Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis.
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ABSTRACT: Background
The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent.Methods
We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall relative risk.Results
Our results showed that LEA was associated with an increased risk of ASD in offspring [HR = 1.3, 95% confidence interval (CI): 1.25-1.35; P < 0.001] after combining crude estimates from the included studies. This association was gradually reduced, but still statistically significant, when potential confounding factors were considered (HR 1.13, 95% CI 1.03-1.25, P = 0.014). However, there was no significant association when we combined data of siblings from other pregnancies (HR = 1.07, 95% CI: 0.99-1.16, P = 0.076), implying that the association was due to confounding factors.Conclusion
The statistically significant association between LEA and ASD in the offspring can be partially explained by unmeasured confounding.Systematic review registration
Identifier CRD42022302892.
SUBMITTER: Fang LL
PROVIDER: S-EPMC9986298 | biostudies-literature | 2022
REPOSITORIES: biostudies-literature
Publications
Labor epidural analgesia and risk of autism Spectrum disorders in offspring: A systematic review and meta-analysis.
Fang Ling-Ling LL Zhou Yuan-Yue YY Jiang Hai-Yin HY Shi Yu-Dan YD
Frontiers in pediatrics 20230220
<h4>Background</h4>The effect of labor epidural anesthesia (LEA) on the risk of autism spectrum disorder (ASD) in offspring has been investigated recently, and available results are inconsistent.<h4>Methods</h4>We searched the PubMed and EMBASE databases for relevant studies and performed a systematic review and meta-analysis of the literature. Subgroup analyses were conducted to assess the sources of heterogeneity. Both fixed and random effects models were used was used to estimate overall rela ...[more]
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Project description:ImportanceEpidural labor analgesia (ELA) has been associated with an increased offspring risk of autism spectrum disorder (ASD). Whether this finding may be explained by residual confounding remains unclear.ObjectiveTo assess the association between ELA and offspring risk of ASD.Design, setting, and participantsLongitudinal cohort study of vaginal deliveries of singleton live infants born from 2005 to 2016 from a population-based data set linking information from health care databases in Manitoba, Canada; offspring were followed from birth until 2019 or censored by death or emigration. Data were analyzed from October 19, 2020, to January 22, 2021.ExposuresEpidural labor analgesia.Main outcomes and measuresAt least 1 inpatient or outpatient diagnosis of ASD in offspring aged at least 18 months. For the full population and a sibling cohort, inverse probability of treatment-weighted Cox proportional hazards regression analyses were used to control for potential confounders.ResultsOf the 123 175 offspring included in this study (62 647 boys [50.9%]; mean [SD] age of mothers, 28.2 [5.8] years), 47 011 (38.2%) were exposed to ELA; 2.1% (985 of 47 011) of exposed vs 1.7% (1272 of 76 164) of unexposed offspring were diagnosed with ASD in the follow-up period (hazard ratio [HR], 1.25; 95% CI, 1.15-1.36). After adjusting for maternal sociodemographic, prepregnancy, pregnancy, and perinatal covariates, ELA was not associated with an offspring risk of ASD (inverse probability of treatment-weighted HR, 1.08; 95% CI, 0.97-1.20). In the within-siblings design adjusting for baseline covariates, ELA was not associated with ASD (inverse probability of treatment-weighted HR, 0.97; 95% CI, 0.78-1.22). Results from sensitivity analyses restricted to women without missing data who delivered at or after 37 weeks of gestation, firstborn infants only, and offspring with ASD classified with at least 2 diagnostic codes were consistent with findings from the main analyses.Conclusions and relevanceIn a Canadian population-based birth cohort study, no association between ELA exposure and an increased offspring risk of ASD was found.
