Leo Sher, M.D.

A British research group examined associations between offspring behavioral problems and maternal prenatal acetaminophen use, maternal postnatal acetaminophen use, and partner’s acetaminophen use (1). Acetaminophen, also known as paracetamol, relieves pain and fever and is the active ingredient in Tylenol and a large number of over-the-counter and prescription drugs. Acetaminophen is not considered a nonsteroidal anti-inflammatory drug (NSAID) because it does not exhibit significant anti-inflammatory activity. More than half of all pregnant women in the United States and Europe use acetaminophen (2,3).

In 2015-2016, the researchers collected and analyzed data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective birth cohort. The authors studied about 8000 mothers enrolled in ALSPAC in 1991-1992 along with their children and partners.

The researchers found that maternal prenatal acetaminophen use at 18 and 32 weeks of pregnancy was associated with higher odds of having conduct problems and hyperactivity symptoms, while maternal acetaminophen use at 32 weeks was also associated with higher odds of having emotional symptoms and total difficulties. This was not the case for maternal postnatal or partner’s acetaminophen use. The authors concluded that children exposed to acetaminophen prenatally are at elevated risk of various behavioral problems, and the associations do not appear to be explained by unmeasured behavioral or social factors linked to acetaminophen use. It has previously been suggested that prenatal exposure to acetaminophen may lead to compromised neurodevelopment via inflammatory and immunologic mechanisms, via predisposition to oxidative stress, and via endocrine, endogenous cannabinoid, and other mechanisms (4).

Acetaminophen was synthesized for the first time by Harmon Northrop Morse (1848-1920), a chemist at John Hopkins University in Baltimore in 1877. In 1887, Joseph von Mering (1849-1908), a German physician tried acetaminophen on patients for the first time. Currently, acetaminophen is available in a tablet, capsule, liquid suspension, suppository, intravenous, intramuscular and effervescent form.

References

1. Stergiakouli E, Thapar A, Davey Smith G. Association of acetaminophen use during pregnancy with behavioral problems in childhood: evidence against confounding. JAMA Pediatr. Published online ahead of print August 15, 2016.

2. Werler  MM, Mitchell  AA, Hernandez-Diaz  S, Honein  MA.  Use of over-the-counter medications during pregnancy. Am J Obstet Gynecol. 2005;193(3, pt 1):771-777.

3. Lupattelli A, Spigset O, Twigg MJ, Zagorodnikova K, Mårdby AC, Moretti ME, Drozd M, Panchaud A, Hämeen-Anttila K, Rieutord A, Gjergja Juraski R, Odalovic M, Kennedy D, Rudolf G, Juch H, Passier A, Björnsdóttir I, Nordeng H. Medication use in pregnancy: a cross-sectional, multinational web-based study. BMJ Open. 2014;4(2):e004365.

4. Andrade C. Use of acetaminophen (paracetamol) during pregnancy and the risk of attention-deficit/hyperactivity disorder in the offspring. J Clin Psychiatry. 2016 Mar;77(3):e312-4.