ED-CORTISOL-CBCL

Main results

Author

M. Rolland

Published

June 23, 2025

Note:

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
Maternal BMI (kg/m2)


<0.001
    Normal (18.5 to 24.9) 687 (71%) 375 (67%) 312 (75%)
    Underweight (<18.5) 48 (4.9%) 20 (3.6%) 28 (6.8%)
    Overweight (>=25) 238 (24%) 164 (29%) 74 (18%)
    Missing 51 48 3
Maternal age (years) 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%)
    Missing 2 0 2
Ethnicity


<0.001
    European 894 (88%) 495 (82%) 399 (97%)
    Other 126 (12%) 112 (18%) 14 (3.4%)
    Missing 4 0 4
Anxiety z-score 0.00 (-0.70, 0.60) -0.18 (-0.70, 0.55) 0.00 (-0.70, 0.60) 0.9
    Missing 80 67 13
Parity


<0.001
    Nulliparous 587 (57%) 393 (65%) 194 (47%)
    Multiparous 437 (43%) 214 (35%) 223 (53%)
Passive smoking during pregnancy 305 (31%) 229 (39%) 76 (19%) <0.001
    Missing 45 21 24
Alcohol intake during pregnancy 262 (27%) 169 (29%) 93 (23%) 0.014
    Missing 38 34 4
Folic acid intake during pregnancy 705 (82%) 338 (76%) 367 (88%) <0.001
    Missing 163 161 2
Active smoking during pregnancy 68 (6.9%) 45 (7.5%) 23 (6.0%) 0.4
    Missing 44 8 36
Timing of second trimester urine sample (gest. weeks) 18.9 (17.4, 20.9) 20.3 (18.4, 22.6) 17.7 (16.4, 18.9) <0.001
    Missing 172 135 37
Timing of third trimester urine sample (gest. weeks) 35.70 (34.35, 37.00) 36.71 (35.71, 37.71) 34.00 (32.30, 35.30) <0.001
    Missing 112 70 42
Hair collection (gest. weeks) 33.0 (31.7, 41.9) 31.9 (31.1, 32.4) 42.0 (41.1, 42.9) <0.001
    Missing 98 98 0
Time between hair coll. and horm. assessment (months) 12 (5, 49) 6 (4, 11) 51 (45, 59) <0.001
    Missing 155 98 57
∑Cortisol (nmol/g) 0.024 (0.016, 0.037) 0.027 (0.020, 0.037) 0.019 (0.010, 0.037) <0.001
    Missing 171 102 69
Season of birth


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


0.075
    Male 528 (52%) 299 (49%) 229 (55%)
    Female 496 (48%) 308 (51%) 188 (45%)
Breasfeeding (N weeks) 35 (17, 48) 48 (26, 48) 26 (15, 42) <0.001
    Missing 18 9 9
Child in daycare at 12 months 378 (45%) 255 (51%) 123 (35%) <0.001
    Missing 175 111 64
Age at CBCL questionnaire (months) 19.72 (18.74, 24.55) 18.84 (18.44, 19.44) 24.68 (24.45, 25.12) <0.001
Externalizing problems 11 (7, 16) 10 (5, 14) 12 (9, 17) <0.001
    Missing 1 0 1
Internalizing problems 4.0 (2.0, 8.0) 3.0 (1.0, 6.0) 6.0 (3.0, 9.0) <0.001
1 n (%); Median (Q1, Q3)
2 Pearson’s Chi-squared test; Wilcoxon rank sum test

1.3 Exposure description

Table 2: Exposure Detection Rates and Description Stratified by Cohort and by Pool
Raw data
Standardized data
BiSC
SEPAGES
BiSC
SEPAGES
N %>LOD p5 p50 p95 N %>LOD p5 p50 p95 N %>LOD p5 p50 p95 N %>LOD p5 p50 p95
Trimester 2
Benzophenone-3 455 100% 0.91 5.18 140.43 415 100% 0.25 1.14 37.35 455 100% 0.68 3.54 81.91 415 100% 0.17 0.81 26.13
Bisphenol A 455 86% 0.03 2.52 25.22 415 99% 0.67 2.00 7.97 455 86% 0.02 1.00 11.53 415 100% 0.65 1.83 7.93
Bisphenol S 455 59% 0.03 0.50 3.55 415 24% 0.00 0.00 3.69 455 61% 0.03 0.33 2.83 415 13% 0.00 0.00 1.01
Ethylparaben 455 100% 0.85 2.53 48.86 415 100% 0.26 0.70 30.09 455 100% 0.90 2.20 40.21 415 100% 0.29 0.87 35.45
Methylparaben 455 100% 4.48 14.91 231.49 415 100% 2.68 12.33 280.62 455 100% 7.08 19.98 313.08 415 100% 2.15 10.77 212.00
Propylparaben 455 87% 0.02 0.52 37.27 415 80% 0.01 0.40 59.34 455 87% 0.02 0.52 37.27 415 78% 0.00 0.32 42.51
Triclosan 455 93% 0.04 0.79 126.12 415 98% 0.21 0.91 186.31 455 94% 0.03 0.59 88.67 415 98% 0.21 0.91 186.31
Trimester 3
Benzophenone-3 523 100% 0.82 4.89 128.64 409 100% 0.24 0.99 27.55 523 100% 0.51 3.39 71.23 409 100% 0.17 0.71 16.77
Bisphenol A 523 87% 0.03 2.90 25.39 409 98% 0.52 1.78 9.20 523 87% 0.02 1.16 10.46 409 99% 0.49 1.66 7.83
Bisphenol S 523 56% 0.03 0.43 3.30 407 27% 0.00 0.00 2.94 523 58% 0.02 0.30 2.76 407 11% 0.00 0.00 0.32
Ethylparaben 523 100% 0.93 2.70 30.83 409 100% 0.21 0.73 21.85 523 100% 0.98 2.54 23.86 409 100% 0.25 0.91 25.45
Methylparaben 523 100% 5.16 17.63 1,160.68 409 100% 2.86 12.24 2,635.94 523 100% 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 80% 0.00 0.56 158.91 523 89% 0.02 0.69 149.33 409 77% 0.00 0.38 110.42
Triclosan 523 89% 0.02 0.71 110.14 409 98% 0.19 0.86 197.39 523 90% 0.02 0.50 61.85 409 98% 0.19 0.86 197.39

1.4 EWAS

See Table 5 for detail on model Ns.

1.4.1 Direct association

Figure 2: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure
Figure 3: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure
Figure 4: Adjusted estimates and CIs for externalising and internalising CBCL, stratified by cohort for associations that were significant in the overall EWAS
Figure 5: Adjusted estimates and CIs for externalising and internalising CBCL, stratified by cohort for associations that were significant in the overall EWAS
Figure 6: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, complete case analysis
Figure 7: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using unstandardised exposure data
Figure 8: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using unstandardised exposure data
Figure 9: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, without top and bottom 1%
Figure 10: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, without top and bottom 1%
Figure 11: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, adjusted for urine SG

1.4.1.1 Non linear (quartiles)

see allp-values Table 6

Figure 12: Adjusted estimates and CIs for BPA and PRPA coded as quartiles and for Pool 2 only (as determined in ADD REF)

1.4.2 Sex interaction

Figure 13: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1)
Figure 14: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1)
Figure 15: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1)
Figure 16: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1)
Figure 17: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), complete case data
Figure 18: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), on not standardised exposure data
Figure 19: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), on not standardised exposure data
Figure 20: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), without top and bottom 1%
Figure 21: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), without top and bottom 1%
Figure 22: Adjusted estimates and CIs for compound/score couples that showed signs of interaction with sex (p < 0.1), further adjusted for SG

2 BKMR

2.1 Overall

Figure 23: Overall risk (did not include BPS and BUPA)

2.2 By sex

Figure 24: Overall risk (did not include BPS and BUPA), by sex

3 Mediation

Nonparametric Bootstrap Confidence Intervals with the Percentile Method

3.1 Main and by sex

Table 3: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis
Male + Female
Female
Male
Est. (95% CI) p Est. (95% CI) p Est. (95% CI) p
Methylparaben - Trimester 3 - Internalizing
∑Cortisol 0.000 (-0.001, 0.002) 0.9 — — — —
∑Cortisone 0.000 (-0.002, 0.003) 0.8 — — — —
11-dehydrocorticosterone -0.000 (-0.003, 0.001) 0.7 — — — —
Testosterone -0.000 (-0.002, 0.001) 0.8 — — — —
Progesterone 0.001 (-0.001, 0.004) 0.6 — — — —
Methylparaben - Trimester 3 - Externalizing
∑Cortisol 0.000 (-0.002, 0.002) >0.9 — — — —
∑Cortisone 0.000 (-0.002, 0.003) 0.8 — — — —
11-dehydrocorticosterone 0.000 (-0.002, 0.002) >0.9 — — — —
Testosterone -0.000 (-0.003, 0.002) 0.8 — — — —
Progesterone 0.001 (-0.001, 0.003) 0.6 — — — —
Propylparaben - Trimester 2 - Externalizing
∑Cortisol — — -0.002 (-0.008, 0.004) 0.5 0.000 (-0.003, 0.003) >0.9
∑Cortisone — — -0.002 (-0.010, 0.004) 0.4 0.000 (-0.002, 0.003) 0.8
11-dehydrocorticosterone — — -0.000 (-0.003, 0.002) 0.8 0.001 (-0.002, 0.006) 0.6
Testosterone — — 0.000 (-0.003, 0.003) >0.9 0.000 (-0.004, 0.003) >0.9
Progesterone — — -0.002 (-0.007, 0.004) 0.6 0.002 (-0.001, 0.006) 0.4
Butylparaben - Trimester 2 - Internalizing
∑Cortisol — — -0.011 (-0.053, 0.012) 0.4 0.000 (-0.015, 0.013) >0.9
∑Cortisone — — -0.005 (-0.049, 0.014) 0.6 -0.001 (-0.023, 0.015) >0.9
11-dehydrocorticosterone — — -0.002 (-0.026, 0.016) 0.7 0.001 (-0.016, 0.015) >0.9
Testosterone — — -0.007 (-0.039, 0.015) 0.6 0.006 (-0.013, 0.032) 0.6
Progesterone — — -0.001 (-0.031, 0.018) 0.9 0.000 (-0.018, 0.022) >0.9
Bisphenol S - Trimester 3 - Internalizing
∑Cortisol — — 0.004 (-0.009, 0.027) 0.6 0.000 (-0.013, 0.012) >0.9
∑Cortisone — — 0.002 (-0.011, 0.022) 0.8 -0.000 (-0.012, 0.009) >0.9
11-dehydrocorticosterone — — 0.000 (-0.011, 0.014) >0.9 0.000 (-0.012, 0.011) >0.9
Testosterone — — 0.010 (-0.009, 0.041) 0.4 0.005 (-0.014, 0.024) 0.6
Progesterone — — 0.000 (-0.016, 0.014) >0.9 -0.001 (-0.022, 0.016) 0.8

