A Few Things to Know About Tylenol and Pregnancy.
In light of the announcements this week, I thought I would share some research on Tylenol (acetaminophen) use during pregnancy. I know this is a very sensitive topic. Autism, ADHD, and other neurodevelopmental conditions can profoundly affect families, and it’s never easy to navigate.
Unfortunately, autism rates are increasing. Historically, it was diagnosed in about 1 in 2,500 children in the 1970s. By 2000, the rate was closer to 1 in 150. Today, the CDC estimates that approximately 1 in 36 children in the U.S. are diagnosed with autism spectrum disorder. This sharp increase cannot be explained away as “just better diagnosis.” Today there are many environmental, nutritional, and medical factors in modern life that are interacting with vulnerable biology. Every child deserves the best chance at life, which is why it’s essential that we investigate all possible contributors.
Acetaminophen, better known by the brand name Tylenol, was first introduced in the United States in the 1950s as an alternative to aspirin. At the time, aspirin was widely used for pain relief and fever reduction, but when research linked it to Reye’s syndrome, Tylenol quickly became a household staple. Over the decades, it has grown into one of the most widely used over-the-counter drugs in the world.
Unlike aspirin or ibuprofen, acetaminophen is not considered a classic anti-inflammatory drug. Its main effect is reducing pain (analgesia) and lowering fever (antipyresis).
Interestingly, the exact mechanism isn’t fully understood, but research suggests it works primarily in the central nervous system, rather than at sites of inflammation. Some evidence also points to acetaminophen’s interaction with the endocannabinoid system and serotonin pathways, which may contribute to its pain-relieving effects.
Despite its reputation as a “safe” drug, acetaminophen carries serious risks when taken in high doses or combined with alcohol. The liver is the main organ responsible for metabolizing acetaminophen.
Most of the drug is broken down into harmless compounds, but a small fraction is converted into a toxic metabolite called NAPQI (N-acetyl-p-benzoquinone imine). Normally, NAPQI is quickly neutralized by glutathione, the body’s master antioxidant. However, when too much acetaminophen is taken, or when glutathione stores are depleted, NAPQI accumulates and causes severe liver cell damage.
Acetaminophen overdose is the leading cause of acute liver failure in the United States and many other countries. Each year, thousands of people are hospitalized, and hundreds die, from either accidental or intentional overdoses.
Even modest overdoses, taken over several days, can overwhelm the liver and cause irreversible injury. Because acetaminophen is included in hundreds of prescription and over-the-counter combination medications—like cold and flu remedies—people often ingest more than they realize, increasing the risk of toxicity.
In recent years, acetaminophen has come under scrutiny for its safety during pregnancy. Observational studies and meta-analyses have suggested an association between prenatal acetaminophen exposure and increased risk of neurodevelopmental disorders, including ADHD, autism spectrum disorder (ASD), and behavioral problems.
For example, a 2019 NIH-supported study measured acetaminophen metabolites in umbilical cord blood and found that higher levels were linked with a significantly greater risk of both ADHD and ASD in childhood. The proposed mechanism involves acetaminophen’s ability to cross the placenta and potentially interfere with fetal brain development by disrupting endocrine function, oxidative stress pathways, or prostaglandin signaling, all of which play roles in early neurodevelopment.
More recently, a 2025 review led by Harvard and Mount Sinai researchers examined 46 studies on prenatal acetaminophen use. They found consistent evidence that longer or higher use during pregnancy was associated with increased risk of ADHD and autism in children. The authors stressed that the drug crosses the placenta and may disrupt fetal brain development, though causation isn’t proven. Their recommendation: use acetaminophen only when necessary, at the lowest dose and shortest duration possible.
Possible mechanisms:
- Endocrine disruption:
Acetaminophen may interfere with sex hormone signaling (estrogen/ androgen pathways). In animal studies, acetaminophen reliably lowers testosterone and acts as a feminizing agent. This disruption of androgen signaling can have long-term consequences for male development.
