Common pain-relief drug acetaminophen increases risk of autism and ADHD when taken during pregnancy, says study
Fetal exposure to a common type of drug that is prescribed to pregnant women for mild to moderate pain and to reduce fever has been associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in children.
The drug—acetaminophen—is used by more than 65% of women in the US and 50% in Europe during pregnancy, according to study estimates.
“For a long time, acetaminophen has been considered as the few safe pain and fever relief medications during pregnancy. However, previous studies based on maternal self-report and our study based on acetaminophen metabolite biomarkers have shown consistent findings between prenatal acetaminophen exposure and offspring increased risk of ADHD and ASD,” study author Dr. Xiaobin Wang from the Center on the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health, Baltimore, told MEA WorldWide (MEAWW).
“Our study is the first to provide direct biomarker evidence for fetal acetaminophen exposure on the risk of childhood ADHD and ASD. However, due to the observational study design, our findings should not be interpreted as causal. More study is needed to further explore the sensitive time window and dose-response effect of acetaminophen use during pregnancy,” Dr. Wang told MEAWW.
For the study, umbilical cord blood samples were used to examine an association between fetal exposure to acetaminophen and risk of childhood attention-deficit/hyperactivity disorder, autism spectrum disorder and other developmental disabilities in a group of nearly 1,000 mother-child pairs. They were enrolled at birth and followed up at the Boston Medical Center from October 1, 1998, to June 30, 2018.
The analysis shows that of 996 participants, the final sample included 257 children (25.8%)with ADHD only, 66 (6.6%) with ASD only, 42 (4.2%) with both ADHD and ASD, 304 (30.5%) with other developmental disabilities and 327 (32.8%) who were neurotypical, that is, those who did not display or was not characterized by autism or any other intellectual or developmental difference.
“In this cohort study of 996 mother-infant dyads from the Boston Birth Cohort, cord plasma biomarkers of fetal exposure to acetaminophen were associated with significantly increased risk of childhood attention-deficit/hyperactivity disorder and autism spectrum disorder. These findings suggest that in utero exposure to acetaminophen is associated with an increased risk of ADHD and autism spectrum disorder in children and warrant additional investigations,” state the findings published in JAMA Psychiatry.
Limitations of previous research
According to the research team, despite its widespread use, previous studies in animals and humans have found an association between prenatal acetaminophen exposure and increased risks of adverse childhood outcomes, including asthma, cryptorchidism, and neurodevelopmental disorders. Human studies have found that acetaminophen could cross the human placental barrier and remain in an infant’s blood circulation for a long duration, says the team.
“In the past five years, an increasing number of large, prospective cohort studies (mostly from Europe) found significant associations between maternal self-reported acetaminophen use during pregnancy and increased risk of ADHD and related symptoms in offspring in later life. In addition, a longer duration of reported use was also associated with a higher risk of ADHD. Two recent meta-analyses found significant associations between maternal-reported acetaminophen use during pregnancy and the risk of ADHD,” say experts.
So far, the Society for Maternal-Fetal Medicine (SMFM) and the US Food and Drug Administration (FDA) have refrained from making recommendations regarding its use, citing limited evidence, including recall bias, and lack of dose information, among others.
However, researchers say the FDA has called on pregnant women and healthcare professionals to carefully evaluate the benefits and risks of using acetaminophen during pregnancy. Similarly, the American Academy of Pediatrics (AAP) grand rounds concluded that there was no definitive causal link between acetaminophen exposure and ADHD.
Accordingly, this study aimed to address the limitations highlighted by the FDA, and AAP in relevant previous studies by examining the prospective association between cord plasma acetaminophen metabolites - direct evidence of fetal exposure - and childhood ADHD, ASD, as well as other developmental disabilities.
“Our study findings suggest that the provider and patient should weigh the risks and benefits of acetaminophen use during pregnancy and delivery. At this point, there is no definite data to support a threshold effect for acetaminophen intake. Furthermore, no study had identified any pregnancy period is safe to use,” Dr. Wang said.