Episode #92 No, Epidurals Do Not Cause Autism, Part 1

April 5, 2022

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Welcome to the next installment of the Anesthesia Patient Safety podcast hosted by Alli Bechtel.  This podcast will be an exciting journey towards improved anesthesia patient safety.

Join us on the show today as we discuss an important patient safety concern on the labor and delivery wards. Our featured article is “Do Epidurals Cause Autism? (No.) A Review of the Controversy and What Patients and Providers Need to Know” by Caroline Thomas and Jennifer Banayan from the February 2022 APSF Newsletter.

Here is the citation for the JAMA Pediatrics article that we discuss on the show today:

  1. Qiu C, Lin JC, Shi JM, et al. Association between epidural analgesia during labor and risk of autism spectrum disorders in offspring. Jama Pediatr.2020;174:1168-1175. org/10.1001/jamapediatrics.2020.3231

Here is the link for the Joint statement of the Society for Obstetric Anesthesia and Perinatology, the American Society of Anesthesiologists, the Society of Pediatric Anesthesia, the 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” that we discuss on the show today. This statement was published online 12 October 2020.

https://soap.memberclicks.net/assets/docs/JAMAPeds_Epidurals_SOAP_ASA_SPA_ACOG_SMFM_Media_Response_101220%20%281%29.pdf

Here are the citations for the additional three studies that we review from Table 1 in the article:

  1. Wall-Wieler E, Bateman BT, Hanlon-Dearman A, et al. Association of epidural labor analgesia with offspring risk of autism spectrum disorders.Jama Pediatr. 2021;175:698–705. org/10.1001/jamapediatrics.2021.0376
  2. Hanley GE, Ip A, Oberlander TF. Epidural analgesia and autism spectrum disorder risk—the challenges inherent in complex observational research. Jama Pediatr. 2021;175:675–677. org/10.1001/jamapediatrics.2021.0382
  3. Mikkelsen AP, Greiber IK, Scheller NM, Lidegaard Ø. Association of labor epidural analgesia with autism spectrum disorder in children. JAMA. 2021;326:1170–1177. org/10.1001/jama.2021.12655

Make sure you submit your abstract for the SNACC Annual Meeting. The deadline is right around the corner on May 2nd. For more information, check out this link: https://www.abstractscorecard.com/cfp/submit/login.asp?EventKey=AQYBMVCV

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© 2022, The Anesthesia Patient Safety Foundation

Hello and welcome back to the Anesthesia Patient Safety Podcast.  My name is Alli Bechtel, and I am your host. Thank you for joining us for another show. We are returning to the February 2022 Newsletter once again today. Our show today is all about a question that comes up on the labor and delivery wards regarding the safety of lumbar epidurals for labor analgesia. So, stay tuned…

Before we dive into the episode today, we’d like to recognize BD, a major corporate supporter of APSF. BD has generously provided unrestricted support to further our vision that “no one shall be harmed by anesthesia care”. Thank you, BD – we wouldn’t be able to do all that we do without you!”

Without further delay, our featured article today is “Do Epidurals Cause Autism? (No.) A Review of the Controversy and What Patients and Providers Need to Know” by Caroline Thomas and Jennifer Banayan. To follow along with us, head over to APSF.org and click on the Newsletter heading. First one down is Current Issue. Then, scroll down until you see our featured article today. I will include a link in the show notes as well. Have you ever discussed epidural analgesia options with a pregnant patient and been asked this question, “Do epidurals cause autism?” The short answer is no and we are going to explore more about this important topic for pregnant patients and anesthesiology professionals including a review of the literature and the surrounding controversy.

Before we get into the article, we are going to hear from one of the authors, Caroline Thomas. Let’s take a listen now.

[Caroline Thomas] “Hello, my name is Caroline Thomas and I am a current obstetric anesthesiology fellow at Northwestern University in Chicago. In a past life, I was also a pediatrician and completed pediatrics residency at Stanford University. I really would like to thank the Anesthesia Patient Safety Foundation for having me on your podcast and for discussing this important topic with your listeners.”

[Bechtel] We are so excited to have Thomas on the show today. To kick things off, I asked Thomas, “Why did you write this article? Let’s take a listen to what she had to say.

