You’ve likely heard that Advil (generic name: ibuprofen) and Aleve (naproxen) are discouraged for pain relief during pregnancy, but have you heard that even Tylenol (acetaminophen), long considered the gold-standard of pain relief during pregnancy, might be on the chopping block now, too? Below, I’ll review the potential problem with taking Tylenol while you’re pregnant, what recent research suggests, and what other options you have for pain relief while expecting.
What’s all the fuss about Tylenol during pregnancy?
Some research suggests that frequent maternal consumption of acetaminophen during pregnancy is associated with increased risk of autism—which is often diagnosed by age 3, disproportionately impacts boys, and affects roughly 2% of American children—and/or attention deficit hyperactivity disorder (ADHD), which impacts nearly 10% of American children aged 3-17. Currently, multiple lawsuits have been filed nationwide against retail pharmacies who sell acetaminophen and Tylenol, “alleging that acetaminophen manufacturers and distributors failed to warn consumers of an elevated risk of Autism and ADHD developing in babies of mothers who use the product during pregnancy.” The U.S. District Court for the Southern District of New York is hearing the consolidated case.
What does the research about Tylenol during pregnancy say?
Supporting evidence
A 2016 research study of 2,644 mom-baby pairs in Spain published in the International Journal of Epidemiology found that “Prenatal acetaminophen exposure was associated with a greater number of autism spectrum symptoms in males and showed adverse effects on attention-related outcomes for both genders” [1]. A 2018 meta-analysis published in the American Journal of Epidemiology read similarly, “our analysis of the available evidence indicates that acetaminophen exposure during pregnancy is associated with a 20%–30% increased risk for neurodevelopmental disorders” [2]. Another meta-analysis, this one in 2019, likewise found “an association between maternal acetaminophen use during pregnancy and the risk of attention deficit/hyperactivity disorder in offspring. The timing and duration of acetaminophen use during pregnancy may have a major effect on the risk of attention deficit/hyperactivity disorder” [3].
Research limitations
Critiques of much research done into the Tylenol/neurological disorders connection have centered on small sample sizes, the possibility of recall bias, and absent or insufficient information about dosage consumed, duration of use, or the reason why patients were taking the medication. For instance, prolonged fever in mothers, as might be treated with Tylenol, suggests an active, untreated infection, which could also contribute to the development of neurological conditions in their unborn babies.
A National Institutes of Health-funded study published in 2019 aimed to remove some of these potentially confounding variables. 966 mom-baby pairs were studied in the research, which started in 1998 and concluded in 2018. Tylenol levels in the babies’ umbilical cord blood samples were tested at birth and then those babies were tracked for 21 years. Researchers did find an association between maternal use of Tylenol and childhood development of autism and/or ADHD [4].
The 2019 NIH study offered several potential mechanisms of action, or explanations of how specifically Tylenol might cause problems. The study authors wrote, “Studies23,24 in rodents reported acetaminophen toxicity in cortical neurons and inhibition of fetal testosterone production, which would critically disrupt brain development. In addition, the therapeutic effect of acetaminophen can selectively inhibit cyclooxygenase 2, which may affect multiple brain functions, including long-term potentiation,25 spatial learning,26 and cerebellar development.27” [4] The authors further noted, “Human studies12–22,28–32 have found that acetaminophen could cross the human placental barrier and remain in an infant’s blood circulation for a long duration.28,29” [4]
Why it’s difficult to establish a direct connection between use of Tylenol and autism/ADHD
Detecting a link between Tylenol consumption and risk of autism and/or ADHD and then quantifying that risk is complicated because, as the American College of Obstetricians and Gynecologists (ACOG) points out, factors after birth can play a role in the childhood development of neurological disorders in addition to in-utero exposures. Certainly, genetic vulnerability plays some role in the development of autism, with or without Tylenol use, acknowledges Dr. Roberta Ness, the same epidemiologist who raised the alarm about talcum powder (baby powder) use potentially leading to increased risk of ovarian cancer. In other words, while there is some compelling evidence linking Tylenol use and autism/ADHD, more research is needed in this area.
What might constitute “frequent use” of Tylenol?
“The dose makes the poison,” as they say. So just how many days of consecutive Tylenol consumption are too many for a pregnant mother? That’s not clear. The general principle seems to be that the more Tylenol a woman takes, and especially the longer she takes it, the higher the risk for her baby or babies of developing autism or ADHD. The 2016 Spanish study researchers wrote that “These [autism and ADHD] associations seem to be dependent on the frequency of exposure.” And, as University of Texas Southwestern OB/GYN Dr. Robyn Horsager-Boehrer pointed out, none of the studies reviewed in the 2018 meta-analysis found an increased risk of ADHD when mothers used Tylenol for a week or less. A 2022 USA Today story noted that “Roughly 10% [of pregnant women] take [Tylenol] for more than a month” but no source for that statistic was cited.
Have recommendations from medical organizations about using Tylenol in pregnancy changed?
A consensus statement….
While not a research study, in 2021, the journal Nature Reviews Endocrinology published a consensus statement* signed by more than 90 researchers, scientists, and clinicians, cautioning pregnant women to limit their use of Tylenol. The statement, which listed more than 160 references as evidence, read:
“We recognize that limited medical alternatives exist to treat pain and fever; however, we believe the combined weight of animal and human scientific evidence is strong enough for pregnant women to be cautioned by health professionals against its indiscriminate use, both as a single ingredient and in combination with other medications….Packaging should include warning labels including these recommendations.”
