Mendelian randomization analysis of the genetic causal relationship between different labor anesthesia methods and adverse neonatal outcomes

Abstract

Background Despite the lack of data from randomized controlled trials, studies have indicated that labor anesthesia may be associated with neonatal asphyxia and adverse neonatal neurological outcomes. We used a two-sample Mendelian randomization (MR) study to investigate the causal relationships between different labor anesthesia methods, neonatal asphyxia, and adverse neonatal neurological outcomes. Method We collected genome-wide association study (GWAS) data, including spinal, epidural, and other labor anesthesia methods, as well as neonatal asphyxia and adverse neurological outcomes (cerebral palsy, mental retardation, and attention deficit hyperactivity disorder). Data on different delivery analgesia methods sourced from the Integrative Epidemiology Unit Open GWAS project were used as exposure data. Neonatal asphyxia and neurological adverse outcomes sourced from the FinnGen consortium R10 were used as the outcome data. A two-sample MR was used to evaluate the effects of different delivery analgesia methods on neonatal asphyxia and three adverse neurological outcomes in newborns to determine the existence of a causal relationship between them. The inverse-variance weighted (IVW) method was used for MR analysis and a series of sensitivity analyses were conducted. Results Spinal, epidural, and other methods of labor anesthesia were not associated with neonatal asphyxia (odds ratio [OR]_IVW = 1.302, P = 0.749; OR_IVW = 1.431, P = 0.622; OR_IVW = 0.695, P = 0.688, respectively), cerebral palsy (OR_IVW = 0.759, P = 0.480; OR_IVW = 0.701, P = 0.319; OR_IVW = 0.695, 95% P = 0.688; OR_IVW = 1.288, P = 0.523, respectively), intellectual disability (OR_IVW = 1.309, P = 0.351; OR_IVW = 0.744, P = 0.331; OR_IVW = 0.712, P = 0.313, respectively), or attention deficit hyperactivity disorder (OR_IVW = 1.163, P = 0.778; OR_IVW = 1.012, 95% P = 0.979; OR_IVW = 0.972, P = 0.944, respectively). Sensitivity analysis showed no heterogeneity or pleiotropic effects, and the results were reliable. Conclusion Our MR study based on genetic data does not support the existence of a causal relationship between different labor anesthesia methods and neonatal asphyxia or adverse neonatal neurological outcomes. Thus, labor pain relief methods can be selected based on the mother's needs and condition without increasing associated risks.