Risks Associated With Use of Acetaminophen in Pregnancy

Over-the-counter medications are generally regarded as safe. And one of the most effective pain relievers most commonly recommended and used during pregnancy is acetaminophen. Acetaminophen or paracetamol (the generic name for Tylenol or Excedrin) has the fewest risks compared with aspirin or ibuprofen. However, this does not mean that it is unquestionably safe: studies have found that there are certain risks associated with prolonged used of acetaminophen during pregnancy.

Effect on the Brain
A study by Liew and colleagues noted that acetaminophen, whichis a hormone disrupter, can cross the placental barrier and, when used during pregnancy may affected the development of the fetal brain. To confirm their hypothesis they studied over 64,000 children and mothers who were enrolled in the Danish National Birth Cohort during the 1996-2002 period. They found that over 50% of mothers used acetaminophen during pregnancy, and the children of these mothers were at

  • 13% higher risk of being diagnosed with attention-deficit-hyperactivity disorder (ADHD) at age 7 years
  • 29% higher risk for being prescribed medication for ADHD
  • 37% higher risk for a diagnosis of hyperkinetic disorder (a severe form of ADHD)

There was a correlation between the frequency of acetaminophen use during pregnancy and the three noted outcomes, despite accounting for all possible confounders. The association was stronger if acetaminophen was taken in the second and third trimester. Currently there is insufficient research to determine if the association is causal.

Effect on Reproduction
Testosterone is essential for male health throughout life. It is produced in the testicles and prenatal reduction in exposure may lead to

  • undescended testicles
  • infertility
  • reproductive problems
  • testicular cancer

Since this hormone is vital and reduced prenatal exposure has life-long consequences, van de Driesche and colleagues tested their hypothesis – that the use of acetaminophen may have an effect on testosterone production – on mice onto which human testicular tissue had been grafted. The mice were given doses of acetaminophen for either 24 hours or for an entire week. They found that while the 24-hour test did not affect testosterone production, the amount produced during the extended time (7 days) dropped by 45%. They concluded that prolonged use of acetaminophen during pregnancy may reduce testosterone production in male fetuses.

Effect on the Lungs
The most recent study on the use of acetaminophen in pregnancy worked with data from the Norwegian Mother and Child Cohort Study of over 114,000 children.  After analyzing the data and discounting for possible confounders, the researchers found that among the children whose mothers used acetaminophen during pregnancy

  • 5.7% had asthma at age 3
  • 5.1% had asthma at age 7

The researchers even examined the association between the use of acetaminophen for pain, fever or influenza and found that the reason for use did not affect the correlation with asthma. The strongest association was noted between the amount of acetaminophen use and asthma at age 3. A sequential analysis of prenatal ibuprofen exposure also found a positive correlation with asthma at age 3 but not at age 7.

This new evidence of the possible effects of taking acetaminophen during pregnancy should serve as an additional warning. Pregnant women should be strongly advised that if it is necessary to take acetaminophen, then it should be taken at the lowest possible effective dose and for the shortest period of time.

References

Liew Z, Ritz B et al. Acetaminophen use during pregnancy, behavioral problems, and hyperkinetic disorders. JAMA Pediatrics, 2014; DOI: 10.1001/jamapediatrics.2013.4914

van den Driesche S, Macdonald J, et al. Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model. Science Translational Medicine, 2015; 7 (288): 288ra80 DOI: 10.1126/scitranslmed.aaa4097

Magnus MC, Karlstad Ø, et al. Prenatal and infant paracetamol exposure and development of asthma: the Norwegian Mother and Child Cohort Study. International J Epidemiology, 2016; dyv366 DOI: 10.1093/ije/dyv366