Nonchromosomal birth defects and risk of childhood acute leukemia: An assessment in 15 000 leukemia cases and 46 000 controls from the Childhood Cancer and Leukemia International Consortium.

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia (AML, n = 2120) cases, along with 46 172 controls. We used the false discovery rate to account for multiple comparisons. In the questionnaire-based studies, the prevalence of birth defects was 5% among cases vs 4% in controls, whereas, in the registry-based studies, the prevalence was 11% among cases vs 7% in controls. In pooled adjusted analyses, there were several notable associations, including (1) digestive system defects and ALL (OR = 2.70, 95% CI: 1.46-4.98); (2) congenital anomalies of the heart and circulatory system and AML (OR = 2.86, 95% CI: 1.81-4.52) and (3) nervous system defects and AML (OR = 4.23, 95% CI: 1.50-11.89). Effect sizes were generally larger in registry-based studies. Overall, our results could point to novel genetic and environmental factors associated with birth defects that could also increase leukemia susceptibility. Additionally, differences between questionnaire- and registry-based studies point to the importance of complementary sources of birth defect phenotype data when exploring these associations.

Effects on household income and earnings from chronic kidney disease of non-traditional origins: PREP project findings from Chichigalpa, Nicaragua.

OBJECTIVE: Our purpose with this study is to examine the socioeconomic outcomes associated with chronic kidney disease not related to well-known risk factors (CKDnt) in four communities in Chichigalpa, Nicaragua that are home to a substantial number of sugarcane workers. METHODS: We employed a cluster-based systematic sampling design to identify differences in outcomes between those households affected directly by CKDnt and those that are not. RESULTS: Overall, we find that approximately one-third of households surveyed had a household member diagnosed with CKDnt. 86% of CKDnt households reported that the head of the household had been without work for the last 6 months or more, compared with 53% of non-CKDnt households. Non-CKDnt households took in more than double the earnings income on average than CKDnt households ($C52 835 and $C3120, respectively). Nonetheless, on average, CKDnt households' total income exceeded that of non-CKDnt households due to Nicaragua's national Instituto Nicaraguense de Seguridad Social Social Security payments to CKDnt households, suggestive of a substantial economic burden on the state resulting from the disease. Households headed by widows or widowers who are widowed as a result of CKDnt demonstrate distinct deficits in total income when compared with either non-widowed households or to households widowed by causes other than CKDnt. CONCLUSIONS: Despite strong similarities in terms of demographic characteristics and despite residing in the same communities with similar access to the available resources, households experiencing CKDnt exhibit distinct and statistically significant differences in important socioeconomic outcomes when compared to non-CKDnt households.

Markers of kidney tubular and interstitial injury and function among sugarcane workers with cross-harvest serum creatinine elevation.

OBJECTIVES: Serum creatinine (SCr) is a routine marker of kidney injury but also increases with dehydration and muscular work. This study was to elucidate whether increase in SCr is associated with more specific markers of kidney tubular and interstitial injury and function, during prolonged heat stress among workers at high risk of chronic kidney disease of non-traditional origin (CKDnt). METHODS: Urine monocyte chemoattractant protein-1 (MCP-1), kidney injury molecule-1 (KIM-1), calbindin, glutathione S-transferase-π (GST-π), clusterin, interleukin 18 and albumin, fractional excretion of potassium (FEK), blood haemoglobin, serum potassium, ferritin and erythropoietin were measured before and after harvest in a sample of 30 workers with a ≥0.3 mg/dL SCr increase across harvest (cases), and 53 workers with stable SCr (controls). RESULTS: Urine MCP-1 (p for differential cross-harvest trend <0.001), KIM-1 (p=0.002), calbindin (p=0.02), GST-π (p=0.04), albumin (p=0.001) and FEK (p<0.001) increased in cases, whereas blood haemoglobin (p<0.001) and serum erythropoietin (p<0.001) decreased. CONCLUSION: Several markers of tubular and interstitial injury and function changed as SCr increased across a harvest season, supporting the use of SCr as an indicator of kidney injury in physically active workers regularly exposed to heat stress. Repeated injury similar to that described here, and continued work under strenuous and hot conditions with similarly elevated injury markers is likely to worsen and possibly initiate CKDnt.