3.2 Main and by sex (MI)

Table 4: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis
Male + Female
Female
Male
Est. (95% CI) p Est. (95% CI) p Est. (95% CI) p
Methylparaben - Trimester 3 - Internalizing
∑Cortisol 0.000 (-0.002, 0.002) 0.9 — — — —
∑Cortisone 0.000 (-0.002, 0.002) 0.8 — — — —
11-dehydrocorticosterone -0.000 (-0.002, 0.002) 0.7 — — — —
Testosterone -0.000 (-0.002, 0.002) 0.9 — — — —
Progesterone 0.001 (-0.002, 0.003) 0.7 — — — —
Methylparaben - Trimester 3 - Externalizing
∑Cortisol -0.000 (-0.002, 0.002) >0.9 — — — —
∑Cortisone 0.000 (-0.002, 0.002) 0.9 — — — —
11-dehydrocorticosterone 0.000 (-0.002, 0.002) >0.9 — — — —
Testosterone -0.000 (-0.003, 0.002) 0.8 — — — —
Progesterone 0.001 (-0.002, 0.003) 0.7 — — — —
Propylparaben - Trimester 2 - Externalizing
∑Cortisol — — -0.001 (-0.007, 0.004) 0.6 0.000 (-0.003, 0.003) >0.9
∑Cortisone — — -0.002 (-0.009, 0.004) 0.5 0.000 (-0.003, 0.003) 0.9
11-dehydrocorticosterone — — -0.000 (-0.003, 0.002) 0.8 0.001 (-0.003, 0.005) 0.7
Testosterone — — 0.000 (-0.003, 0.003) >0.9 0.000 (-0.003, 0.004) >0.9
Progesterone — — -0.002 (-0.007, 0.004) 0.6 0.002 (-0.003, 0.006) 0.4
Butylparaben - Trimester 2 - Internalizing
∑Cortisol — — -0.011 (-0.044, 0.023) 0.5 0.000 (-0.014, 0.014) >0.9
∑Cortisone — — -0.005 (-0.034, 0.024) 0.7 -0.000 (-0.018, 0.017) >0.9
11-dehydrocorticosterone — — -0.002 (-0.021, 0.017) 0.8 0.001 (-0.016, 0.018) >0.9
Testosterone — — -0.007 (-0.034, 0.020) 0.6 0.006 (-0.017, 0.029) 0.6
Progesterone — — -0.001 (-0.027, 0.024) >0.9 0.000 (-0.019, 0.020) >0.9
Bisphenol S - Trimester 3 - Internalizing
∑Cortisol — — 0.003 (-0.014, 0.021) 0.7 0.000 (-0.013, 0.013) >0.9
∑Cortisone — — 0.002 (-0.014, 0.018) 0.8 -0.000 (-0.011, 0.011) >0.9
11-dehydrocorticosterone — — 0.000 (-0.013, 0.013) >0.9 0.000 (-0.010, 0.011) >0.9
Testosterone — — 0.010 (-0.016, 0.035) 0.5 0.005 (-0.016, 0.026) 0.6
Progesterone — — 0.000 (-0.015, 0.016) >0.9 -0.001 (-0.021, 0.018) 0.9

4 Supplementary data

4.1 N for each model

Table 5: 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 Non linearity test

Table 6: Non linearity test
Internalizing
Externalizing
Anova Trend Coding Anova Trend Coding
Trimester 2
Benzophenone-3 0.044 0.036 Linear 0.10 — Linear
Bisphenol A 0.4 — Linear 0.4 — Linear
Ethylparaben 0.3 — Linear 0.3 — Linear
Methylparaben 0.002 0.037 Linear 0.002 0.013 Linear
Propylparaben 0.4 — Linear 0.5 — Linear
Triclosan 0.080 — Linear 0.10 — Linear
Trimester 3
Benzophenone-3 0.005 <0.001 Linear 0.8 — Linear
Bisphenol A 0.024 0.3 Quartiles 0.2 — Linear
Ethylparaben 0.044 0.008 Linear 0.7 — Linear
Methylparaben <0.001 0.4 Quartiles 0.3 — Linear
Propylparaben 0.015 0.5 Quartiles 0.2 — Linear
Triclosan 0.046 0.3 Quartiles 0.011 0.060 Quartiles

4.3 Model outputs

4.3.1 Interaction with cohort

Table 7: Interaction between cohort and exp p-val
compound pool externalizing_sqrt internalizing_sqrt
bp3 pool1 >0.9 0.6
bp3 pool2 0.3 0.4
bpa pool1 0.9 >0.9
bpa pool2 >0.9 0.6
bps_cat2 pool1 0.8 0.084
bps_cat2 pool2 >0.9 0.9
bupa_cat2 pool1 >0.9 0.6
bupa_cat2 pool2 0.8 0.5
etpa pool1 0.7 0.3
etpa pool2 0.3 0.6
mepa pool1 0.7 0.7
mepa pool2 0.3 0.7
prpa pool1 0.5 0.7
prpa pool2 0.2 0.7
trcs pool1 0.3 0.8
trcs pool2 0.7 0.8

