Is There a causal relation between maternal acetaminophen administration and ADHD?

Antonio Saad, Shruti Hegde, Talar Kechichian, Phyllis Gamble, Mahbubur Rahman, Sonja J. Stutz, Noelle C. Anastasio, Wael Alshehri, Jun Lei, Susumu Mori, Bridget Kajs, Kathryn A. Cunningham, George Saade, Irina Burd, Maged Costantine

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Objective Recent epidemiological studies reported an association between maternal intake of acetaminophen (APAP) and attention deficit hyperactivity disorder (ADHD) in their children. However, none of these studies demonstrated causality. Our objective was to determine whether exposure to APAP during pregnancy result in hyperkinetic dysfunctions in offspring, using a murine model. Material and Methods Pregnant CD1 mice (N = 8/group) were allocated to receive by gavage either APAP (150 mg/kg/day, equivalent to the FDA-approved maximum human clinical dose), or 0.5% carboxymethylcellulose (control group), starting on embryonic day 7 until delivery. Maternal serum APAP and alanine transaminase (ALT) concentrations were determined by ELISA and kinetic colorimetric assays, respectively. Open field locomotor activity (LMA) in the 30-day old mouse offspring was quantified using Photobeam Activity System. Mouse offspring were then sacrificed, whole brains processed for magnetic resonance imaging (MRI; 11.7 Tesla magnet) and for neuronal quantification using Nissl stain. The association between APAP exposure and LMA in mouse offspring was analyzed using a mixed effects Poisson regression model that accounted for mouse offspring weight, gender, random selection, and testing time and day. We corrected for multiple comparisons and considered P<0.008 as statistically significant. Results Maternal serum APAP concentration peaked 30 minutes after gavage, reaching the expected mean of 117 μg/ml. Serum ALT concentrations were not different between groups. There were no significant differences in vertical (rearing), horizontal, or total locomotor activity between the two rodent offspring groups at the P level fixed to adjust for multiple testing. In addition, no differences were found in volumes of 29 brain areas of interest on MRI or in neuronal quantifications between the two groups. Conclusion This study refutes that hypothesis that prenatal exposure to APAP causes hyperkinetic dysfunction in mouse offspring. Due to lack of accurate assessment of ADHD in murine models, our results should be taken with caution when compared to the reported clinical data.

Original languageEnglish (US)
Article numbere0157380
JournalPloS one
Volume11
Issue number6
DOIs
StatePublished - Jun 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

Fingerprint Dive into the research topics of 'Is There a causal relation between maternal acetaminophen administration and ADHD?'. Together they form a unique fingerprint.

  • Cite this

    Saad, A., Hegde, S., Kechichian, T., Gamble, P., Rahman, M., Stutz, S. J., Anastasio, N. C., Alshehri, W., Lei, J., Mori, S., Kajs, B., Cunningham, K. A., Saade, G., Burd, I., & Costantine, M. (2016). Is There a causal relation between maternal acetaminophen administration and ADHD? PloS one, 11(6), [e0157380]. https://doi.org/10.1371/journal.pone.0157380