Background: Bacterial endotoxin is a potently inflammatory antigen that is abundant in the human gut. Endotoxin circulates at low concentrations in the blood of all healthy individuals, although elevated concentrations are associated with an increased risk of atherosclerosis. Objective: We sought to determine whether a high-fat meal or smoking increases plasma endotoxin concentrations and whether such concentrations are of physiologic relevance. Design: Plasma endotoxin and endotoxin neutralization capacity were measured for 4 h in 12 healthy men after no meal, 3 cigarettes, a high-fat meal, or a high-fat meal with 3 cigarettes by using the limulus assay. Results: Baseline endotoxin concentrations were 8.2 pg/mL (interquartile range: 3.4 -13.5 pg/mL) but increased significantly (P 0.05) by Ȃ50% after a high-fat meal or after a high-fat meal with cigarettes but not after no meal or cigarettes alone. These results were validated by the observations that a high-fat meal with or without cigarettes, but not no meal or smoking, also significantly (P 0.05) reduced plasma endotoxin neutralization capacity, which is an indirect measure of endotoxin exposure. Human monocytes, but not aortic endothelial cells, were responsive to transient (30 s) or lowdose (10 pg/mL) exposure to endotoxin. However, plasma from whole blood treated with as little as 10 pg endotoxin/mL increased the endothelial cell expression of E-selectin, at least partly via tumor necrosis factor-␣-induced cellular activation. Conclusions: Low-grade endotoxemia may contribute to the postprandial inflammatory state and could represent a novel potential contributor to endothelial activation and the development of atherosclerosis.Am J Clin Nutr 2007;86:1286 -92.

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Objectives To assess associations of caesarean section with body mass from birth through adolescence. Design Longitudinal birth cohort study, following subjects up to 15 years of age. Setting and Participants Children born in 1991–1992 in Avon, UK who participated in the Avon Longitudinal Study of Parents and Children [ALSPAC] (n = 10,219). Outcome measures Primary outcome: standardized measures of body mass (weight-for length z-scores at 6 weeks, 10, and 20 months; and Body Mass Index [BMI] z-scores at 38 months, 7, 9, 11, and 15 years). Secondary outcome: Categorical overweight or obese (BMI >= 85th percentile) for age and gender, at 38 months, 7, 9, 11, and 15 years. Results Of the 10,219 children, 926 (9.06%) were delivered by caesarean section. Those born by caesarean had lower birth weights than those born vaginally (−46.1g, 95% CI: 14.6 to 77.6 g; p = 0.004). In mixed multivariable models adjusting for birth weight, gender, parental body mass, family sociodemographics, gestational factors and infant feeding patterns, caesarean delivery was consistently associated with increased adiposity, starting at six weeks (+0.11 SD units, 95% CI 0.03 to 0.18; p=0.005), through age 15 (BMI z-score increment + 0.10 SD units, 95% CI 0.001 to 0.198; p=0.042). By age 11 caesarean–delivered children had 1.83 times the odds of overweight or obesity (95% CI: 1.24 to 2.70; p=0.002). When the sample was stratified by maternal pre-pregnancy weight, the association among children born of overweight/obese mothers was strong and long-lasting. In contrast, evidence of an association among children born of normal weight mothers was weak. Conclusion Caesarean delivery is associated with increased body mass in childhood and adolescence. Research is needed to further characterize the association in children of normal weight women. Additional work is also needed to understand the mechanism underlying the association, which may involve relatively enduring changes in the intestinal microbiome.

Endocrine Society, Ralph S French Charitable Foundation, and Broad Reach Foundation.

Background: Children’s blood lead levels have declined worldwide, especially after the removal of lead in gasoline. However, significant exposure remains, particularly in low- and middle-income countries. To date, there have been no global estimates of the costs related to lead exposure in children in developing countries.Objective: Our main aim was to estimate the economic costs attributable to childhood lead exposure in low- and middle-income countries.Methods: We developed a regression model to estimate mean blood lead levels in our population of interest, represented by each 1-year cohort of children < 5 years of age. We used an environmentally attributable fraction model to estimate lead-attributable economic costs and limited our analysis to the neurodevelopmental impacts of lead, assessed as decrements in IQ points. Our main outcome was lost lifetime economic productivity due to early childhood exposure.Results: We estimated a total cost of $977 billions of international dollars in low- and middle-income countries, with economic losses equal to $134.7 billion in Africa [4.03% of gross domestic product (GDP)], $142.3 billion in Latin America and the Caribbean (2.04% of GDP), and $699.9 billion in Asia (1.88% of GDP). Our sensitivity analysis indicates a total economic loss in the range of $728.6–1162.5 billion.Conclusions: We estimated that, in low- and middle-income countries, the burden associated with childhood lead exposure amounts to 1.20% of world GDP in 2011. For comparison, in the United States and Europe lead-attributable economic costs have been estimated at $50.9 and $55 billion, respectively, suggesting that the largest burden of lead exposure is now borne by low- and middle-income countries.Citation: Attina TM, Trasande L. 2013. Economic costs of childhood lead exposure in low- and middle-income countries. Environ Health Perspect 121:1097–1102; http://dx.doi.org/10.1289/ehp.1206424