title: Metals exposure and risk of small-for-gestational age birth in a Canadian birth cohort: The MIREC study.
abstract: BACKGROUND
  Lead, mercury, cadmium and arsenic are some of the most common toxic metals to which Canadians are exposed. The effect of exposure to current low levels of toxic metals on fetal growth restriction is unknown.
  
  
  OBJECTIVE
  The aim of this study was to examine relationships between exposure to lead, mercury, cadmium and arsenic during pregnancy, and risk of small for gestational age (SGA) birth.
  
  
  METHODS
  Lead, mercury, cadmium and arsenic levels were measured in blood samples from the first and third trimesters in 1835 pregnant women from across Canada. Arsenic species in first trimester urine were also assessed. Relative risks and 95% confidence intervals were estimated using log binomial multivariate regression. Important covariates including maternal age, parity, pre-pregnancy BMI, and smoking, were considered in the analysis. An exploratory analysis was performed to examine potential effect modification of these relationships by single nucleotide polymorphisms (SNPs) in GSTP1 and GSTO1 genes.
  
  
  RESULTS
  No association was found between blood lead, cadmium or arsenic and risk for SGA. We observed an increased risk for SGA for the highest compared to the lowest tertile of exposure for mercury (>1.6 µg/L, RR=1.56.; 95% CI=1.04-2.58) and arsenobetaine (>2.25 µg/L, RR=1.65; 95% CI=1.10-2.47) after adjustment for the effects of parity and smoking. A statistically significant interaction was observed in the relationship between dimethylarsinic acid (DMA) levels in urinary arsenic and SGA between strata of GSTO1 A104A (p for interaction=0.02). A marginally significant interaction was observed in the relationship between blood lead and SGA between strata of GSTP1 A114V (p for interaction=0.06).
  
  
  CONCLUSIONS
  These results suggest a small increase in risk for SGA in infants born to women exposed to mercury and arsenic. Given the conflicting evidence in the literature this warrants further investigation in other pregnant populations.
authors.affiliation: Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Shari
authors.initials: S
authors.lastname: Thomas
authors.affiliation: Population Studies Division, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Canada. Electronic address: Tye.Arbuckle@hc-sc.gc.ca.
authors.forename: Tye E
authors.initials: TE
authors.lastname: Arbuckle
authors.affiliation: Population Studies Division, Healthy Environments and Consumer Safety Branch, Health Canada, Ottawa, Canada.
authors.forename: Mandy
authors.initials: M
authors.lastname: Fisher
authors.affiliation: Sainte Justine University Hospital Research Center, University of Montreal, Montreal, Canada.
authors.forename: William D
authors.initials: WD
authors.lastname: Fraser
authors.affiliation: Center for Perinatal, Pediatric & Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA.
authors.forename: Adrienne
authors.initials: A
authors.lastname: Ettinger
authors.affiliation: Department of Public Health Sciences, Queen's University, Kingston, Ontario, Canada.
authors.forename: Will
authors.initials: W
authors.lastname: King
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007236:Infant, Small for Gestational Age; D018811:Maternal Exposure; D008670:Metals / Q000633:toxicity*; D009864:Ontario; D020641:Polymorphism, Single Nucleotide; D011247:Pregnancy; D011256:Pregnancy Outcome; D012307:Risk Factors
chemical_list: D008670:Metals
keywords: Arsenic; Biomonitoring; Cadmium; Lead; Mercury; Pregnancy cohort study; Small for gestational age