Fetal acetaminophen exposure increases the likelihood that a child will develop attention-deficit/hyperactivity disorder (ADHD), according to a study published in Nature Mental Health.

Prior research shows that upward of 70% of pregnant women in the United States use acetaminophen during pregnancy to control pain or reduce fever. The drug, which is the active ingredient of many pain-relief medications, including Tylenol, is one of the few considered safe to take during pregnancy by the Food and Drug Administration (FDA).

The new findings suggest, however, that doctors should reconsider prescribing medications with acetaminophen to mothers during pregnancy, the researchers said.

This medication was also approved decades ago, and may need reevaluation by the FDA, said lead author Sheela Sathyanarayana, also the study’s senior author. Acetaminophen was never evaluated for fetal exposures in relation to long-term neurodevelopmental impacts.

Acetaminophen, commonly known by its brand name Tylenol, and other pain relievers are widely used during pregnancy. The FDA’s current guidelines classify acetaminophen as a safe and effective option for pregnant women. A staggering 41-70% of pregnant individuals in the United States report using it, indicating its ubiquity in prenatal care. Despite this classification, accumulating evidence suggests a potential link between prenatal acetaminophen exposure and adverse neurodevelopmental outcomes, including ADHD and autism spectrum disorder.

The research conducted by the team tracked a cohort of 307 women from 2006 to 2011. During their pregnancy, the women agreed to provide blood samples. Researchers tracked plasma biomarkers for acetaminophen in the samples.

The children born to these mothers were followed for 8 to 10 years. Among the women who did not use acetaminophen during pregnancy, the rate of ADHD was 9%, but for the women who used acetaminophen, the ADHD rate among their offspring was 18%. Acetaminophen metabolites were detected in 20.2% of maternal plasma samples. Children whose mothers had these biomarkers present in their plasma had a 3.15 times higher likelihood of an ADHD diagnosis compared with those without detected exposure.

The association was stronger among daughters than sons, with the daughters of acetaminophen-exposed mothers showing a 6.16 times higher likelihood of ADHD whereas the association was weaker and nonsignificant in males. Researchers did not know why the association was stronger in females.

The investigators’ analysis used data from the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) research cohort, which comprised 1,031 pregnant individuals in Memphis, Tennessee, who were enrolled between 2006 and 2011. By happenstance, and not by design, the study cohort included only Black women. This singular focus on one demographic raises questions about the broader applicability of the findings. However, researchers have acknowledged that the results could potentially be generalized to women and children of any race or ethnicity, underscoring the need for further diverse representation in future studies.

Mothers often are advised to turn to acetaminophen, the primary agent in Tylenol, rather than ibuprofen, which is more likely to adversely affect the fetal kidney or heart.Acetaminophen is really the only option to control fever or pain during pregnancy, says Sathyanarayana.

There is obviously more work that needs to be done in this area, he said. And we need to continually update our guidance.

During prenatal visits, patients should discuss the dosage of their acetaminophen-containing drug or talk about what pain it is intended to help manage. Another drug class, such as Triptans, is safe and effective for managing migraines, he added.

Researchers also highlighted the need for more robust investigations. For instance, one recent study in Sweden showed no link between maternal acetaminophen use and ADHD in their children, while another study in Norway did find a link. The Swedish study, however, relied on self-reported data, which could have underestimated the exposure. This discrepancy in findings underscores the need for standardized and accurate data collection methods in future studies. Sathyanarayana suggested that medical societies and the FDA should update their guidance on the use of acetaminophen as safety data continues to emerge.

In the face of these new findings, mothers-to-be should be more cautious. American College of Obstetricians and Gynecologists recommends women consult with their healthcare provider before taking any medication during pregnancy. There are alternative pain management options, such as Triptans for migraines, which can be safely used during pregnancy.

This study also received funding from the National Institutes of Health (UG3UH3OD023271).

What is the link between fetal acetaminophen exposure and ADHD?

A recent study published in Nature Mental Health indicates that fetal exposure to acetaminophen increases the likelihood that a child will develop attention-deficit/hyperactivity disorder (ADHD). The study found that among women who did not use acetaminophen during pregnancy, the rate of ADHD in their children was 9%. In contrast, the ADHD rate among offspring of women who used acetaminophen was 18%. Children with detectable acetaminophen metabolites in maternal plasma had a 3.15 times higher likelihood of being diagnosed with ADHD [1].

How prevalent is acetaminophen use among pregnant women in the U.S.?

Acetaminophen is widely used during pregnancy due to its classification by the FDA as safe for pain and fever management. Upward of 70% of pregnant women in the United States use acetaminophen for these purposes [2]. Given these statistics, the potential implications of its use on fetal progress are significant.

Why might the FDA reconsider acetaminophen guidelines for pregnant women?

Lead researcher Sheela Sathyanarayana suggests that, given the decades-old approval of acetaminophen, the FDA may need to reevaluate its safety in terms of fetal exposure and long-term neurodevelopmental impacts. This proposal is bolstered by accumulating evidence associating acetaminophen exposure with adverse outcomes like ADHD and potentially autism spectrum disorder [1].

Why might acetaminophen exposure have a stronger association with ADHD in daughters than in sons?

The study indicated that the association between acetaminophen exposure and ADHD was stronger in daughters, with an increased likelihood of a 6.16 times higher ADHD rate compared to sons, for whom the association was weaker and nonsignificant. The reasons for this gender disparity remain unclear and warrant further investigation.

What are the implications of the study’s demographic focus?

The research cohort, the Conditions Affecting Neurocognitive Development and Learning in early Childhood (CANDLE), included only Black women. while researchers suggest that the results might be generalizable across different races and ethnicities, the lack of diverse representation raises questions about the broader applicability of the findings, highlighting the need for additional studies with diverse populations.

Are ther choice pain management options for pregnant women?

Safety concerns over acetaminophen use during pregnancy have prompted discussions about alternative medications. Triptans, for instance, are considered a safe and effective option for managing migraines during pregnancy, providing a viable alternative for pain relief. It’s crucial for pregnant individuals to consult healthcare providers about the safety and efficacy of any medication they use [3].

What further research is suggested by these findings?

The study underlines the necessity for more thorough research. While some studies, such as those conducted in Sweden and Norway, have shown conflicting results regarding acetaminophen and ADHD, discrepancies like those caused by self-reported data highlight the need for standardized and accurate data collection methods in future investigations. Updating guidance on acetaminophen’s use by medical societies and the FDA is also recommended as new safety data continues to emerge.

What should pregnant women consider regarding acetaminophen use?

Considering these studies, pregnant women are advised to exercise caution when using acetaminophen. Consulting with healthcare providers before taking any medication can help manage potential risks effectively. The American College of Obstetricians and Gynecologists supports this approach to ensure both maternal and fetal health.

This study received funding from the National Institutes of Health (UG3UH3OD023271).