Arnaldo Cézar Couto

In Utero Pesticide Exposure and Leukemia in Brazilian Children < 2 Years of Age

Background: An association between pesticide exposure and cancer has been suggested. Infant leukemia is a rare neoplasm and its association with maternal pesticide exposure has been poorly explored. Objectives: We investigated the association between pesticide exposure during pregnancy and leukemia in children < 2 years of age. Methods: A hospital-based case–control study was carried out in 13 Brazilian states during 1999–2007. Mothers of 252 cases and those of 423 controls were interviewed. Information on pesticide exposures 3 months before pregnancy, throughout pregnancy, and during breastfeeding was obtained. Unconditional logistic regression was used to estimate adjusted odds ratios (aORs) for associations between pesticide exposures and leukemia. Results: Associations with ever use of pesticides during pregnancy were observed for acute lymphoid leukemia (ALL) (aOR = 2.10; 95% CI: 1.14, 3.86) and acute myeloid leukemia (AML) (aOR = 5.01; 95% CI: 1.97, 12.7) in children 0–11 months of age, and with ALL (aOR = 1.88; 95% CI: 1.05, 5.23) at 12–23 months of age. According to reported maternal exposure to permethrin, higher risk estimates were verified for children 0–11 months of age (aOR = 2.47; 95% CI: 1.17, 5.25 for ALL; and aOR = 7.28; 95% CI: 2.60, 20.38 for AML). Maternal pesticide exposure related to agricultural activities showed an aOR of 5.25 (95% CI: 1.83, 15.08) for ALL, and an aOR of 7.56 (95% CI: 1.83, 31.23) for AML. Conclusions: These results support the hypothesis that pesticide exposure during pregnancy may be involved in the etiology of acute leukemia in children < 2 years of age.

Pregnancy, maternal exposure to hair dyes and hair straightening cosmetics, and early age leukemia

OBJECTIVE To investigate the association between maternal exposure to hair dyes and hair straightening cosmetics (HDSC) during pregnancy and leukemia at an early age (<2yr., EAL). METHODS A multicenter hospital-based case-control study was carried out in 13 states in Brazil between 1999 and 2007. Mothers of 176 ALL (acute lymphocytic leukemia) and 55 AML (acute myeloid leukemia) cases and 419 controls were enrolled and interviewed. Data on maternal exposure to HDSC occurring 3months before pregnancy, during pregnancy and during breastfeeding were obtained. Data were also gathered on paternal exposure to HDSC before pregnancy. Unconditional logistic regression was performed and odds ratios (OR) on the association between HDSC use and EAL were obtained after adjustment for hormonal intake during pregnancy, maternal age, education, birth weight, and the child skin color. RESULTS An adjusted OR of 1.78 (95% C.I. 1.13-2.81) was observed between maternal exposure to HDSC in the first trimester of pregnancy and ALL. Regarding AML, an adjusted OR of 2.43 (95% C.I. 1.13-5.22) was found for maternal exposure to HDSC during breastfeeding. No association between maternal exposure to HDSC during pregnancy and ALL or AML was observed in children with MLL (Mixed Lineage Leukemia) gene rearrangement. CONCLUSIONS Results in this study seem to support the hypothesis that maternal exposure to HDSC during pregnancy may be involved in the etiology of leukemia in children under 2years of age.

Pregnancy, maternal tobacco smoking, and early age leukemia in Brazil

Background: Cigarette smoking has been associated with acute myeloid leukemia (AML) but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia remains unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (<2 year) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999–2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children (193 acute lymphoid leukemia – ALL, 59 AML and 423 controls), being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR) on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery) and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy). Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% CI 1.40–19.95) for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% CI 1.33–45.5). No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and EAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.

Pregnancy maternal exposure to analgesic medicines and leukemia in Brazilian children below 2 years of age.

Childhood leukemia etiology, and mainly the interactions of genetic and environmental risk factors, remains largely unexplored. This national hospital-based case–control study was carried out in Brazil among children aged 0–23 months who were recruited at cancer and general hospitals in 13 states. Maternal medicine intake during pregnancy, including analgesic intake, was assessed by face-to-face interviews with the mothers of 231 leukemia patients and 411 controls. Unconditional logistic regression was used to ascertain crude and adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the association between maternal analgesic use during pregnancy and early age leukemia. Acetaminophen use during the first trimester of pregnancy showed an OR=0.39 (95% CI 0.17–0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI 0.16–0.88) for use in the second trimester. For acute myeloid leukemia, an OR=0.11 (95% CI 0.02–0.97) was found following acetaminophen use in the second trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during preconception showed an OR=1.63 (95% CI 1.06–2.53) and dipyrone intake during lactation showed an OR=2.00 (95% CI 1.18–3.39). These results suggest that acetaminophen use during pregnancy may protect against development of early age leukemia in the offspring, whereas dipyrone use may act as a risk factor for such an outcome.

