No significant association between anesthetics administered during delivery and autism spectrum disorder: a Mendelian randomization study.

Background: Autism spectrum disorder (ASD) has a complex etiology. Anesthesia during childbirth may influence the ASD risk, but the available data remain conflicting. This study aimed to explore the associations between anesthetics administered during delivery and the development of ASD.

Methods: A two-sample Mendelian randomization (MR) design was used to determine the association between anesthetics exposure during delivery and ASD using summary data from genome-wide association studies (GWAS). Analysis was conducted using the inverse variance weighted (IVW), weighted median, weighted mode, and MR-Egger regression methods. Heterogeneity among instrumental variables (IVs) was assessed using Cochran's Q-test. Horizontal pleiotropy was evaluated using the MR-Egger regression method. Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) was used to detect horizontal pleiotropy and outliers. The robustness and consistency of the results were tested using the leave-one-out method.

Results: There were no statistically significant associations between the use of anesthesia during childbirth and the risk of ASD (P=0.153 for general anesthesia; P=0.295 for epidural/caudal anesthetics; P=0.609 for spinal anesthetics; P=0.889 for epidural or caudal and spinal anesthetics; P=0.441 for other anesthetics). The Q test and MR-Egger analysis indicated that the results were homogeneous and not influenced by horizontal pleiotropy, thus demonstrating their robustness. The MR-PRESSO analysis suggested no horizontal pleiotropy effects but one outlier; excluding the outlier did not change the conclusions. The leave-one-out analysis also supports the robustness of the results.

Conclusions: This MR study does not support an association between general, epidural/caudal, spinal, epidural/caudal and spinal, or other anesthetics during delivery and the occurrence of ASD, suggesting that concerns about ASD should not serve as a basis for decision-making regarding labor analgesia.