Fetal programming of mental health by acetaminophen? Response to the SMFM statement: prenatal acetaminophen use and ADHD

ABSTRACT

Introduction: A number of studies indicate that acetaminophen taken during pregnancy may have a programming effect on the fetal brain development. The potential adverse consequences may only surface to clinical detection years later. Should we act on these findings now or do we wait for additional evidence?

Areas covered: We argue for action inspired by these well analyzed studies that are based on five prospective cohorts data collected from different countries. Several analytical options have been employed especially to address confounding, and all analyses have consistently suggested that confounding alone is an unlikely explanation for this disturbing observation.

Expert opinion: Acetaminophen is often used for minor symptom or discomfort where the treatment has no strong indication and carries little, if any risk for the pregnant women. The harm of doing nothing may well exceed the harm for taking precautionary actions considering the consequences at stake.

KEYWORDS:

• Acetaminophen (paracetamol)
• neurodevelopment
• fetal programming
• mental health
• bias

Article highlights

• A number of independent investigations using five prospective cohorts have consistently estimated a positive link between maternal acetaminophen intake in pregnancy and on a range of neurobehavioral outcomes in childhood.

• Acetaminophen is often used for minor symptom or discomfort in pregnancy where the treatment often has no strong indication.

• The claims that these findings are due to ‘confounding by indication’ should be supported by evidence, not just opinions. Triangulation approach has been used to address confounding and the results remain robust. Other source of bias such as non-differential exposure misclassification should also be considered and evaluated.

• We disagree with the Society for Maternal-Fetal Committee that suggested these findings should have no regulatory consequences at present. The harm of doing nothing may well exceed the harm for taking precautionary actions considering the consequences at stake.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.