| S-EPMC8056314 | biostudies-literature
Project description:ImportanceAlthough the safety of labor epidural analgesia (LEA) for neonates has been well documented, the long-term health effects of LEA on offspring remain to be investigated.ObjectiveTo assess the association between maternal LEA exposure and risk of autism spectrum disorders (ASDs) in offspring.Design, setting, and participantsData for this retrospective longitudinal birth cohort study were derived from electronic medical records from a population-based clinical birth cohort. A total of 147 895 singleton children delivered vaginally between January 1, 2008, and December 31, 2015, in a single integrated health care system were included. Children were followed up from the age of 1 year until the first date of the following occurrences: clinical diagnosis of ASD, last date of health plan enrollment, death, or the study end date of December 31, 2018.ExposuresUse and duration of LEA.Main outcomes and measuresThe main outcome was clinical diagnosis of ASD. Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) of ASD associated with LEA exposure.ResultsAmong the cohort of 147 895 singleton children (74 425 boys [50.3%]; mean [SD] gestational age at delivery, 38.9 [1.5] weeks), 109 719 (74.2%) were exposed to maternal LEA. Fever during labor was observed in 13 055 mothers (11.9%) in the LEA group and 510 of 38 176 mothers (1.3%) in the non-LEA group. Autism spectrum disorders were diagnosed in 2039 children (1.9%) in the LEA group and 485 children (1.3%) in the non-LEA group. After adjusting for potential confounders, including birth year, medical center, maternal age at delivery, parity, race/ethnicity, educational level, household income, history of comorbidity, diabetes during pregnancy, smoking during pregnancy, preeclampsia or eclampsia, prepregnancy body mass index, gestational weight gain, gestational age at delivery, and birth weight, the HR associated with LEA vs non-LEA exposure was 1.37 (95% CI, 1.23-1.53). Relative to the unexposed group, the adjusted HR associated with LEA exposure of less than 4 hours was 1.33 (95% CI, 1.17-1.53), with LEA exposure of 4 to 8 hours was 1.35 (95% CI, 1.20-1.53), and with LEA exposure of more than 8 hours was 1.46 (95% CI, 1.27-1.69). Within the LEA group, there was a significant trend of ASD risk associated with increasing duration of LEA exposure after adjusting for covariates (HR for linear trend, 1.05 [95% CI, 1.01-1.09] per 4 hours). Adding fever to the model did not change the HR estimate associated with LEA exposure (adjusted HR for LEA vs non-LEA, 1.37 [95% CI, 1.22-1.53]).Conclusions and relevanceThis study suggests that maternal LEA may be associated with increased ASD risk in children. The risk appears to not be directly associated with epidural-related maternal fever.
| S-EPMC7551212 | biostudies-literature
Project description:ImportanceMaternal labor epidural analgesia (LEA) and oxytocin use for labor and delivery have been reported to be associated with child autism spectrum disorders (ASD). However, it remains unclear whether these 2 common medications used during labor and delivery have synergistic associations with ASD risk in children.ObjectiveTo assess the independent associations of LEA and oxytocin during labor and delivery with ASD, as well as outcome modification associated with the concurrent use of both interventions.Design, setting, and participantsData for this cohort study included 205 994 singleton births with vaginal deliveries in a single integrated health care system in Southern California from calendar years 2008 to 2017. Children were followed up to December 31, 2021. Data on use of LEA and oxytocin, covariates, and ASD outcome in children were obtained from electronic medical records. Cox proportional hazards regression was used to estimate the hazard ratios (HRs) adjusting for covariates.ExposuresLabor epidural analgesia and/or oxytocin use during labor and delivery.Main outcomes and measuresA child's clinical diagnosis of ASD during follow-up and at age of diagnosis.ResultsAmong the cohort, 153 880 children (74.7%) were exposed to maternal LEA and 117 808 children (57.2%) were exposed to oxytocin during labor and delivery. The population of children was approximately half boys and half girls. The median (IQR) age of the mothers was 30.8 (26.8-34.5) years for those not exposed to LEA, 30.0 (25.9-33.8) years for those exposed to LEA, 30.4 (26.5-34.1) years for those unexposed to oxytocin, and 30.0 (25.9-33.9) years for those exposed to oxytocin during labor and delivery. A total of 5146 children (2.5%) had ASD diagnosed during follow-up. Oxytocin exposure was higher among LEA-exposed (67.7%) than -unexposed (26.1%) children. The ASD risk associated with LEA was independent of oxytocin exposure (HR, 1.28; 95% CI, 1.18-1.38); however, the ASD risk associated with oxytocin was not significant after adjusting for LEA exposure (HR, 1.05; 95% CI, 0.99-1.12). A significant interaction of LEA and oxytocin on child ASD risk was found (P = .02 for interaction). Compared with no exposure, HRs were 1.20 (95% CI, 1.09-1.32) for LEA alone, 1.30 (95% CI, 1.20-1.42) for both LEA and oxytocin, and 0.90 (95% CI, 0.78-1.04) for oxytocin alone.Conclusions and relevanceThe findings of this cohort study suggest an association between maternal LEA and ASD risk in children, and the risk appeared to be further increased if oxytocin was also administered. Oxytocin exposure without LEA exposure was not associated with ASD risk in children. These findings must be interpreted with caution. Further studies are needed to replicate or refute the study results and examine biological plausibility.
