Anesthesia, sex and miscarriage history may influence the association between cesarean delivery and autism spectrum disorder

Abstract

Background To explore the association between cesarean section (CS) and risk of autism spectrum disorder (ASD), and evaluate the possible factors influencing this association. Methods In total, 950 patients diagnosed with ASD and 764 healthy controls were recruited in this study. Socio-demographic characteristics and prenatal, perinatal, and neonatal characteristics were compared between the two groups. Univariate and multivariable conditional logistic regression analyses were applied to adjust for confounders. Further stratified analyses based on sex and miscarriage history were similarly performed to explore the factors influencing the association between CS and ASD. Results CS was evidently associated with an elevated risk of ASD (adjusted odds ratio [aOR] = 1.606, 95% confidence interval (CI) = 1.311–1.969). Unlike regional anesthesia (RA), only CS performed under general anesthesia (GA) consistently elevated the risk of ASD (aOR = 1.887, 95% CI = 1.273–2.798) in females and males in further stratified analysis. The risk of children suffering from ASD following emergency CS was apparently increased in males (aOR = 2.390, 95% CI = 1.392–5.207), whereas a higher risk of ASD was observed among voluntary CS and indicated CS subgroups (aOR = 2.167, 95% CI = 1.094–4.291; aOR = 2.919, 95% CI = 1.789–4.765, respectively) in females. Moreover, the interaction term of CS and past miscarriage history (β = − 0.68, Wald χ2 = 7.5, df = 1, p = 0.006)) was similarly defined as influencing ASD. Conclusions The exposure of children to GA during CS may explain the possible/emerging association between CS and ASD. In addition, sex and miscarriage history could equally be factors influencing the association between CS and ASD.

Association between Cesarean section and neurodevelopmental disorders in a Japanese birth cohort: the Japan Environment and Children’s Study

“…After adjustment for potential confounding factors, the risk of ASD was 38% higher in children born by CS than in those born by vaginal delivery in this study. In the literature, there are conflicting reports regarding the association between CS and ASD [ 7 , 10 , 11 , 17 ]. Previous studies and a meta-analysis indicated that CS increased the risk of ASD [ 7 , 11 , 17 ], which is line with the findings of the present study.…”

“…However, in a meta-analysis including 13 studies, CS birth was linked to a greater risk of future ASD (odds ratio (OR) 1.23) than vaginal birth [ 11 ]. Although ASD is a highly inheritable disorder with male preponderance, relevant environmental factors may be sex-specific [ 9 ]; for example, the indications for CS and the anesthesia method used during CS were found to have some effects on ASD morbidity depending on the infants’ sex [ 8 , 17 , 18 ]. Some environmental factors in the perinatal period may also be involved in ASD morbidity.…”

A National Population Cohort Study Showed That Exposure to General Anesthesia in Early Childhood Is Associated with an Increase in the Risk of Developmental Delay

“…It must be noted that the within-pair analysis suggested that anesthesia exposure was associated with a higher ADHD score [24] and the later ADHD are associated with prolonged or multiple exposure to anaesthetics [25]. Fortunately, some studies have concluded that children receiving anesthesia in utero [26], in their first 2 years life or later, are not more likely to develop ASD [27]. In addition, an international, multicenter, randomized, controlled equivalence trial has strongly evidenced that an hour of GA in early infancy does not change neurodevelopmental outcome and behavioral measures compared to awake-regional anaesthesia [28].…”

Association between previous abortion history and risk of autism spectrum disorders among offspring: a meta-analysis

“…Therefore, 13 studies were included in this meta-analysis (Figure 1). Seven studies 10,11,13,15,[18][19][20] had a case-control design, four 12,14,21,22) had a cohort design, and two 23,24) had a crosssectional design. Among the included studies, seven were performed in Europe, four in the Americas, and one each in Africa and Europe.…”