Dataset Information

Association of Epidural Analgesia in Women in Labor With Neonatal and Childhood Outcomes in a Population Cohort

ABSTRACT: Key Points

Question

Is the use of epidural analgesia during labor associated with adverse neonatal and childhood outcomes?

Findings

In this population-based cohort study of 435 281 mother-offspring pairs, the use of epidural analgesia in labor was not associated with adverse neonatal outcomes after adjustment for confounders and mediation by mode of delivery. Epidural analgesia was, however, associated with a small reduction in some adverse developmental outcomes at 2 years.

Meaning

In this study, epidural analgesia in labor was not associated with adverse immediate or longer-term offspring outcomes. This cohort study uses data on mother-infant pairs from the Scottish National Health Service to investigate the association of epidural anesthesia use during labor with neonatal and childhood outcomes.

Importance

Although use of epidural analgesia during labor is safe, detailed information about its association with neonatal and child outcomes is limited.

Objective

To investigate the association of labor epidural analgesia with neonatal outcomes and childhood development during the first 1000 days of life.

Design, Setting, and Participants

This population-based cohort study used Scottish National Health Service hospital administrative data of all 435 281 singleton live births in Scotland between January 1, 2007, and December 31, 2016, with follow-up over the first 1000 days of life. All 435 281 mother-infant pairs delivering between 24 weeks 0 days and 43 weeks 6 days’ gestation who were in active labor with cephalic presentation and who delivered vaginally or via unplanned cesarean delivery were included. Stillbirths and infants with known congenital anomalies were excluded. Data were analyzed between August 1, 2020, and July 23, 2021.

Exposures

Epidural analgesia in labor.

Main Outcomes and Measures

Neonatal outcomes included resuscitation, Apgar score less than 7 at 5 minutes, and neonatal unit admission. Childhood development measures (gross and fine motor function, communication, and social functioning) were obtained from standardized national childhood surveillance assessments performed at 2 years.

Results

This study included a total of 435 281 live births with cephalic presentation in labor (median gestational age at delivery, 40 weeks [IQR, 39-41 weeks]; 221 153 male infants [50.8%]), of which 94 323 (21.7%) had labor epidural. Epidural analgesia was associated with a reduction in spontaneous vaginal deliveries (confounder-adjusted [Cadj] relative risk [RR], 0.46; 95% CI, 0.42-0.50), an increased risk of neonatal resuscitation (Cadj RR, 1.07; 95% CI, 1.03-1.11), and an increased risk of neonatal unit admission (Cadj RR, 1.14; 95% CI, 1.11-1.17). With additional analysis for mediation by mode of delivery (CMadj), these associations were reversed (CMadj RR, 0.83; 95% CI, 0.79-0.86 for neonatal resuscitation and CMadj RR, 0.94; 95% CI, 0.91-0.97 for neonatal unit admission). Epidural analgesia was associated with a reduced risk of an Apgar score less than 7 at 5 minutes in both confounder and confounder/mediation analyses. Epidural analgesia was associated with a reduced risk of having developmental concern in any domain at 2 years in confounder and confounder/mediation analyses (CMadj RR, 0.96; 95% CI, 0.93-0.98), with specifically fewer concerns regarding communication (CMadj RR, 0.96; 95% CI, 0.93-0.99) and fine motor skills (CMadj RR, 0.89; 95% CI, 0.82-0.97).

Conclusions and Relevance

The results of this cohort study suggest that labor epidural analgesia is not independently associated with adverse neonatal or childhood development outcomes. Associations with neonatal resuscitation and admission were likely mediated by mode of delivery.

SUBMITTER: Kearns R

PROVIDER: S-EPMC8554639 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

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.

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.

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.

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.