TY - JOUR
T1 - Perinatal acetaminophen exposure and childhood attention-deficit/hyperactivity disorder (Adhd)
T2 - Exploring the role of umbilical cord plasma metabolites in oxidative stress pathways
AU - Anand, Neha S.
AU - Raghavan, Ramkripa
AU - Wang, Guoying
AU - Hong, Xiumei
AU - Azuine, Romuladus E.
AU - Pearson, Colleen
AU - Zuckerman, Barry
AU - Xie, Hehuang
AU - Wang, Xiaobin
N1 - Funding Information:
Funding: This study is supported in part by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number UJ2MC31074, Autism Single Investigator Innovation Program. The Boston Birth Cohort (the parent study) is supported in part by the National Institutes of Health (NIH) grants (R01HD086013, 2R01HD041702, R01HD098232, R01ES031272, and R01ES031521). This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government. The funding agencies had no involvement in the collection, analysis, or interpretation of data; in the writing of the report; or in the decision to submit the article for publication. The authors thank Linda Rosen of the Boston University Clinical Data Warehouse for assistance in obtaining relevant clinical information; the Clinical Data Warehouse service is supported by Boston University Clinical and Translational Institute and the National Institutes of Health Clinical and Translational Science Award (grant U54-TR001012). Neha S. Anand is supported by the Johns Hopkins Institute for Clinical and Translational Research (ICTR) which is funded in part by Grant Number TL1 TR003100 from the National Center for Advancing Translational Sciences (NCATS) a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the Johns Hopkins ICTR or UMB, NCATS or NIH.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/10
Y1 - 2021/10
N2 - Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother–child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, p < 0.001), serine (R = 0.30, p < 0.001), glycine (R = 0.34, p < 0.001), and glutamate (R = 0.16, p < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, p = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, p = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted.
AB - Oxidative stress mechanisms may explain associations between perinatal acetaminophen exposure and childhood attention-deficit hyperactivity disorder (ADHD). We investigated whether the changes in umbilical cord plasma amino acids needed to synthesize the antioxidant glutathione and in the oxidative stress biomarker 8-hydroxy-deoxyguanosine may explain the association between cord plasma acetaminophen and ADHD in the Boston Birth Cohort (BBC). Mother–child dyads were followed at the Boston Medical Center between 1998 and 2018. Cord plasma analytes were measured from archived samples collected at birth. Physician diagnoses of childhood ADHD were obtained from medical records. The final sample consisted of 568 participants (child mean age [SD]: 9.3 [3.5] years, 315 (52.8%) male, 248 (43.7%) ADHD, 320 (56.3%) neurotypical development). Cord unmetabolized acetaminophen was positively correlated with methionine (R = 0.33, p < 0.001), serine (R = 0.30, p < 0.001), glycine (R = 0.34, p < 0.001), and glutamate (R = 0.16, p < 0.001). Children with cord acetaminophen levels >50th percentile appeared to have higher risk of ADHD for each increase in cord 8-hydroxy-deoxyguanosine level. Adjusting for covariates, increasing cord methionine, glycine, serine, and 8-hydroxy-deoxyguanosine were associated with significantly higher odds for childhood ADHD. Cord methionine statistically mediated 22.1% (natural indirect effect logOR = 0.167, SE = 0.071, p = 0.019) and glycine mediated 22.0% (natural indirect effect logOR = 0.166, SE = 0.078, p = 0.032) of the association between cord acetaminophen >50th percentile with ADHD. Our findings provide some clues, but additional investigation into oxidative stress pathways and the association of acetaminophen exposure and childhood ADHD is warranted.
KW - ADHD
KW - Acetaminophen
KW - Cord blood
KW - Glutathione
KW - Neurodevelopment
KW - Oxidative stress
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U2 - 10.3390/brainsci11101302
DO - 10.3390/brainsci11101302
M3 - Article
C2 - 34679367
AN - SCOPUS:85116148833
SN - 2076-3425
VL - 11
JO - Brain Sciences
JF - Brain Sciences
IS - 10
M1 - 1302
ER -