| S-EPMC10362468 | biostudies-literature
Project description:ImportanceEvidence from studies investigating the association of epidural analgesia use during labor and delivery with risk of autism spectrum disorder (ASD) in offspring is conflicting.ObjectiveTo assess the association of maternal use of epidural analgesia during labor and delivery with ASD in offspring using a large population-based data set with clinical data on ASD case status.Design, setting, and participantsThis population-based retrospective cohort study included term singleton children born in British Columbia, Canada, between April 1, 2000, and December 31, 2014. Stillbirths and cesarean deliveries were excluded. Clinical ASD diagnostic data were obtained from the British Columbia Autism Assessment Network and the British Columbia Ministry of Education. All children were followed up until clinical diagnosis of ASD, death, or the study end date of December 31, 2016.ExposuresUse of epidural analgesia during labor and delivery.Main outcomes and measuresA clinical diagnosis of ASD made by pediatricians, psychiatrists, and psychologists with specialty training to assess ASD. Cox proportional hazards models were used to estimate the hazard ratio of epidural analgesia use and ASD. Models were adjusted for maternal sociodemographics; maternal conditions during pregnancy; labor, delivery, and antenatal care characteristics; infant sex; gestational age; and status of small or large for gestational age. A conditional logistic regression model matching women with 2 births or more and discordance in ASD status of the offspring also was performed.ResultsOf the 388 254 children included in the cohort (49.8% female; mean gestational age, 39.2 [SD, 1.2] weeks; mean follow-up, 9.05 [SD, 4.3] years), 5192 were diagnosed with ASD (1.34%) and 111 480 (28.7%) were exposed to epidural analgesia. A diagnosis of ASD was made for 1710 children (1.53%) among the 111 480 deliveries exposed to epidural analgesia (94 157 women) vs a diagnosis of ASD in 3482 children (1.26%) among the 276 774 deliveries not exposed to epidural analgesia (192 510 women) (absolute risk difference, 0.28% [95% CI, 0.19%-0.36%]). The unadjusted hazard ratio was 1.32 (95% CI, 1.24-1.40) and the fully adjusted hazard ratio was 1.09 (95% CI, 1.00-1.15). There was no statistically significant association of epidural analgesia use during labor and delivery with ASD in the within-woman matched conditional logistic regression (839/1659 [50.6%] in the exposed group vs 1905/4587 [41.5%] in the unexposed group; fully adjusted hazard ratio, 1.07 [95% CI, 0.87-1.30]).Conclusions and relevanceIn this population-based study, maternal epidural analgesia use during labor and delivery was associated with a small increase in the risk of autism spectrum disorder in offspring that met the threshold for statistical significance. However, given the likelihood of residual confounding that may account for the results, these findings do not provide strong supporting evidence for this association.
