Postnatal Acetaminophen: Contribution to Risk of Autism Spectrum Disorder Among Males
Objectives: Determine the contribution of postnatal acetaminophen exposure to risk of ASD among male children in the USA.
Methods: Using a retrospectively collected data set from a previous study that was derived from an Internet-based survey among parents of children ages 3 through 12 years old (n=1,515), calculate an adjusted odds ratio (aOR) and gender specific aORs for postnatal acetaminophen measured in doses consumed before age two relative to the outcome of ASD using logistic regression. For comparison, calculate an analogous set of aORs for postnatal ibuprofen measured in doses consumed before age two relative to the outcome of ASD. Also, calculate aORs in joint analyses that include both analgesic variables against the outcome of ASD. Akaike information criterion was used to select a consistent sets of covariates for these analyses.
A contribution to risk of ASD from postnatal acetaminophen among males was calculated using the aOR for postnatal acetaminophen among males, the distribution of the number of doses of acetaminophen consumed up to age two by male children later diagnosed with ASD, and data from the literature.
Results: In this data set, postnatal acetaminophen exposure, measured in number of doses consumed before age two, is associated with increased risk of ASD among males (aOR 1.023, CI 1.005 - 1.043, p=0.020*). While there is also a weak association between postnatal ibuprofen and ASD among males, it is not statistically significant and is completely dominated by the association between acetaminophen and ASD in the joint analysis. Thus, it is conceivable that the weak association observed between ibuprofen and ASD could merely be a result of ibuprofen use being correlated with acetaminophen use.
Covariates in the above analyses include age of the child, ethnicity, Midwest, South, maternal education, age of the mother at birth of the child, and relationship to the child. Gender was also included as a covariate in the regressions that were not gender specific.
Postnatal acetaminophen is associated with approximately 20.6% of the total risk of ASD among males in the USA. Alternatively, the incidence of ASD associated with postnatal acetaminophen consumption is approximately 5.5 per 1,000 males annually, which is equivalent to an estimated annualized incidence of 11,600 cases of ASD among male children in the USA. This data set also provides hints of gender specific effects of postnatal acetaminophen on risk of ASD, although the p-value for interaction of 0.253 is not statistically significant.
Conclusions: While there may be some measurement error, as this data set was collected retrospectively, this study suggests that postnatal acetaminophen is associated with a significant proportion of the risk of ASD among male children in the USA.