The statement signers recommend pregnant women take Tylenol “cautiously at the lowest effective dose for the shortest possible time” [5].
*Of note, outside the U.S., Tylenol is commonly known as paracetamol, and it is referred to by this name in the statement.
….And ACOG’s response
In response to the consensus statement, ACOG published a clinical bulletin reading:
“This consensus statement, and studies that have been conducted in the past, show no clear evidence that proves a direct relationship between the prudent use of acetaminophen during any trimester and fetal developmental issues”
and
“The authors are not recommending anything counter to what is already done by obstetrician-gynecologists when prescribing acetaminophen for a given clinical condition. ACOG’s clinical guidance remains the same and physicians should not change clinical practice until definitive prospective research is done.”
Differentiating correlation from causation
A 2017 position statement of the Society for Maternal Fetal Medicine, which issues practice guidelines for high-risk pregnancy specialists, called the research thus far “inconclusive.” While it’s true that research to date does not definitively establish causation, meaning that it doesn’t spell out ‘this amount of Tylenol use can definitely cause autism or ADHD in offspring,’ those raising the alarm point out that pregnant women deserve to know about the possibility of a connection because it may impact their decision to take Tylenol or not.
Is Tylenol during pregnancy better than other pain medications?
The USA Today story quoted Dr. Andrea Edlow, an OB/GYN and obstetric research director at Massachusetts General Hospital, noting that whereas she believes the potential Tylenol-neurodevelopmental disorders connection is “a nuanced area,” the common pain relief alternatives to Tylenol are already known to be unequivocally problematic for pregnant women and/or their preborn children. As Dr. Edlow points out, “Ibuprofen is clearly associated with developmental risk and maternal opioid use is also associated with maternal, fetal and neonatal risks.”
Frustratingly, women who might not otherwise take Tylenol or Ibuprofen when they’re not pregnant may be tempted to turn to them precisely for pregnancy-induced issues like backaches and migraines. Recognizing this, Dr. Edlow insisted that pregnant women need to be able to take something for pain relief.
What other pain relief options do women have?
So what’s the bottom line? Should pregnant women go out and toss their Tylenol? Maybe not, but they probably should exercise caution before taking the drug, especially for extended periods of time. Fortunately, those seeking to obtain mild to moderate pain relief, especially for pregnancy-related aches and pains, have many non-pharmacological or non-medication options. Among these are use of support belts (as for back pain), heat or ice, rest, prenatal massage, pregnancy-safe acupuncture, chiropractic care, or pelvic floor physical therapy (pelvic floor physical therapists are specially trained to treat pregnancy-related problems). Still, utilizing some of the above non-medication pain relief options can be time-consuming and costly, especially in the context of (often) little or no insurance coverage for services like massage, acupuncture, chiropractic care, and/or pelvic floor physical therapy.
“The data are inconclusive” is an unsatisfactory answer to medication safety in pregnant women
The lack of good data for pregnant women surrounding the safety of such commonplace medications as Tylenol is just one facet of a larger problem. Pregnant women, as well as breastfeeding and even just regularly menstruating women (i.e. women not on hormonal birth control), are routinely excluded from pharmaceutical research trials, as covered in-depth by Natural Womanhood Editor Grace Emily Stark here.
While there is good reason to exercise caution in conducting clinical trials on pregnant women given potential risks to themselves or their preborn children, an estimated 90% of women will require medication at some point, or throughout, their pregnancies, according to the Centers for Disease Control and Prevention (CDC). As Stark points out, “many pregnant and breastfeeding women require treatment through pharmaceuticals for various conditions, but must make these health-care choices without the benefit of clinical data.” Pregnant women deserve accurate, evidence-based information about the potential risks of medication, especially frequently used medications, to themselves and their preborn children.
This article was last updated on February 1, 2023 to include possible mechanisms of action explaining a link between Tylenol use and development of ADHD and/or autism.
References:
[1] Avella-Garcia, Claudia B et al. “Acetaminophen use in pregnancy and neurodevelopment: attention function and autism spectrum symptoms.” International Journal of Epidemiology, vol. 45, no. 6 (2016): pp. 1987-96. https://doi.org/10.1093/ije/dyw115 [2] Masarwa, Reem et al. “Prenatal Exposure to Acetaminophen and Risk for Attention Deficit Hyperactivity Disorder and Autistic Spectrum Disorder: A Systematic Review, Meta-Analysis, and Meta-Regression Analysis of Cohort Studies.” American Journal of Epidemiology, vol. 187, no. 8 (2018): pp. 1817-27. https://doi.org/10.1093/aje/kwy086 [3] Gou, Xiaoyun et al. “Association of maternal prenatal acetaminophen use with the risk of attention deficit/hyperactivity disorder in offspring: A meta-analysis.” The Australian and New Zealand journal of psychiatry, vol. 53, no. 3 (2019): pp. 195-206. doi:10.1177/0004867418823276 [4] Y Ji, R E Azuine, and Y Zhang. “Association of Cord Plasma Biomarkers of In Utero Acetaminophen Exposure With Risk of Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder in Childhood.” JAMA Psychiatry, vol. 77, iss. 2 (2020): pp. 180-89. doi:10.1001/jamapsychiatry.2019.3259 [5] Bauer, A.Z., Swan, S.H., Kriebel, D. et al. Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol 17, 757–766 (2021). https://doi.org/10.1038/s41574-021-00553-7Additional Reading:
Cervical checks during pregnancy: What they can and can’t tell you
Is your pregnancy diet up to date with science?
Induction drug Pitocin is not the same as natural oxytocin: Some cautions for future moms