| S-EPMC8479579 | biostudies-literature
Project description:ImportanceThere is conflicting evidence on the association between intrapartum epidural analgesia and risk of autism spectrum disorder (ASD) in offspring.ObjectiveTo evaluate the association between intrapartum epidural analgesia and the risk of ASD in offspring.Design, setting, and participantsThis population-based cohort study was conducted in Ontario, Canada, using the health and administrative records of singleton live births by vaginal delivery between April 1, 2006, and March 31, 2014. Neonates with less than 24 weeks' gestation or weighing less than 500 g were excluded. Offspring were followed up from 18 months of age until ASD diagnosis, loss to follow-up, or the end of the study (December 31, 2020), whichever occurred first. Exposure, covariate, and outcome data were obtained using provincial health administrative databases.ExposuresAny intrapartum exposure to epidural or combined spinal-epidural analgesia.Main outcomes and measuresThe primary outcome was ASD diagnosis after 18 months of age. Inverse probability of treatment weighting (IPTW) of Cox proportional hazards regression models was used to estimate the hazard ratio (HR) of intrapartum epidural analgesia and ASD in offspring. Offspring head injury was used as a control outcome. Models were adjusted for maternal sociodemographic factors, health behaviors, and medical and obstetrical history as well as labor, delivery, and offspring characteristics. Post hoc analyses included restriction to term neonates, a conditional within-mother analysis, exclusion of records with concomitant intrapartum pain management exposures, a complete case analysis, use of an alternative ASD definition, and estimation of the average treatment effect in the treated group.ResultsAmong the 650 373 mother-offspring pairs included in the study, 418 761 (64.4%) were exposed to intrapartum epidural analgesia. The mean (SD) maternal age at delivery was 29.7 (5.5) years; the offspring had a mean (SD) gestational age at delivery of 39.1 (1.6) weeks and included 329 808 male newborns (50.7%). The exposed and unexposed groups were similar in all maternal and newborn characteristics after IPTW (standardized difference <0.10). Autism spectrum disorder was diagnosed in 7546 offspring (1.8%) of mothers who received intrapartum epidural analgesia (incidence rate, 18.8 [95% CI, 18.4-19.3] per 10 000 person-years) compared with 3234 offspring (1.4%) who were unexposed (incidence rate, 14.4 [95% CI, 13.9-14.9] per 10 000 person-years). The crude HR for ASD associated with intrapartum epidural analgesia was 1.30 (95% CI, 1.25-1.36), and the IPTW-adjusted HR was 1.14 (95% CI, 1.08-1.21). Results did not qualitatively differ in post hoc analyses.Conclusions and relevanceResults of this study showed that intrapartum epidural analgesia was associated with a small increase in risk for ASD in offspring. The biological plausibility of this association, however, remains unclear, and the finding must be interpreted with caution.
| S-EPMC9136620 | biostudies-literature
Project description:ImportanceA recent cohort study found that epidural analgesia during labor was associated with an increased risk of autism in offspring.ObjectiveTo investigate if labor epidural increases the risk of autism in offspring.Design, setting, and participantsThis nationwide retrospective cohort study identified all live-born children in Denmark between January 2006 and December 2013. Follow-up commenced at children's first birthday and ended in December 2017. Among 485 093 live-born children, 5915 were excluded because of occurrences during the first year of life including death, emigration, misregistration of birth, diagnosis of disease inherently linked to autism, or diagnosis of autism.ExposuresAdministration of epidural analgesia during labor, as identified by procedure code.Main outcomes and measuresThe main outcome of interest was incident diagnosis of autism spectrum disorder based on International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes in the Danish Psychiatric Central Register or National Patient Register. Hazard ratios were estimated using Cox regression, adjusted for covariates describing maternal comorbidity, sociodemographic factors, lifestyle, pregnancy, psychiatric illness, psychotropic medication, medical-seeking behavior, and family history of autism. A secondary analysis used a within-mother design including only children of mothers with both exposure and nonexposure to labor epidural analgesia in different deliveries.ResultsThe cohort included 479 178 children (233 405 girls [48.7%]; median maternal age at delivery, 30.9 [IQR, 27.6-34.2] years); of these, 92 900 (19.4%) were exposed to epidural analgesia during labor. Median follow-up was 7.0 years (IQR, 4.9-9.0 years), and by the end of follow-up, 6428 children (1.3%) had been diagnosed with autism. Exposed children had an autism diagnosis incidence rate of 23.1 per 10 000 person-years compared with 18.5 per 10 000 person-years in the unexposed group (crude hazard ratio, 1.29 [95% CI, 1.21-1.37]; adjusted hazard ratio, 1.05 [95% CI, 0.98-1.11]). A secondary within-mother analysis including 59 154 children (12.3%) estimated an autism diagnosis incidence rate of 20.8 per 10 000 person-years in the exposed group and 17.1 per 10 000 person-years in the unexposed group (adjusted hazard ratio, 1.05 [95% CI, 0.90-1.21]).Conclusions and relevanceIn this nationwide cohort study of Danish children, maternal exposure to epidural analgesia during labor was not significantly associated with autism spectrum disorder in offspring.
