The Irish Centre for Fetal and Neonatal Translational Research (INFANT), Department of Obstetrics and Gynaecology, Cork University Maternity Hospital, Cork, Ireland.
Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Stockholm, Sweden.
JAMA Psychiatry. 2015 Sep;72(9):935-42. doi: 10.1001/jamapsychiatry.2015.0846.
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.
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.
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).
The ASD status as defined using codes from the ICD-9 (code 299) and ICD-10 (code F84).
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).
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.
由于剖宫产率在全球范围内呈上升趋势，因此越来越有必要了解分娩方式对儿童发展可能产生的长期影响。
调查产科分娩方式与自闭症谱系障碍（ASD）之间的关联。
设计、地点和参与者：基于国际疾病分类第 9 版（ICD-9）和国际疾病分类第 10 版（ICD-10），我们从瑞典围产期登记册和瑞典国家患者登记册中确定了围产期因素和 ASD 诊断。我们进行了分层 Cox 比例风险回归分析，以检验分娩方式对 ASD 的影响。然后，我们使用条件逻辑回归来进行同胞设计研究，该研究由 ASD 状态不一致的同胞对组成。分析调整了出生年份（即部分调整），然后根据各种围产期和社会人口统计学因素进行了全面调整。该基于人群的队列研究包括 1982 年 1 月 1 日至 2010 年 12 月 31 日期间瑞典所有单胎活产儿。儿童随访至首次诊断为 ASD、死亡、迁移或 2011 年 12 月 31 日（研究期结束），以先发生者为准。全队列包括 2697315 名儿童和 28290 例 ASD。同胞对照分析包括 13411 对同胞。
产科分娩方式定义为非辅助阴道分娩（VD）、辅助 VD、选择性剖宫产和紧急剖宫产（定义为分娩前或分娩后）。
使用 ICD-9（代码 299）和 ICD-10（代码 F84）中的代码定义 ASD 状态。
在调整后的 Cox 比例风险回归分析中，与非辅助 VD 相比，选择性 CS（危险比，1.21；95%CI，1.15-1.27）和紧急 CS（危险比，1.15；95%CI，1.10-1.20）与 ASD 相关。在同胞对照分析中，选择性 CS 在部分调整（比值比[OR]，0.97；95%CI，0.85-1.11）或完全调整（OR，0.89；95%CI，0.76-1.04）模型中与 ASD 无关。紧急 CS 在部分调整分析中与 ASD 显著相关（OR，1.20；95%CI，1.06-1.36），但在完全调整模型中这种影响消失（OR，0.97；95%CI，0.85-1.11）。
本研究证实了先前的发现，即剖宫产出生的儿童被诊断为 ASD 的可能性约高 20%。然而，当使用同胞对照时，这种关联并没有持续存在，这表明这种关联是由于遗传和/或环境因素的家族性混杂造成的。