4.3.2 EWAS

4.3.2.1 Main

Table 8: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.03 (-0.08, 0.13) 0.6 870.00 0.01 (-0.09, 0.11) 0.8
Bisphenol A 869.00 -0.05 (-0.16, 0.05) 0.3 870.00 -0.07 (-0.18, 0.04) 0.2
Bisphenol S 869.00 -0.12 (-0.26, 0.03) 0.11 870.00 -0.06 (-0.2, 0.08) 0.4
Butylparaben 869.00 -0.11 (-0.28, 0.06) 0.2 870.00 -0.06 (-0.23, 0.11) 0.5
Ethylparaben 869.00 -0.07 (-0.19, 0.05) 0.3 870.00 0 (-0.12, 0.11) >0.9
Methylparaben 869.00 -0.1 (-0.22, 0.02) 0.088 870.00 -0.04 (-0.16, 0.07) 0.4
Propylparaben 869.00 -0.05 (-0.11, 0.01) 0.12 870.00 -0.04 (-0.09, 0.02) 0.2
Triclosan 869.00 0.07 (0, 0.15) 0.065 870.00 0.02 (-0.06, 0.09) 0.6
Trimester 3
Benzophenone-3 931.00 0.06 (-0.03, 0.16) 0.2 932.00 -0.08 (-0.18, 0.02) 0.11
Bisphenol A 931.00 0 (-0.1, 0.09) >0.9 932.00 -0.02 (-0.12, 0.07) 0.6
Bisphenol S 931.00 0.04 (-0.1, 0.17) 0.6 932.00 0.05 (-0.08, 0.19) 0.4
Butylparaben 931.00 0.07 (-0.1, 0.24) 0.4 932.00 -0.01 (-0.18, 0.16) >0.9
Ethylparaben 931.00 0.05 (-0.07, 0.17) 0.4 932.00 -0.06 (-0.18, 0.06) 0.3
Methylparaben 931.00 0.1 (0.02, 0.18) 0.017 932.00 0.11 (0.03, 0.19) 0.010
Propylparaben 931.00 0.03 (-0.02, 0.08) 0.3 932.00 0.02 (-0.03, 0.07) 0.5
Triclosan 931.00 0.05 (-0.02, 0.12) 0.15 932.00 0 (-0.07, 0.07) >0.9
Table 9: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.02 (-0.08, 0.12) 0.7 870.00 0.01 (-0.09, 0.11) 0.8
Bisphenol A 869.00 -0.05 (-0.16, 0.05) 0.3 870.00 -0.07 (-0.18, 0.04) 0.2
Bisphenol S 869.00 -0.12 (-0.26, 0.03) 0.11 870.00 -0.06 (-0.2, 0.09) 0.4
Butylparaben 869.00 -0.11 (-0.28, 0.06) 0.2 870.00 -0.06 (-0.23, 0.11) 0.5
Ethylparaben 869.00 -0.06 (-0.18, 0.05) 0.3 870.00 0 (-0.12, 0.12) >0.9
Methylparaben 869.00 -0.09 (-0.21, 0.02) 0.11 870.00 -0.04 (-0.16, 0.08) 0.5
Propylparaben 869.00 -0.05 (-0.11, 0.01) 0.13 870.00 -0.03 (-0.09, 0.02) 0.2
Triclosan 869.00 0.07 (-0.01, 0.15) 0.067 870.00 0.02 (-0.06, 0.09) 0.6
Trimester 3
Benzophenone-3 931.00 0.06 (-0.04, 0.16) 0.2 932.00 -0.08 (-0.18, 0.02) 0.10
Bisphenol A 931.00 0 (-0.1, 0.09) >0.9 932.00 -0.02 (-0.12, 0.07) 0.6
Bisphenol S 931.00 0.04 (-0.09, 0.17) 0.6 932.00 0.06 (-0.08, 0.19) 0.4
Butylparaben 931.00 0.07 (-0.1, 0.24) 0.4 932.00 -0.01 (-0.18, 0.16) >0.9
Ethylparaben 931.00 0.06 (-0.06, 0.18) 0.4 932.00 -0.06 (-0.18, 0.06) 0.3
Methylparaben 931.00 0.1 (0.02, 0.18) 0.017 932.00 0.11 (0.03, 0.19) 0.011
Propylparaben 931.00 0.03 (-0.02, 0.08) 0.3 932.00 0.02 (-0.03, 0.07) 0.5
Triclosan 931.00 0.05 (-0.02, 0.12) 0.2 932.00 0 (-0.07, 0.07) >0.9
Table 10: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.17 (-0.51, 0.87) 0.6 870.00 0.05 (-0.35, 0.47) 0.8
Bisphenol A 869.00 -0.35 (-1.03, 0.36) 0.3 870.00 -0.28 (-0.68, 0.14) 0.2
Bisphenol S 869.00 -0.77 (-1.67, 0.17) 0.11 870.00 -0.24 (-0.77, 0.34) 0.4
Butylparaben 869.00 -0.74 (-1.81, 0.39) 0.2 870.00 -0.25 (-0.88, 0.44) 0.5
Ethylparaben 869.00 -0.45 (-1.2, 0.33) 0.3 870.00 -0.02 (-0.47, 0.46) >0.9
Methylparaben 869.00 -0.67 (-1.41, 0.1) 0.088 870.00 -0.18 (-0.62, 0.29) 0.4
Propylparaben 869.00 -0.31 (-0.7, 0.08) 0.12 870.00 -0.14 (-0.37, 0.09) 0.2
Triclosan 869.00 0.48 (-0.03, 1.01) 0.065 870.00 0.07 (-0.23, 0.39) 0.6
Trimester 3
Benzophenone-3 931.00 0.43 (-0.22, 1.1) 0.2 932.00 -0.31 (-0.68, 0.07) 0.11
Bisphenol A 931.00 -0.01 (-0.63, 0.63) >0.9 932.00 -0.1 (-0.46, 0.28) 0.6
Bisphenol S 931.00 0.25 (-0.63, 1.15) 0.6 932.00 0.22 (-0.31, 0.78) 0.4
Butylparaben 931.00 0.48 (-0.64, 1.65) 0.4 932.00 -0.04 (-0.68, 0.66) >0.9
Ethylparaben 931.00 0.36 (-0.44, 1.18) 0.4 932.00 -0.23 (-0.68, 0.24) 0.3
Methylparaben 931.00 0.67 (0.12, 1.24) 0.017 932.00 0.44 (0.1, 0.8) 0.010
Propylparaben 931.00 0.2 (-0.14, 0.53) 0.3 932.00 0.06 (-0.14, 0.27) 0.5
Triclosan 931.00 0.35 (-0.12, 0.83) 0.15 932.00 0.01 (-0.26, 0.3) >0.9
Table 11: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.15 (-0.53, 0.84) 0.7 870.00 0.04 (-0.36, 0.46) 0.8
Bisphenol A 869.00 -0.35 (-1.04, 0.36) 0.3 870.00 -0.28 (-0.68, 0.14) 0.2
Bisphenol S 869.00 -0.76 (-1.66, 0.19) 0.11 870.00 -0.23 (-0.76, 0.35) 0.4
Butylparaben 869.00 -0.72 (-1.79, 0.41) 0.2 870.00 -0.24 (-0.87, 0.45) 0.5
Ethylparaben 869.00 -0.42 (-1.18, 0.36) 0.3 870.00 0 (-0.46, 0.48) >0.9
Methylparaben 869.00 -0.62 (-1.36, 0.15) 0.11 870.00 -0.16 (-0.6, 0.31) 0.5
Propylparaben 869.00 -0.3 (-0.69, 0.09) 0.13 870.00 -0.14 (-0.36, 0.1) 0.2
Triclosan 869.00 0.48 (-0.03, 1) 0.067 870.00 0.08 (-0.23, 0.39) 0.6
Trimester 3
Benzophenone-3 931.00 0.4 (-0.25, 1.07) 0.2 932.00 -0.32 (-0.68, 0.06) 0.10
Bisphenol A 931.00 -0.01 (-0.63, 0.62) >0.9 932.00 -0.09 (-0.45, 0.29) 0.6
Bisphenol S 931.00 0.26 (-0.62, 1.17) 0.6 932.00 0.23 (-0.3, 0.79) 0.4
Butylparaben 931.00 0.46 (-0.65, 1.64) 0.4 932.00 -0.04 (-0.68, 0.67) >0.9
Ethylparaben 931.00 0.38 (-0.42, 1.2) 0.4 932.00 -0.23 (-0.68, 0.25) 0.3
Methylparaben 931.00 0.67 (0.12, 1.24) 0.017 932.00 0.44 (0.1, 0.79) 0.011
Propylparaben 931.00 0.19 (-0.14, 0.53) 0.3 932.00 0.06 (-0.14, 0.27) 0.5
Triclosan 931.00 0.34 (-0.13, 0.82) 0.2 932.00 0.02 (-0.26, 0.3) >0.9
4.3.2.1.1 Non linear
Table 12: Non linear models
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 3
Bisphenol A — — — 932.00 -0.39 (-1.07, 0.35) 0.3
Bisphenol A — — — 932.00 -0.23 (-0.93, 0.54) 0.5
Bisphenol A — — — 932.00 -0.42 (-1.1, 0.32) 0.3
Methylparaben — — — 932.00 0.17 (-0.56, 0.97) 0.7
Methylparaben — — — 932.00 0.43 (-0.32, 1.27) 0.3
Methylparaben — — — 932.00 0.76 (-0.01, 1.59) 0.053
Propylparaben — — — 932.00 -0.35 (-1.02, 0.39) 0.3
Propylparaben — — — 932.00 -0.64 (-1.27, 0.05) 0.069
Propylparaben — — — 932.00 0.21 (-0.49, 0.99) 0.6
Triclosan 931.00 -0.99 (-2.1, 0.19) 0.10 932.00 -0.83 (-1.44, -0.16) 0.017
Triclosan 931.00 0.35 (-0.87, 1.64) 0.6 932.00 -0.23 (-0.92, 0.53) 0.5
Triclosan 931.00 0.82 (-0.41, 2.13) 0.2 932.00 0.05 (-0.66, 0.83) 0.9

