Caitlin G Howe1, Sara S Nozadi2, Erika Garcia3, Thomas G O'Connor4, Anne P Starling5, Shohreh F Farzan3, Brian P Jackson6, Juliette C Madan7, Akram N Alshawabkeh8, José F Cordero9, Theresa M Bastain3, John D Meeker10, Carrie V Breton3, Margaret R Karagas1. 1. Department of Epidemiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Dr, Lebanon, NH 03766, USA. 2. Community Environmental Health Program, College of Pharmacy, University of New Mexico Health Sciences Center, 1 University of New Mexico, Albuquerque, NM 87131, USA. 3. Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, 2001 N Soto St, Los Angeles, CA 90032, USA. 4. Department of Psychiatry, University of Rochester Medical Center, 601 Elmwood, Ave, Rochester, NY 14642, USA. 5. Department of Epidemiology, University of North Carolina at Chapel Hill, 2101 McGavran-Greenberg, Campus Box 7435, Chapel Hill, NC 27599, USA. 6. Department of Earth Sciences, Dartmouth College, 39 College St, Hanover, NH 03755, USA. 7. Department of Epidemiology, Geisel School of Medicine at Dartmouth, 1 Medical Center Dr, Lebanon, NH 03766, USA; Departments of Pediatrics and Psychiatry, Children's Hospital at Dartmouth, Dartmouth Hitchcock Medical Center, 1 Medical Center Drive, Lebanon, NH 03756, USA. 8. Department of Engineering, Northeastern University, 360 Huntington Ave, Boston, MA 02115, USA. 9. Department of Epidemiology & Biostatistics, College of Public Health, University of Georgia, 101 Buck Rd, Athens, GA 30602, USA. 10. Department of Environmental Health Sciences, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, USA.
Abstract
BACKGROUND: A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. METHODS: The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. RESULTS: In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. CONCLUSIONS: Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation.
BACKGROUND: A growing number of studies have identified both toxic and essential metals which influence fetal growth. However, most studies have conducted single-cohort analyses, which are often limited by narrow exposure ranges, and evaluated metals individually. The objective of the current study was to conduct an environmental mixture analysis of metal impacts on fetal growth, pooling data from three geographically and demographically diverse cohorts in the United States participating in the Environmental Influences on Child Health Outcomes program. METHODS: The pooled sample (N = 1,002) included participants from the MADRES, NHBCS, and PROTECT cohorts. Associations between seven metals (antimony, cadmium, cobalt, mercury, molybdenum, nickel, tin) measured in maternal urine samples collected during pregnancy (median: 16.0 weeks gestation) and birth weight for gestational age z-scores (BW for GA) were investigated using Bayesian Kernel Machine Regression (BKMR). Models were also stratified by cohort and infant sex to investigate possible heterogeneity. Chromium and uranium concentrations fell below the limits of detection for most participants and were evaluated separately as binary variables using pooled linear regression models. RESULTS: In the pooled BKMR analysis, antimony, mercury, and tin were inversely and linearly associated with BW for GA, while a positive linear association was identified for nickel. The inverse association between antimony and BW for GA was observed in both males and females and for all three cohorts but was strongest for MADRES, a predominantly low-income Hispanic cohort in Los Angeles. A reverse j-shaped association was identified between cobalt and BW for GA, which was driven by female infants. Pooled associations were null for cadmium, chromium, molybdenum, and uranium, and BKMR did not identify potential interactions between metal pairs. CONCLUSIONS: Findings suggest that antimony, an understudied metalloid, may adversely impact fetal growth. Cohort- and/or sex-dependent associations were identified for many of the metals, which merit additional investigation.
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