Preventing kidney injury among sugarcane workers: promising evidence from enhanced workplace interventions.

OBJECTIVES: To assess if improvement of working conditions related to heat stress was associated with improved kidney health outcomes among sugarcane harvest workers in Chichigalpa, Nicaragua, a region heavily affected by the epidemic of chronic kidney disease of non-traditional origin. METHODS: Based on our findings during the 2017-2018 harvest (harvest 1), recommendations that enhanced the rest schedule and improved access to hydration and shade were given before the 2018-2019 harvest (harvest 2). Actual work conditions during harvest 2 were then observed. Serum creatinine (SCr) was measured before and at end-harvest, and cross-harvest changes in estimated glomerular filtration rate (eGFR) and incident kidney injury (IKI, ie, SCr increase by ≥0.30 mg/dL or ≥1.5 times the baseline value) were compared between harvest 1 and harvest 2 for three jobs with different physical workloads using regression modelling. Workers who left during harvest were contacted at home, to address the healthy worker selection effect. RESULTS: In burned cane cutters, mean cross-harvest eGFR decreased 6 mL/min/1.73 m2 (95% CI 2 to 9 mL/min/1.73 m2) less and IKI was 70% (95% CI 90% to 50%) lower in harvest 2 as compared with harvest 1 data. No such improvements were seen among seed cutters groups with less successful intervention implementation. CONCLUSION: Kidney injury risk was again elevated in workers with strenuous jobs. The results support further efforts to prevent kidney injury among sugarcane workers, and other heat-stressed workers, by improving access to water, rest and shade. The distinction between design and implementation of such interventions should be recognised.

Pesticide risk perceptions among bystanders of aerial spraying on bananas in Costa Rica.

Little is known about how bystanders perceive risks from pesticide use in areas with frequent aerial spraying of pesticides. This research aims to better understand how bystanders (school workers) from three counties of the Limón province in Costa Rica, who did not have a contractual relationship with agricultural production, perceive risks of pesticides in the areas where they work and live. A face-to-face survey was carried out among 475 school workers, of whom 455 completed all 33 questions on pesticide risk perception. An exploratory factor analysis characterized underlying perceptions of pesticide exposure. Nine factors explained 40% of total variance and concerned severity and magnitude of perceived risk, manageability, benefits and support of pesticide use, amongst others. We subsequently analyzed what variables explained the five factors with satisfactory internal consistency, using separate multivariable linear regression models. Older school workers, (male) elementary teachers, and women school workers (particularly from schools situated near agricultural fields with aerial spraying of pesticides), felt greater severity and/or magnitude of risk from pesticide use. This study shows that bystanders are concerned about health risks from pesticide use. Their risk perceptions are not only shaped by gender and age like previously reported in the literature, but also by job title and geographical context. Understanding of what hazards people care about and how they deal with them is essential for successful risk management, bystanders should therefore be considered as a relevant actor in debates around pesticide issues and for informing the development of regulations and risk reduction strategies.

Early immune stimulation and childhood acute lymphoblastic leukemia in Costa Rica: A comparison of statistical approaches.