4.3.2.2 Sensitivity

Table 13: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort
cohort
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 BiSC 455.00 0.24 (-0.7, 1.22) 0.6 455.00 0.18 (-0.33, 0.74) 0.5
Benzophenone-3 SEPAGES 414.00 0.37 (-0.59, 1.37) 0.5 415.00 -0.02 (-0.68, 0.67) >0.9
Bisphenol A BiSC 455.00 -0.41 (-1.18, 0.38) 0.3 455.00 -0.23 (-0.63, 0.21) 0.3
Bisphenol A SEPAGES 414.00 -0.47 (-2.1, 1.27) 0.6 415.00 -0.55 (-1.63, 0.65) 0.4
Bisphenol S BiSC 455.00 -0.78 (-1.98, 0.5) 0.2 455.00 0.26 (-0.43, 1.04) 0.5
Bisphenol S SEPAGES 414.00 -0.79 (-2.14, 0.63) 0.3 415.00 -1.08 (-1.94, -0.13) 0.026
Butylparaben BiSC 455.00 -0.63 (-2.22, 1.1) 0.5 455.00 -0.39 (-1.19, 0.56) 0.4
Butylparaben SEPAGES 414.00 -0.71 (-2.1, 0.78) 0.3 415.00 -0.01 (-1, 1.08) >0.9
Ethylparaben BiSC 455.00 -0.54 (-1.71, 0.72) 0.4 455.00 0.3 (-0.38, 1.05) 0.4
Ethylparaben SEPAGES 414.00 -0.16 (-1.13, 0.84) 0.7 415.00 -0.14 (-0.8, 0.57) 0.7
Methylparaben BiSC 455.00 -0.45 (-1.63, 0.82) 0.5 455.00 -0.22 (-0.84, 0.47) 0.5
Methylparaben SEPAGES 414.00 -0.67 (-1.61, 0.31) 0.2 415.00 0.05 (-0.63, 0.76) 0.9
Propylparaben BiSC 455.00 -0.15 (-0.75, 0.46) 0.6 455.00 -0.15 (-0.47, 0.18) 0.4
Propylparaben SEPAGES 414.00 -0.42 (-0.92, 0.08) 0.10 415.00 -0.06 (-0.4, 0.3) 0.8
Triclosan BiSC 455.00 0.22 (-0.48, 0.95) 0.5 455.00 0.1 (-0.28, 0.5) 0.6
Triclosan SEPAGES 414.00 0.77 (0.02, 1.53) 0.043 415.00 0.01 (-0.49, 0.54) >0.9
Trimester 3
Benzophenone-3 BiSC 523.00 0.17 (-0.66, 1.03) 0.7 523.00 -0.18 (-0.61, 0.29) 0.4
Benzophenone-3 SEPAGES 408.00 1.07 (0.05, 2.13) 0.039 409.00 -0.54 (-1.18, 0.15) 0.12
Bisphenol A BiSC 523.00 -0.1 (-0.78, 0.6) 0.8 523.00 -0.13 (-0.49, 0.25) 0.5
Bisphenol A SEPAGES 408.00 -0.01 (-1.45, 1.54) >0.9 409.00 0.25 (-0.77, 1.37) 0.6
Bisphenol S BiSC 523.00 0.09 (-1.02, 1.27) 0.9 523.00 0.2 (-0.41, 0.88) 0.5
Bisphenol S SEPAGES 408.00 0.33 (-1.04, 1.78) 0.6 409.00 0.31 (-0.65, 1.36) 0.5
Butylparaben BiSC 523.00 0.27 (-1.35, 2.03) 0.8 523.00 0.01 (-0.83, 1) >0.9
Butylparaben SEPAGES 408.00 0.44 (-1.05, 2.03) 0.6 409.00 -0.08 (-1.09, 1.03) 0.9
Ethylparaben BiSC 523.00 -0.17 (-1.39, 1.12) 0.8 523.00 -0.27 (-0.89, 0.43) 0.4
Ethylparaben SEPAGES 408.00 0.73 (-0.29, 1.79) 0.2 409.00 -0.17 (-0.85, 0.55) 0.6
Methylparaben BiSC 523.00 1.02 (0.17, 1.89) 0.018 523.00 0.48 (0.01, 0.98) 0.046
Methylparaben SEPAGES 408.00 0.47 (-0.25, 1.22) 0.2 409.00 0.57 (0.05, 1.1) 0.032
Propylparaben BiSC 523.00 0.41 (-0.09, 0.91) 0.11 523.00 0.01 (-0.25, 0.29) >0.9
Propylparaben SEPAGES 408.00 0.03 (-0.42, 0.49) 0.9 409.00 0.21 (-0.11, 0.54) 0.2
Triclosan BiSC 523.00 0.44 (-0.18, 1.08) 0.2 523.00 0.05 (-0.28, 0.4) 0.8
Triclosan SEPAGES 408.00 0.31 (-0.41, 1.06) 0.4 409.00 0.06 (-0.44, 0.59) 0.8
Table 14: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort
cohort
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 BiSC 455.00 0.15 (-0.79, 1.14) 0.8 455.00 0.19 (-0.33, 0.75) 0.5
Benzophenone-3 SEPAGES 414.00 0.35 (-0.61, 1.36) 0.5 415.00 -0.02 (-0.67, 0.67) >0.9
Bisphenol A BiSC 455.00 -0.44 (-1.21, 0.36) 0.3 455.00 -0.22 (-0.62, 0.22) 0.3
Bisphenol A SEPAGES 414.00 -0.49 (-2.12, 1.26) 0.6 415.00 -0.55 (-1.63, 0.65) 0.4
Bisphenol S BiSC 455.00 -0.77 (-1.97, 0.51) 0.2 455.00 0.29 (-0.41, 1.06) 0.4
Bisphenol S SEPAGES 414.00 -0.79 (-2.14, 0.64) 0.3 415.00 -1.09 (-1.95, -0.15) 0.024
Butylparaben BiSC 455.00 -0.54 (-2.13, 1.21) 0.5 455.00 -0.36 (-1.16, 0.59) 0.4
Butylparaben SEPAGES 414.00 -0.73 (-2.13, 0.76) 0.3 415.00 0.01 (-0.98, 1.1) >0.9
Ethylparaben BiSC 455.00 -0.42 (-1.62, 0.85) 0.5 455.00 0.33 (-0.36, 1.09) 0.4
Ethylparaben SEPAGES 414.00 -0.16 (-1.12, 0.85) 0.8 415.00 -0.13 (-0.79, 0.57) 0.7
Methylparaben BiSC 455.00 -0.31 (-1.5, 0.97) 0.6 455.00 -0.19 (-0.81, 0.51) 0.6
Methylparaben SEPAGES 414.00 -0.66 (-1.61, 0.32) 0.2 415.00 0.06 (-0.61, 0.78) 0.9
Propylparaben BiSC 455.00 -0.12 (-0.72, 0.5) 0.7 455.00 -0.15 (-0.46, 0.19) 0.4
Propylparaben SEPAGES 414.00 -0.42 (-0.92, 0.08) 0.10 415.00 -0.06 (-0.4, 0.3) 0.8
Triclosan BiSC 455.00 0.22 (-0.48, 0.95) 0.5 455.00 0.11 (-0.27, 0.51) 0.6
Triclosan SEPAGES 414.00 0.75 (0.01, 1.52) 0.048 415.00 -0.01 (-0.51, 0.51) >0.9
Trimester 3
Benzophenone-3 BiSC 523.00 0.1 (-0.73, 0.97) 0.8 523.00 -0.16 (-0.59, 0.31) 0.5
Benzophenone-3 SEPAGES 408.00 1.05 (0.03, 2.1) 0.044 409.00 -0.54 (-1.19, 0.14) 0.12
Bisphenol A BiSC 523.00 -0.11 (-0.8, 0.59) 0.7 523.00 -0.11 (-0.48, 0.27) 0.6
Bisphenol A SEPAGES 408.00 -0.03 (-1.48, 1.51) >0.9 409.00 0.24 (-0.78, 1.36) 0.7
Bisphenol S BiSC 523.00 0.13 (-0.99, 1.31) 0.8 523.00 0.22 (-0.4, 0.9) 0.5
Bisphenol S SEPAGES 408.00 0.31 (-1.06, 1.76) 0.7 409.00 0.28 (-0.67, 1.32) 0.6
Butylparaben BiSC 523.00 0.29 (-1.34, 2.05) 0.7 523.00 0.02 (-0.83, 1.01) >0.9
Butylparaben SEPAGES 408.00 0.43 (-1.06, 2.02) 0.6 409.00 -0.11 (-1.11, 0.99) 0.8
Ethylparaben BiSC 523.00 -0.16 (-1.38, 1.14) 0.8 523.00 -0.24 (-0.87, 0.46) 0.5
Ethylparaben SEPAGES 408.00 0.74 (-0.29, 1.8) 0.2 409.00 -0.13 (-0.81, 0.6) 0.7
Methylparaben BiSC 523.00 1.01 (0.16, 1.89) 0.019 523.00 0.47 (0, 0.97) 0.050
Methylparaben SEPAGES 408.00 0.47 (-0.26, 1.21) 0.2 409.00 0.57 (0.05, 1.11) 0.031
Propylparaben BiSC 523.00 0.41 (-0.08, 0.92) 0.10 523.00 0 (-0.26, 0.28) >0.9
Propylparaben SEPAGES 408.00 0.03 (-0.42, 0.49) 0.9 409.00 0.21 (-0.11, 0.53) 0.2
Triclosan BiSC 523.00 0.43 (-0.19, 1.07) 0.2 523.00 0.05 (-0.28, 0.4) 0.8
Triclosan SEPAGES 408.00 0.3 (-0.42, 1.05) 0.4 409.00 0.03 (-0.47, 0.56) 0.9
Table 15: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Limited to Complete Cases
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 567.00 0.11 (-0.73, 0.98) 0.8 567.00 0.32 (-0.18, 0.85) 0.2
Bisphenol A 567.00 -0.31 (-1.19, 0.61) 0.5 567.00 -0.29 (-0.79, 0.25) 0.3
Bisphenol S 567.00 -1.01 (-2.12, 0.16) 0.089 567.00 -0.22 (-0.87, 0.5) 0.5
Butylparaben 567.00 -0.6 (-1.92, 0.81) 0.4 567.00 0.03 (-0.76, 0.9) >0.9
Ethylparaben 567.00 -0.15 (-1.05, 0.8) 0.8 567.00 0.11 (-0.42, 0.69) 0.7
Methylparaben 567.00 -0.28 (-1.17, 0.65) 0.6 567.00 -0.08 (-0.59, 0.48) 0.8
Propylparaben 567.00 -0.1 (-0.55, 0.37) 0.7 567.00 -0.12 (-0.38, 0.15) 0.4
Triclosan 567.00 0.34 (-0.27, 0.96) 0.3 567.00 0.06 (-0.29, 0.43) 0.7
Trimester 3
Benzophenone-3 581.00 0.52 (-0.32, 1.39) 0.2 581.00 0.09 (-0.38, 0.58) 0.7
Bisphenol A 581.00 -0.25 (-1.04, 0.57) 0.5 581.00 0.14 (-0.32, 0.63) 0.6
Bisphenol S 581.00 0.46 (-0.65, 1.62) 0.4 581.00 0.21 (-0.42, 0.88) 0.5
Butylparaben 581.00 1.79 (0.32, 3.35) 0.016 581.00 0.64 (-0.18, 1.55) 0.13
Ethylparaben 581.00 0.7 (-0.33, 1.77) 0.2 581.00 0.09 (-0.47, 0.7) 0.8
Methylparaben 581.00 0.76 (0.09, 1.45) 0.025 581.00 0.55 (0.16, 0.96) 0.005
Propylparaben 581.00 0.18 (-0.24, 0.6) 0.4 581.00 0.13 (-0.11, 0.37) 0.3
Triclosan 581.00 0.62 (0.01, 1.24) 0.046 581.00 0.04 (-0.3, 0.39) 0.8
Table 16: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Using Non-Standardised Exposures Data
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.15 (-0.52, 0.83) 0.7 870.00 0.08 (-0.32, 0.49) 0.7
Bisphenol A 869.00 -0.27 (-0.93, 0.42) 0.4 870.00 -0.19 (-0.58, 0.22) 0.4
Bisphenol S 869.00 -0.77 (-1.67, 0.17) 0.11 870.00 -0.24 (-0.77, 0.34) 0.4
Butylparaben 869.00 -0.74 (-1.81, 0.39) 0.2 870.00 -0.25 (-0.88, 0.44) 0.5
Ethylparaben 869.00 -0.52 (-1.25, 0.23) 0.2 870.00 -0.04 (-0.48, 0.43) 0.9
Methylparaben 869.00 -0.78 (-1.5, -0.04) 0.039 870.00 -0.17 (-0.6, 0.29) 0.5
Propylparaben 869.00 -0.32 (-0.71, 0.08) 0.11 870.00 -0.11 (-0.34, 0.13) 0.4
Triclosan 869.00 0.45 (-0.06, 0.97) 0.082 870.00 0.06 (-0.24, 0.37) 0.7
Trimester 3
Benzophenone-3 931.00 0.42 (-0.21, 1.08) 0.2 932.00 -0.29 (-0.65, 0.08) 0.13
Bisphenol A 931.00 -0.02 (-0.62, 0.6) >0.9 932.00 -0.05 (-0.41, 0.32) 0.8
Bisphenol S 931.00 0.25 (-0.63, 1.15) 0.6 932.00 0.22 (-0.31, 0.78) 0.4
Butylparaben 931.00 0.48 (-0.64, 1.65) 0.4 932.00 -0.04 (-0.68, 0.66) >0.9
Ethylparaben 931.00 0.29 (-0.47, 1.09) 0.5 932.00 -0.21 (-0.65, 0.26) 0.4
Methylparaben 931.00 0.64 (0.1, 1.2) 0.020 932.00 0.43 (0.09, 0.77) 0.011
