Supplementary Online Material Article: The Impact of Obstetric Mode of Delivery on Childhood Behavior Journal: Social Psychiatry and Psychiatric Epidemiology Authors: Sukainah Y Al Khalaf1, Sinéad M O’Neill2,3, Linda M O’Keeffe1,2, Tine B Henriksen4, Louise C Kenny3, John F Cryan5, Ali S Khashan1,3 Affiliations: 1Department of Epidemiology and Public Health, University College Cork, Cork, Ireland 2 National Perinatal Epidemiology Centre (NPEC), Department of Obstetrics and Gynaecology, Wilton, Cork, Ireland; 3The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Department of Obstetrics and Gynaecology, University College Cork, Cork, Ireland; 4Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Skejby, Denmark; 5Alimentary Pharmabiotic Centre, Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland Corresponding Author: Ali Khashan, Email: a.khashan@ucc.ie; OR Linda O’Keeffe, Email: l.okeeffe@ucc.ie Table S1: Summary of the association between mode of delivery and abnormal SDQ scores at age three years Variable (N) n (%) abnormal SDQ Crude OR (95%CI) aOR (95%CI) Effect of mode of delivery by sex OR (95% CI) Male Female P-value for interaction females vs. males Spontaneous vaginal (37,711) Instrumental vaginal (9,524) Elective CS (8,456) Emergency CS (8,900) Peer Problems (≥4)b 2,820 (7.5) Ref. Ref. Ref. Ref. - 908 (9.5) 1.30 (1.01, 1.68)* 1.34 (1.02, 1.77)* 1.09 (0.77, 1.55) 1.92 (1.28, 2.87)* 0.034 564 (6.7) 0.88 (0.66, 1.18) 0.99 (0.73, 1.34) 1.00 (0.70, 1.45) 0.96 (0.57, 1.62) 0.895 910 (10.2) 1.41 (1.11, 1.80)* 1.38 (1.06, 1.80)* 1.32 (0.97, 1.82)* 1.47 (0.95, 2.28) 0.704 Spontaneous vaginal (37,719) Instrumental vaginal (9,524) Elective CS (8,456) Emergency CS (8,900) Conduct problems (≥4)a 2,647 (7.1) Ref. Ref. Ref. Ref. - 760 (8) 1.14 (0.88, 1.50) 1.03 (0.78, 1.36) 0.97 (0.68, 1.39) 1.12 (0.74, 1.70) 0.584 580 (6.9) 0.98 (0.72, 1.32) 1.10 (0.81, 1.50) 0.93 (0.62, 1.41) 1.34 (0.85, 2.11) 0.244 894 (10) 1.48 (1.15, 1.90)* 1.29 (0.98, 1.69) 1.21 (0.86, 1.69) 1.42 (0.93, 2.17) 0.542 Spontaneous vaginal (37,712) Instrumental vaginal (9,524) Elective CS (8,456) Emergency CS (8,900) Emotional problems (≥5)c 8,727 (23.1) Ref. Ref. Ref. Ref. - 1,921 (20.2) 0.84 (0.71, 0.99)* 0.96 (0.80, 1.15) 0.94 (0.74, 1.19) 0.99 (0.75, 1.30) 0.765 1,706 (20.2) 0.84 (0.70, 1.00) 0.90 (0.74, 1.08) 0.85 (0.66, 1.10) 0.94 (0.72, 1.22) 0.601 1,861 (20.9) 0.87 (0.74, 1.05) 0.91 (0.78, 1.12) 0.88 (0.69, 1.12) 1.00 (0.76, 1.31) 0.489 Spontaneous vaginal (37,726) Instrumental vaginal (9,524) Elective CS (8,456) Emergency CS (8,900) Pro-social behavior (≤4) d 1,193 (3.2) Ref. Ref. Ref. Ref. - 273 (2.9) 0.91 (0.61, 1.35) 0.99 (0.69, 1.41) 0.71 (0.40, 1.25) 1.17 (0.65, 2.12) 0.220 313 (3.7) 1.18 (0.77, 1.81) 0.90 (0.60, 1.34) 1.26 (0.70, 2.29) 1.11 (0.55, 2.22) 0.776 363 (4.1) 1.30 (0.90, 1.89) 1.08 (0.76, 1.53) 1.10 (0.65, 1.86) 1.14 (0.64, 2.00) 0.929 Hyperactivity (≥7)a Spontaneous vaginal 1,476 (3.9) Ref. Ref. Ref. Ref. (37,712) Instrumental vaginal 270 (2.8) 0.72 (0.49, 1.04) 0.75 (0.49, 1.13) 0.80 (0.49, 1.28) 0.62 (0.28, 1.36) 0.585 (9,524) Elective CS 376 (4.4) 1.14 (0.80, 1.63) 1.16 (0.80, 1.70) 1.22 (0.77, 1.93) 1.07 (0.57, 2.01) 0.738 (8,456) Emergency CS 347 (3.9) 1.00 (0.70, 1.41) 0.91 (0.61, 1.34) 0.84 (0.53, 1.34) 1.08 (0.56, 2.08) 0.532 (8,899) Data refer to crude and adjusted odds ratios (OR) with 95% confidence intervals (CI) in a weighted sample. P-value for interaction: 0.05 significance level. All models were a priori adjusted for maternal age, educational level, preeclampsia, gestational age, birth weight and gender. *Statistically significant P<0.05. a A priori adjusted + parity. b A priori adjusted + parity and ethnicity. c A priori adjusted + BMI and parity. d A priori adjusted + parity, BMI and ethnicity. Summary of Table S1: In