The pain relieving drug acetaminophen (commonly known as Tylenol or paracetamol) is considered safe for use during pregnancy by the Food and Drug Administration and European Medicines Authority; however, recent evidence suggests that acetaminophen may increase the risk of fetal neurodevelopmental, reproductive, and urogenital disorders.. A group of expert scientists, clinicians, and public health professionals recently issued a statement calling for greater caution in recommending acetaminophen use during pregnancy.

Acetaminophen is the most common medication used during pregnancy. Most often, pregnant women use the medication to reduce headache, muscle pain, and back pain; however 8 percent of pregnant women use acetaminophen to reduce fever, which is a risk factor for fetal neural tube defects and later life cardiovascular disorders. There are very few alternative medications for reducing pain and fever, so acetaminophen use in pregnancy may be difficult to eliminate.

The authors conducted a systematic review of studies conducted over a 25-year period involving acetaminophen use during pregnancy. Then they used a set of criteria to select only relevant studies with appropriate study design. The 13 authors discussed the results of their systematic review and issued a statement that was later signed by 78 scientists, clinicians, and epidemiologists.

Acetaminophen use in pregnant rats and mice directly interfered with the fetal production of sex hormones and other steroids; perturbed immune function by excessive dampening of inflammation; and increased oxidative stress. All of these changes increased the risk of neurodevelopmental and urogenital and reproductive disorders in offspring. This preclinical evidence in animals may provide a mechanistic understanding of the effects of acetaminophen use in humans.

Epidemiological evidence from a sample of 130,000 mother-child pairs demonstrated increased risk of male urogenital abnormalities, including undescended testicles and reduced anogenital distance (i.e., the distance between the anus and penis), both markers of male sexual immaturity, in children born to mothers who used acetaminophen. Further epidemiological evidence from a sample of over 220,000 mother-child pairs demonstrated an increased risk of attention deficit hyperactivity disorder, autism spectrum disorder, and other neurodevelopmental abnormalities with acetaminophen use during pregnancy. One important observational study published in 2021 found an association between acetaminophen metabolites in umbilical cord blood collected at birth and the incidence of physician-diagnosed neurodevelopmental disorders in childhood. However, it is important to note that there are many factors that interfere with these statistical relationships, such as the incidence of maternal infection, other health conditions, and use of other medications.

Given this evidence and more presented in the literature, the experts recommended that pregnant women should be cautioned at the beginning of pregnancy to reduce or stop use of acetaminophen unless it is medically necessary and should consult with a physician or pharmacist before using acetaminophen long-term. The authors recognize the need for rigorous meta-analyses to understand the hormonal, epigenetic, and metabolic mechanisms by which acetaminophen affects development in humans.

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