Updates from the Director of Scientific & Clinical Initiatives
September 2025
As many of you have seen, the Trump administration had a press conference where they announced countless initiatives changing the way autism is treated and studied in this country. he headline that received the most attention was the claim that acetaminophen use during pregnancy leads to increased autism risk. This claim was a misinterpretation of studies, the most recent of which was published in August.
The recent study in question looked at many other previous studies assessing links between acetaminophen and autism. This summary study identifies a “strong, consistent association between prenatal acetaminophen exposure and ADHD/ASD.” In the discussion portion of the manuscript, the authors offer a lengthy description of possible biases from each individual study they looked at. They ended their discussion by clearly stating that, “unmeasured or residual confounding remains a potential source of bias…This highlights the need for future studies to employ quantitative methods to further refine these associations further.” In other words, the study correlates acetaminophen use during pregnancy with autism diagnoses but does not show causation. Learn more about why the distinction between correlation and causation is so important in the Learn section of our Spotlight!
-Dylan Ritter
LEARN
Correlation ≠ Causation
I want to take this opportunity to make sure everybody in the Dup15q community understands the difference between correlation and causation. Both words are used to look at two variables changing, like autism diagnosis rates and acetaminophen usage during pregnancy.
Correlation would say that there is an association between pregnancy acetaminophen use and autism diagnosis, i.e. if a woman takes acetaminophen while pregnant, the odds of having a child with autism increases. But other factors could contribute to increased likelihood of an autism diagnosis as well, including genetics, environmental influences, and widening diagnostic criteria for an autism diagnosis.
Causation would say that there is a proven connection between pregnancy acetaminophen use and autism diagnosis, i.e. if a woman takes acetaminophen while pregnant, then the acetaminophen will increase the risk of having a child with autism. The key difference is reporting that two things happen vs claiming one thing causes a second thing. In order to prove this causation, we would need to consider several other factors that contribute to either one of these variables increasing with time.
We know that diagnostic criteria for autism have broadened recently, and clinicians are becoming more adept at detecting and diagnosing autism in individuals. This means that the likelihood of an autism diagnosis is higher in a person born in 2015 than a person born in 2005. Does that mean there was something added to the drinking water in 2014 that causes autism? No! Autism is also a combination of environmental and genetic causes. We know that autism risk in Dup15q syndrome is very high, and that is linked to the genetics of the disorder. If you’re a Dup15q mom reading this, you probably are already confident that your child doesn’t have Dup15q or autism because you took acetaminophen during pregnancy. Your child has extra genetic material that contributes to the Dup15q diagnosis and an increased risk of autism.
Looking at acetaminophen use, fever during pregnancy can increase the risk of adverse effects in babies, including autism. As a result, physicians make sure that pregnant women take acetaminophen to reduce the fever and decrease the risk for adverse effects in their unborn baby. In this instance, it has been shown that a fever is much more harmful for a baby than acetaminophen use. Yet, if a mother has many fevers during pregnancy (and thus, took acetaminophen), and those fevers could harm the unborn baby, then it would appear that acetaminophen causes problems, as opposed to the fevers the acetaminophen was attempting to assuage. When you consider all these factors together, you see several confounders, or other explanations to the data that could explain the correlation, without proving causation.
This website, introduced by my graduate school biostatistics teacher (thank you, Dr, Bowman!), shows how two things can appear correlated, while it is clear there is zero causation between them. One example shows that over time, burglary rates in the US seem to be changing in lockstep with the distance between Neptune and the sun. Surely, one must cause the other, right? Of course not! These are just two things being measured that happen to change similarly over time. Burglary rates in the US decreasing can be explained by the rise of improved home security technology, like cameras, locks, and lights. Neptune happens to be in a stage of its 165 year orbit where it is moving slightly farther from the sun before oscillating back. These other explanations serve as examples of confounders that can explain why two variables (burglaries and Neptune) appear to follow similar (and statistically significant!) changes, even though one does not cause the other. These two datasets are correlated, not causative.
TREAT
Epilepsy Clinical Trials
A clinical trial is a standardized research study for the safety and efficacy of a test drug on a given health outcome. Traditionally, clinical trials are specific to one health outcome or disease, like seizures in Dup15q syndrome. However, there are some clinical trials that are called “basket clinical trials” that include patients with different diagnoses as long as they share a specific symptom. In the context of this discussion, the basket clinical trials I will be discussing revolve around epilepsy.
Epilepsy is a common symptom in neurodevelopmental disorders, and current treatments of epilepsy in Dup15q syndrome are not designed for the genes implicated in Dup15q syndrome. Instead, epilepsy is treated with common anti-seizure medications. This is also true for other rare neurodevelopmental disorders that have epilepsy as a symptom. Many patients diagnosed with rare neurodevelopmental disorders qualify for trials looking at treating seizures in developmental and epileptic encephalopathies (DEEs).
Below are three clinical trials that are actively recruiting across the rare neurodevelopmental epilepsy space by targeting common cell functions that are not specific to one disorder or another but are instead involved in seizures generally. Inclusion criteria vary for each, but we wanted to lay out these opportunities for any of our families struggling with seizures who are open to trying something new!
CURE
ASO, BBB, and CSF
Last month, we discussed why you can’t take an ASO like a pill. To better understand how an ASO can reach the cells in the brain, we must consider the blood-brain barrier. The blood-brain barrier prevents many drugs from reaching the brain unless they have specific properties. ASOs are too big to pass through the blood-brain barrier, so clinicians need another way to administer the ASO so it reaches the brain.
To reach the brain, clinicians can inject ASOs into a circulating fluid called the cerebrospinal fluid (CSF). CSF is a circulating fluid that directly contacts the brain to cushion the brain from your skull, supply key nutrients, and remove waste from the brain. It is fully replenished naturally every 6 hours and serves as a critical way for researchers and clinicians to access the brain indirectly. Injecting a medication into the CSF is the most direct way to help medication get to the brain without having to undergo brain surgery for direct injection into the brain.
ASOs are injected into the CSF using a needle through a lumbar puncture (also called a spinal tap). The ASO is delivered towards the base of the spinal column in an area below the spinal cord, meaning there is no risk of severe nerve damage! Many families may be more familiar with epidurals, commonly used during childbirth, as a medication administration very similar to how an ASO would be administered in the spine.
If I were to receive a lumbar puncture, clinicians would only need local anesthesia to numb the site of injection. However, clinicians may opt to use light sedation in patients where there is a risk of moving during the injection process. Many of our loved ones with Dup15q syndrome would fall into the light sedation category, which can lead to some anxiety in parents and family members. Rest assured, lumbar punctures are routine procedures performed many times daily across the country. If you want to learn more about what a lumbar puncture for CSF collection or ASO administration looks like, watch Dr. Diana Walleigh describe what to expect from the Big Give 2025.
