Exposure to paracetamol in the womb may increase a child’s risk for ADHD and ASD


Exposure to acetaminophen in the womb may increase a child’s risk for attention deficit/hyperactivity disorder and autism spectrum disorder, suggests a study funded by the National Institutes of Health and the Agency for Health Care Research and Quality.

The study was conducted by Xiaobing Wang, M.D., of the Johns Hopkins University Bloomberg School of Public Health, Baltimore, and colleagues. It appears in JAMA Psychiatry.

Attention deficit/hyperactivity disorder (ADHD) is marked by a pattern of hyperactivity and impulsive behavior.

Autism spectrum disorder (ASD) is a complex developmental disorder that affects how a person behaves, interacts with others and learns.

Researchers analyzed data from the Boston Birth Cohort, a long-term study of factors influencing pregnancy and child development.

They collected umbilical cord blood from 996 births and measured the amount of acetaminophen and two of its byproducts in each sample. By the time the children were an average of 8.9 years, 25.8% had been diagnosed with ADHD only, 6.6% with ASD only and 4.2% with ADHD and ASD.

The researchers classified the amount of acetaminophen and its byproducts in the samples into thirds, from lowest to highest. Compared to the lowest third, the middle third of exposure was associated with about 2.26 times the risk for ADHD. The highest third of exposure was associated with 2.86 times the risk.

Similarly, ASD risk was higher for those in the middle third (2.14 times) and highest third (3.62 times).

The authors conclude that their results support earlier studies linking acetaminophen exposure in the womb with ADHD and ASD and underscore the need for additional research. The image is in the public domain.

The authors conclude that their results support earlier studies linking acetaminophen exposure in the womb with ADHD and ASD and underscore the need for additional research. The U.S. Food and Drug Administration urges careful consideration before using any pain-relieving medication during pregnancy.

NIH funding for the study was provided by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute of Allergy and Infectious Diseases and the National Institute of Environmental Health Sciences.

Acetaminophen (or paracetamol) is one of the most commonly used analgesics worldwide [1].

It is the first choice for pain and fever medication among pregnant women [2].

In Brazil, studies reporting acetaminophen use during pregnancy are scarce [35].

These studies are restricted to convenience samples, and to our knowledge, there are no population-based studies that have evaluated its use.

Several birth cohort studies have reported that prenatal exposure to acetaminophen is associated with neurobehavioral and neurodevelopmental disorders during childhood [612].

Intrauterine exposure to acetaminophen has been associated with

(i) attention-deficit/hyperactivity disorder (ADHD) [812];

(ii) hyperactivity/inattention and behavioral symptoms [711];

(iii) autism spectrum disorder (ASD) [610]; and

(iv) impaired motor development, difficulty in communication and behavioral disorders [913].

In a recent meta-analysis, acetaminophen exposure during pregnancy was associated with a 20–30% increase in the risk of neurodevelopmental disorders [14].

Only one study has evaluated behavioral outcomes at two different time points during childhood [7].

Acetaminophen crosses the human placental barrier, and in vitro and in vivo findings provide additional evidence in support of observational epidemiological studies.

Acetaminophen use has been shown to interfere with neurotransmitter, endocrine and immune systems, as well as with the regulation of brain-derived neurotrophic factor and cell oxidative stress, which are processes associated with brain development [1522].

Although several variables have been included as covariates in previous studies, the results are susceptible to potential confounding effects [14], which makes it difficult to ascertain whether the use of acetaminophen is safe during pregnancy and indicates the need for more studies in the field.

It is of note that current observational studies have been conducted in only European populations [2325]. In this sense, studies in other populations, such as those from low and medium-income countries, would contribute to the knowledge in the literature and improve the current understanding of the risk of intrauterine exposure to acetaminophen.

This study aims to investigate the association between intrauterine exposure to acetaminophen and the presence of emotional and behavioral symptoms at the ages of 6 and 11 years in the 2004 Pelotas birth cohort.

Media Contacts:
Meredith Daly – NIH
Image Source:
The image is in the public domain.

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.


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