Summary: A new analysis supports earlier research suggesting that fetal exposure to acetaminophen is associated with an increased risk of later diagnosis of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).
Source: NIH
A study funded by the National Institutes of Health and the Agency for Health Care Research and Quality suggests that acetaminophen exposure before birth may raise a child’s risk of developing attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). The analysis, led by Xiaobing Wang, M.D., of the Johns Hopkins Bloomberg School of Public Health, used long-term data from the Boston Birth Cohort and appears in JAMA Psychiatry.
ADHD is characterized by patterns of inattention, hyperactivity, and impulsive behavior. ASD is a developmental condition that affects social interaction, communication, and behavior. Both conditions are diagnosed by clinicians based on established criteria and observation of developmental history.
The researchers measured biomarkers of acetaminophen exposure in umbilical cord plasma collected at birth from 996 infants enrolled in the Boston Birth Cohort. In each cord plasma sample the team quantified unchanged acetaminophen and two metabolites. All samples contained detectable levels of unchanged acetaminophen. The children were followed for several years; at follow-up—around nine years of age on average—25.8% had been diagnosed with ADHD only, 6.6% with ASD only, and 4.2% with both ADHD and ASD.
To evaluate dose-related risk, the investigators divided cord plasma acetaminophen burden into three groups (tertiles) from lowest to highest. Compared with children in the lowest exposure tertile, those in the middle tertile had more than double the odds of an ADHD diagnosis (odds ratio [OR], 2.26; 95% CI, 1.40–3.69). Children in the highest tertile had still higher odds (OR, 2.86; 95% CI, 1.77–4.67). A similar dose-response pattern was observed for ASD: the middle tertile was associated with increased odds (OR, 2.14; 95% CI, 0.93–5.13) and the highest tertile with a larger increase (OR, 3.62; 95% CI, 1.62–8.60).
The study team conducted multiple sensitivity and subgroup analyses to test the robustness of their findings. Associations between higher cord acetaminophen burden and ADHD or ASD remained consistent across strata defined by potential confounders such as maternal indication for medication, maternal substance use, preterm birth, and child age and sex. Reported point estimates for the associations ranged approximately from 2.3 to 3.5 for ADHD and from 1.6 to 4.1 for ASD across various subgroup and sensitivity tests.
The authors state that their results reinforce prior research indicating a link between prenatal acetaminophen exposure and increased risks of neurodevelopmental disorders. They emphasize that the observed relationships follow a dose-response pattern and call for further research to clarify mechanisms, causal pathways, and clinical implications. The U.S. Food and Drug Administration recommends that pain-relieving medications, including acetaminophen, be used during pregnancy only after careful consideration and consultation with a healthcare professional.
This study received NIH funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Allergy and Infectious Diseases (NIAID), and the National Institute of Environmental Health Sciences (NIEHS).
Source:
NIH
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Meredith Daly – NIH
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Original Research: Closed access
“Association of cord plasma biomarkers of in utero acetaminophen exposure with risk of attention deficit/hyperactivity disorder and autism spectrum disorder in childhood.” Ji, Y., et al. JAMA Psychiatry. DOI: 10.1001/jamapsychiatry.2019.3259.
Abstract (condensed)
Importance: Several previous studies have suggested a possible link between maternal use of acetaminophen during pregnancy and increased risk of ADHD and ASD in offspring; many of those studies relied on maternal self-report of medication use. Objective: To investigate associations between objectively measured cord plasma acetaminophen metabolites at birth and later physician-diagnosed ADHD, ASD, both conditions, and other developmental disabilities during childhood. Design, Setting, and Participants: A prospective cohort analysis of 996 mother–infant pairs from the Boston Birth Cohort enrolled at birth and followed at Boston Medical Center from 1998 to 2018. Exposures: Three acetaminophen-related biomarkers measured in archived cord plasma: unchanged acetaminophen, acetaminophen glucuronide, and 3-[N-acetyl-l-cystein-S-yl]-acetaminophen. Main Outcomes and Measures: Clinician-documented diagnoses of ADHD, ASD, and other developmental disabilities in the child’s medical record. Results: Detectable unchanged acetaminophen was present in all cord samples. Relative to the lowest tertile of cord acetaminophen burden, the second and third tertiles were associated with elevated odds of ADHD (ORs 2.26 and 2.86, respectively) and elevated odds of ASD (ORs 2.14 and 3.62, respectively). Sensitivity and subgroup analyses yielded consistent associations across multiple potential confounders. Conclusions and Relevance: Cord plasma biomarkers reflecting fetal exposure to acetaminophen were associated with significantly increased risks of childhood ADHD and ASD in a dose-response manner. These findings support prior work linking prenatal acetaminophen exposure with neurodevelopmental risk and underscore the need for further investigation.