Trends in childhood leukemia mortality over a 25-year period.

OBJECTIVE To analyze trends in childhood leukemia mortality in the state of Rio de Janeiro, Brazil, between 1980 and 2006. METHOD Gender-stratified leukemia mortality data for children aged < 15 years from 1980 to 2006 were retrieved from the Brazilian Mortality Information System for the state of Rio de Janeiro. Data were stratified by place of death (city of Rio de Janeiro proper, the state capital; Rio de Janeiro Metropolitan Region, excluding the capital; and rest of the state). Leukemia deaths were defined according to death certificate ICD-9 and ICD-10 coding (for deaths occurring in 1980-1995 and 1996-2006, respectively). Leukemia mortality rates were calculated by age and calendar year and age-adjusted to a standard world population. Polynomial linear regression with a 5% significance level was used to evaluate mortality trends in the study regions. RESULTS The three studied regions revealed similar trends, with a continuous downward pattern; the most substantial decline was detected in the municipality of Rio de Janeiro (city proper). In all studied areas, leukemia mortality was highest among males. CONCLUSION A downward trend in childhood leukemia mortality was detected throughout the state of Rio de Janeiro. The most pronounced reduction occurred in the state capital.

Familial history of cancer and leukemia in children younger than 2 years of age in Brazil.

The objective of this study was to determine the contribution of a familial history of cancer (FHC) to the development of leukemia in children below 2 years of age. This is a national hospital-based case–control study of children 0–24 months of age recruited from 15 Brazilian hospitals from several regions providing oncological care and local general hospitals. Participants’ FHC antecedents were obtained through face-to-face interviews with the mothers of cases and controls using a standardized questionnaire. Unconditional logistic regression was used to determine crude and adjusted (adj.) odds ratios (OR), and the respective 95% confidence intervals (CI), of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) after adjustment for selected variables. FHC antecedents were obtained from 178 ALL, 51 AML, and 428 controls. FHC in second-degree relatives (grandparents, uncles, cousins) showed an adj. OR=1.66 (95% CI 1.12–2.45) for ALL. Antecedents of two or more relatives with cancer showed a statistically significant two-fold higher risk of either ALL or AML. Paternal, and joint paternal and maternal antecedents of cancer also showed statistically significant higher adj. OR, respectively: 1.80 and 1.89 for ALL, and 2.34 and 3.23 for AML. Hematological malignancies among second-degree relatives showed an adj. OR=3.48 (95% CI 1.72–7.09) for ALL. According to the anatomic site, antecedents of leukemia/lymphoma among case relatives, compared with the control ones, showed an OR=2.98 (95% CI 1.52–5.82) for ALL, whereas stomach cancer antecedents showed an OR=3.55 (95% CI 1.02–12.39) for AML. The observed results support the hypothesis that FHC antecedents are associated with leukemogenesis in children below 2 years of age.

Tendência de mortalidade por leucemia infantil num período de 25 anos

OBJECTIVE: To analyze trends in childhood leukemia mortality in the state of Rio de Janeiro, Brazil, between 1980 and 2006. METHOD: Gender-stratified leukemia mortality data for children aged < 15 years from 1980 to 2006 were retrieved from the Brazilian Mortality Information System for the state of Rio de Janeiro. Data were stratified by place of death (city of Rio de Janeiro proper, the state capital; Rio de Jane iro Metropolitan Region, excluding the capital; and rest of the state). Leukemia deaths were defined according to death certificate ICD-9 and ICD-10 coding (for deaths occurring in 1980-1995 and 1996-2006, respectively). Leukemia mortality rates were calculated by age and calendar year and age-adjusted to a standard world population. Polynomial linear regression with a 5% significance level was used to evaluate mortality trends in the study regions. RESULTS: The three studied regions revealed similar trends, with a continuous downward pattern; the most substantial decline was detected in the municipality of Rio de Janeiro (city proper). In all studied areas, leukemia mortality was highest among males. CONCLUSION: A downward trend in childhood leukemia mortality was detected throughout the state of Rio de Janeiro. The most pronounced reduction occurred in the state capital.

Exposições ambientais e leucemias na infância no Brasil: uma análise exploratória de sua associação

