Faculty Bibliography

Background: suPAR is an inflammatory mediator that has been linked to the pathogenesis of FSGS and progression of chronic kidney disease in children and adults. Overexpression of suPAR leads to reduced nephron development in preclinical models. This study was designed to measure suPAR in pregnant women to determine the range of fetal exposure to this molecule and its potential influence on antenatal human kidney growth.
Method(s): Pregnant women enrolled in the Children's Health and Environment Study (CHES) provided serum samples obtaining during 1-3 trimesters. Clinical information was obtained from the electronic health record. suPAR levels were determined by ELISA (Virogates, Copenhagen, Denmark). Data are presented as mean+/-SD. Results were analyzed by Pearson correlation and ANOVA.
Result(s): 515 mothers were studied, age 31+/-6 yr, and racial distribution 44% Caucasian, 7% African American, 9 % Asian, and 41% other/unspecified. 46% of the women were Hispanic. 29% had completed a high school education or less and 28% had an annual income <$50,000. There were 464 livebirths, 50.4% girls. The serum suPAR levels (mean, SD, minimum, maximum) are summarized in the Table. The suPAR levels in the subgroup of women who provided more than one sample during pregnancy were closely correlated (r=0.79-0.94, P<0.0001)). The decline in serum suPAR levels from trimester 1 to 3 was highly significant (P<0.001).
Conclusion(s): Maternal suPAR levels are detectable throughout pregnancy but decline from trimester 1 to 3. The levels are highly correlated and steady during the course of pregnancy in an individual woman. There is more than a 10-fold range in suPAR concentration which may contribute to the biological variation in nephron number at birth. Follow-up assessment in the infants will be performed in the prospective Environmental Influences on Child Health Outcomes (ECHO) cohort study. (Table Presented)

Background: Environmental chemical exposures are linked to oxidative stress and kidney injury in children and adults. This applies to short-lived organic compounds such as bisphenol A and phthalates and persistent synthetic chemicals such as perfluoroalkyl acids (PFAAs). Most investigations to date have been conducted in developed countries with few data about environmental chemical exposures in children living in Africa.
Method(s): Clinical and laboratory data about pediatric patients enrolled in the H3 Africa observational cohort study including age, gender, BMI, serum creatinine, eGFR, proteinuria were collected. Serum samples that had been collected at enrollment were retrieved from the Biorepository and analyzed for PFAAs and polybrominated diphenyl ethers (PBDEs) and DDE presticides using established methods. Proteinuria was assessed in a first morning urine sample. Results are presented as mean+/-SD.
Result(s): 86 patients with CKD (41 M:45 F), age 12.6+/-2.6 yr old, were included in this nested case control study. The eGFR was 75+/-4 and the albumin:creatinine ratio was 65+/-186. The chemical exposures are summarized in the Table. There was no association between exposure (log of serum concentration) to PFAAs and proteinuria. However, controlling for age, gender, and BMI, there was an inverse relationship between eGFR and exposure to PFNA, -21.2 [95% CI:-41.6 -0.8] and PFDA -18.3 [95% CI:-35.3 --1.3] ml/min/log unit increase in exposure and a trend towards a similar effect for PFOS. PBDE/DDEs were detected in a small fraction of children and because of small sample size associations with effect markers were not made
Conclusion(s): PFAA exposure is substantially lower in H3 Africa participants than in healthy US children, age 12-19 enrolled in NHANES 2003-2010. However, even at these lower levels of exposure there was an adverse association between select PFAAs and GFR. These studies indicate the feasibility of measuring environmental chemical exposure in developing countries. The impact of these chemical exposures on kidney function will require larger cohorts of children followed for more extended periods of time

: 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.