BACKGROUND: Although epidemiologic studies suggest that early immune stimulation is protective against childhood leukemia, evidence for this relationship is equivocal for Hispanic children, who are disproportionately affected by this disease. The complex biological processes underlying immune stimulation and leukemogenesis may benefit from novel statistical approaches that account for mixed exposures and their nonlinear interactions. In this study, we utilized targeted machine learning and traditional statistical methods to investigate the association of multiple measures of early immune stimulation with acute lymphoblastic leukemia (ALL) in Costa Rican children. MATERIALS AND METHODS: We used data from a population-based case-control study conducted in Costa Rica (2001-2003). Cases of ALL (n = 240) were diagnosed in 1995-2000 (age >1 year and <15 years at diagnosis) and were identified through the National Cancer Registry and National Children's Hospital. Population controls (n = 578) were frequency-matched to cases by birth year and drawn from the National Birth Registry. Data on surrogate measures of early immune stimulation were collected through in-home interviews. We fitted multivariable models, utilizing targeted causal inference (varimpact), unconditional logistic regression, and latent class analysis (LCA). RESULTS: In varimpact analysis, contact with any pet [risk difference (RD) = -0.17, 95% CI: -0.25, -0.10)] or any farm animal (RD = -0.07, 95% CI: -0.13, 0.00) and allergies (RD = -0.08, 95% CI: -0.17, 0.01) were associated with a reduced risk of ALL, whereas experiencing a fever longer than one week was associated with an increased risk (RD = 0.23, 95% CI: 0.12, 0.33). In unconditional logistic regression models, contact with any pet or farm animal and a complete vaccination scheme were inversely associated with odds of ALL (OR = 0.44, 95% CI: 0.31, 0.62; OR = 0.66, 95% CI: 0.49, 0.90; OR = 0.45, 95% CI: 0.24, 0.83; respectively), whereas experiencing a fever longer than one week was positively associated with ALL (OR = 2.44, 95% CI: 1.61, 3.70). Two-class and three-class LCA revealed a group with elevated risk for ALL whose exposure profile was mainly characterized by reduced exposure to pets and farm animals. CONCLUSIONS: Using distinct statistical approaches, we observed that exposure to pets and farm animals was inversely associated with ALL risk, whereas having a fever longer than one week (a putative proxy of severe infection) was associated with an increased risk. For multifactorial diseases such as childhood leukemia, we recommend estimating the joint effects of multiple exposures by applying diverse statistical methods and interpreting their results together. Overall, we found support for the hypothesis that early immune stimulation offers protection against childhood ALL.

Parental tobacco smoking and risk of childhood leukemia in Costa Rica: A population-based case-control study.

INTRODUCTION: The role of environmental and behavioral exposures on childhood leukemia etiology is poorly understood. We examined the association of maternal and paternal tobacco smoking at different time points with the risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) in Costa Rican children. MATERIALS AND METHODS: We conducted a population-based case-control study on childhood leukemia in Costa Rica. Cases (n ALL = 252; n AML = 40) were diagnosed between 1995 and 2000 (aged <15 years at diagnosis) and identified from the Costa Rican Cancer Registry and the National Children's Hospital. A total of 578 frequency-matched population controls were sampled from the National Birth Registry. Parental tobacco smoking was assessed via face-to-face interviews. We used logistic regression models to examine the association of paternal and maternal tobacco smoking before conception, during pregnancy, and after birth with childhood ALL and AML risk, adjusted for child sex, birth year, maternal/paternal age, and parental education. RESULTS: Paternal smoking before conception, during pregnancy, and after birth was associated with an increased risk of childhood AML (Odds Ratio (OR): 2.51, 95% CI: 1.21-5.17; OR: 3.21, 95% CI: 1.56-6.60; and OR: 2.83, 95% CI: 1.36-5.90, respectively). Maternal smoking during pregnancy was also associated with a modest, but imprecise increase in AML risk. We observed null associations of maternal and paternal smoking with ALL in the offspring. CONCLUSION: Our results suggest an association between parental smoking and risk of AML, but not ALL, in Costa Rican children. These findings add to the established evidence of numerous health risks associated with smoking and highlight the potential harm of smoking during sensitive windows of the development of fetus and child.

Chronic kidney disease of non-traditional origin in Mesoamerica: a disease primarily driven by occupational heat stress.

The death toll of the epidemic of chronic kidney disease of nontraditional origin (CKDnt) in Mesoamerica runs into the tens of thousands, affecting mostly young men. There is no consensus on the etiology. Anecdotal evidence from the 1990s pointed to work in sugarcane; pesticides and heat stress were suspected. Subsequent population-based surveys supported an occupational origin with overall high male-female ratios in high-risk lowlands, but small sex differences within occupational categories, and low prevalence in non-workers. CKDnt was reported in sugarcane and other high-intensity agriculture, and in non-agricultural occupations with heavy manual labor in hot environments, but not among subsistence farmers. Recent studies with stronger designs have shown cross-shift changes in kidney function and hydration biomarkers and cross-harvest kidney function declines related to heat and workload. The implementation of a water-rest-shade intervention midharvest in El Salvador appeared to halt declining kidney function among cane cutters. In Nicaragua a water-rest-shade program appeared sufficient to prevent kidney damage among cane workers with low-moderate workload but not among cutters with heaviest workload. Studies on pesticides and infectious risk factors have been largely negative. Non-occupational risk factors do not explain the observed epidemiologic patterns. In conclusion, work is the main driver of the CKDnt epidemic in Mesoamerica, with occupational heat stress being the single uniting factor shown to lead to kidney dysfunction in affected populations. Sugarcane cutters with extreme heat stress could be viewed as a sentinel occupational population. Occupational heat stress prevention is critical, even more so in view of climate change.

