Mohammad L Rahman1, Emily Oken1, Marie-France Hivert2, Sheryl Rifas-Shiman1, Pi-I D Lin1, Elena Colicino3, Robert O Wright4, Chitra Amarasiriwardena4, Birgit G Claus Henn5, Diane R Gold6, Brent A Coull7, Andres Cardenas8. 1. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. 2. Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 4. Department of Environmental Medicine and Institute for Exposomic Research, Icahn School of Medicine at Mount Sinai, New York, NY, USA. 5. Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA. 6. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. 7. Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Biostatistics, Harvard T. H. Chan School of Public Health, Boston, MA, USA. 8. Division of Environmental Health Sciences, School of Public Health, University of California, Berkeley, Berkeley, CA, USA. Electronic address: andres.cardenas@berkeley.edu.
Abstract
BACKGROUND: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. OBJECTIVES: To estimate individual and joint effects of metal mixture components on birth outcomes. METHODS: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. RESULTS: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. DISCUSSION: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.
BACKGROUND: Prenatal exposure to metals has been individually associated with birth outcomes. However, little is known about the effect of metal mixture, particularly at low exposure levels. OBJECTIVES: To estimate individual and joint effects of metal mixture components on birth outcomes. METHODS: We used data from 1,391 mother-infant pairs in Project Viva (1999-2002). We measured 11 metals in maternal 1st trimester erythrocyte; abstracted birth weight from medical records; calculated gestational age from last menstrual period or ultrasound; and obtained birth length (n = 729) and head circumference (n = 791) from research measurements. We estimated individual and joint effects of metals using multivariable linear and Bayesian kernel machine regressions. RESULTS: In both single metal and metal mixture analyses, exposure to higher concentrations of arsenic was associated with lower birth weight in males, zinc with higher head circumference in females, and manganese with higher birth length in sex-combined analysis. We also observed sex-specific metal interactions with birth outcomes. Arsenic and manganese showed a synergistic association with birth weight in males, in whom an interquartile range (IQR) increase in arsenic was associated with 25.3 g (95% CI: -79.9, 29.3), 47.9 g (95% CI: -98.0, 2.1), and 72.2 g (95% CI: -129.8, -14.7) lower birth weight when manganese concentrations were at 25th, 50th, and 75th percentiles, respectively. Lead and zinc showed an antagonistic association with head circumference in males, where an IQR increase in lead was associated with 0.18 cm (95% CI: -0.35, -0.02), 0.10 cm (95% CI: -0.25, 0.04), 0.03 cm (95% CI: -0.2, 0.14) smaller head circumference when zinc concentrations were at 25th, 50th, and 75th percentiles, respectively. Exposure to higher concentrations of arsenic was also associated with lower gestational age in males when concentrations of manganese and lead were higher. DISCUSSION: Maternal erythrocyte concentrations of arsenic, manganese, lead, and zinc were individually and interactively associated with birth outcomes. The associations varied by infant sex and exposure level of other mixture components.
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