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The development of safe and effective epidural analgesia, a process that began in the mid-19th century, was a marvel of modern medical achievement. First implemented for reduction of pain during surgical procedures, it initially used intermittently injected cocaine as the anesthetic agent. It took a few decades before it was introduced into obstetrical practice, which was a huge improvement over chloroform but still far from ideal. Sorting out the ideal depth of the injection for each indication and synthesizing less toxic agents would eventually improve the safety and reliability of the procedure considerably, but there were even more advancements on the horizon.

It wasn’t until the 1930s that the use of continuous infusions into the epidural space came into practice, which improved the reliability of pain control throughout a potentially lengthy labor. On January 6th, 1942 at the Marine Hospital in New York, continuous epidural analgesia was used during childbirth for the first time when a woman with rheumatic heart disease required an emergency C-section. Currently epidural analgesia is the most common form of pain control during labor, and involves a combination of drugs that provide fast pain relief with the ability to maintain that relief for the duration of childbirth. There are few side effects for mother, even fewer for baby, and serious complications are rare.

The use of epidural labor analgesia (ELA), which involves the injection of an anesthetic and/or analgesic agents into the space between the inner surface of the vertebral column and the outer surface of the membrane covering the spinal cord in order to provide pain reduction or numbness distal to the site of injection, is not without controversy. This post is not going to serve as an all-encompassing discussion of the history of the pushback against pain control during labor, which is replete with misogyny and pseudoscience. Rather I’m going to focus on one particular concern that has come up in recent years: a potential link between epidural labor analgesia and autism.

In late 2020, the Journal of the American Medical Association published a study that found a 37% increase in the relative risk of autism in children who where “exposed to epidural analgesia” during a vaginal delivery. There was intense skepticism and the relevant medical societies and associations responded:

Importantly, in this study many of the details about the course of these deliveries are not available. There are multiple other possible causes of autism that the study does not address.

The joint statement further points out the lack of plausibility that epidural analgesia would increase the risk of autism:

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.

Low plausibility combined with a positive yet inadequate study is a common pattern discussed on the pages of SBM. Unfortunately, this is also a combination that frequently finds itself covered excitedly by journalists of varying quality, with the end result of a worried public. In order to answer this question more definitively, and hopefully put fears to rest or guide new patient care recommendations depending on the outcome, a study that better addressed the many potential confounding factors was needed. Earlier this month that’s exactly what we got.

Also published in JAMA, the new study found no association between ELA and autism. This time there was an improved “accounting for maternal sociodemographic, preexisting, pregnancy-related, and birth-specific factors”, which means that the results are much more likely to be accurate. Here is a solid piece on the situation (not just because I contributed) by Tara Haelle, who consistently does excellent work covering healthcare topics.

Although we have learned a great deal about autism over the decades, there remain plenty of questions yet to be answered. We don’t know with certainty the totality of factors that might contribute to a child receiving the diagnosis. That being said, we know it is largely genetic in origin and any evidence showing an environmental trigger would need to be compelling for it to change the way we approach pain control during labor.

Now for the elephant in the room. Why was this investigated at all? Is this an example of researchers throwing random crap against a wall just to see what sticks? Probably. It happens a lot. People are desperate to find modifiable risk factors for autism. This isn’t one. Hopefully this doesn’t turn into another zombie belief that returns every few years to scare women into foregoing adequate pain control during labor.

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Posted by Clay Jones

Clay Jones, M.D. is a pediatrician and a regular contributor to the Science-Based Medicine blog. He primarily cares for healthy newborns and hospitalized children, and devotes his full time to educating pediatric residents and medical students. Dr. Jones first became aware of and interested in the incursion of pseudoscience into his chosen profession while completing his pediatric residency at Vanderbilt Children’s Hospital a decade ago. He has since focused his efforts on teaching the application of critical thinking and scientific skepticism to the practice of pediatric medicine. Dr. Jones has no conflicts of interest to disclose and no ties to the pharmaceutical industry. He can be found on Twitter as @SBMPediatrics and is the co-host of The Prism Podcast with fellow SBM contributor Grant Ritchey. The comments expressed by Dr. Jones are his own and do not represent the views or opinions of Newton-Wellesley Hospital or its administration.