Faculty Bibliography

: media-1vid110.1542/5839981580001PEDS-VA_2018-0290Video Abstract OBJECTIVES: To determine the association of antibiotic use with weight outcomes in a large cohort of children.

Substantial effort has been devoted to explaining secular trends in childhood obesity and metabolic risks to unhealthy diet and physical activity. While some studies have suggested these factors may play a role in the obesity epidemic, even these studies have only been able to conclude that these factors have a moderate role. Given that a single-generation transformation in the human genome is even more unlikely to have transformed susceptibility to excess weight gain in early life, we are left with the reality that environmental influences represent important risks for obesity and dysmetabolism. In contrast to diet and physical activity, which can require intensive attention, effort and costs to modify through behavioral and other interventions, government action can fundamentally transform the environment and prevent disease and disability. The costs of regulations to limit environmental obesogens can also be much lower than the benefits to society.

Concerns remain about the health of children conceived by infertility treatment. Studies to date have predominantly not identified substantial long-term health effects after accounting for plurality, which is reassuring given the increasing numbers of children conceived by infertility treatment worldwide. However, as technological advances in treatment arise, ongoing studies remain critical for monitoring health effects. To study whether the techniques used in infertility treatment cause health differences, however, remains challenging due to identification of an appropriate comparison group, heterogeneous treatment, and confounding by the underlying causes of infertility. In fact, the factors that are associated with underlying infertility, including parental obesity and other specific male and female factors, may be important independent factors to consider. This review will summarize key methodological considerations in studying children conceived by infertility treatment including the evidence of associations between underlying infertility factors and child health.

BACKGROUND:Melamine and cyanuric acid, which are currently used in a variety of common consumer products and present in foods, have been implicated in the development of urolithiasis and acute kidney injury in Chinese children. To determine whether US children have measurable concentrations of these chemicals in their bodies and whether they are at greater risk of acute kidney injury, we measured melamine and cyanuric acid exposure in a cohort of US children and determined their relationship with markers of kidney injury. METHODS:We measured urinary melamine and cyanuric acid in a convenience sample of 109 children (4 months - 8 years) from Seattle, WA and New York City, NY using liquid chromatography with tandem mass spectrometry. We measured several urinary markers of kidney injury: fatty acid binding protein 3 (FABP3), kidney injury molecule 1 (KIM1), neutrophil gelatinase-associated lipocalin (NGAL) using Luminex xMAP methods, and urine urea was measured using standard laboratory methods. We described urinary melamine and cyanuric acid concentrations and assessed predictors of the exposures. We used multivariable linear regression to assess relationships between melamine/cyanuric acid and kidney injury markers in unadjusted and adjusted (creatinine, age, sex) analyses. RESULTS:Melamine and cyanuric acid were above the limit of detection (LOD) in 78% and 95% of all samples, respectively. The mean concentrations (SD) for melamine and cyanuric acid were 27.4 ng/ml (141.9 ng/ml) and 35.3 ng/ml (42.4 ng/ml). In unadjusted analyses, we observed statistically significant increases in the percentages of FABP3 and KIM1 in relation to a one log unit change in melamine and cyanuric acid, respectively. In adjusted analyses, we observed a 55% (95% CI 0, 141) increase in KIM1 in relation to a one log unit increase in cyanuric acid. CONCLUSIONS:US children have detectable concentrations of melamine and cyanuric acid in urine, and these concentrations are higher than those reported in children from other countries. This is a novel finding that improves upon previous exposure estimates using questionnaires only and suggests widespread exposure in the population. Cyanuric acid is associated with increased KIM 1 concentrations, suggesting kidney injury. Given the potential widespread exposure, future analyses should examine melamine and cyanuric acid in relation to chronic kidney disease and markers of kidney injury in a larger cohort that is representative of the general population.

Perfluoroalkyl substances (PFAS) may have been released during the collapse of the World Trade Center (WTC) on 9/11. Evidence suggests PFAS can cross the placental barrier in humans and cause harm to the developing fetus; however, no studies have measured PFAS in mothers exposed to the WTC disaster during pregnancy. We measured PFAS in maternal plasma (n = 48) or cord blood (n = 231) from pregnant women in the Columbia University WTC birth cohort, enrolled between December 13, 2001 and June 26, 2002 at one of three hospitals located near the WTC site. In order to maximize sample size, we used a linear regression to transform the 48 maternal plasma samples to cord blood equivalents in our study; cord blood and transformed maternal plasma-to-cord blood samples were then analyzed together. We evaluated the association between WTC exposure and PFAS concentrations using three exposure variables: 1) living/working within two miles of WTC; 2) living within two miles of WTC regardless of work location; and 3) working but not living within two miles of WTC. Exposure was compared with those not living/working within two miles of WTC (reference group). Living/working within two miles of WTC was associated with 13% higher perfluorooctanoic acid (PFOA) concentrations compared with the reference group [GMR (95% CI): 1.13 (1.01, 1.27)]. The association was stronger when comparing only those who lived within two miles of WTC to the reference group [GMR (95% CI): 1.17 (1.03, 1.33)], regardless of work location. Our results provide evidence that exposure to the WTC disaster during pregnancy resulted in increases in PFAS concentrations, specifically PFOA. This work identifies a potentially vulnerable and overlooked population, children exposed to the WTC disaster in utero, and highlights the importance of future longitudinal studies in this cohort to investigate later life effects resulting from these early life exposures.

