Association of Labor Epidural Analgesia With Autism Spectrum Disorder in Children

Mikkelsen, A. B.; Greiber, Iben Katinka; Scheller, Nikolai Madrid; Lidegaard, Øjvind

doi:10.1001/jama.2021.12655

Cited by 43 publications

(80 citation statements)

References 26 publications

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“…The PubMed search using our defined search criteria initially yielded 37 citations, of which 15 were directly related to this research question, and 4 presented original data. 3 , 8 , 9 , 10 All 4 studies were included in the meta-analysis and were pooled with the results from our analyses. Results from the meta-analysis yielded a pooled adjusted HR of 1.10 (95% CI, 1.06-1.13) ( Figure 4 ) with a P value from the χ 2 test of .001, suggesting between-study heterogeneity.…”

Section: Resultsmentioning

confidence: 99%

Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder

et al. 2021

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IMPORTANCERecent studies have reported conflicting findings regarding a potential association between analgesia used during labor and autism spectrum disorder in the offspring. OBJECTIVE To evaluate whether neuraxial labor analgesia increases the risk of autism spectrum disorder in the offspring. DESIGN, SETTING, AND PARTICIPANTS This cohort study included mother-child dyads who underwent vaginal delivery and were exposed to neuraxial labor analgesia. Delivery data were collected from the Medicaid Analytic eXtract (2005-2014) for mothers with public insurance and the IBM Health MarketScan Research Database (2005-2015) for mothers with private insurance. Data analysis was conducted from January to October 2021. EXPOSURES Presence of a procedure code indicating neuraxial labor analgesia. MAIN OUTCOMES AND MEASURESChildren with autism spectrum disorder, identified using a validated algorithm (positive predictive value: 94% [95% CI, 83%-99%]). Cumulative incidence curves stratified by exposure were assessed using Kaplan-Meier analyses. Hazard ratios were estimated through Cox proportional hazards regression, using propensity-score fine stratification for confounding control. Estimates from both insurance cohorts were combined through fixed-effects meta-analysis. Subsequently, results from these analyses were combined with existing published studies. RESULTSThe cohort of mother-child dyads with public insurance consisted of 910 696 deliveries (mean [SD] maternal age, 24.3 [5.7] years; 286 025 [31.4%] Black mothers; 374 282 [41.1%] White mothers), with 484 752 (53.2%) being exposed to neuraxial labor analgesia. The cohort of motherchild dyads with private insurance included 696 883 deliveries (mean [SD] maternal age , 31.0 [4.5] years; race and ethnicity data not available), with 513 347 (73.7%) being exposed. Cumulative incidence of autism spectrum disorder by 10 years of age was 1.93% (95% CI, 1.73%-2.13%) among children in the exposed group vs 1.64% (95% CI, 1.51%-1.76%) among children in the unexposed group in the publicly insured cohort. Respective numbers were 1.33% (95% CI, 1.19%-1.46%) and 1.19% (95% CI, 0.99%-1.38%) in the privately insured cohort. Adjusting for potential confounders and pooling across both cohorts resulted in a hazard ratio of 1.08 (95% CI, 1.02-1.15). Results were consistent when additionally adjusting for empirically identified variables through high-dimensional propensity score analyses (pooled hazard ratio, 1.07; 95% CI, 1.00-1.14) or expanding the cohorts to include cesarean deliveries and assisted vaginal deliveries (pooled hazard ratio, 1.07; 95% CI, 1.03-1.12). Meta-analysis of this study and recently published observational studies yielded similar findings with a pooled hazard ratio of 1.10 (95% CI, 1.06-1.13).

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Section: Resultsmentioning

confidence: 99%

Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder

et al. 2021

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“…The other two studies from Denmark used the same data sources and classifications for ELA and ASD but reported different adjusted hazard ratios [ 16 , 17 ]. The first study conducted by Mikkelsen et al identified all live-born children in Denmark between January 2006 and December 2013 with the offspring follow-up up to December 2017.…”

Section: Resultsmentioning

confidence: 99%

Is There an Association between the Use of Epidural Analgesia during Labor and the Development of Autism Spectrum Disorder in the Offspring?—A Review of the Literature

Król

Stanirowski

Mazanowska

et al. 2022

IJERPH

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Autism spectrum disorders (ASDs) are multifactorial and complex neurodevelopmental conditions usually diagnosed in the early childhood. The etiology of ASDs is commonly described as a genetic predisposition combined with an environmental impact. As a result of broadening of the diagnostic criteria the prevalence of ASDs has been increasing worldwide and the search for the modifiable factors is still on-going. Epidural analgesia (ELA) provides effective pain relief during labor and is currently the most preferred method of anesthesia during the delivery. The safety of the procedure is well-discussed and documented; nonetheless, in 2020 a single population-based study indicated an association between the use of ELA during labor and newborn risk of ASD development, which led to widespread concern. To explore the possible association between the ELA and ASD occurrence in the offspring several studies in different countries have been conducted to date. In this review we aimed to summarize the current state of knowledge concerning the association between the use of epidural analgesia during labor and risk of ASD. In conclusion, the literature review indicates that there is no significant association.

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“…In United States, 70% of the expectant mothers receive LEA during their birth-giving ( 8 ), and it is demonstrated to be safe for the newborns ( 9 ). Our previous study explored a possible association between LEA and long-term adverse neurodevelopment in newborns, and the results indicated autism spectrum disorder (ASD) ( 10 , 11 ). ASD is a term used to describe a range of early-onset social communication deficits, and is also used on the repetitive sensory–motor behaviors related to genetics ( 12 ).…”

Section: Introductionmentioning

confidence: 99%

Effects of epidural analgesia exposure during parturition on autism spectrum disorder in newborns: A systematic review and meta-analysis based on cohort study

Wang

Liu

2022

Front. Psychiatry

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BackgroundLabor epidural analgesia (LEA) is one of the most effective and widely used approaches for pain relief during parturition. we conducted this meta-analysis to evaluate the association between LEA exposure during parturition and ASD in newborns.MethodsPubMed, Cochrane Library, EMBASE and Web of Science database were searched from inception to January 2, 2022 to identify related articles. Literature screening was carried out strictly according to the inclusion and exclusion criteria, and data were extracted and imported into STATA 15.0 software for meta-analysis.ResultsA total of 5 studies with 1763454 participants were included. A statistically significant correlation was observed between LEA and changed ASD (RR = 1.20, 95%CI (1.17, 1.24)), and the correlation between LEA and ASD were analyzed by univariate HR (ES = 1.34, 95%CI(1.27,1.40), P < 0.05) and Multivariate HR (ES = 1.13, 95%CI (1.05,1.21), P < 0.05).LimitationFirst, few studies were included, and most patients were from the United States. Second, the included studies were observational cohort designs, which cannot avoid selection and measurement bias. Third, the results of the included studies were heterogeneous, and a more detailed subgroup analysis was not possible.ConclusionThere is a correlation between LEA during parturition and the risk of ASD in newborns. The Newborn whose mother received LEA during her birth-giving might be more likely to develop ASD.

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Association of Labor Epidural Analgesia With Autism Spectrum Disorder in Children

Cited by 43 publications

References 26 publications

Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder

Association of Neuraxial Labor Analgesia for Vaginal Childbirth With Risk of Autism Spectrum Disorder

Is There an Association between the Use of Epidural Analgesia during Labor and the Development of Autism Spectrum Disorder in the Offspring?—A Review of the Literature

Effects of epidural analgesia exposure during parturition on autism spectrum disorder in newborns: A systematic review and meta-analysis based on cohort study

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