La mortalidad por la epidemia de enfermedad renal crónica de origen no tradicional (ERCnt) en Mesoamérica asciende a decenas de miles de personas, principalmente hombres jóvenes. No existe consenso sobre su etiología. En la década de 1990, informes anecdóticos apuntaban como factor de riesgo al trabajo en plantaciones de caña de azúcar; se consideró como posibles causantes a los plaguicidas y el estrés térmico. Estudios de prevalencia de base poblacional subsiguientes apoyaron un origen ocupacional, con una proporción elevada de hombres respecto de las mujeres en las tierras bajas donde el riesgo era elevado, pero con pequeñas diferencias de sexo dentro de las categorías ocupacionales y baja prevalencia en el ámbito no laboral. Se reportó ERCnt en los trabajadores de la caña de azúcar y otros cultivos con alta exigencia física y en ocupaciones no agrícolas que implican trabajo manual intenso en ambientes calurosos, pero no entre los agricultores de subsistencia. Estudios recientes con diseños más sólidos han demostrado cambios en la función renal y en los biomarcadores de hidratación en el curso de los turnos laborales, y disminución de la función renal relacionada con el calor y la carga de trabajo en el curso de la cosecha. La implementación de una intervención basada en la provisión de agua, descanso y sombra a mitad de la cosecha en El Salvador detuvo la disminución de la función renal en los cortadores de caña. En Nicaragua, un programa de provisión de agua, descanso y sombra evitó la lesión renal en los trabajadores de la caña con una carga de trabajo baja y moderada, pero no entre los cortadores, quienes tienen la mayor carga de trabajo. Los estudios sobre plaguicidas y factores de riesgo infecciosos han sido en gran medida negativos. Los factores de riesgo no ocupacionales no explican los patrones epidemiológicos observados. En conclusión, el trabajo es el principal desencadenante de la epidemia de ERCnt en Mesoamérica, y el estrés térmico ocupacional es el único factor que consistentemente conduce a la disfunción renal en las poblaciones afectadas. Los cortadores que trabajan en los ingenios azucareros y están expuestos a un estrés térmico extremo podrían ser considerados una población ocupacional centinela. La prevención del estrés térmico ocupacional es crítica, más aún si se consideran los efectos del cambio climático.

A mortalidade devida à epidemia de doença renal crônica de origem não tradicional (DRCnt) na Mesoamérica atinge dezenas de milhares de pessoas, principalmente homens jovens. Não há consenso sobre a sua etiologia. Na década de 1990, informações empíricas apontavam o trabalho em plantações de cana de açúcar como um fator de risco; pesticidas e estresse térmico também eram considerados causas possíveis. As pesquisas populacionais subsequentes sustentam uma origem ocupacional da doença, com uma elevada proporção de homens quando comparados à de mulheres, em areas de baixa altitude, onde o risco da doença é mais elevado, mas com pequenas diferenças de gênero quando se consideram as categorias ocupacionais e baixa prevalência no ambiente não-ocupacional. A DRCnt foi identificada em trabalhadores agrícolas da cana de açúcar e de outras culturas que exigem trabalho físico de alta intensidade e em ocupações não agrícolas envolvendo um trabalho manual intenso em ambientes quentes, mas não entre os agricultores de subsistência. Estudos recentes com desenhos mais robustos demonstraram mudanças na função renal e nos biomarcadores de hidratação ao longo dos turnos de trabalho, e diminuição da função renal relacionada à exposição ao calor e à carga de trabalho ao longo da colheita. A implementação de uma intervenção de água-descanso-sombra durante a colheita em El Salvador interrompeu o declínio da função renal em cortadores de cana. Na Nicarágua, intervenções água-descanso-sombra parecem ter sido suficientes para evitar lesões renais em trabalhadores canavieiros com cargas de trabalho baixa e moderada, mas não entre os cortadores de cana que têm carga de trabalho mais pesada. Estudos sobre exposição a pesticidas e a fatores de risco de origem infecciosa têm sido largamente negativos. Os fatores de risco não-ocupacionais não explicam os padrões epidemiológicos observados. Em conclusão, ocupação é o principal desencadeador da epidemia de DRCnt na Mesoamérica, e o estresse térmico ocupacional é o único fator comprovado que leva à disfunção renal nas populações afetadas. Os cortadores de cana que trabalham em engenhos de açúcar e expostos a um estresse térmico extremo podem ser considerados uma população ocupacional sentinela. A prevenção do estresse térmico ocupacional é crítica, especialmente considerando os efeitos das mudanças climáticas.