Experimental studies suggest that prenatal exposure to endocrine disrupting chemicals interferes with developmental processes in the fetal brain. Yet, epidemiological evidence is inconclusive. In a birth cohort (2008-2010, upstate New York), we quantified concentrations of perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and bisphenol A (BPA) in stored newborn dried blood spots using liquid chromatography/tandem mass spectrometry. Mothers reported on children's behavior using the Strengths and Difficulties Questionnaire at age 7 (650 singletons and 138 twins). Difficulties in total behavior (i.e., emotional, conduct, hyperactivity, and peer problems) and prosocial behavior were classified using validated cut-offs. We used logistic regression with generalized estimating equations to estimate the odds of having difficulties per exposure category. In total, 111 children (12.1%) had total behavioral difficulties and 60 (6.5%) had difficulties in prosocial behavior. The median (interquartile range) of PFOS, PFOA, and BPA were 1.74 ng/ml (1.33), 1.12 ng/ml (0.96), and 7.93 ng/ml (10.79), respectively. Higher PFOS levels were associated with increased odds of having behavioral difficulties (OR per SD of log PFOS = 1.30, 95%CI: 1.03-1.65). We observed associations between PFOS in the highest relative to the lowest quartile and behavioral difficulties (OR for PFOS_1.14-1.74 = 1.65, 95%CI: 0.84-3.34; PFOS_1.75-2.47 = 1.73, 95%CI: 0.87-3.43; and PFOS_>2.47 = 2.47, 95%CI: 1.29-4.72 compared to PFOS_<1.41). The associations between higher concentrations of PFOS and behavioral difficulties at age 7 years were driven by problems in conduct and emotional symptoms. Higher PFOA levels were associated with difficulties in prosocial behavior (OR = 1.35, 95%CI: 1.03-1.75). There was an inverse association between BPA concentrations and difficulties in prosocial behavior but only in the 2nd and 4th quartiles. We found no interactions between sex and chemical concentrations. Increasing prenatal exposure to PFOS and PFOA, as reflected in neonatal concentrations, may pose risk for child behavioral difficulties.

RATIONALE AND OBJECTIVE/OBJECTIVE:Exposure to Bisphenol A (BPA) and phthalates is ubiquitous among adults and children in the United States. Among children and adolescents, those with chronic kidney disease (CKD) are potentially at greater risk of adverse effects from BPA and phthalate exposure. The objective of this study was to evaluate BPA and phthalate exposure among children with CKD and evaluate associations with three measures of kidney function. STUDY DESIGN/METHODS:Cross sectional study. SETTING, PARTICIPANTS, AND MEASUREMENTS/UNASSIGNED:The CKD population was represented by the Chronic Kidney Disease in Children (CKiD) Study, a multicenter, prospective cohort study of children with impaired kidney function in the US. The main outcome was assessment of the relationship between chemical exposures and clinical laboratory findings at enrollment into CKiD. Data collected at baseline from participants 1 to 17 years old (N = 538) were analyzed. Urinary BPA and phthalate levels were evaluated at this time point. Data from the National Health and Nutrition Examination Survey (NHANES), a nationally representative pediatric population, were used for comparison to the CKiD cohort. RESULTS:Urinary BPA and phthalate levels in the CKiD population were consistently lower than levels detected in healthy children. Additionally, BPA was not significantly associated with blood pressure, proteinuria, or estimated glomerular filtration rate (eGFR). Within the CKiD population, for select individual and combined phthalates, there was an inverse relationship with the urinary protein:creatinine ratio (LMW phthalates, - 9.53% change; 95% CI: - 14.21, - 4.21; p = 0.001), and in most cases, a positive relationship with eGFR (LMW phthalates, a 3.46 unit increase in eGFR, 95% CI: 1.85, 5.07; p < 0.001). LIMITATIONS/CONCLUSIONS:Lack of longitudinal data, limited assessment of diet and nutritional status. CONCLUSION/CONCLUSIONS:In the study cohort, children with CKD did not have increased exposure to BPA and phthalates. Longitudinal studies with repeated measures are likely to be more informative about the possible health effects of prolonged exposure to BPA and phthalates in pediatric patients with CKD.

Our purposes with this policy statement and its accompanying technical report are to review and highlight emerging child health concerns related to the use of colorings, flavorings, and chemicals deliberately added to food during processing (direct food additives) as well as substances in food contact materials, including adhesives, dyes, coatings, paper, paperboard, plastic, and other polymers, which may contaminate food as part of packaging or manufacturing equipment (indirect food additives); to make reasonable recommendations that the pediatrician might be able to adopt into the guidance provided during pediatric visits; and to propose urgently needed reforms to the current regulatory process at the US Food and Drug Administration (FDA) for food additives. Concern regarding food additives has increased in the past 2 decades, in part because of studies in which authors document endocrine disruption and other adverse health effects. In some cases, exposure to these chemicals is disproportionate among minority and low-income populations. Regulation and oversight of many food additives is inadequate because of several key problems in the Federal Food, Drug, and Cosmetic Act. Current requirements for a "generally recognized as safe" (GRAS) designation are insufficient to ensure the safety of food additives and do not contain sufficient protections against conflict of interest. Additionally, the FDA does not have adequate authority to acquire data on chemicals on the market or reassess their safety for human health. These are critical weaknesses in the current regulatory system for food additives. Data about health effects of food additives on infants and children are limited or missing; however, in general, infants and children are more vulnerable to chemical exposures. Substantial improvements to the food additives regulatory system are urgently needed, including greatly strengthening or replacing the "generally recognized as safe" (GRAS) determination process, updating the scientific foundation of the FDA's safety assessment program, retesting all previously approved chemicals, and labeling direct additives with limited or no toxicity data.