Methylparaben Girls 0.06 0.01 0.11 0.020 0.07 0.03 0.12 0.003

4.3.2.4 Sensitivity: Without top and bottom 1%

Table 13: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, excludeing top and bottom 1% exposure and outcome values
sex Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Bisphenol A Boys −0.01 −0.08 0.05 0.7 — — — —
Bisphenol A Girls −0.06 −0.13 0.00 0.061 — — — —
Propylparaben Boys −0.01 −0.05 0.03 0.6 −0.02 −0.06 0.01 0.2
Propylparaben Girls −0.03 −0.07 0.01 0.10 −0.01 −0.05 0.03 0.6
Triclosan Boys 0.01 −0.03 0.06 0.6 — — — —
Triclosan Girls 0.05 0.00 0.10 0.061 — — — —
Trimester 3
Ethylparaben Boys −0.02 −0.10 0.05 0.5 — — — —
Ethylparaben Girls 0.05 −0.02 0.13 0.2 — — — —
Methylparaben Boys 0.00 −0.05 0.05 >0.9 0.03 −0.01 0.07 0.2
Methylparaben Girls 0.04 −0.01 0.09 0.12 0.03 −0.02 0.08 0.2

4.3.2.5 Sensitivity: By cohort

Table 14: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort and by child sex
cohort sex Externalizing Internalizing
estimate conf.low conf.high p.value estimate conf.low conf.high p.value
Trimester 2
Bisphenol A BiSC Boys 0.02 −0.05 0.10 0.5 — — — —
Bisphenol A SEPAGES Boys −0.09 −0.23 0.06 0.2 — — — —
Bisphenol A BiSC Girls −0.08 −0.16 −0.01 0.032 — — — —
Bisphenol A SEPAGES Girls 0.04 −0.12 0.19 0.6 — — — —
Butylparaben BiSC Boys — — — — −0.07 −0.43 0.28 0.7
Butylparaben SEPAGES Boys — — — — 0.28 0.00 0.57 0.054
Butylparaben BiSC Girls — — — — −0.18 −0.59 0.24 0.4
Butylparaben SEPAGES Girls — — — — −0.34 −0.65 −0.03 0.034
Propylparaben BiSC Boys 0.01 −0.05 0.07 0.8 −0.06 −0.12 0.00 0.060
Propylparaben SEPAGES Boys 0.00 −0.04 0.05 0.9 0.00 −0.05 0.04 0.8
Propylparaben BiSC Girls −0.03 −0.09 0.03 0.3 0.01 −0.04 0.07 0.6
Propylparaben SEPAGES Girls −0.07 −0.12 −0.02 0.006 −0.01 −0.05 0.04 0.8
Triclosan BiSC Boys 0.01 −0.06 0.08 0.8 — — — —
Triclosan SEPAGES Boys 0.02 −0.04 0.09 0.4 — — — —
Triclosan BiSC Girls 0.02 −0.05 0.09 0.6 — — — —
Triclosan SEPAGES Girls 0.07 0.01 0.14 0.029 — — — —
Trimester 3
Bisphenol S BiSC Boys 0.28 0.02 0.53 0.037 0.29 0.03 0.55 0.026
Bisphenol S SEPAGES Boys 0.04 −0.23 0.30 0.8 0.15 −0.11 0.41 0.3
Bisphenol S BiSC Girls −0.22 −0.47 0.02 0.078 −0.16 −0.40 0.09 0.2
Bisphenol S SEPAGES Girls 0.06 −0.25 0.37 0.7 −0.06 −0.36 0.25 0.7
Ethylparaben BiSC Boys −0.03 −0.15 0.08 0.6 — — — —
Ethylparaben SEPAGES Boys 0.00 −0.09 0.09 >0.9 — — — —
Ethylparaben BiSC Girls 0.02 −0.11 0.15 0.8 — — — —
Ethylparaben SEPAGES Girls 0.09 0.00 0.18 0.050 — — — —
Methylparaben BiSC Boys 0.08 −0.01 0.16 0.088 0.04 −0.05 0.12 0.4
Methylparaben SEPAGES Boys 0.00 −0.06 0.06 >0.9 0.03 −0.03 0.09 0.3
Methylparaben BiSC Girls 0.06 −0.01 0.14 0.10 0.07 0.00 0.15 0.055
Methylparaben SEPAGES Girls 0.06 0.00 0.13 0.057 0.07 0.01 0.14 0.032

4.3.3 Mediation

4.3.3.1 Main

Table 15: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis
estimate conf.low conf.high p.value
Methylparaben, Trimester 3, Internalising
Indirect effect 0.0001 −0.0015 0.0020 0.9
Direct effect 0.0508 0.0155 0.0853 0.002
Total Effect 0.0510 0.0158 0.0850 0.002
Prop. Mediated 0.0028 −0.0391 0.0486 0.9
Methylparaben, Trimester 3, Externalising
Indirect effect 0.0000 −0.0019 0.0017 >0.9
Direct effect 0.0481 0.0105 0.0852 0.012
Total Effect 0.0481 0.0108 0.0852 0.012
Prop. Mediated 0.0002 −0.0540 0.0522 >0.9

4.3.3.2 By sex

Table 16: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis, by sex
estimate conf.low conf.high p.value
Bisphenol S Trimester 3 Internalising male
Indirect effect 0.00 −0.01 0.01 >0.9
Direct effect 0.23 0.05 0.43 0.010
Total Effect 0.23 0.06 0.43 0.012
Prop. Mediated 0.00 −0.07 0.09 >0.9
Methylparaben Trimester 3 Internalising female
Indirect effect 0.00 −0.01 0.00 0.8
Direct effect 0.08 0.02 0.13 0.002
Total Effect 0.08 0.02 0.13 0.004
Prop. Mediated −0.01 −0.11 0.05 0.8
Methylparaben Trimester 3 Externalising female
Indirect effect 0.00 −0.01 0.00 0.8
Direct effect 0.07 0.02 0.12 <0.001
Total Effect 0.07 0.02 0.12 0.002
Prop. Mediated −0.01 −0.12 0.06 0.8
Butylparaben Trimester 2 Internalising female
Indirect effect −0.01 −0.05 0.01 0.4
Direct effect −0.27 −0.54 −0.01 0.044
Total Effect −0.29 −0.55 −0.02 0.042
Prop. Mediated 0.04 −0.08 0.27 0.5