Workload and cross-harvest kidney injury in a Nicaraguan sugarcane worker cohort.

OBJECTIVES: To examine the association between workload and kidney injury in a fieldworker cohort with different levels of physically demanding work over a sugarcane harvest, and to assess whether the existing heat prevention efforts at a leading occupational safety and health programme are sufficient to mitigate kidney injury. METHODS: Biological and questionnaire data were collected before (n=545) and at the end (n=427) of harvest among field support staff (low workload), drip irrigation workers (moderate), seed cutters (high) and burned sugarcane cutters (very high). Dropouts were contacted (87%) and reported the reason for leaving work. Cross-harvest incident kidney injury (IKI) was defined as serum creatinine increase ≥0.30 mg/dL or ≥1.5 times the baseline value, or among dropouts reporting kidney injury leading to leaving work. RESULTS: Mean cross-harvest estimated glomerular filtration rate change was significantly associated with workload, increasing from 0 mL/min/1.73 m2 in the low-moderate category to -5 mL/min/1.73 m2 in the high and -9 mL/min/1.73 m2 in the very high workload group. A similar pattern occurred with IKI, where low-moderate workload had 2% compared with 27% in the very high workload category. A healthy worker selection effect was detected, with 32% of dropouts reporting kidney injury. Fever and C reactive protein elevation were associated with kidney injury. CONCLUSIONS: Workers considered to have the highest workload had more cross-harvest kidney damage than workers with less workload. Work practices preventing heat stress should be strengthened and their role in preventing kidney damage examined further. Future occupational studies on chronic kidney disease of unknown aetiology should account for a healthy worker effect by pursuing those lost to follow-up.

Environmental exposures in young adults with declining kidney function in a population at risk of Mesoamerican nephropathy.

OBJECTIVES: There is an epidemic of Mesoamerican nephropathy (MeN) in Central America, where sugarcane production is prominent. Numerous causes are proposed, but to date limited evidence supports any one hypothesis. A nested case-control study using biosamples from a rural, community-based follow-up study of 350 young adults from Northwest Nicaragua at risk of MeN was conducted with the aim of characterising the associations between urinary concentrations of metals, pesticides and mycotoxins from samples collected in the first 6 months and decline in kidney function over 2 years. METHODS: Urine samples collected at baseline (pre-sugarcane harvest) and the first 6 month follow-up (post-sugarcane harvest) visit were tested. Twelve metals and metalloids (aluminium, total arsenic, cadmium, chromium, cobalt, copper, lead, manganese, mercury, selenium, silicon and strontium) were analysed by inductively coupled plasma-mass spectrometry. Twelve pesticides or their metabolites (2,4-dichlorophenoxyacetic acid, 3-phenoxybenzoic acid, 4-fluoro-3-phenoxybenzoic acid, chloro-3,3,3-trifluoro-1-propen-1-yl-2,2-dimethylcyclopropanecarboxylic acid, cis/trans 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid, ethylenethiourea, glyphosate, 4-chloro-2-methylphenoxy acetic acid, 3-hydroxy-pyrimetanil, 5-hydroxytiabendazole, hydroxy-tebuconazole and 3,5,6-trichloro-2-pyridinol) and two mycotoxins (ochratoxin A (OTA) and citrinin (CIT)) were analysed by liquid chromatography coupled-mass spectrometry. Differences in the creatinine-corrected urinary concentrations of the measured exposures between outcome groups (participants with stable vs declining kidney function) were examined. RESULTS: Elevated levels of aluminium and total arsenic as well as metabolites of several pesticides were detected across the population. No differences were identified between the declining and stable groups in the levels of metals or pesticides tested. OTA and CIT were below the limit of detection. CONCLUSIONS: The tested metals, metalloids, pesticides and mycotoxins were not associated with loss of kidney function in participants at-risk of MeN.