This study aims to explore the unapparent relations that several factors related to environmental exposure and individual characteristics existing in our environment may have with the process of developing childhood leukemia. From a database obtained from a clinical and epidemiological hospital-based, case-control study on risk factors for childhood leukemia, an exploratory multivariate analysis was performed using principal component analysis and factor analysis. This research is part of a national multicenter study that included 292 cases of leukemia in children aged 0 to 12 years and 541 controls of the same age, hospitalized for non-neoplastic causes in general hospitals near the centers the cases originated in. Information on selected environmental exposure was obtained in interviews with the mothers of both cases and controls by means of a standardized questionnaire. The model with the greatest explanatory power for the variance observed in the data analyzed was of approximately 52%. Three factors were considered most appropriate for predicting leukemogenesis in childhood, each including variables with factor loadings greater than 0.6: factor “conditions related to chemical exposures during pregnancy”, which explained 20% of the final variance and included the variables pesticide exposure, exposure to solvents and paint exposure in pregnancy; factor “lifestyle habits during pregnancy” explained 17% of the variance and included exposure to hair dyes and cosmetics for hair straightening; and factor “use of health services during pregnancy”, which explained 15% of the variance and included the variables type of delivery (vaginal or caesarean) and use of radiography in pregnancy. Logistic regression analysis revealed a statistically significant association between the development of leukemia in childhood and maternal history of chemical exposure during pregnancy (OR=1.36, 95% CI=1.16-1.59) and use of health services during pregnancy (OR=1.27, 95% CI=1.08-1.49). The results indicate the joint contribution of not just individual but environmental exposure in the development of leukemia in childhood, and are supported by evidence in the literature that the process of carcinogenesis in general and of leukemogenesis in particular, result from effects of multiple mutations related to joint environmental exposure.

Environmental exposure and childhood leukemia in Brazil: an exploratory analysis of their association

This study aims to explore the unapparent relations that several factors related to environmental exposure and individual characteristics existing in our environment may have with the process of developing childhood leukemia. From a database obtained from a clinical and epidemiological hospital-based, case-control study on risk factors for childhood leukemia, an exploratory multivariate analysis was performed using principal component analysis and factor analysis. This research is part of a national multicenter study that included 292 cases of leukemia in children aged 0 to 12 years and 541 controls of the same age, hospitalized for non-neoplastic causes in general hospitals near the centers the cases originated in. Information on selected environmental exposure was obtained in interviews with the mothers of both cases and controls by means of a standardized questionnaire. The model with the greatest explanatory power for the variance observed in the data analyzed was of approximately 52%. Three factors were considered most appropriate for predicting leukemogenesis in childhood, each including variables with factor loadings greater than 0.6: factor “conditions related to chemical exposures during pregnancy”, which explained 20% of the final variance and included the variables pesticide exposure, exposure to solvents and paint exposure in pregnancy; factor “lifestyle habits during pregnancy” explained 17% of the variance and included exposure to hair dyes and cosmetics for hair straightening; and factor “use of health services during pregnancy”, which explained 15% of the variance and included the variables type of delivery (vaginal or caesarean) and use of radiography in pregnancy. Logistic regression analysis revealed a statistically significant association between the development of leukemia in childhood and maternal history of chemical exposure during pregnancy (OR=1.36, 95% CI=1.16-1.59) and use of health services during pregnancy (OR=1.27, 95% CI=1.08-1.49). The results indicate the joint contribution of not just individual but environmental exposure in the development of leukemia in childhood, and are supported by evidence in the literature that the process of carcinogenesis in general and of leukemogenesis in particular, result from effects of multiple mutations related to joint environmental exposure.

Exposiciones ambientales y leucemias en la infancia en Brasil: un análisis exploratorio de su asociación

This study aims to explore the unapparent relations that several factors related to environmental exposure and individual characteristics existing in our environment may have with the process of developing childhood leukemia. From a database obtained from a clinical and epidemiological hospital-based, case-control study on risk factors for childhood leukemia, an exploratory multivariate analysis was performed using principal component analysis and factor analysis. This research is part of a national multicenter study that included 292 cases of leukemia in children aged 0 to 12 years and 541 controls of the same age, hospitalized for non-neoplastic causes in general hospitals near the centers the cases originated in. Information on selected environmental exposure was obtained in interviews with the mothers of both cases and controls by means of a standardized questionnaire. The model with the greatest explanatory power for the variance observed in the data analyzed was of approximately 52%. Three factors were considered most appropriate for predicting leukemogenesis in childhood, each including variables with factor loadings greater than 0.6: factor “conditions related to chemical exposures during pregnancy”, which explained 20% of the final variance and included the variables pesticide exposure, exposure to solvents and paint exposure in pregnancy; factor “lifestyle habits during pregnancy” explained 17% of the variance and included exposure to hair dyes and cosmetics for hair straightening; and factor “use of health services during pregnancy”, which explained 15% of the variance and included the variables type of delivery (vaginal or caesarean) and use of radiography in pregnancy. Logistic regression analysis revealed a statistically significant association between the development of leukemia in childhood and maternal history of chemical exposure during pregnancy (OR=1.36, 95% CI=1.16-1.59) and use of health services during pregnancy (OR=1.27, 95% CI=1.08-1.49). The results indicate the joint contribution of not just individual but environmental exposure in the development of leukemia in childhood, and are supported by evidence in the literature that the process of carcinogenesis in general and of leukemogenesis in particular, result from effects of multiple mutations related to joint environmental exposure.