[Thomas] “I wrote this article because as a pediatrician, I know how important it is for new and upcoming parents to make medical decisions they feel are in their child’s best interest, and this includes decisions regarding labor analgesia. The goal of this article was to provide a summary of the available scientific data in a field of research that is evolving in real-time. My biggest concern is that women may not opt for epidural analgesia due to unwarranted fear that epidurals might cause autism.”

[Bechtel] And now it’s time to review autism and the available data related to epidural analgesia. The authors start with background information about autism which is a developmental disorder with persistent deficits in communication and social interaction. Patients with autism may also have stereotypic or repetitive behaviors. The etiology for autism is unknown, but is likely related to environmental and genetic risk factors. In the United States, the incidence of autism has increased with more research being done to evaluate risk factors. Perinatal and neonatal exposures have been evaluated as well as obstetric and delivery risk factors, but the results have not provided reliable answers for the risk factors for autism and why the incidence is increasing. Then, on October 12, 2020 an article was published in JAMA Pediatrics, “Association between epidural analgesia during labor and risk of autism spectrum disorder in offspring” that highlighted this important patient safety concern and kicked off a debate that we are going to discuss today. I will include a citation for this article in the show notes as well.

First up, let’s discuss the JAMA Pediatrics article that evaluated the association between lumbar epidural anesthesia exposure and the risk of developing autism in offspring. This was a retrospective longitudinal cohort analysis of almost 150,000 singleton children born by vaginal delivery between 28 and 44 weeks gestational age in the Kaiser Permanente Southern California hospital system between 2008 and 2015. The authors used electronic medical records to assess anesthetic records and standardized autism evaluations at 18 months and 24 months old. Now, for the results: The authors reported the following: epidural usage rate of 74.2% with 1.9 % of children in the lumbar epidural exposure group being diagnosed with autism compared to 1.3% of children in the non-epidural group. Looking closer at the lumbar epidural group, longer duration of epidural exposure was associated with a higher risk for the offspring developing autism, but maternal fever related to the epidural was not associated with an increased risk of autism in children. The authors highlight that this is a concerning finding about the safety of lumbar epidurals related to long term health outcomes for the offspring following the exposure and state that more research in this area is needed to further evaluate this association.

This study had a big impact in terms of questions about the safety of epidural exposure during labor as well as the methodology of the study and the response to this publication was quick…on the same day in fact. Five medical societies including the ASA, American College of Obstetricians and Gynecologists, the Society for Obstetric Anesthesia and Perinatology, the Society for Pediatric Anesthesia, and the Society for Maternal-Fetal Medicine published a joint statement with the goal to reassure pregnant patients. The joint statement includes the following key points:

  • the article “does not provide credible scientific evidence that labor epidurals for pain relief cause autism” since an association between the treatment (the lumbar epidural analgesia) and the outcome (development of autism in exposed offspring) does not prove that the treatment caused the outcome. This is such an important point that cannot be understated.
  • The article may cause anxiety for pregnant patients when deciding on analgesia options during labor
  • Labor epidurals are safe and effective for analgesia during labor and should continue to be offered especially since they are the “gold-standard” and have been shown to improve maternal and neonatal outcomes.
  • Limitations of the study include unknown details about the deliveries or other possible causes of autism.

I’m going to read the last paragraph of the joint statement now.

“Additionally, while the authors speculate about mechanisms (like maternal fever) that could explain a link between epidural pain relief and autism, none of these are plausible or confirmed in the analysis. Epidural analgesia involves administering small amounts of dilute local anesthetics and opioids into the mother’s epidural space. Very low levels of these drugs are transferred to the infant, and there is no evidence that these very low levels of drug exposure cause any harm to an infant’s brain. We urge women to continue to choose safe ways to relieve pain, including epidurals, for a positive childbirth experience. Our organizations will continue to foster research and education in all aspects of childbirth care, including the safety of labor analgesia for mother and child.”

I will also include a link to the joint statement in the show notes. This is a must read for all anesthesia professionals who take care of obstetric patients.