Decline in Kidney Function among Apparently Healthy Young Adults at Risk of Mesoamerican Nephropathy.

Background Epidemic levels of CKD of undetermined cause, termed Mesoamerican nephropathy in Central America, have been found in low- and middle-income countries. We investigated the natural history of, and factors associated with, loss of kidney function in a population at high risk for this disease.Methods We conducted a 2-year prospective, longitudinal study with follow-up every 6 months in nine rural communities in northwestern Nicaragua and included all men (n=263) and a random sample of women (n=87) ages 18-30 years old without self-reported CKD, diabetes, or hypertension. We used growth mixture modeling to identify subgroups of eGFR trajectory and weighted multinomial logistic regression to examine associations with proposed risk factors.Results Among men, we identified three subpopulations of eGFR trajectory (mean baseline eGFR; mean eGFR change over follow-up): 81% remained stable (116 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), 9.5% experienced rapid decline despite normal baseline function (112 ml/min per 1.73 m2; -18.2 ml/min per 1.73 m2 per year), and 9.5% had baseline dysfunction (58 ml/min per 1.73 m2; -3.8 ml/min per 1.73 m2 per year). Among women: 96.6% remained stable (121 ml/min per 1.73 m2; -0.6 ml/min per 1.73 m2 per year), and 3.4% experienced rapid decline (132 ml/min per 1.73 m2; -14.6 ml/min per 1.73 m2 per year; n=3 women). Among men, outdoor and agricultural work and lack of shade availability during work breaks, reported at baseline, were associated with rapid decline.Conclusions Although Mesoamerican nephropathy is associated with agricultural work, other factors may also contribute to this disease.

Neuropsychological effects among workers exposed to organic solvents.

OBJECTIVE: To assess neuropsychological performance among workers at a paint factory in Mexico City. MATERIALS AND METHODS: During 2004 and 2005 we assessed the neuropsychological performance of 208 workers who were exposed to organic solvents at a paint factory, mainly toluene and xylene. We categorized workers into low and high exposure groups using a cumulative index for toluene, based on times spent in different tasks. We evaluated cognitive and motor functions with 13 neuropsychological tests. RESULTS: We found lower attention, longer time to complete the test ß=5.5 (R2=12.3%), and a lower score in the motor-cognitive test ß=-15.7 (R2=19.5%) in the high exposure group through multiple linear regression model analysis, with adjustment for age and education. CONCLUSIONS: Our results are similar to the ones reported in the literature, but the effects are less severe, probably due to lower exposure to organic solvents.

OBJETIVO: Evaluar el desempeño neuropsicológico de los trabajadores de una fábrica de pintura en la Ciudad de México. MATERIAL Y MÉTODOS: Se evaluó el desempeño neuropsicológico de 208 trabajadores expuestos a disolventes orgánicos, principalmente tolueno y xileno, en una fábrica de pintura en la Ciudad de México durante 2004 y 2005. Se categorizaron en grupos de baja y alta exposición con un índice acumulado de tolueno con base en el tiempo empleado por actividad. Se evaluaron funciones motoras y cognitivas con 13 pruebas neuropsicológicas. RESULTADOS: Se registró un tiempo más largo para completar la prueba ß=5.5 (R2=12.3%) y una puntuación baja en la prueba motor-cognitiva de ß=- 15.7 (R2=19.5%) en el grupo de alta exposición en los modelos de regresión lineal múltiple, ajustados por confusores. CONCLUSIONES: Los presentes resultados son similares a los reportados en la literatura, aunque los efectos son menos graves, probablemente debido a la baja exposición.

