PMID- 34166661 OWN - NLM STAT- MEDLINE DCOM- 20211007 LR - 20240323 IS - 1096-0953 (Electronic) IS - 0013-9351 (Print) IS - 0013-9351 (Linking) VI - 201 DP - 2021 Oct TI - Prenatal exposure to a mixture of elements and neurobehavioral outcomes in mid-childhood: Results from Project Viva. PG - 111540 LID - S0013-9351(21)00834-3 [pii] LID - 10.1016/j.envres.2021.111540 [doi] AB - BACKGROUND: Lead (Pb), manganese (Mn), selenium (Se) and methylmercury (MeHg) can be neurotoxic individually, despite Mn and Se also being essential elements. Little is known about the joint effects of essential and non-essential elements on neurobehavior, particularly for prenatal exposures. OBJECTIVES: To evaluate associations of prenatal exposure to multiple elements with executive function and neurobehavior in children. METHODS: Participants included 1009 mother-child pairs from the Project Viva pre-birth cohort. We estimated maternal erythrocyte Pb, Mn, Se, and Hg concentrations prenatally. In 6-11-year old children (median 7.6 years), parents and teachers rated children's executive function-related behaviors using the Behavior Rating Inventory of Executive Function (BRIEF) Global Executive Composite score and behavioral difficulties using the Strengths and Difficulties Questionnaire (SDQ) total difficulties score. We evaluated associations of element mixtures with neurobehavior using Bayesian kernel machine regression (BKMR), multivariable linear regression, and quantile g-computation. RESULTS: Median erythrocyte Pb, Mn, Se, and Hg concentrations were 1.1 mug/dL, 33.1 mug/L, 204.5 ng/mL, and 3.1 ng/g, respectively. Findings from BKMR and quantile g-computation models both showed worse (higher) parent-rated BRIEF and SDQ z-scores with higher concentrations of the mixture, although estimates were imprecise. When remaining elements were set at their median within BKMR models, increases in Pb and Se from the 25th to 75th percentile of exposure distributions were associated with 0.08 (95% CI: 0.02, 0.19) and 0.07 (95% CI: 0.03, 0.16) standard deviation increases in parent-rated BRIEF scores, and 0.08 (95% CI: 0.02, 0.17) and 0.05 (95% CI: 0.03, 0.13) standard deviation increases in SDQ scores, respectively. There was no evidence of element interactions. DISCUSSION: Although associations were small in magnitude, we found a trend of worsening neurobehavioral ratings with increasing prenatal exposure to an element mixture. However, we may be observing a limited range of dose-dependent impacts given the levels of exposure within our population. CI - Copyright (c) 2021 The Authors. Published by Elsevier Inc. All rights reserved. FAU - Fruh, Victoria AU - Fruh V AD - Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA. Electronic address: vfru1212@bu.edu. FAU - Rifas-Shiman, Sheryl L AU - Rifas-Shiman SL AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. FAU - Coull, Brent A AU - Coull BA AD - Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Devick, Katrina L AU - Devick KL AD - Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic, Scottsdale, AZ, USA. FAU - Amarasiriwardena, Chitra AU - Amarasiriwardena C AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine, Mount Sinai, New York, NY, USA. FAU - Cardenas, Andres AU - Cardenas A AD - Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. FAU - Bellinger, David C AU - Bellinger DC AD - Department of Neurology, Boston Children's Hospital, Boston, MA, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA. FAU - Wise, Lauren A AU - Wise LA AD - Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA. FAU - White, Roberta F AU - White RF AD - Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA. FAU - Wright, Robert O AU - Wright RO AD - Department of Environmental Medicine and Public Health, Icahn School of Medicine, Mount Sinai, New York, NY, USA. FAU - Oken, Emily AU - Oken E AD - Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. FAU - Claus Henn, Birgit AU - Claus Henn B AD - Department of Environmental Health, Boston University School of Public Health, Boston, MA, USA. LA - eng GR - R01 ES016314/ES/NIEHS NIH HHS/United States GR - T32 ES007142/ES/NIEHS NIH HHS/United States GR - P30 ES023515/ES/NIEHS NIH HHS/United States GR - R01 HD034568/HD/NICHD NIH HHS/United States GR - R01 ES028800/ES/NIEHS NIH HHS/United States GR - P50 HD105351/HD/NICHD NIH HHS/United States GR - R00 ES022986/ES/NIEHS NIH HHS/United States GR - P30 ES000002/ES/NIEHS NIH HHS/United States GR - T32 ES014562/ES/NIEHS NIH HHS/United States GR - R01 ES031259/ES/NIEHS NIH HHS/United States GR - UH3 OD023286/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20210621 PL - Netherlands TA - Environ Res JT - Environmental research JID - 0147621 RN - 42Z2K6ZL8P (Manganese) SB - IM MH - Bayes Theorem MH - Child MH - Cohort Studies MH - Executive Function MH - Female MH - Humans MH - Manganese/toxicity MH - Pregnancy MH - *Prenatal Exposure Delayed Effects/chemically induced PMC - PMC8502495 MID - NIHMS1722555 OTO - NOTNLM OT - Childhood neurobehavior OT - Executive function OT - Metals OT - Mixtures OT - Prenatal exposure EDAT- 2021/06/25 06:00 MHDA- 2021/10/08 06:00 PMCR- 2022/10/01 CRDT- 2021/06/24 20:10 PHST- 2021/02/16 00:00 [received] PHST- 2021/05/26 00:00 [revised] PHST- 2021/06/13 00:00 [accepted] PHST- 2021/06/25 06:00 [pubmed] PHST- 2021/10/08 06:00 [medline] PHST- 2021/06/24 20:10 [entrez] PHST- 2022/10/01 00:00 [pmc-release] AID - S0013-9351(21)00834-3 [pii] AID - 10.1016/j.envres.2021.111540 [doi] PST - ppublish SO - Environ Res. 2021 Oct;201:111540. doi: 10.1016/j.envres.2021.111540. Epub 2021 Jun 21.