| S-EPMC8479581 | biostudies-literature
Project description:We performed a systematic literature search regarding maternal diabetes before and during pregnancy and the risk of autism spectrum disorders (ASD) in the offspring. Of the 178 potentially relevant articles, 12 articles including three cohort studies and nine case-control studies were included in the meta-analysis. Both the meta-analyses of cohort studies and case-control studies showed significant associations. The pooled relative risk and 95% confidence interval (CI) among cohort studies was 1.48 (1.25-1.75, p < 0.001). For case-control studies, the pooled odds ratio and 95% CI was 1.72 (1.24-2.41, p = 0.001). No indication of significant heterogeneity across studies or publication bias was observed. In conclusion, maternal diabetes was significantly associated with a greater risk of ASD in the offspring.
| S-EPMC4181720 | biostudies-literature
Project description:BACKGROUND:Previous studies have demonstrated that appropriate treatment for postoperative pain can lead to improvement in depressive symptoms, however the association between adequate intrapartum pain control and the development of postpartum depression is not clear. The purpose of the study was to examine the effects of labor epidural analgesia and postpartum depression. METHODS:We performed a quantitative systematic review in compliance with the PRISMA statement. We conducted a search of PubMed, Embase, the Cochrane Database of Systematic Reviews and Google Scholar databases. The primary outcome was a positive screen of postpartum depression among women who received labor epidural analgesia up to 3 months into the postpartum period. Meta-analysis was performed using the random effect model. RESULTS:Of the 148 studies available, 9 studies with 4442 patients were included in the analysis. The use of labor analgesia on positive depression screen compared to control revealed no significant effect, OR (95% CI) of 1.02 (0.62 to 1.66, P = 0.94). CONCLUSION:Based on current literature, the use of epidural analgesia for pain relief during labor doesn't appear to affect the likelihood of postpartum depression. Future studies are warranted to further investigate these findings and identity other possible preventative interventions that reduce postpartum depression.
| S-EPMC7216422 | biostudies-literature
Project description:ImportanceRecent studies have reported conflicting findings regarding a potential association between analgesia used during labor and autism spectrum disorder in the offspring.ObjectiveTo evaluate whether neuraxial labor analgesia increases the risk of autism spectrum disorder in the offspring.Design, setting, and participantsThis 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.ExposuresPresence 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 mother-child 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).Conclusions and relevanceAlthough a small increase in risk cannot be ruled out, the combined evidence from observational studies does not support the notion that neuraxial labor analgesia is associated with an increased risk of autism spectrum disorder.
| S-EPMC8696569 | biostudies-literature
Project description:With the development of medical equipment and techniques in labor anesthesia, it is a major issue to investigate the risks and treatment effects among techniques such as continuous epidural infusion (CEI) and intermittent epidural bolus (IEB). However, there is a controversial result regarding two techniques. This study was conducted through meta-analysis of randomized controlled trials (RCTs) for labor analgesia between the CEI and IEB techniques. The pooled results were presented as weighted mean differences (WMDs) together with 95% confidence intervals (CIs) and odds ratios (ORs) together with 95% CIs, respectively. Eleven RCTs were included in this meta-analysis. Four hundred sixty-five parturients accepted CEI, whereas 473 parturients accepted IEB labor analgesia. Elven identified low- risk bias studies were recruited for meta-analysis. The results presented no statistical difference in cesarean delivery rate between IEB and CEI (OR, 0.96; 95% CI, 0.67-1.37) and duration of second stage of labor (WMD, -3.82 min; 95% CI, -8.28 to 0.64). IEB had statistically significant lessened risk of instrumental delivery (OR, 0.59; 95% CI, 0.39-0.90) and for the use in local anesthetic (WMD, -1.71 mg bupivacaine equivalents per hour; 95% CI, -1.88 and -1.55). Accepted IEB had a higher score of maternal satisfaction (WMD, -6.95 mm; 95% CI, -7.77 to -6.13). Based on evidence, IEB showed a greater benefit for slightly reducing the use in local anesthetic, reduced risk of instrumental delivery, and improved maternal satisfaction for the requirement of labor epidural analgesia for healthy women. In the future, more studies need to be conducted to practice the IEB regimen and explore its influence on labor analgesia.
| S-EPMC7579642 | biostudies-literature