Let’s continue our literature review by looking at several other studies published in 2021 related to the association between epidurals and autism. Check out table 1 in the article for more information. The first column is the Jama Pediatrics study. Remember, this study found an association between maternal use and duration of labor epidural analgesia and autism with important limitations including duration of epidural exposure not cumulative dose, single center retrospective cohort study, baseline difference between patients in the two groups, and the risk for residual confounding factors. The response to this article from the medical community included critiques, criticisms, and letters to the editor all related to the limitations with the study especially the residual and uncontrolled confounding. The JAMA Pediatrics Editor in Chief replied with an Editor’s Note that stated that he did not think that the article succeed in establishing the association and that JAMA Pediatrics was committed to publishing a more definitive study in the future. The highlighted limitations included the following:

  • failure to consider whether the parents had autism since there is a genetic component to the development of autism
  • and the biological plausibility of low-dose local anesthetic administration into the epidural space for the mother leading to affecting the developing brain in the child. The authors tell us that “There is very sparse data regarding any causal relationship between LEA and abnormal neurologic development in both humans and animals.”

If we go back to Table 1 in the article, we can look at the next study by Wall-Weiler and colleagues from April 2021 which was a longitudinal population-based cohort study of over 120,000 children born in Manitoba, Canada. The exposure was maternal use of epidural labor analgesia and the neuraxial rate for this study was much lower at 38.2%. The investigators found that there was no association between autism and labor epidural exposure. Limitations for this study included less risk for residual confounding since more covariates were included, no information about drug dosing, baseline difference between patients in both groups, and low epidural utilization.

Fast forward to September 2021 and another study came out by Mikkelsen and colleagues that was a nationwide retrospective cohort study of almost 500,000 children born in Denmark that evaluated the exposure of labor epidural analgesia. The neuraxial utilization rate was 19.4%. Once again, autism was not associated with labor epidural exposure. This study has the same limitations as the Wall-Weiler study including less risk for residual confounding since more covariates were included, no information about drug dosing, baseline difference between patients in both groups, and low epidural utilization.

Another article was published in September 2021 by Hanley and colleagues. This was a another longitudinal population based cohort study of almost 400,000 children born in British Columbia, Canada. The epidural utilization rate was 28.7%. This time there was a small association between autism and labor epidural exposure and there were the same limitations. Don’t worry I will include citations for these studies in the show notes for you to review as well. Keep in mind, that the follow-up studies included more covariates to decrease the impact of residual confounding. In the study by Hanley and colleagues that reported a small association, the investigators performed multiple sensitivity analyses that did not show an association leading to the conclusion that there was a high likelihood for residual confounding and that there was not enough evidence for an association between labor epidural exposure and autism.

We have so much more to discuss related to this article including the most serious concern with the JAMA Pediatrics study as well as how to discuss this important topic with your patients, so tune in again next week. Plus, we are going to here from Thomas again, so mark your calendar.

The Society for Neuroscience in Anesthesiology and Critical Care 50th Annual Meeting is going to be in Seattle on September 8-10th. The online submission site for abstracts is open now. but you need to get your abstract in soon because the deadline to submit 11:59pm US Eastern Time on Monday, May 2nd, which is coming up! Abstract categories include the following:

  • Basic Science
  • Clinical Science
  • Medically-challenging Case
  • Education
  • Neuromonitoring
  • Neuroprotection
  • Cerebral Ischemia
  • Patient Safety
  • Quality Assessment
  • Cerebrovascular and/or Subarachnoid Hemorrhage
  • Stroke
  • Delirium
  • Cognition
  • EEG Monitoring
  • Clinical Trial
  • Other

One of the annual award categories is the APSF Patient Safety Abstract Award of $500. That’s right, so go ahead and submit your patient safety related abstract for the annual SNACC Meeting and you could win this award and present your patient safety related abstract at the meeting. I will include a link to the submission site in the show notes as well.

Thank you so much to Thomas for contributing to the show today and for helping to share the critical message that labor epidurals do not cause autism. We are looking forward to hearing from you again next week. This is important information for anesthesia professionals, obstetricians, nurses, our patients, and other members of the obstetric healthcare team so we hope that you will share this podcast and article. We have the answer to the question, “Do epidurals cause autism?” The short answer is No and the longer answer is there is not a correlation or a causative relationship between autism and lumbar epidurals for labor analgesia

If you have any questions or comments from today’s show, please email us at [email protected]. Please keep in mind that the information in this show is provided for informational purposes only and does not constitute medical or legal advice. We hope that you will visit APSF.org for detailed information and check out the show notes for links to all the topics we discussed today.

Until next time, stay vigilant so that no one shall be harmed by anesthesia care.

© 2022, The Anesthesia Patient Safety Foundation