Maternal residential pesticide use and risk of childhood leukemia in Costa Rica.

Evidence suggests that early-life exposure to pesticides inside the home may be associated with childhood leukemia, however data from Latin American countries are limited. We examined whether self-reported maternal residential pesticide use and nearby pesticide applications-before and after child's birth-were associated with acute lymphoblastic leukemia (ALL) in the Costa Rican Childhood Leukemia Study (CRCLS), a population-based case-control study (2001-2003). Cases (n = 251 ALL) were diagnosed between 1995 and 2000 (age <15 years at diagnosis) and were identified through the Costa Rican Cancer Registry and National Children's Hospital. Population controls (n = 577) were drawn from the National Birth Registry. We fitted unconditional logistic regression models adjusted for child sex, birth year, and socioeconomic status to estimate the exposure-outcome associations and also stratified by child sex. We observed that self-reported maternal insecticide use inside the home in the year before pregnancy, during pregnancy, and while breastfeeding was associated with increased odds of ALL among boys [adjusted Odds Ratio (aOR) = 1.63 (95% confidence interval [95% CI]: 1.05-2.53), 1.75 (1.13-2.73), and 1.75 (1.12-2.73), respectively. We also found evidence of exposure-response relationships between more frequent maternal insecticide use inside the home and increased odds of ALL among boys and girls combined. Maternal report of pesticide applications on farms or companies near the home during pregnancy and at any time period were also associated with ALL. Our study in Costa Rica highlights the need for education to minimize pesticide exposures inside and around the home, particularly during pregnancy and breastfeeding.

Pesticide exposures and chronic kidney disease of unknown etiology: an epidemiologic review.

The main causes of chronic kidney disease (CKD) globally are diabetes and hypertension but epidemics of chronic kidney disease of unknown etiology (CKDu) occur in Central America, Sri Lanka, India and beyond. Althoug also being observed in women, CKDu concentrates among men in agricultural sectors. Therefore, suspicions fell initially on pesticide exposure, but currently chronic heat stress and dehydration are considered key etiologic factors. Responding to persistent community and scientific concerns about the role of pesticides, we performed a systematic review of epidemiologic studies that addressed associations between any indicator of pesticide exposure and any outcome measure of CKD. Of the 21 analytical studies we identified, seven were categorized as with low, ten with medium and four with relatively high explanation value. Thirteen (62%) studies reported one or more positive associations, but four had a low explanation value and three presented equivocal results. The main limitations of both positive and negative studies were unspecific and unquantified exposure measurement ('pesticides'), the cross-sectional nature of most studies, confounding and selection bias. The four studies with stronger designs and better exposure assessment (from Sri Lanka, India and USA) all showed exposure-responses or clear associations, but for different pesticides in each study, and three of these studies were conducted in areas without CKDu epidemics. No study investigated interactions between pesticides and other concommittant exposures in agricultural occupations, in particular heat stress and dehydration. In conclusion, existing studies provide scarce evidence for an association between pesticides and regional CKDu epidemics but, given the poor pesticide exposure assessment in the majority, a role of nephrotoxic agrochemicals cannot be conclusively discarded. Future research should procure assessment of lifetime exposures to relevant specific pesticides and enough power to look into interactions with other major risk factors, in particular heat stress.

Rationale, description and baseline findings of a community-based prospective cohort study of kidney function amongst the young rural population of Northwest Nicaragua.