Propylparaben 931.00 0.24 (-0.09, 0.58) 0.2 932.00 0.09 (-0.11, 0.29) 0.4
Triclosan 931.00 0.34 (-0.12, 0.82) 0.15 932.00 -0.01 (-0.29, 0.27) >0.9
Table 17: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Using Non-Standardised Exposures Data
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.12 (-0.54, 0.81) 0.7 870.00 0.07 (-0.33, 0.48) 0.7
Bisphenol A 869.00 -0.27 (-0.94, 0.41) 0.4 870.00 -0.19 (-0.58, 0.22) 0.4
Bisphenol S 869.00 -0.76 (-1.66, 0.19) 0.11 870.00 -0.23 (-0.76, 0.35) 0.4
Butylparaben 869.00 -0.72 (-1.79, 0.41) 0.2 870.00 -0.24 (-0.87, 0.45) 0.5
Ethylparaben 869.00 -0.5 (-1.23, 0.26) 0.2 870.00 -0.03 (-0.47, 0.44) >0.9
Methylparaben 869.00 -0.74 (-1.46, 0) 0.051 870.00 -0.15 (-0.59, 0.3) 0.5
Propylparaben 869.00 -0.31 (-0.7, 0.09) 0.13 870.00 -0.1 (-0.33, 0.13) 0.4
Triclosan 869.00 0.45 (-0.06, 0.97) 0.086 870.00 0.06 (-0.23, 0.37) 0.7
Trimester 3
Benzophenone-3 931.00 0.39 (-0.25, 1.05) 0.2 932.00 -0.3 (-0.66, 0.08) 0.12
Bisphenol A 931.00 -0.02 (-0.62, 0.6) >0.9 932.00 -0.04 (-0.4, 0.33) 0.8
Bisphenol S 931.00 0.26 (-0.62, 1.17) 0.6 932.00 0.23 (-0.3, 0.79) 0.4
Butylparaben 931.00 0.46 (-0.65, 1.64) 0.4 932.00 -0.04 (-0.68, 0.67) >0.9
Ethylparaben 931.00 0.31 (-0.46, 1.1) 0.4 932.00 -0.21 (-0.65, 0.26) 0.4
Methylparaben 931.00 0.65 (0.1, 1.21) 0.020 932.00 0.42 (0.09, 0.77) 0.012
Propylparaben 931.00 0.24 (-0.09, 0.58) 0.2 932.00 0.09 (-0.11, 0.29) 0.4
Triclosan 931.00 0.33 (-0.14, 0.81) 0.2 932.00 -0.01 (-0.29, 0.27) >0.9
Table 18: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.18 (-0.51, 0.89) 0.6 870.00 0.07 (-0.33, 0.5) 0.7
Bisphenol A 869.00 -0.35 (-1.05, 0.36) 0.3 870.00 -0.28 (-0.68, 0.14) 0.2
Bisphenol S 869.00 -0.78 (-1.68, 0.16) 0.10 870.00 -0.23 (-0.76, 0.34) 0.4
Butylparaben 869.00 -0.72 (-1.78, 0.4) 0.2 870.00 -0.25 (-0.87, 0.43) 0.5
Ethylparaben 869.00 -0.41 (-1.19, 0.4) 0.3 870.00 0.02 (-0.45, 0.51) >0.9
Methylparaben 869.00 -0.65 (-1.41, 0.14) 0.11 870.00 -0.2 (-0.64, 0.28) 0.4
Propylparaben 869.00 -0.32 (-0.71, 0.07) 0.11 870.00 -0.15 (-0.38, 0.08) 0.2
Triclosan 869.00 0.48 (-0.04, 1) 0.069 870.00 0.06 (-0.24, 0.38) 0.7
Trimester 3
Benzophenone-3 931.00 0.42 (-0.25, 1.1) 0.2 932.00 -0.32 (-0.69, 0.07) 0.10
Bisphenol A 931.00 -0.01 (-0.63, 0.64) >0.9 932.00 -0.09 (-0.45, 0.29) 0.6
Bisphenol S 931.00 0.21 (-0.66, 1.11) 0.6 932.00 0.22 (-0.3, 0.78) 0.4
Butylparaben 931.00 0.46 (-0.65, 1.63) 0.4 932.00 -0.05 (-0.69, 0.64) 0.9
Ethylparaben 931.00 0.38 (-0.44, 1.22) 0.4 932.00 -0.19 (-0.66, 0.3) 0.4
Methylparaben 931.00 0.64 (0.09, 1.21) 0.023 932.00 0.44 (0.1, 0.79) 0.010
Propylparaben 931.00 0.19 (-0.15, 0.53) 0.3 932.00 0.06 (-0.14, 0.27) 0.6
Triclosan 931.00 0.34 (-0.13, 0.83) 0.2 932.00 0.01 (-0.27, 0.29) >0.9
Table 19: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.16 (-0.53, 0.87) 0.7 870.00 0.06 (-0.34, 0.49) 0.8
Bisphenol A 869.00 -0.36 (-1.05, 0.36) 0.3 870.00 -0.28 (-0.68, 0.14) 0.2
Bisphenol S 869.00 -0.77 (-1.67, 0.17) 0.11 870.00 -0.22 (-0.75, 0.35) 0.4
Butylparaben 869.00 -0.7 (-1.76, 0.43) 0.2 870.00 -0.24 (-0.86, 0.44) 0.5
Ethylparaben 869.00 -0.39 (-1.17, 0.42) 0.3 870.00 0.03 (-0.44, 0.52) >0.9
Methylparaben 869.00 -0.6 (-1.36, 0.19) 0.13 870.00 -0.18 (-0.63, 0.3) 0.5
Propylparaben 869.00 -0.31 (-0.7, 0.08) 0.12 870.00 -0.15 (-0.38, 0.09) 0.2
Triclosan 869.00 0.47 (-0.04, 1) 0.071 870.00 0.07 (-0.23, 0.38) 0.7
Trimester 3
Benzophenone-3 931.00 0.39 (-0.28, 1.07) 0.3 932.00 -0.32 (-0.69, 0.06) 0.10
Bisphenol A 931.00 -0.01 (-0.63, 0.64) >0.9 932.00 -0.08 (-0.45, 0.3) 0.7
Bisphenol S 931.00 0.22 (-0.65, 1.12) 0.6 932.00 0.23 (-0.29, 0.78) 0.4
Butylparaben 931.00 0.45 (-0.66, 1.62) 0.4 932.00 -0.05 (-0.68, 0.65) 0.9
Ethylparaben 931.00 0.4 (-0.42, 1.25) 0.3 932.00 -0.19 (-0.65, 0.31) 0.5
Methylparaben 931.00 0.64 (0.09, 1.22) 0.023 932.00 0.44 (0.1, 0.79) 0.011
Propylparaben 931.00 0.19 (-0.15, 0.53) 0.3 932.00 0.06 (-0.14, 0.26) 0.6
Triclosan 931.00 0.33 (-0.14, 0.81) 0.2 932.00 0.01 (-0.27, 0.29) >0.9
Table 20: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, further adjusted for SG
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 869.00 0.18 (-0.5, 0.89) 0.6 870.00 0.06 (-0.34, 0.49) 0.8
Bisphenol A 869.00 -0.32 (-1.02, 0.4) 0.4 870.00 -0.26 (-0.67, 0.16) 0.2
Bisphenol S 869.00 -0.8 (-1.71, 0.15) 0.10 870.00 -0.25 (-0.79, 0.33) 0.4
Butylparaben 869.00 -0.7 (-1.77, 0.44) 0.2 870.00 -0.22 (-0.86, 0.47) 0.5
Ethylparaben 869.00 -0.39 (-1.16, 0.4) 0.3 870.00 0.02 (-0.44, 0.51) >0.9
Methylparaben 869.00 -0.6 (-1.35, 0.19) 0.13 870.00 -0.14 (-0.59, 0.34) 0.6
Propylparaben 869.00 -0.3 (-0.68, 0.1) 0.14 870.00 -0.13 (-0.36, 0.1) 0.3
Triclosan 869.00 0.5 (-0.02, 1.03) 0.058 870.00 0.09 (-0.22, 0.4) 0.6
Trimester 3
Benzophenone-3 930.00 0.37 (-0.29, 1.04) 0.3 931.00 -0.32 (-0.69, 0.06) 0.10
Bisphenol A 930.00 -0.06 (-0.69, 0.59) 0.9 931.00 -0.09 (-0.46, 0.3) 0.7
Bisphenol S 930.00 0.35 (-0.54, 1.28) 0.4 931.00 0.24 (-0.3, 0.81) 0.4
Butylparaben 930.00 0.42 (-0.7, 1.61) 0.5 931.00 -0.03 (-0.68, 0.68) >0.9
Ethylparaben 930.00 0.36 (-0.45, 1.21) 0.4 931.00 -0.22 (-0.68, 0.28) 0.4
Methylparaben 930.00 0.67 (0.11, 1.26) 0.020 931.00 0.47 (0.13, 0.84) 0.007
Propylparaben 930.00 0.18 (-0.16, 0.52) 0.3 931.00 0.07 (-0.14, 0.27) 0.5
Triclosan 930.00 0.29 (-0.18, 0.78) 0.2 931.00 0.01 (-0.28, 0.3) >0.9
Table 21: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Limited to participants with a sample at Pool 1 AND Pool 2
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 794.00 0.37 (-0.31, 1.08) 0.3 795.00 0.08 (-0.32, 0.51) 0.7
Bisphenol A 794.00 -0.54 (-1.24, 0.19) 0.14 795.00 -0.39 (-0.8, 0.05) 0.079
Bisphenol S 794.00 -0.88 (-1.79, 0.08) 0.072 795.00 -0.29 (-0.84, 0.3) 0.3
Butylparaben 794.00 -0.58 (-1.67, 0.57) 0.3 795.00 -0.23 (-0.88, 0.48) 0.5
Ethylparaben 794.00 -0.5 (-1.25, 0.28) 0.2 795.00 -0.05 (-0.5, 0.44) 0.8
Methylparaben 794.00 -0.54 (-1.29, 0.24) 0.2 795.00 -0.12 (-0.57, 0.36) 0.6
Propylparaben 794.00 -0.21 (-0.6, 0.19) 0.3 795.00 -0.11 (-0.34, 0.13) 0.4
Triclosan 794.00 0.72 (0.19, 1.25) 0.007 795.00 0.14 (-0.17, 0.46) 0.4
Trimester 3
Benzophenone-3 794.00 0.42 (-0.27, 1.13) 0.2 795.00 -0.26 (-0.65, 0.16) 0.2
Bisphenol A 794.00 0.02 (-0.67, 0.74) >0.9 795.00 0.12 (-0.3, 0.56) 0.6
Bisphenol S 794.00 0.13 (-0.81, 1.11) 0.8 795.00 0.19 (-0.38, 0.81) 0.5
Butylparaben 794.00 0.29 (-0.89, 1.53) 0.6 795.00 -0.14 (-0.82, 0.6) 0.7
Ethylparaben 794.00 0.4 (-0.43, 1.27) 0.3 795.00 -0.22 (-0.69, 0.29) 0.4
Methylparaben 794.00 0.77 (0.18, 1.37) 0.010 795.00 0.51 (0.15, 0.89) 0.005
Propylparaben 794.00 0.25 (-0.1, 0.61) 0.2 795.00 0.11 (-0.1, 0.33) 0.3
Triclosan 794.00 0.4 (-0.11, 0.92) 0.12 795.00 0.13 (-0.18, 0.44) 0.4
Table 22: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Limited to participants with a sample at Pool 1 AND Pool 2
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Benzophenone-3 794.00 0.34 (-0.34, 1.05) 0.3 795.00 0.07 (-0.34, 0.5) 0.7
Bisphenol A 794.00 -0.54 (-1.25, 0.19) 0.14 795.00 -0.39 (-0.8, 0.05) 0.078
Bisphenol S 794.00 -0.87 (-1.79, 0.08) 0.073 795.00 -0.28 (-0.83, 0.31) 0.3
Butylparaben 794.00 -0.57 (-1.66, 0.59) 0.3 795.00 -0.23 (-0.87, 0.48) 0.5
Ethylparaben 794.00 -0.48 (-1.23, 0.3) 0.2 795.00 -0.04 (-0.5, 0.45) 0.9
Methylparaben 794.00 -0.5 (-1.25, 0.28) 0.2 795.00 -0.11 (-0.56, 0.37) 0.6
Propylparaben 794.00 -0.2 (-0.59, 0.19) 0.3 795.00 -0.11 (-0.34, 0.13) 0.4
Triclosan 794.00 0.71 (0.19, 1.24) 0.008 795.00 0.14 (-0.17, 0.47) 0.4
Trimester 3
Benzophenone-3 794.00 0.39 (-0.3, 1.1) 0.3 795.00 -0.27 (-0.66, 0.15) 0.2
Bisphenol A 794.00 0.02 (-0.68, 0.73) >0.9 795.00 0.13 (-0.29, 0.57) 0.6
Bisphenol S 794.00 0.14 (-0.8, 1.12) 0.8 795.00 0.2 (-0.38, 0.81) 0.5
Butylparaben 794.00 0.28 (-0.9, 1.52) 0.6 795.00 -0.14 (-0.82, 0.6) 0.7
Ethylparaben 794.00 0.43 (-0.4, 1.3) 0.3 795.00 -0.21 (-0.68, 0.3) 0.4
Methylparaben 794.00 0.77 (0.18, 1.37) 0.010 795.00 0.51 (0.15, 0.89) 0.005
Propylparaben 794.00 0.25 (-0.11, 0.6) 0.2 795.00 0.11 (-0.11, 0.33) 0.3
Triclosan 794.00 0.39 (-0.12, 0.91) 0.13 795.00 0.13 (-0.18, 0.44) 0.4

