Maternal blood metal levels and fetal markers of metabolic function

Abstract

Exposure to metals commonly found in the environment has been hypothesized to be associated with measures of fetal growth but the epidemiological literature is limited. The Maternal-Infant Research on Environmental Chemicals (MIREC) study recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. Our objective was to assess the association between prenatal exposure to metals (lead, arsenic, cadmium, and mercury) and fetal metabolic function. Average maternal metal concentrations in 1st and 3rd trimester blood samples were used to represent prenatal metals exposure. Leptin and adiponectin were measured in 1363 cord blood samples and served as markers of fetal metabolic function. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between metals and both high (≥ 90%) and low (≤ 10%) fetal adiponectin and leptin levels. Leptin levels were significantly higher in female infants compared to males. A significant relationship between maternal blood cadmium and odds of high leptin was observed among males but not females in adjusted models. When adjusting for birth weight z-score, lead was associated with an increased odd of high leptin. No other significant associations were found at the top or bottom 10th percentile in either leptin or adiponectin models. This study supports the proposition that maternal levels of cadmium influence cord blood adipokine levels in a sex-dependent manner. Further investigation is required to confirm these findings and to determine how such findings at birth will translate into childhood anthropometric measures.

Metabolism disrupting chemicals and metabolic disorders

“…The animal [400] and epidemiological data on obesogenic effects of prenatal exposure to arsenic [401, 402] while limited are consistent across species. Cd, Pb and As exposures are associated with smaller size at birth [403-406] which is a risk factor for subsequent weight gain and greater adiposity. Prenatal exposure to toxic metals is also related to higher leptin at birth [407, 408].…”

Air Pollution Exposure During Pregnancy And Fetal Markers Of Metabolic Function: The Mirec Study

“…As part of the MIREC Study, stored umbilical cord blood samples were analyzed to measure levels of leptin and adiponectin using Meso Scale Discovery immunoassay kits (Meso Scale Diagnostics, Rockville, Maryland) at Mount Sinai Laboratory (Toronto, Ontario, Canada). Repeated analysis was performed on all samples with a coefficient of variation greater than 15% (12). The inter-and intraassay coefficients of variation, respectively, were 11.8% and 9.3% for leptin and 8% and 9% for adiponectin.…”

“…Covariates were identified as potential confounders based on a priori knowledge of their relationships with the exposures and outcomes (12,(14)(15)(16). Covariates were assessed during study clinic visits throughout pregnancy or at delivery, and included maternal age at delivery (≤24, 25-29, 30-34, or ≥35 years), prepregnancy BMI (weight (kg)/height (m) 2 ), using categories set by the World Health Organization (30), gestational weight gain according to the Institute of Medicine's recommendations (inadequate, adequate, or excessive) (31), parity (nulliparous or parous), maternal educational level (high school diploma or less, trade school or some college, undergraduate university degree, or graduate university degree), annual household income (in Canadian dollars; ≤30,000, 30,001-50,000, 50,001-100,000, or >100,000), ethnicity (white or nonwhite), maternal smoking (never smoked or quit before pregnancy, quit smoking when pregnancy was confirmed, or current smoker), infant sex, and birth weight z score (which was used as a surrogate of fetal fat mass) (12)(13)(14). Previous literature has shown associations between outdoor air pollution and low birth weight (15), and size at birth has been shown to be positively associated with cord blood leptin levels (8).…”

“…We also evaluated effect modification of infant sex by including a term for interaction between infant sex and each exposure. In addition, analyses were stratified by infant sex because in utero exposure to environmental contaminants might be associated with cord blood adipokine levels in a sexdependent manner (12). All models for leptin and adiponectin…”

“…Although the relationship between cord blood adiponectin and childhood BMI is less clear, higher adiponectin levels at birth seem to be related to increases in central adiposity and elevated lipid levels during infancy (7,9). Recently, higher levels of arsenic, lead, cadmium, and phthalate metabolites measured in blood or urine were associated with elevated leptin levels in umbilical cord blood (12)(13)(14). However, to our knowledge, the association between prenatal exposure to air pollution and cord blood adipokine levels has not yet been investigated.…”