Association between maternal urinary arsenic species and infant cord blood leptin levels in a New Hampshire Pregnancy Cohort

Abstract

Leptin is an important pleiotropic hormone involved in the regulation of nutrient intake and energy expenditure, and is known to influence body weight in infants and adults. High maternal levels of arsenic have been associated with reduced infant birth weight, but the mechanism of action is not yet understood. This study aimed to investigate the association between in utero arsenic exposure and infant cord blood leptin concentrations within 156 mother-infant pairs from the New Hampshire Birth Cohort Study (NHBCS) who were exposed to low to moderate levels of arsenic through well water and diet. In utero arsenic exposure was obtained from maternal second trimester urinary arsenic concentration, and plasma leptin levels were assessed through immunoassay. Results indicate that urinary arsenic species concentrations were predictive of infant cord blood leptin levels following adjustment for creatinine, infant birth weight for gestational age percentile, infant sex, maternal pregnancy-related weight gain, and maternal education level amongst 149 white mother-infant pairs in multivariate linear regression models. A doubling or 100% increase in total urinary arsenic concentration (iAs + MMA + DMA) was associated with a 10.3% (95% CI: 0.8–20.7%) increase in cord blood leptin levels. A 100% increase in either monomethylarsonic acid (MMA) or dimethylarsinic acid (DMA) was also associated with an 8.3% (95% CI: −1.0–18.6%) and 10.3% (95% CI: 1.2–20.2%) increase in cord blood leptin levels, respectively. The association between inorganic arsenic (iAs) and cord blood leptin was of similar magnitude and direction as other arsenic species (a 100% increase in iAs was associated with a 6.5% (95% CI: −3.4–17.5%) increase in cord blood leptin levels), albeit not significant. These results suggest in utero exposure to low levels of arsenic influences cord blood leptin concentration and presents a potential mechanism by which arsenic may impact early childhood growth.

Prenatal Metal Concentrations and Childhood Cardiometabolic Risk Using Bayesian Kernel Machine Regression to Assess Mixture and Interaction Effects

“…We also observed a negative association between prenatal As and Sb and child leptin. One study found a positive association between maternal urinary As and cord blood leptin 34 , in contrast to the negative association observed here. To our knowledge there are no studies to date examining the impact of prenatal Sb on cardio-metabolic risk.…”

Prenatal Arsenic Exposure and Birth Outcomes among a Population Residing near a Mining-Related Superfund Site

“…Arsenic may also modulate expression of two arsenic-related genes ( AQP9 , ENPP2 ) in the placenta that are involved in arsenic transport and regulation of angiogenesis, respectively ( Fei et al 2013 ). The hormone leptin, which regulates appetite and metabolism, may also be involved: Positive associations have recently been reported between prenatal arsenic and cord blood leptin ( Gossai et al 2015 ), and cord blood leptin was negatively associated with length and head circumference at birth, as well as with lower weight gain from birth to 4 months, in 136–197 infants in the ALSPAC (Avon Longitudinal Study of Parents and Children) cohort ( Ong et al 1999 ). Cord blood leptin was also associated with lower BMI z -score, lower height-for-age z -score, and shorter leg length in 3-year-old children in the Project Viva cohort ( Mantzoros et al 2009 ).…”

The role of arsenic in obesity and diabetes

“…It has been postulated that the increased level of leptin in umbilical cord blood was related to high birth weight and also to the risk of obesity in future (Ahmed et al, 2011). Further works have also proved that exposure to low dose arsenite (up to 2 mM) for 8 weeks decreased glucose transporter type 4 (GLUT-4) expression upon insulin stimulation in 3T3-L1 adipocytes primed to differentiate (Gossai et al, 2015). An invitro study indicated that incubation of adipocytes with arsenic disrupts multiple metabolic pathways.…”