Faculty Bibliography

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.

OBJECTIVES/OBJECTIVE:To compare lung function in a representative sample of World Trade Center (WTC)-exposed children with matched comparisons, and examine relationships with reported exposures. STUDY DESIGN/METHODS:Study population consisted of 402 participants. Oscillometry, spirometry, and plethysmography were performed on WTC Health Registry (WTCHR) respondents who were ≤8 years of age on September 11, 2001 (n = 180) and a sociodemographically matched group of New York City residents (n = 222). We compared lung function by study arm (WTCHR and comparison group) as well as dust cloud (acute); home dust (subchronic); and other traumatic, nondust exposures. RESULTS:In multivariable models, post-9/11 risk of incident asthma was higher in the WTCHR participants than in the comparison group (OR 1.109, 95% CI 1.021, 1.206; P = .015). Comparing by exposure rather than by group, dust cloud (OR 1.223, 95% CI 1.095, 1.365; P < .001) and home dust (OR 1.123, 95% CI 1.029, 1.226; P = .009) exposures were also associated with a greater risk of incidence of post-9/11 asthma. No differences were identified for lung function measures. CONCLUSIONS:Although we cannot exclude an alternative explanation to the null findings, these results may provide some measure of reassurance to exposed children and their families regarding long-term consequences. Further study with bronchodilation and/or methacholine challenge may be needed to identify and further evaluate effects of WTC exposure. Biomarker studies may also be more informative in delineating exposure-outcome relationships. TRIAL REGISTRATION/BACKGROUND:ClinicalTrials.gov: NCT02068183.

Background/UNASSIGNED:Increasing evidence suggests that exposure to synthetic chemicals such as bisphenols and phthalates can influence fecundability. The current study describes associations of first trimester urinary concentrations of bisphenol A (BPA), BPA analogues and phthalate metabolites with time to pregnancy (TTP). Methods/UNASSIGNED:Among 877 participants in the population-based Generation R pregnancy cohort, we measured first trimester urinary concentrations of bisphenols and phthalates (median gestational age 12.9 weeks [inter-quartile range 12.1-14.4 weeks]). We used fitted covariate-adjusted Cox proportional hazard models to examine associations of bisphenol and phthalate concentrations with TTP. Participants who conceived using infertility treatment were censored at 12 months. Biologically plausible effect measure modification by folic acid supplement use was tested. Results/UNASSIGNED:In the main models, bisphenol and phthalate compounds were not associated with fecundability. In stratified models, total bisphenols and phthalic acid were associated with longer TTP among women who did not use folic acid supplements preconceptionally (respective fecundability ratios per each natural log increase were 0.90 [95% Confidence Interval (CI) 0.81, 1.00] and 0.88 [95% CI 0.79, 0.99]). Using an interaction term for the exposure and folic acid supplement use showed additional effect measure modification by folic acid supplement use for high molecular weight phthalate metabolites. Conclusions/UNASSIGNED:We found no associations of bisphenols and phthalates with fecundability. Preconception folic acid supplementation seems to modify effects of bisphenols and phthalates on fecundability. Folic acid supplements may protect against reduced fecundability among women exposed to these chemicals. Further studies are needed to replicate these findings and investigate potential mechanisms.

BACKGROUND:Exposure to air pollution during pregnancy may increase attention-deficit/ hyperactivity disorder (ADHD) symptoms in children, but findings have been inconsistent. We aimed to study this association in a collaborative study of eight European population-based birth/child cohorts, including 29,127 mother-child pairs. METHODS:Air pollution concentrations [nitrogen dioxide (NO2) and particulate matter (PM)] were estimated at the birth address by land-use regression models based on monitoring campaigns performed between 2008 and 2011. We extrapolated concentrations back in time to exact pregnancy periods. Teachers or parents assessed ADHD symptoms at 3-10 years of age. We classified children as having ADHD symptoms within the borderline/clinical range and within the clinical range using validated cut-offs. We combined all adjusted area-specific effect estimates using random-effects meta-analysis and multiple imputation and applied inverse probability weighting methods to correct for loss to follow-up. RESULTS:We classified a total of 2,801 children as having ADHD symptoms within the borderline/clinical range, and 1,590 within the clinical range. Exposure to air pollution during pregnancy was not associated with a higher odds of ADHD symptoms within the borderline/clinical range (e.g., adjusted odds ratio (OR) for ADHD symptoms of 0.95, 95% confidence interval (CI) 0.89-1.01 per 10µg/m increase in NO2 and 0.98, 95%CI 0.80-1.19 per 5µg/m increase in PM2.5). We observed similar associations for ADHD within the clinical range. CONCLUSIONS:There was no evidence for an increase in risk of ADHD symptoms with increasing prenatal air pollution levels in children aged 3 to 10 years.

PURPOSE OF REVIEW/OBJECTIVE:To assess the strength of evidence for associations between environmental toxicants and hypertensive disorders of pregnancy, suggest potential biological mechanisms based on animal and in vitro studies, and highlight avenues for future research. RECENT FINDINGS/RESULTS:Evidence is strongest for links between persistent chemicals, including lead, cadmium, organochlorine pesticides, and polycyclic biphenyls, and preeclampsia, although associations are sometimes not detectable at low-exposure levels. Results have been inconclusive for bisphenols, phthalates, and organophosphates. Biological pathways may include oxidative stress, epigenetic changes, endocrine disruption, and abnormal placental vascularization. Additional prospective epidemiologic studies beginning in the preconception period and extending postpartum are needed to assess the life course trajectory of environmental exposures and women's reproductive and cardiovascular health. Future studies should also consider interactions between chemicals and consider nonlinear associations. These results confirm recommendations by the International Federation of Gynecology and Obstetrics, the American Society for Reproductive Medicine, the American Academy of Pediatrics, and the Endocrine Society that providers counsel their pregnant patients to limit exposure to environmental toxicants.

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.

BACKGROUND:Evidence shows cytokine dysregulation in children with developmental disabilities. The association between immune activity during the perinatal period and child development is less clear. METHODS:We examined the relationship between newborn concentrations of immune markers and child development. Within Upstate KIDS, a population-based birth cohort (2008-2010, upstate New York), we assayed immune markers, which are postulated to have neuro-modulatory effects, in newborn dried blood spots (NDBS, n = 3038). Mothers completed the Ages & Stages Questionnaire© (ASQ) for their children repeatedly through age 36 months. At 30 and 36 months, mothers also reported whether their children received any developmental services. We used generalised linear mixed models adjusted for maternal and child characteristics to test associations. RESULTS:Sixteen immune markers were associated with failing ASQ in unadjusted models. After full adjustment (for gestational age, mode of delivery, parity, pregnancy smoking, etc.), we observed that higher levels of 4 markers, including platelet-derived growth factor-AA (PDGF-AA, OR 0.77, 95% CI 0.67, 0.89), plasminogen activator inhibitor-1 (OR 0.80, 95% CI 0.68, 0.94), stromal cell derived factor-1 (OR 0.85, 95% CI 0.73, 0.98), and macrophage inflammatory protein-1beta (OR 0.87, 95% CI 0.77, 0.98) were associated with lower odds of ASQ failure. The associations did not exist if correction for multiple comparisons was performed, except for PDGF-AA. Analyses with developmental service use revealed similar null findings. CONCLUSIONS:Immune marker concentrations in NDBS may not be associated with developmental delay in the general population. Newborn concentrations of growth factor PDGF-AA may be protective of developmental delay in childhood.

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.