The Dangers of Acetaminophen for Neurodevelopment Outweigh Scant Evidence for Long-Term Benefits

Abstract

Based on available data that include approximately 20 lines of evidence from studies in laboratory animal models, observations in humans, correlations in time, and pharmacological/toxicological considerations, it has been concluded without reasonable doubt and with no evidence to the contrary that exposure of susceptible babies and children to acetaminophen (paracetamol) induces many, if not most, cases of autism spectrum disorder (ASD). However, the relative number of cases of ASD that might be induced by acetaminophen has not yet been estimated. Here, we examine a variety of evidence, including the acetaminophen-induced reduction of social awareness in adults, the prevalence of ASD through time, and crude estimates of the relative number of ASD cases induced by acetaminophen during various periods of neurodevelopment. We conclude that the very early postpartum period poses the greatest risk for acetaminophen-induced ASD, and that nearly ubiquitous use of acetaminophen during early development could conceivably be responsible for the induction in the vast majority, perhaps 90% or more, of all cases of ASD. Despite over a decade of accumulating evidence that acetaminophen is harmful for neurodevelopment, numerous studies demonstrate that acetaminophen is frequently administered to children in excess of currently approved amounts and under conditions in which it provides no benefit. Further, studies have failed to demonstrate long-term benefits of acetaminophen for the pediatric population, leaving no valid rationale for continued use of the drug in that population given its risks to neurodevelopment.

Keywords: acetaminophen; autism; fever; pain; paracetamol; postnatal; prenatal.

Figure 1

The sales of acetaminophen (APAP) in Denmark and Finland correlated with the prevalence of autism spectrum disorder (ASD) in those countries. The sale of acetaminophen is limited to the sale of drugs containing acetaminophen as the only active ingredient and is measured in units of a “defined daily doses” (equal to 3 g of active ingredient) per 1000 inhabitants per day. The sales for each year from 2006 to 2010, as reported by Wastesson and colleagues [15], were averaged and the mean plotted. Sales for both Denmark and Finland showed upward trends every year, and the upper limit of the range (data from 2010) is shown by the error bars. The prevalence of ASD in Denmark and Finland was reported by Delobel-Ayoub and colleagues [16]. Data are shown for all children, including males and females, born in 2006, with prevalence measured at 9 years of age. The 95% confidence interval reported by Delobel-Ayoub and colleagues is indicated by the error bars.

Figure 2

Schematic diagram showing prevalence of acetaminophen (APAP)-induced ASD as a function of age. The neurodevelopmental window of sensitivity is broad, possibly bounded by the first trimester of pregnancy and the end of the 4th or 5th year of life. The shape of the curve is apparently determined by levels of exposure to acetaminophen, and sensitivity to acetaminophen, a function of oxidative stress and ability to metabolize acetaminophen [9]. ASD, autism spectrum disorder; APAP, acetaminophen (paracetamol).