Study Reveals a Possible Downside of Acetaminophen Use in Pregnancy

Children exposed to prenatal paracetamol (acetaminophen) had poorer gross motor development, worse communication skills, and more behavioral problems than their unexposed counterparts, according to research published October 25 in the International Journal of Epidemiology.

Duration of exposure does seem to matter, according to study results. Although children exposed prenatally to between 1 and 27 days of acetaminophen use also showed poorer gross motor outcomes, the effects were smaller than in those who were exposed to 28 days or more of the medicine in utero. Ibuprofen exposure was not associated with the neurodevelopment outcomes, according to the researchers.

The new study, which is part of The Norwegian Mother and Child Cohort Study at the Norwegian Institute of Public Health, looked at the outcomes of 3-year-olds, using data on 48,631 children whose mothers had reported data during their pregnancies and also returned the 3-year follow-up questionnaire by May 2011. The data on acetaminophen use was collected between 1999 and 2008 by having mothers report their use at gestational weeks 17 and 30 and at 6 months postpartum.

Within the sample there were 2919 same-sex sibling pairs who were used to adjust for genetic and environmental factors, such as infections, fever, use of other medications, alcohol intake, and smoking.

The analysis indicated that siblings who were exposed to prenatal acetaminophen for more than 28 days had poorer gross motor development [β 0.24; 95% confidence interval (CI), 0.12 - 0.51], communication (β 0.20; 95% CI, 0.01 - 0.39), externalizing behavior (β 0.28; 95% CI, 0.15 - 0.42), internalizing behavior (β 0.14; 95% CI, 0.01 - 0.28), and higher activity levels (β 0.24; 95% CI, 0.11 - 0.38).

The researchers said the results suggest a need for additional studies but build the case for concern with the long-term use of acetaminophen during pregnancy.

“Importantly, we cannot assume that there is a causal relationship between maternal use of paracetamol during pregnancy and adverse effects in children from an epidemiological study,” said one of the authors, Hedvig Nordeng, a professor at the School of Pharmacy, University of Oslo and a researcher at the Division of Mental Health, Norwegian Institute of Public Health. “Since this is the only study to show this, there is a need for further research to confirm or refute these results.”

Nordeng also noted that while the first choice for pain medicine during pregnancy remains acetaminophen, physicians should advise pregnant women to be “restrictive with all medicine use in pregnancy.”

Pertinent Points:
- Children who were exposed to acetaminophen for more than 28 days of pregnancy had poorer gross motor skills, poor communication skills, and more behavioral problems compared with their unexposed siblings.
- The same trend was seen with acetaminophen taken for less than 28 days, but the impact on the child’s development was less.
- Additional research is needed, but researchers cautioned that although acetaminophen remains the first drug of choice in treating pain in pregnant women, all medicine use should be restricted during pregnancy.