SUMMARY:

ACOG, MFM, Society for Obstetric Anesthesia and Perinatology, American Society for Anesthesiologists and the Society of Pediatric Anesthesia have released a joint statement in response to a retrospective study (Qui et al. JAMA Pediatrics, 2020) that suggests an association between epidural anesthesia and autism. The joint statement states  that this study “…does not provide credible scientific evidence that labor epidurals for pain relief cause autism.”

Study Overview (Qui et al. JAMA Pediatrics, 2020)

Methods

• Retrospective longitudinal cohort study (2008 to 2015)
  • Kaiser Permanente Southern California
  • Vaginal delivery (singleton)
  • 28 to 44 weeks’ gestation
  • Data derived from EMR
  • Children not enrolled as KPSC health plan members by 1 year of age were not included
• Covariates
  • Maternal social demographic characteristics (age at delivery, parity, educational level | Self-reported maternal race/ethnicity, and median family household income based on census tract of residence) | Medical center of delivery | History of comorbidity (≥1 diagnoses of heart, lung, kidney, or liver disease or cancer) | Maternal obesity |Diabetes | Preeclampsia or eclampsia | Smoking during pregnancy | Child characteristics at delivery (gestational age at delivery, birth weight, sex, and presence of any birth defect)

Results

• 147,895 singleton children | males: 50.3% | Mean GA: 38.9 weeks
  •  Exposure to epidural during labor: 74.2%
• Autism spectrum disorders
  • Epidural group: 1.9%
  • No epidural:  1.3%
  • Hazard ratio (adjusted): 1.37 (95% CI, 1.23-1.53) | Fever did not affect results
• Length of exposure (epidural group vs no epidural group)
  • <4 hours: Risk was 33% greater
  • 4 to 8 hours: Risk was 35% greater
  • >8 hours: Risk was 46% greater

KEY POINTS:

• There were significant limitations related to this study  
  • Retrospective analysis
  • Important potential uncontrolled confounders (before, during and after pregnancy) not included in the model, inlcuding
    • Paternal history | Genetic predisposition | Viral or bacterial infection | Toxic exposures
  • Epidural information not assessed: Medication | Additives | Dosing
• The researchers state that

…our findings should be interpreted with caution given the wide varieties of LEA practice and cannot be interpreted as a demonstration of a causal link between LEA exposure and subsequent development of ASD

Joint Statement by Professional Societies

• As noted by researchers, there is no evidence of causation provided by this study
• Details regarding the course of labor are not available
• There is no evidence for biologic plausibility provided in this study or previous literature for detrimental neurologic effects of very low doses of epidural medications on fetus or infant
• Neuraxial analgesia remains the gold standard for labor pain relief
• Furthermore, the joint statement reinforces the following points

…if anything, epidurals improve maternal and neonatal outcomes

…five medical societies that represent more than 100,000 physicians want to assure the public that an association between a mother’s use of epidural analgesia during childbirth, and her infant’s risk of developing autism does not imply causation

Millions of women worldwide benefit from epidural pain relief every year and give birth without any complications to mother or baby 

Royal College of Anaesthetists

• In the statement released by the Royal College of Anaesthetists, they provide a review of study limitations including
  • Patient characteristics: Children not enrolled with the health insurance scheme by one year of age were excluded | “Lower socioeconomic status is widely recognised to be associated with under diagnosis of autism” | Results may have been different if researchers had included the results from this excluded group
• In addition, this document addresses the absence of antepartum and intrapartum clinical information

…one of the surprising aspects of this study is lack of data about pregnancy and delivery complications which are known to increase the risk of autism

Such complications as prolonged duration of labour, fetal distress, fetal malposition and assisted vaginal delivery are also known to be associated with an increased request rate for epidurals. It is possible therefore that birth complications are actually the hidden factor linking epidurals and autism

Learn More – Primary Sources:

Association Between Epidural Analgesia During Labor and Risk of Autism Spectrum Disorders in Offspring (Qui et al. JAMA Pediatrics, 2020)

Joint Statement of the Society for Obstetric Anesthesia and Perinatology, American Society of Anesthesiologists, Society for Pediatric Anesthesia, American College of Obstetricians and Gynecologists and the Society for Maternal-Fetal Medicine: Labor epidurals do not cause autism; Safe for mothers and infants, say anesthesiology, obstetrics, and pediatric medical societies

Position Statement from the Canadian Anesthesiologists’ Society (CAS), the Society for Obstetrics and Gynecology of Canada (SOGC), and the Canadian
Paediatric Society (CPS): Lack of evidence that epidural pain relief during labour causes autism spectrum disorder

Royal College of Anaesthetists: No evidence that labour epidurals cause autism

Related ObG Topics:

Epidural Timing: The Earlier the Better?

Cochrane Review: What are the Risks and Benefits of Epidural Analgesia During Labor?

Does Epidural Anesthesia Impact the Second Stage of Labor?

Does Fentanyl Epidural in Labor Reduce Breastfeeding Success?