TY - JOUR
T1 - Early pregnancy exposure to metal mixture and birth outcomes – A prospective study in Project Viva
AU - Rahman, Mohammad L.
AU - Oken, Emily
AU - Hivert, Marie France
AU - Rifas-Shiman, Sheryl
AU - Lin, Pi I.D.
AU - Colicino, Elena
AU - Wright, Robert O.
AU - Amarasiriwardena, Chitra
AU - Claus Henn, Birgit G.
AU - Gold, Diane R.
AU - Coull, Brent A.
AU - Cardenas, Andres
N1 - Funding Information:
The measurement of metals was funded by the Children’s Health Exposure Analysis Resource (CHEAR) award (2017–1740, NIH grant U2CES026561) and was carried out at the Mount Sinai CHEAR Network Laboratory.
Funding Information:
The authors would like to thank the participants Project Viva for their time and willingness to participate in the study; all members of the Project Viva team at the Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute for collecting and managing data, in particular, Inbar Brenner, Karen Ruderman, Marleny Ortega, and Chelsea Jenter for providing administrative support for this project; and the Children's Health Exposure Analysis Resource (CHEAR) Data Center of the Department of Environmental Medicine and Public Health at Icahn School of Medicine at Mount Sinai for performing the quantification of metal concentrations in red blood cells. Persons named in the Acknowledgments section have provided the corresponding author with written permission to be named in the manuscript. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the National Institutes of Health, National Institute of Environmental Health Sciences, or the Environmental influences on Child Health Outcomes (ECHO) program.
Funding Information:
This work was supported by the US National Institutes of Health grants R01 HD034568, UH3 OD023286, ES000002, and R01 ES031259. The Children’s Health Exposure Analysis Resource (CHEAR) funded the measurement of elements (CHEAR award #2017–1740) supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number (U2CES026561) and was carried out at the Mount Sinai CHEAR Network Laboratory with data processed by the CHEAR Data Center (U2CES026555).
Publisher Copyright:
© 2021 The Authors
PY - 2021/11
Y1 - 2021/11
N2 - 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.
AB - 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.
KW - Arsenic
KW - Birth outcome
KW - Environmental exposure
KW - Lead
KW - Manganese
KW - Metals
KW - Mixture analysis
KW - Pregnancy
UR - http://www.scopus.com/inward/record.url?scp=85108061799&partnerID=8YFLogxK
U2 - 10.1016/j.envint.2021.106714
DO - 10.1016/j.envint.2021.106714
M3 - Article
C2 - 34147999
AN - SCOPUS:85108061799
SN - 0160-4120
VL - 156
JO - Environment international
JF - Environment international
M1 - 106714
ER -