Is Tylenol Safe in Pregnancy?

News reports came out this week regarding a consensus statement that more studies be done on the safety of acetaminophen in pregnancy (Bauer, Swan, Kriebel, Liew, Taylor, Bornhag, et al, 2021).  Some of the headlines are alarming:  FOX news headline stated,  “Common painkiller acetaminophen could alter fetal development, researchers warn”, and the Daily Mail stated, “Pregnant women should NOT routinely take Tylenol because it may harm the development of babies in the womb”.

PDF Report attached or you can find it at Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol (2021).

What did the report say?  What should we tell our patients?

Acetaminophen, whose most common brand name is Tylenol and is also known as APAP, is one of the most common pain and fever-reducing medications.  Per the Consumer Healthcare Organization, “Acetaminophen is the most common drug ingredient in the United States. It’s found in more than 600 different medicines, including prescription and OTC pain relievers, fever reducers, and sleep aids as well as cough, cold, and allergy medicines.”  It has long been considered the safest option in pregnancy, and a benign treatment.  Many patients leave Acetaminophen off their list of over-the-counter medications because it is considered so common and safe.

This consensus report, though, will raise questions from patients about its safety.  This article will try to drill down on how to talk to our patients about the news report. 

Benefits of Acetaminophen

We have few alternatives for pain and fever in pregnancy.  Non-steroidal anti-inflammatory agents (NSAIDs) can delay closure of the ductus arteriosus so are not used in late pregnancy.  Given the increase in opiate use disorders in the US, as well as other adverse side effects, opioid use is also minimized.  We know that one common use of Acetaminophen, to reduce fever, may decrease the incidence of fever-related fetal effects such as neural tube defects, oral clefts, and congenital heart disease.   Women with migraine headaches often rely upon Acetaminophen for pain relief.

Concerns about Acetaminophen

We know that Acetaminophen does cross the placenta, but it has not been associated with major congenital malformations, miscarriage, or stillbirth.  However, after maternal overdose, there may be an increase in fetal death or miscarriage if treatment is delayed (UpToDate, 2021)

The concerns raised by this panel are not new, but they revolve around two areas:  the idea that acetaminophen is an “endocrine disrupter”, which may have adverse effects on the urogenital system of the developing fetus, and that neurobehavioral development may be affected as well.  The panel feels that the preponderance of evidence, with study limitations, led them to call for further research and awareness.

What is an endocrine disrupter?

Many chemicals, both natural and man-made, may mimic or interfere with the endocrine system. Called endocrine disruptors, these chemicals are linked with developmental, reproductive, brain, immune, and other problems, according to the National Institute of Environmental Health Sciences. Endocrine disruptors are becoming more widely identified as they are found in many common household goods, such as BPA plastics, detergents, toys, and cosmetics (NIH.gov). 

APAP exposure in rodent studies has been shown to cause reproductive disorders of the male urogenital tract, including abnormalities in testicular function, sperm abnormalities and sexual behavior. Experiments have also shown disruption of female ovarian development resulting in reduced oocyte number and subsequent early female pubertal development, ovarian insufficiency and subsequently reduced fertility (Bauer, et al, 2021). 

Neurobehavioral effects:

The scientists in the report review increasing incidence of cognitive, learning, and developmental problems. They report that epidemiological studies consistently suggest prenatal APAP exposure might increase the risk of adverse neurodevelopmental and behavioral outcomes, pointing to attention deficit hyperactivity disorder (ADHD), autism spectrum disorder, language delay (in girls) and decreased intelligence quotient.  However, adverse events such as wheezing and asthma in early childhood and adverse neurodevelopmental effects such as ADHD following acetaminophen exposure have been evaluated in multiple studies.  The outcome information was inconclusive, and a causal association has not been established (UpToDate, 2021).

The scientists putting together the consensus report were an “international group of experts, which included clinicians (specializing in neurology, obstetrics and gynaecology, and paediatrics), epidemiologists and basic scientists (specializing in toxicology, endocrinology, reproductive medicine and neurodevelopment)” (Bauer, et al, 2021).  They acknowledge the limitations of many of the studies they reviewed, but given the evidence from multiple disciplines, are calling for more research that would control for confounding factors, genetic factors, and the timing and dosing of acetaminophen and its effects on the developing fetus

In 2017, Kilcoyne wrote that Acetaminophen is recommended to be used at the lowest effective dose for the shortest duration of time to effectively treat the mother and protect the health of the fetus (Kilcoyne 2017).  The summary of the consensus opinion is the same, with a call for further research and additional warning labels on the packaging of products containing Acetaminophen:

“We recommend that APAP should be used by pregnant women cautiously at the lowest effective dose for the shortest possible time. Long-term or high-dose use should be limited to indications as advised by a health professional. Packaging should include warning labels including these recommendations. Given the high prevalence of APAP use by pregnant women, the public health implications of use reduction might be substantial.” (Bauer, et al, 2021)

Summary

As nurses, patients turn to us for guidance.  Although this report is initially alarming, our advice to patients should remain the same.  Avoid medication use in pregnancy.  If you have a fever, consult your provider.  Acetaminophen, and all other medications, should be used in the lowest dose and for the shortest duration as possible.  If they are pregnant now, and alarmed about potential effects of the medications they have taken, talk with them about the report and how more research may be needed to assess the risks.

References:

Paracetamol use during pregnancy — a call for precautionary action

Kilcoyne KR, Mitchell RT. Assessing the impact of in-utero exposures: potential effects of paracetamol on male reproductive development. Arch Dis Child. 2017;102(12):1169-1175. [PubMed 28588045]

Acetaminophen | Consumer Healthcare Products Association (chpa.org)

Endocrine Disruptors (nih.gov)

Bauer, A.Z., Swan, S.H., Kriebel, D. et al. Paracetamol use during pregnancy — a call for precautionary action. Nat Rev Endocrinol (2021).

Paracetamol-use-during-pregnancy-call-or-precautionary-action.pdf