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Tylenol: An Unexpected Neuroendocrine Disruptor
Acetaminophen (Tylenol). Most people reach for it for everyday headaches like it's no big deal, and 2/3 of women have used it in pregnancy. Yet acetaminophen is not benign. For example, it is one of the major contributors to liver disease in the US each year. Acetaminophen has also long been considered generally safe for use during all stages of pregnancy, making it the first-choice pain and fever medication for pregnant women. Given the large number of pregnant women using the drug, even a small increase in risk of adverse outcomes in offspring can have important implications for public health.
Tylenol started coming under scrutiny over its safety in pregnancy around 2014. Animal studies suggest that its use in pregnancy can have important implications for endocrine function, which is also important for neurodevelopment as well as normal sexual differentiation.
Most recently, in late 2021, a team of 13 scientists are cautioning against the use of pain relievers with acetaminophen (also known as paracetamol) by pregnant women, citing a growing body of research that suggests the drug might alter fetal development. The consensus statement, published in the journal Nature Reviews Endocrinology was supported by 91 researchers, clinicians and public health experts from around the world. They are alerting the medical community that acetaminophen may be at least partially responsible for rising rates of male reproductive disorders and cognitive, learning and behavioral problems among children over the past several years.
Zeyan Liew, Ph.D, M.P.H and assistant professor in the Yale School of Public Health’s Department of Environmental Health Sciences, and one of the authors of the statement said, “It is time to take the growing body of evidence seriously and consider precautionary measures.”
The Human Impact
Previously studies have raised questions about the drug’s safety in pregnancy, including a series of epidemiological studies linking pregnancy intake of acetaminophen with an increased risk for attention deficit hyperactivity disorders (ADHD), and impaired cognitive and executive function, vis a vis its impact on the developing human nervous system.
In a major study of over 64,000 Danish mothers, maternal use during pregnancy was associated with as much as a 37% increase in hyperkinetic disorder, a severe form of ADHD, and a 30% increase in ADHD in their children. Risks of ADHD in children went up to 50% in women who took Tylenol for 20 weeks or more during pregnancy. Stronger associations were observed with use in more than one trimester during pregnancy, and the higher the frequency of use, the higher the risk of ADHD and hyperkinetic disorder.
Another large study, of 7796 pregnant women who used acetaminophen at 18 and 32 weeks of pregnancy, again published in JAMA Pediatrics has confirmed these findings. This study found that children exposed to acetaminophen prenatally are at increased risk of multiple behavioral difficulties, and the associations do not appear to be explained by other behavioral or social factors.
Another study seems to confirm concerns that acetaminophen, which can cross the placenta, does have fetal neurologic effects, and may be implicated in autism. Researchers analyzed umbilical cord blood from 996 births gathered as part of a study called the Boston Birth Cohort, a long-term study examining factors affecting pregnancy and child development. By the time the children were an average of 8.9 years, 25.8% had been diagnosed with ADHD, 6.6% with ASD and 4.2% with both ADHD and ASD. These rates corresponded to levels of prenatal acetaminophen exposure, compared to the lowest third of exposure, the middle third was associated with about 2.26 times the risk for ADHD, the highest third 2.86 times the risk., and for ASD risk the middle third had 2.14 times the risk, and nearly 4 times the risk for the highest third.
It is no surprise that Tylenol could be at the root of problems in developing babies – it depletes a chemical called glutathione that we rely on in our bodies for detoxification, and it also acts as a hormone disruptor. This study, published in JAMA Pediatrics, suggests that acetaminophen may influence fetal brain development.
This is also not the first time lack of acetaminophen safety in pregnancy has been raised – it has been linked to undescended testicles in males, an increased risk factor for infertility and later development of testicular cancer.
Still Relevant When Mom Has a Fever, But Use Caution
While it is unlikely that using acetaminophen a few times over the course of a pregnancy is likely to cause a problem, and the benefits outweigh risk for fever reduction in pregnancy, these studies are a reminder that medications should not be used unquestioningly during pregnancy. As one of the study researchers warned, “We should continually remain vigilant to the need to reappraise the evidence concerning the risk-benefit balances of medications in light of new research findings.”
What's a Mom to Do? Tylenol Alternatives
Headaches are a common prenatal problem, and acetaminophen has been considered safe to use, whereas other commonly used headache medications including ibuprofen and aspirin are not safe for use in pregnancy. So what can you do?
First, if you've taken Tylenol or another form of acetaminophen, don't beat yourself up. The chances are, statistically speaking, still low that this will have any impact on your baby. And for fever and significant pain, it's still considered the safest prenatal option. But we can't just assumed it's safe and it can have an impact, so the goal is to avoid it when you can and keep your duration of use as brief as possible.
Here are 5 safe, natural tips to help reduce headaches in pregnancy:
1. Apply a few drops of lavender oil, peppermint oil, or Tiger Balm to the temples; these have been shown to safely and effectively reduce headaches.
2. Many headaches are a result of neck and shoulder tension, so don't overlook the value of massage, a gentle osteopathic manipulation, or craniosacral therapy for headache prevention and relief.
3. Magnesium can help reduce a tension headache; take 400 – 800 mg/day of magnesium glycinate, or if constipation is also a problem, magnesium citrate in the same dosage.
4. Take 2 ginger capsules once or twice daily if you feel a headache coming on; it is a natural anti-inflammatory herb that is considered safe in pregnancy
5. Take a hot bath with 2 cups of Epsom salts and 5-7 drops of lavender essential oil – the combination of magnesium in the Epsom salts, the aromatherapy from lavender, and hot water is deeply relaxing and can help relieve a headache.
If you suffer from migraines, Riboflavin (Vitamin B2) at 400 mg/day has been found effective for prevention, and safe for daily use in pregnancy. Also do a migraine journal to see if you can identify and remove triggers.
Several herbs that are generally considered safe for use in pregnancy, including ginger, which can be taken as a capsule up to 1 gm/day for pain relief.
If you have a sudden onset of a headache, a more severe headache than usual, any visual changes or upper abdominal pain with your headache, or if you have a history of high blood pressure, please see your midwife or physician promptly as these can be signs of more serious illness, like pregnancy induced hypertension or preeclampsia.
If you have frequent headaches, getting to the root cause by making sure you are getting enough sleep, reducing excessive inflammation with dietary and lifestyle changes, making sure you are getting all of your nutrients, including essential fatty acids and protein, and looking into environmental allergies (sometimes a HEPA air filter can help!) is key to optimal wellness and the best thing you can do for you and baby. You might also want to consider working with a functional medicine, integrative medicine, or naturopathic physician skilled in pregnancy care.