4.3.3 Sex interaction

4.3.3.1 Main

Table 23: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869 0.04 (-0.11, 0.18) 0.6 — —
Bisphenol A Female 869 -0.14 (-0.29, 0) 0.056 — —
Butylparaben Male — — 870 0.11 (-0.12, 0.34) 0.3
Butylparaben Female — — 870 -0.28 (-0.53, -0.03) 0.031
Propylparaben Male 869 0 (-0.08, 0.08) >0.9 — —
Propylparaben Female 869 -0.11 (-0.19, -0.02) 0.016 — —
Trimester 3
Bisphenol S Male 931 0.17 (-0.01, 0.35) 0.068 932 0.22 (0.04, 0.4) 0.018
Bisphenol S Female 931 -0.1 (-0.29, 0.08) 0.3 932 -0.12 (-0.3, 0.07) 0.2
Table 24: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869.00 0.03 (-0.11, 0.18) 0.7 — — —
Bisphenol A Female 869.00 -0.14 (-0.29, 0.01) 0.059 — — —
Butylparaben Male — — — 870.00 0.11 (-0.12, 0.34) 0.3
Butylparaben Female — — — 870.00 -0.28 (-0.53, -0.02) 0.033
Propylparaben Male 869.00 0 (-0.08, 0.09) >0.9 — — —
Propylparaben Female 869.00 -0.1 (-0.19, -0.02) 0.019 — — —
Trimester 3
Bisphenol S Male 931.00 0.17 (-0.01, 0.35) 0.070 932.00 0.22 (0.04, 0.4) 0.019
Bisphenol S Female 931.00 -0.1 (-0.28, 0.09) 0.3 932.00 -0.11 (-0.3, 0.07) 0.2
Table 25: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869 0.24 (-0.71, 1.24) 0.6 — —
Bisphenol A Female 869 -0.93 (-1.84, 0.02) 0.056 — —
Butylparaben Male — — 870 0.45 (-0.46, 1.46) 0.3
Butylparaben Female — — 870 -1.04 (-1.85, -0.1) 0.031
Propylparaben Male 869 0.02 (-0.51, 0.57) >0.9 — —
Propylparaben Female 869 -0.69 (-1.24, -0.13) 0.016 — —
Trimester 3
Bisphenol S Male 931 1.15 (-0.08, 2.44) 0.068 932 0.92 (0.15, 1.76) 0.018
Bisphenol S Female 931 -0.67 (-1.83, 0.56) 0.3 932 -0.46 (-1.12, 0.27) 0.2
Table 26: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869.00 0.22 (-0.73, 1.22) 0.7 — — —
Bisphenol A Female 869.00 -0.92 (-1.83, 0.03) 0.059 — — —
Butylparaben Male — — — 870.00 0.46 (-0.45, 1.47) 0.3
Butylparaben Female — — — 870.00 -1.03 (-1.84, -0.09) 0.033
Propylparaben Male 869.00 0.03 (-0.5, 0.57) >0.9 — — —
Propylparaben Female 869.00 -0.68 (-1.22, -0.11) 0.019 — — —
Trimester 3
Bisphenol S Male 931.00 1.14 (-0.09, 2.44) 0.070 932.00 0.92 (0.15, 1.75) 0.019
Bisphenol S Female 931.00 -0.64 (-1.8, 0.6) 0.3 932.00 -0.45 (-1.11, 0.29) 0.2
4.3.3.1.1 Interaction p values
Table 27: P-value for the interaction term between exposure and sex (Wald p)
externalizing internalizing
Pool 1
BP3 0.63234995 0.80823852
BPA 0.08539536 0.84749853
ETPA 0.83559542 0.24358036
MEPA 0.53975214 0.22777668
PRPA 0.07373820 0.22669166
TRCS 0.42837623 0.65744037
BPS 0.58419661 0.60773029
BUPA 0.83135790 0.02583934
Pool 2
BP3 0.61786260 0.90933922
BPA 0.40127758 0.50262954
ETPA 0.13790031 0.25397850
MEPA 0.25264182 0.15785715
PRPA 0.77563755 0.22897202
TRCS 0.63112594 0.79442487
BPS 0.04109498 0.01042553
BUPA 0.42884176 0.36127697

