TY - JOUR
T1 - Maternal and cord plasma branched-chain amino acids and child risk of attention-deficit hyperactivity disorder
T2 - a prospective birth cohort study
AU - Anand, Neha S.
AU - Ji, Yuelong
AU - Wang, Guoying
AU - Hong, Xiumei
AU - van der Rijn, Madeleine
AU - Riley, Anne
AU - Pearson, Colleen
AU - Zuckerman, Barry
AU - Wang, Xiaobin
N1 - Funding Information:
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 R40MC27443, Autism Field‐initiated Innovative Research Studies Program; and grant number UJ2MC31074, Autism Single Investigator Innovation Program. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (R21ES011666, R21HD066471, U01AI090727, R21AI079872, R01HD086013, 2R01HD041702, and R01HD098232). 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). The authors have declared that they have no competing or potential conflicts of interest. Key points
Publisher Copyright:
© 2020 Association for Child and Adolescent Mental Health.
PY - 2021/7
Y1 - 2021/7
N2 - Background: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. Methods: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups – ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography–tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. Results: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p =.032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p =.002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. Conclusions: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions.
AB - Background: Branched-chain amino acids (BCAA: leucine, isoleucine, and valine) are essential amino acids involved in biological functions of brain development and recently linked with autism. However, their role in attention-deficit hyperactivity disorder (ADHD) is not well-studied. We investigated individual and combined relationships of maternal plasma and newborn cord plasma BCAAs with childhood development of ADHD. Methods: We utilized the Boston Birth Cohort, a predominantly urban, low-income, US minority population. Child developmental outcomes were defined in three mutually exclusive groups – ADHD, neurotypical (NT), or other developmental disabilities based on physician diagnoses per ICD-9 or 10 in medical records. The final sample included 626 children (299 ADHD, 327 NT) excluding other developmental disabilities. BCAAs were measured by liquid chromatography–tandem mass spectrometry. We used factor analysis to create composite scores of maternal and cord BCAA, which we divided into tertiles. Logistic regressions analyzed relationships between maternal or cord BCAA tertiles with child ADHD risk, controlling for maternal race, age, parity, smoking, education, low birth weight, preterm birth, and child sex. Additionally, we analyzed maternal and cord plasma BCAAs jointly on child ADHD risk. Results: Adjusted logistic regression found significantly increased odds of child ADHD diagnosis for the second (OR 1.63, 95% CI: 1.04, 2.54, p =.032) and third tertiles (OR 2.01, 95% CI: 1.28, 3.15, p =.002) of cord BCAA scores compared to the first tertile. This finding held for the third tertile when further adjusting for maternal BCAA score. There was no significant association between maternal BCAA score and child ADHD risk, nor a significant interaction between maternal and cord BCAA scores. Conclusions: In this prospective US birth cohort, higher cord BCAA levels were associated with a greater risk of developing ADHD in childhood. These results have implications for further research into mechanisms of ADHD development and possible early life screening and interventions.
KW - Attention-Deficit Hyperactivity Disorder
KW - branched-chain amino acids
KW - cord blood
KW - metabolome
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U2 - 10.1111/jcpp.13332
DO - 10.1111/jcpp.13332
M3 - Article
C2 - 32960988
AN - SCOPUS:85091283762
SN - 0021-9630
VL - 62
SP - 868
EP - 875
JO - Journal of Child Psychology and Psychiatry and Allied Disciplines
JF - Journal of Child Psychology and Psychiatry and Allied Disciplines
IS - 7
ER -