exploratory analyses, the association between mode of delivery and hyperactivity sub-scale in the crude and adjusted analyses showed that children born by emergency CS (aOR=1.38, 95% CI 1.06, 1.80), and IVD (aOR=1.34, 95% CI 1.02, 1.77) had an increased odds compared with the reference group. There was also evidence of an interaction between gender and mode of delivery, where IVD affected females more than males (aOR=1.92, 95% CI 1.28, 2.87) than male children (aOR=1.09, 95% CI 0.77, 1.55, P-value for interaction=0.03). Peer-problem scores were higher among children who delivered by emergency CS than those who delivered by SVD in the unadjusted analyses. After adjustment for maternal and neonatal factors however, the association disappeared. There was no association between mode of delivery and abnormal conduct problems, emotional problems and pro-social behavior scores. Table S2: Summary of the results from sensitivity analyses Variable aOR (95%CI)a Term babies (≥39) aOR (95%CI)b Excluding preeclampsia aOR (95%CI)c First pregnancies aOR (95%CI)d Parental stress aOR (95%CI)e Attachment quality Personal social domain Spontaneous vaginal Ref. Ref. Ref. Ref. Ref. Instrumental vaginal 0.83 (0.66, 1.04) 0.90 (0.73, 1.11) 0.96 (0.72 1.26) 0.91 (0.74, 1.11) 0.91 (0.75 1.11) Elective CS 1.33 (1.07, 1.65)* 1.22 (1.02, 1.47)* 1.32 (0.87, 1.99) 1.22 (1.02, 1.45)* 1.23 (1.03, 2.46)* Emergency CS 0.96 (0.76, 1.22) 1.06 (0.87, 1.28) 1.04 (0.78, 1.39) 1.01 (0.84, 1.22) 1.03 (0.85, 1.24) Gross motor domain Spontaneous vaginal Ref. Ref. Ref. Ref. Instrumental vaginal 1.14 (0.98, 1.46) 1.20 (0.96, 1.50) 1.04 (0.78, 1.39) 1.14 (0.92, 1.42) 1.15 (0.92, 1.43) Ref. Elective CS 1.67 (1.33, 2.11)* 1.61 (1.33, 1.96)* 2.04 (1.38, 3.01)* 1.55 (1.29, 1.87)* 1.56 (1.29, 1.88)* Emergency CS 1.17 (0.90, 1.55) 1.34 (1.09, 1.66)* 1.06 (0.77, 1.46) 1.28 (1.04, 1.57)* 1.28 (1.05, 1.57)* Hyperactivity (≥7)b Spontaneous vaginal Ref. Ref. Ref. Ref. Ref. Instrumental vaginal 1.36 (0.99, 1.86) 1.36 (1.02, 1.79)* 1.31 (0.94, 1.83) 1.36 (1.04, 1.79)* 1.35 (1.03, 1.77)* Elective CS 0.95 (0.62, 1.46) 1.01 (0.73, 1.38) 0.70 (0.40, 1.24) 1.02 (0.75, 1.38) 1.00 (0.73, 1.36) Emergency CS 1.50 (1.08, 2.08)* 1.42 (1.07, 1.86)* 1.21 (0.84, 1.74) 1.39 (1.06, 1.81)* 1.36 (1.04, 1.77)* Data refer to adjusted odds ratios (OR) with 95% confidence intervals (CI) in a weighted sample. *Statistically significant P<0.05. a Preterm babies were excluded from this model and only term babies with gestational age of ≥39wks were included b Preeclampsia cases were excluded from this model c Multigravida women were excluded and only first pregnancies were included in this model d Parental e Quality stress level included in the models. of mother-child attachment was included in the models. *Statistically significant P<0.05 Summary of Table S2: Overall, restricting the analysis to babies born at 39+ weeks gestation did not change the conclusions although the estimates were slightly higher in this group compared to the analysis of all the children. Excluding offspring of women with pre-eclampsia had very little effect on the associations. When we included first pregnancies only, the OR of the association between elective CS and cognitive problems (personal social domain) was slightly higher but no longer statistically significant. Delay in gross motor function however, was higher among children born by elective CS compared with those born by SVD. The association between emergency CS and hyperactivity was smaller in first time babies compared to the association in all babies and was no longer statistically significant. To assess whether any of the observed associations may be mediated by parental stress or mother-child attachment variables in the logistic models did not change the results materially.