Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: A case control study

Stephen J. McKean, Scott M. Bartell, Robin L Hansen, Gry H. Barfod, Peter G. Green, Irva Hertz-Picciotto

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Methods: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). Results: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR∈=∈0.95, 95 % CI: 0.95, 1.12) or developmental delay (OR∈=∈1.00, 95 % CI: 0.89, 1.13). Conclusions: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.

Original languageEnglish (US)
Article number62
JournalEnvironmental Health: A Global Access Science Source
Volume14
Issue number1
DOIs
StatePublished - Jul 22 2015

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Autistic Disorder
Mercury
Case-Control Studies
Pharmacokinetics
Newborn Infant
Fishes
Biomarkers
Logistic Models
Mothers
Seafood
Neurotoxins
Epidemiologic Studies
Eating
Odds Ratio
Surveys and Questionnaires
Pregnancy
Brain
Toxicokinetics

ASJC Scopus subject areas

  • Health, Toxicology and Mutagenesis
  • Public Health, Environmental and Occupational Health

Cite this

@article{2272bb9fbd794a7bb405cd14c833739d,
title = "Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data: A case control study",
abstract = "Background: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Methods: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). Results: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR∈=∈0.95, 95 {\%} CI: 0.95, 1.12) or developmental delay (OR∈=∈1.00, 95 {\%} CI: 0.89, 1.13). Conclusions: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.",
author = "McKean, {Stephen J.} and Bartell, {Scott M.} and Hansen, {Robin L} and Barfod, {Gry H.} and Green, {Peter G.} and Irva Hertz-Picciotto",
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T1 - Prenatal mercury exposure, autism, and developmental delay, using pharmacokinetic combination of newborn blood concentrations and questionnaire data

T2 - A case control study

AU - McKean, Stephen J.

AU - Bartell, Scott M.

AU - Hansen, Robin L

AU - Barfod, Gry H.

AU - Green, Peter G.

AU - Hertz-Picciotto, Irva

PY - 2015/7/22

Y1 - 2015/7/22

N2 - Background: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Methods: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). Results: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR∈=∈0.95, 95 % CI: 0.95, 1.12) or developmental delay (OR∈=∈1.00, 95 % CI: 0.89, 1.13). Conclusions: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.

AB - Background: Methylmercury (MeHg), known for well over a century as a neurotoxin in adults, has more recently been studied for potential detrimental effects during early brain development. While several studies have estimated mercury exposure, they usually rely on either a single biomarker or questionnaire data, each of which has limitations. The goal of this paper was to develop a toxicokinetic model that incorporates both biomarker and questionnaire data to estimate the cumulative exposure to MeHg through seafood consumption using data collected from the Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Methods: We utilized a previously described discrete-time model that estimates blood MeHg concentration given a piecewise-constant ingestion rate and single-compartment pharmacokinetics. We measured newborn bloodspot Hg concentrations and obtained information pertaining to maternal fish consumption using a questionnaire. Using MeHg concentration estimates from the toxicokinetic model, cumulative MeHg exposure was estimated in children with autism, children with developmental delay, and typically developing children. Median estimated cumulative MeHg was compared among diagnostic groups using the Kruskal-Wallis Test. Multinomial logistic regression models were constructed to assess the association between cumulative MeHg concentration and the risk of autism and developmental delay (vs. typical development). Results: The estimated average MeHg concentration of for all fish species consumed by mothers was 42 ppb. Median cumulative MeHg over gestation was similar across diagnostic groups (p-values raged from 0.91 to 0.98). After adjusting for potential confounding, we found no association between cumulative MeHg exposure and the risk of autism (OR∈=∈0.95, 95 % CI: 0.95, 1.12) or developmental delay (OR∈=∈1.00, 95 % CI: 0.89, 1.13). Conclusions: The toxicokinetic model described in this paper yielded fish MeHg concentration estimates that are consistent with fish species containing lower levels of MeHg. Overall, cumulative MeHg exposure does not appear to detectably elevate the risk of autism or developmental delay. Based on the regression standard error for the association between ASD and TD, we would have reported statistical significance for an adjusted odds ratio of 1.09 or larger. This method can easily be extended to other epidemiologic studies in which there is a biomarker measurement and questionnaire data regarding exposure.

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