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Original Investigation |

Association Between Obstetric Mode of Delivery and Autism Spectrum Disorder A Population-Based Sibling Design Study

Eileen A. Curran, MPH1; Christina Dalman, PhD, MD2; Patricia M. Kearney, PhD, MRCPI3; Louise C. Kenny, PhD, MRCOG1; John F. Cryan, PhD4; Timothy G. Dinan, PhD, MD5; Ali S. Khashan, PhD1,3
[+] Author Affiliations
1The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland
2Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden
3Department of Epidemiology and Public Health, University College Cork, Cork, Ireland
4Alimentary Pharmabiotic Centre, Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland
5Alimentary Pharmabiotic Centre, Department of Psychiatry, University College Cork, Cork, Ireland
JAMA Psychiatry. 2015;72(9):935-942. doi:10.1001/jamapsychiatry.2015.0846.
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Importance  Because the rates of cesarean section (CS) are increasing worldwide, it is becoming increasingly important to understand the long-term effects that mode of delivery may have on child development.

Objective  To investigate the association between obstetric mode of delivery and autism spectrum disorder (ASD).

Design, Setting, and Participants  Perinatal factors and ASD diagnoses based on the International Classification of Diseases, Ninth Revision (ICD-9),and the International Statistical Classification of Diseases, 10th Revision (ICD-10),were identified from the Swedish Medical Birth Register and the Swedish National Patient Register. We conducted stratified Cox proportional hazards regression analysis to examine the effect of mode of delivery on ASD. We then used conditional logistic regression to perform a sibling design study, which consisted of sibling pairs discordant on ASD status. Analyses were adjusted for year of birth (ie, partially adjusted) and then fully adjusted for various perinatal and sociodemographic factors. The population-based cohort study consisted of all singleton live births in Sweden from January 1, 1982, through December 31, 2010. Children were followed up until first diagnosis of ASD, death, migration, or December 31, 2011 (end of study period), whichever came first. The full cohort consisted of 2 697 315 children and 28 290 cases of ASD. Sibling control analysis consisted of 13 411 sibling pairs.

Exposures  Obstetric mode of delivery defined as unassisted vaginal delivery (VD), assisted VD, elective CS, and emergency CS (defined by before or after onset of labor).

Main Outcomes and Measures  The ASD status as defined using codes from the ICD-9 (code 299) and ICD-10 (code F84).

Results  In adjusted Cox proportional hazards regression analysis, elective CS (hazard ratio, 1.21; 95% CI, 1.15-1.27) and emergency CS (hazard ratio, 1.15; 95% CI, 1.10-1.20) were associated with ASD when compared with unassisted VD. In the sibling control analysis, elective CS was not associated with ASD in partially (odds ratio [OR], 0.97; 95% CI, 0.85-1.11) or fully adjusted (OR, 0.89; 95% CI, 0.76-1.04) models. Emergency CS was significantly associated with ASD in partially adjusted analysis (OR, 1.20; 95% CI, 1.06-1.36), but this effect disappeared in the fully adjusted model (OR, 0.97; 95% CI, 0.85-1.11).

Conclusions and Relevance  This study confirms previous findings that children born by CS are approximately 20% more likely to be diagnosed as having ASD. However, the association did not persist when using sibling controls, implying that this association is due to familial confounding by genetic and/or environmental factors.

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