BACKGROUND: An epidemic of Mesoamerican Nephropathy (MeN) is killing thousands of agricultural workers along the Pacific coast of Central America, but the natural history and aetiology of the disease remain poorly understood. We have recently commenced a community-based longitudinal study to investigate Chronic Kidney Disease (CKD) in Nicaragua. Although logistically challenging, study designs of this type have the potential to provide important insights that other study designs cannot. In this paper we discuss the rationale for conducting this study and summarize the findings of the baseline visit. METHODS: The baseline visit of the community-based cohort study was conducted in 9 communities in the North Western Nicaragua in October and November 2014. All of the young men, and a random sample of young women (aged 18-30) without a pre-existing diagnosis of CKD were invited to participate. Glomerular filtration rate (eGFR) was estimated with CKD-EPI equation, along with clinical measurements, questionnaires, biological and environmental samples to evaluate participants' exposures to proposed risk factors for MeN. RESULTS: We identified 520 young adults (286 males and 234 females) in the 9 different communities. Of these, 16 males with self-reported CKD and 5 females with diagnoses of either diabetes or hypertension were excluded from the study population. All remaining 270 men and 90 women, selected at random, were then invited to participate in the study; 350 (97%) agreed to participate. At baseline, 29 (11%) men and 1 (1%) woman had an eGFR <90 mL/min/1.73 m2. CONCLUSION: Conducting a community based study of this type requires active the involvement of communities and commitment from local leaders. Furthermore, a research team with strong links to the area and broad understanding of the context of the problem being studied is essential. The key findings will arise from follow-up, but it is striking that 5% of males under aged 30 had to be excluded because of pre-existing kidney disease, and that despite doing so 11% of males had an eGFR <90 mL/min/1.73 m2 at baseline.

Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.

Heat Stress Nephropathy From Exercise-Induced Uric Acid Crystalluria: A Perspective on Mesoamerican Nephropathy.

Mesoamerican nephropathy (MeN), an epidemic in Central America, is a chronic kidney disease of unknown cause. In this article, we argue that MeN may be a uric acid disorder. Individuals at risk for developing the disease are primarily male workers exposed to heat stress and physical exertion that predisposes to recurrent water and volume depletion, often accompanied by urinary concentration and acidification. Uric acid is generated during heat stress, in part consequent to nucleotide release from muscles. We hypothesize that working in the sugarcane fields may result in cyclic uricosuria in which uric acid concentrations exceed solubility, leading to the formation of dihydrate urate crystals and local injury. Consistent with this hypothesis, we present pilot data documenting the common presence of urate crystals in the urine of sugarcane workers from El Salvador. High end-of-workday urinary uric acid concentrations were common in a pilot study, particularly if urine pH was corrected to 7. Hyperuricemia may induce glomerular hypertension, whereas the increased urinary uric acid may directly injure renal tubules. Thus, MeN may result from exercise and heat stress associated with dehydration-induced hyperuricemia and uricosuria. Increased hydration with water and salt, urinary alkalinization, reduction in sugary beverage intake, and inhibitors of uric acid synthesis should be tested for disease prevention.

Kidney function in sugarcane cutters in Nicaragua--A longitudinal study of workers at risk of Mesoamerican nephropathy.

BACKGROUND: Chronic kidney disease is common among sugarcane workers in Central America. The main risk factor seems to be repeated high-intensity work in hot environments. Several cross-sectional studies have been performed but few longitudinal studies. OBJECTIVES: The aim of the study was to examine whether kidney function changes over a few months of work during the harvest period. METHODS: A group of male sugarcane cutters in Nicaragua (N=29, aged 17-38 years) was examined with renal biomarkers before and after shift on the first day at the start of harvest, on the sixth day during acclimatization, and then in mid-harvest 9 weeks later. A reference group (N=25, mainly office workers) was examined with the same biomarkers at start of harvest, and then at end of harvest 5 months later. RESULTS: The pre-shift renal function decreased significantly during 9 weeks of work in the cane cutters. Mean serum creatinine increased (20%), mean estimated glomerular filtration rate decreased (9%, 10mL/min), serum urea N (BUN) increased (41%), and mean urinary neutrophil gelatinase-associated lipocalin (NGAL) increased (four times). The cane cutters also developed cross-shift increases in these biomarkers, in particular serum creatinine and BUN, and in urinary uric acid. The longitudinal decrease in eGFR tended to be associated with the cross-shift increase in serum creatinine. CONCLUSIONS: There was a remarkable decrease of glomerular kidney function, after only 9 weeks of harvest. The cross-shift increase in serum creatinine may be caused by dehydration (pre-renal dysfunction), and when repeated on a daily basis this may cause permanently reduced GFR.