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
10.1371/journal.pone.0157380
https://plos.figshare.com/articles/dataset/Is_There_a_Causal_Relation_between_Maternal_Acetaminophen_Administration_and_ADHD_/3440561
<div><p>Objective</p><p>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.</p><p>Material and Methods</p><p>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.</p><p>Results</p><p>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.</p><p>Conclusion</p><p>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.</p></div>
2016-06-13 08:01:41
Results Maternal serum APAP concentration
Open field locomotor activity
mouse offspring
APAP causes hyperkinetic dysfunction
Maternal Acetaminophen Administration
Maternal serum APAP
mouse offspring weight
ALT
ADHD
11.7 Tesla magnet
exposure
ELISA
LMA
attention deficit hyperactivity disorder
Methods Pregnant CD 1 mice
rodent offspring groups
effects Poisson regression model
29 brain areas
Photobeam Activity System
MRI