4.3.3.2 Sensitivity

Table 28: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 567 0.52 (-0.75, 1.87) 0.4 — —
Bisphenol A Female 567 -1.05 (-2.18, 0.16) 0.088 — —
Butylparaben Male — — 567 0.62 (-0.49, 1.88) 0.3
Butylparaben Female — — 567 -0.63 (-1.66, 0.57) 0.3
Propylparaben Male 567 0.44 (-0.19, 1.1) 0.2 — —
Propylparaben Female 567 -0.69 (-1.32, -0.03) 0.040 — —
Trimester 3
Bisphenol S Male 581 0.71 (-0.81, 2.34) 0.4 581 0.45 (-0.42, 1.41) 0.3
Bisphenol S Female 581 0.2 (-1.32, 1.82) 0.8 581 -0.04 (-0.87, 0.89) >0.9
Table 29: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using no standardised exposure data
sex
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869 0.29 (-0.66, 1.27) 0.6 — —
Bisphenol A Female 869 -0.81 (-1.71, 0.13) 0.089 — —
Butylparaben Male — — 870 0.45 (-0.46, 1.46) 0.3
Butylparaben Female — — 870 -1.04 (-1.85, -0.1) 0.031
Propylparaben Male 869 0.04 (-0.5, 0.59) 0.9 — —
Propylparaben Female 869 -0.7 (-1.25, -0.14) 0.015 — —
Trimester 3
Bisphenol S Male 931 1.15 (-0.08, 2.44) 0.068 932 0.92 (0.15, 1.76) 0.018
Bisphenol S Female 931 -0.67 (-1.83, 0.56) 0.3 932 -0.46 (-1.12, 0.27) 0.2
Table 30: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, using no standardised exposure data
sex
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869.00 0.27 (-0.68, 1.25) 0.6 — — —
Bisphenol A Female 869.00 -0.81 (-1.71, 0.13) 0.091 — — —
Butylparaben Male — — — 870.00 0.46 (-0.45, 1.47) 0.3
Butylparaben Female — — — 870.00 -1.03 (-1.84, -0.09) 0.033
Propylparaben Male 869.00 0.04 (-0.5, 0.6) 0.9 — — —
Propylparaben Female 869.00 -0.69 (-1.24, -0.12) 0.017 — — —
Trimester 3
Bisphenol S Male 931.00 1.14 (-0.09, 2.44) 0.070 932.00 0.92 (0.15, 1.75) 0.019
Bisphenol S Female 931.00 -0.64 (-1.8, 0.6) 0.3 932.00 -0.45 (-1.11, 0.29) 0.2
Table 31: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, excludeing top and bottom 1% exposure and outcome values
compound pool sex score n est_ci p
bpa pool1 Male externalizing_sqrt 869 0.03 (-0.11, 0.18) 0.6
bpa pool1 Female externalizing_sqrt 869 -0.15 (-0.29, 0.00) 0.055
bps_cat2 pool2 Male internalizing_sqrt 932 0.22 (0.04, 0.40) 0.015
bps_cat2 pool2 Male externalizing_sqrt 931 0.16 (-0.02, 0.34) 0.088
bps_cat2 pool2 Female internalizing_sqrt 932 -0.12 (-0.30, 0.06) 0.2
bps_cat2 pool2 Female externalizing_sqrt 931 -0.10 (-0.29, 0.08) 0.3
bupa_cat2 pool1 Male internalizing_sqrt 870 0.11 (-0.11, 0.34) 0.3
bupa_cat2 pool1 Female internalizing_sqrt 870 -0.29 (-0.54, -0.04) 0.025
prpa pool1 Male externalizing_sqrt 869 0.00 (-0.08, 0.08) >0.9
prpa pool1 Female externalizing_sqrt 869 -0.11 (-0.20, -0.02) 0.017
Table 32: 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
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869.00 0.21 (-0.75, 1.22) 0.7 — — —
Bisphenol A Female 869.00 -0.93 (-1.85, 0.03) 0.057 — — —
Butylparaben Male — — — 870.00 0.48 (-0.42, 1.48) 0.3
Butylparaben Female — — — 870.00 -1.05 (-1.85, -0.13) 0.027
Propylparaben Male 869.00 0.01 (-0.52, 0.57) >0.9 — — —
Propylparaben Female 869.00 -0.69 (-1.24, -0.11) 0.019 — — —
Trimester 3
Bisphenol S Male 931.00 1.06 (-0.16, 2.35) 0.090 932.00 0.92 (0.16, 1.75) 0.016
Bisphenol S Female 931.00 -0.64 (-1.8, 0.59) 0.3 932.00 -0.45 (-1.11, 0.28) 0.2
Table 33: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, further adjusted for SG
sex
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 869.00 0.26 (-0.71, 1.26) 0.6 — — —
Bisphenol A Female 869.00 -0.9 (-1.82, 0.06) 0.067 — — —
Butylparaben Male — — — 870.00 0.48 (-0.44, 1.49) 0.3
Butylparaben Female — — — 870.00 -1.01 (-1.83, -0.07) 0.036
Propylparaben Male 869.00 0.04 (-0.5, 0.58) 0.9 — — —
Propylparaben Female 869.00 -0.67 (-1.22, -0.11) 0.020 — — —
Trimester 3
Bisphenol S Male 930.00 1.27 (0.02, 2.59) 0.047 931.00 0.95 (0.16, 1.79) 0.017
Bisphenol S Female 930.00 -0.57 (-1.75, 0.67) 0.4 931.00 -0.44 (-1.11, 0.3) 0.2
Table 34: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, limited to participants with a sample at pool 1 and pool 2
sex
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 794 0.05 (-0.94, 1.09) >0.9 — —
Bisphenol A Female 794 -1.09 (-2.01, -0.12) 0.027 — —
Butylparaben Male — — 795 0.45 (-0.48, 1.49) 0.4
Butylparaben Female — — 795 -1.02 (-1.85, -0.04) 0.042
Propylparaben Male 794 0.06 (-0.48, 0.6) 0.8 — —
Propylparaben Female 794 -0.5 (-1.06, 0.06) 0.082 — —
Trimester 3
Bisphenol S Male 794 0.48 (-0.81, 1.85) 0.5 795 0.73 (-0.09, 1.63) 0.081
Bisphenol S Female 794 -0.24 (-1.53, 1.13) 0.7 795 -0.35 (-1.08, 0.47) 0.4
Table 35: Adjusted estimates and CIs from EWAS for internalising and externalising CBCL VS pregnancy exposure, limited to participants with a sample at pool 1 and pool 2
sex
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male 794.00 0.03 (-0.97, 1.07) >0.9 — — —
Bisphenol A Female 794.00 -1.08 (-2.01, -0.11) 0.030 — — —
Butylparaben Male — — — 795.00 0.45 (-0.48, 1.49) 0.4
Butylparaben Female — — — 795.00 -1.01 (-1.84, -0.03) 0.044
Propylparaben Male 794.00 0.06 (-0.48, 0.61) 0.8 — — —
Propylparaben Female 794.00 -0.49 (-1.05, 0.08) 0.090 — — —
Trimester 3
Bisphenol S Male 794.00 0.47 (-0.82, 1.84) 0.5 795.00 0.73 (-0.09, 1.62) 0.083
Bisphenol S Female 794.00 -0.22 (-1.51, 1.16) 0.8 795.00 -0.34 (-1.08, 0.48) 0.4
Table 36: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort and by child sex
sex cohort
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male BiSC 455 0.37 (-0.72, 1.51) 0.5 — —
Bisphenol A Male SEPAGES 414 -1.37 (-3.45, 0.94) 0.2 — —
Bisphenol A Female BiSC 455 -1.17 (-2.18, -0.11) 0.032 — —
Bisphenol A Female SEPAGES 414 0.61 (-1.83, 3.31) 0.6 — —
Butylparaben Male BiSC — — 455 -0.24 (-1.29, 1.06) 0.7
Butylparaben Male SEPAGES — — 415 1.47 (-0.02, 3.12) 0.054
Butylparaben Female BiSC — — 455 -0.58 (-1.69, 0.88) 0.4
Butylparaben Female SEPAGES — — 415 -1.54 (-2.77, -0.12) 0.034
Propylparaben Male BiSC 455 0.13 (-0.74, 1.03) 0.8 — —
Propylparaben Male SEPAGES 414 0.06 (-0.6, 0.74) 0.9 — —
Propylparaben Female BiSC 455 -0.41 (-1.21, 0.43) 0.3 — —
Propylparaben Female SEPAGES 414 -1.06 (-1.78, -0.31) 0.006 — —
Trimester 3
Bisphenol S Male BiSC 523 1.82 (0.1, 3.67) 0.037 523 1.11 (0.12, 2.22) 0.026
Bisphenol S Male SEPAGES 408 0.25 (-1.53, 2.18) 0.8 409 0.76 (-0.54, 2.19) 0.3
Bisphenol S Female BiSC 523 -1.35 (-2.73, 0.16) 0.078 523 -0.52 (-1.23, 0.32) 0.2
Bisphenol S Female SEPAGES 408 0.43 (-1.66, 2.71) 0.7 409 -0.27 (-1.65, 1.29) 0.7
Table 37: Adjusted Estimates and Confidence Intervals from EWAS for Internalising and Externalising CBCL Scores vs. Pregnancy Exposure, Stratified by Cohort and by child sex
sex cohort
Externalizing
Internalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Trimester 2
Bisphenol A Male BiSC 455.00 0.29 (-0.8, 1.45) 0.6 — — —
Bisphenol A Male SEPAGES 414.00 -1.39 (-3.48, 0.92) 0.2 — — —
Bisphenol A Female BiSC 455.00 -1.16 (-2.17, -0.09) 0.035 — — —
Bisphenol A Female SEPAGES 414.00 0.6 (-1.85, 3.32) 0.6 — — —
Butylparaben Male BiSC — — — 455.00 -0.2 (-1.26, 1.11) 0.7
Butylparaben Male SEPAGES — — — 415.00 1.4 (-0.08, 3.05) 0.065
Butylparaben Female BiSC — — — 455.00 -0.57 (-1.69, 0.9) 0.4
Butylparaben Female SEPAGES — — — 415.00 -1.46 (-2.7, -0.02) 0.047
Propylparaben Male BiSC 455.00 0.15 (-0.72, 1.06) 0.7 — — —
Propylparaben Male SEPAGES 414.00 0.05 (-0.61, 0.73) 0.9 — — —
Propylparaben Female BiSC 455.00 -0.36 (-1.16, 0.49) 0.4 — — —
Propylparaben Female SEPAGES 414.00 -1.05 (-1.78, -0.29) 0.007 — — —
Trimester 3
Bisphenol S Male BiSC 523.00 1.84 (0.12, 3.7) 0.036 523.00 1.09 (0.1, 2.21) 0.029
Bisphenol S Male SEPAGES 408.00 0.22 (-1.56, 2.15) 0.8 409.00 0.74 (-0.55, 2.17) 0.3
Bisphenol S Female BiSC 523.00 -1.3 (-2.7, 0.22) 0.091 523.00 -0.47 (-1.2, 0.37) 0.3
Bisphenol S Female SEPAGES 408.00 0.43 (-1.67, 2.71) 0.7 409.00 -0.32 (-1.69, 1.24) 0.7

