Cargando…

Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?

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 duri...

Descripción completa

Detalles Bibliográficos
Autores principales: Saad, Antonio, Hegde, Shruti, Kechichian, Talar, Gamble, Phyllis, Rahman, Mahbubur, Stutz, Sonja J., Anastasio, Noelle C., Alshehri, Wael, Lei, Jun, Mori, Susumu, Kajs, Bridget, Cunningham, Kathryn A., Saade, George, Burd, Irina, Costantine, Maged
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905664/
https://www.ncbi.nlm.nih.gov/pubmed/27295086
http://dx.doi.org/10.1371/journal.pone.0157380
_version_ 1782437291523833856
author Saad, Antonio
Hegde, Shruti
Kechichian, Talar
Gamble, Phyllis
Rahman, Mahbubur
Stutz, Sonja J.
Anastasio, Noelle C.
Alshehri, Wael
Lei, Jun
Mori, Susumu
Kajs, Bridget
Cunningham, Kathryn A.
Saade, George
Burd, Irina
Costantine, Maged
author_facet Saad, Antonio
Hegde, Shruti
Kechichian, Talar
Gamble, Phyllis
Rahman, Mahbubur
Stutz, Sonja J.
Anastasio, Noelle C.
Alshehri, Wael
Lei, Jun
Mori, Susumu
Kajs, Bridget
Cunningham, Kathryn A.
Saade, George
Burd, Irina
Costantine, Maged
author_sort Saad, Antonio
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4905664
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-49056642016-06-28 Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD? Saad, Antonio Hegde, Shruti Kechichian, Talar Gamble, Phyllis Rahman, Mahbubur Stutz, Sonja J. Anastasio, Noelle C. Alshehri, Wael Lei, Jun Mori, Susumu Kajs, Bridget Cunningham, Kathryn A. Saade, George Burd, Irina Costantine, Maged PLoS One Research Article 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. Public Library of Science 2016-06-13 /pmc/articles/PMC4905664/ /pubmed/27295086 http://dx.doi.org/10.1371/journal.pone.0157380 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication.
spellingShingle Research Article
Saad, Antonio
Hegde, Shruti
Kechichian, Talar
Gamble, Phyllis
Rahman, Mahbubur
Stutz, Sonja J.
Anastasio, Noelle C.
Alshehri, Wael
Lei, Jun
Mori, Susumu
Kajs, Bridget
Cunningham, Kathryn A.
Saade, George
Burd, Irina
Costantine, Maged
Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title_full Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title_fullStr Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title_full_unstemmed Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title_short Is There a Causal Relation between Maternal Acetaminophen Administration and ADHD?
title_sort is there a causal relation between maternal acetaminophen administration and adhd?
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905664/
https://www.ncbi.nlm.nih.gov/pubmed/27295086
http://dx.doi.org/10.1371/journal.pone.0157380
work_keys_str_mv AT saadantonio isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT hegdeshruti isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT kechichiantalar isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT gamblephyllis isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT rahmanmahbubur isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT stutzsonjaj isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT anastasionoellec isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT alshehriwael isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT leijun isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT morisusumu isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT kajsbridget isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT cunninghamkathryna isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT saadegeorge isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT burdirina isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd
AT costantinemaged isthereacausalrelationbetweenmaternalacetaminophenadministrationandadhd