Acetaminophen lowers DHEA-S and pregnenolone sulfate (PS), the body’s storage forms of vital neurosteroids. These sulfated steroids fuel placental development, fetal brain growth, and long-term hormone balance.Depleting them mimics accelerated aging inside the womb.
- Oxidative stress & glutathione depletion:
Acetaminophen is metabolized to a toxic intermediate (NAPQI) that requires glutathione (GSH) for detoxification. Chronic or high use can deplete GSH reserves in mother and fetus, leading to oxidative stress and DNA/protein damage.
- Neurotransmitter alteration:
It interacts with the endocannabinoid system and serotonin pathways. Animal and human evidence shows that blocking serotonin receptors reduces acetaminophen’s pain relief, suggesting that part of its action depends on boosting serotonin signaling. Incidentally, serotonin is often elevated in autism.
- Epigenetic changes:
Prenatal acetaminophen exposure has been linked to specific DNA methylation shifts in placental and cord blood tissue. Studies have found altered methylation at dozens of CpG sites, including in genes involved in prostaglandin signaling (PTGDR) and drug metabolism (CYP2E1). These changes may affect how the fetus regulates growth, detoxification, and stress responses, potentially influencing long-term neurodevelopment.
- Placental transfer:
Acetaminophen readily crosses the placenta; fetal tissues, including the brain, may accumulate drugs or its metabolites, increasing vulnerability.
It’s important to note that these studies show associations, not definitive causation. However, this is because it would be unethical to run controlled experiments exposing pregnant women to acetaminophen. So we have to rely on observational data, which are always subject to confounding factors.
Historically, pregnancy has been underrepresented in medical research for this very reason, and the default has been to err on the side of caution. This has been to protect women and babies, not as a political issue, but because exposing developing life to potential harm without certainty of safety carries risks that are simply too great.
However, the mounting evidence across multiple large cohorts suggests that acetaminophen may not be as safe in pregnancy as once believed, and caution is an act of empowerment, not restriction: women deserve the full truth so they can make informed decisions for themselves and their children.
I want to also note that this is not a fringe perspective. Before the issue became political, experts were saying similar things:
“Higher-quality studies are more likely to show a link between prenatal acetaminophen exposure and increased risks of autism and ADHD,” said Diddier Prada, MD, PhD, Assistant Professor of Population Health Science and Policy, and Environmental Medicine and Climate Science, at the Icahn School of Medicine at Mount Sinai. “Given the widespread use of this medication, even a small increase in risk could have major public health implications.”
Alternatives for pain, headaches, and fever include:
- Aspirin: lowers inflammation, pain, and fever; reduces excess serotonin; supports circulation; and restores oxidative metabolism. It is even used in obstetrics to help prevent preeclampsia and miscarriage (though dosing should always be guided by a physician).
- Epsom salt baths: provide magnesium through the skin, relaxing muscles, easing aches, and calming the nervous system.
- Magnesium and electrolytes: support muscle relaxation, reduce cramping and tension headaches, and restore balance if dehydration is a factor.
- Vitamin C: supports immune defense, reduces oxidative stress, and can help shorten the duration of viral illness that often drives fevers.
- Heat packs: help soothe muscle tightness or joint pain when applied locally (avoid directly on the abdomen during pregnancy).
- Gentle movement: such as stretching, prenatal yoga, or walking, improves circulation and helps reduce stiffness and pain.
- Herbal teas: ginger tea for nausea and mild pain, chamomile for relaxation (moderation advised).
For mothers, this is never about blame. But every effect has a cause. We can only make real progress by asking hard questions and looking honestly at the data. I also want to be clear that acetaminophen may be one factor, but autism is a complex condition with many influences. Research has also linked higher risk to low maternal thyroid function (PMID: 38149625), elevated serotonin (PMID: 26577932), high intake of polyunsaturated fatty acids (PUFAs) (PMID: 39041066), environmental toxins, and more.
We must look at everything if we want to ensure a better future for our children.
Published by Connealy, MD on September 26, 2025