4.3.4 Mediation

4.3.4.1 By cohort

Table 38: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis, by cohort
Internalizing
Externalizing
N Estimate (95% CI) p N Estimate (95% CI) p
Methylparaben, Trimester 3, BiSC
∑Cortisol 463 0.001 (-0.002, 0.007) 0.6 463 0.001 (-0.002, 0.007) 0.6
∑Cortisone 465 0.002 (-0.002, 0.007) 0.4 465 0.001 (-0.003, 0.005) 0.7
11-dehydrocorticosterone 465 0.000 (-0.005, 0.003) >0.9 465 0.000 (-0.004, 0.004) >0.9
Testosterone 464 0.001 (-0.002, 0.006) 0.5 464 0.002 (-0.003, 0.007) 0.4
Progesterone 465 -0.001 (-0.008, 0.003) 0.6 465 -0.001 (-0.007, 0.003) 0.5
Methylparaben, Trimester 3, SEPAGES
∑Cortisol 344 0.002 (-0.003, 0.007) 0.5 343 0.001 (-0.003, 0.006) 0.7
∑Cortisone 344 0.003 (-0.002, 0.010) 0.3 343 0.002 (-0.004, 0.009) 0.5
11-dehydrocorticosterone 344 -0.001 (-0.008, 0.002) 0.5 343 0.000 (-0.005, 0.006) >0.9
Testosterone 344 0.001 (-0.004, 0.005) 0.9 343 0.001 (-0.004, 0.005) 0.8
Progesterone 344 0.002 (-0.006, 0.012) 0.7 343 0.001 (-0.007, 0.010) 0.9

4.3.4.2 By cohort (MI)

4.3.4.3 By sex and by cohort

Table 39: Adjusted estimates and CIs for Direct and Indirect effect of mediation analysis, by cohort and by sex
Female
Male
N Estimate (95% CI) p N Estimate (95% CI) p
Bisphenol S, Trimester 3, Internalizing, BiSC
∑Cortisol 249 -0.007 (-0.049, 0.023) 0.7 214 -0.006 (-0.038, 0.020) 0.7
∑Cortisone 250 -0.011 (-0.053, 0.019) 0.5 215 0.002 (-0.020, 0.032) >0.9
11-dehydrocorticosterone 250 0.000 (-0.013, 0.016) >0.9 215 0.005 (-0.023, 0.038) 0.8
Testosterone 249 0.012 (-0.023, 0.055) 0.5 215 -0.002 (-0.035, 0.029) >0.9
Progesterone 250 0.001 (-0.018, 0.020) >0.9 215 0.011 (-0.016, 0.050) 0.5
Bisphenol S, Trimester 3, Internalizing, SEPAGES
∑Cortisol 150 0.003 (-0.050, 0.080) 0.9 194 -0.000 (-0.031, 0.019) >0.9
∑Cortisone 150 -0.007 (-0.056, 0.071) 0.9 194 -0.000 (-0.030, 0.020) 0.9
11-dehydrocorticosterone 150 0.002 (-0.024, 0.056) 0.8 194 0.002 (-0.021, 0.030) 0.8
Testosterone 150 0.002 (-0.064, 0.081) >0.9 194 0.011 (-0.026, 0.055) 0.6
Progesterone 150 -0.030 (-0.117, 0.031) 0.3 194 0.015 (-0.045, 0.086) 0.6
Butylparaben, Trimester 2, Internalizing, BiSC
∑Cortisol 195 0.010 (-0.043, 0.060) 0.8 173 0.003 (-0.047, 0.038) 0.9
∑Cortisone 196 0.003 (-0.053, 0.046) >0.9 173 0.004 (-0.041, 0.038) 0.9
11-dehydrocorticosterone 196 -0.000 (-0.030, 0.025) >0.9 173 -0.004 (-0.076, 0.034) 0.7
Testosterone 196 -0.005 (-0.036, 0.049) >0.9 173 -0.001 (-0.033, 0.023) 0.9
Progesterone 196 -0.002 (-0.054, 0.032) 0.8 173 0.005 (-0.048, 0.056) >0.9
Butylparaben, Trimester 2, Internalizing, SEPAGES
∑Cortisol 154 -0.025 (-0.101, 0.028) 0.4 192 0.000 (-0.026, 0.022) >0.9
∑Cortisone 154 -0.027 (-0.126, 0.025) 0.3 192 -0.001 (-0.035, 0.030) >0.9
11-dehydrocorticosterone 154 -0.002 (-0.038, 0.026) 0.9 192 0.001 (-0.024, 0.022) >0.9
Testosterone 153 -0.005 (-0.074, 0.054) 0.9 192 0.016 (-0.022, 0.072) 0.5
Progesterone 154 0.026 (-0.044, 0.103) 0.4 192 0.011 (-0.023, 0.065) 0.6
Propylparaben, Trimester 2, Externalizing, BiSC
∑Cortisol 195 0.003 (-0.003, 0.015) 0.4 173 -0.000 (-0.008, 0.005) 0.9
∑Cortisone 196 0.004 (-0.002, 0.015) 0.3 173 -0.000 (-0.008, 0.004) 0.9
11-dehydrocorticosterone 196 -0.000 (-0.008, 0.004) 0.8 173 0.001 (-0.006, 0.006) 0.8
Testosterone 196 0.001 (-0.006, 0.007) >0.9 173 0.002 (-0.006, 0.009) 0.6
Progesterone 196 -0.000 (-0.006, 0.005) 0.8 173 0.002 (-0.008, 0.015) 0.7
Propylparaben, Trimester 2, Externalizing, SEPAGES
∑Cortisol 154 -0.007 (-0.019, 0.002) 0.2 191 0.000 (-0.004, 0.007) 0.9
∑Cortisone 154 -0.010 (-0.024, 0.001) 0.11 191 0.000 (-0.004, 0.007) 0.8
11-dehydrocorticosterone 154 -0.001 (-0.007, 0.004) 0.7 191 0.001 (-0.003, 0.008) 0.7
Testosterone 153 0.004 (-0.005, 0.016) 0.4 191 -0.000 (-0.005, 0.003) 0.8
Progesterone 154 0.003 (-0.007, 0.020) 0.6 191 0.002 (-0.003, 0.010) 0.6

4.3.4.4 By sex and by cohort (MI)

4.4 Correlation between phenols

Table 40: Correlation matrix between phenols (SPearman correaltion)