Introdução. A etiologia da leucemia linfocítica aguda (LLA), câncer mais comum na infância, não é completamente conhecida. Objetivo. Examinar a associação de infecções na infância e características maternas com a LLA em crianças residentes no Estado de São Paulo. Métodos. Estudo caso-controle com 241 casos recrutados em oito hospitais do Estado de São Paulo e diagnosticados com LLA de janeiro de 2003 a fevereiro de 2009. Os 598 controles foram selecionados na base de Declarações de Nascidos Vivos da Fundação Sistema Estadual de Análise de Dados. Entrevistas com a mãe ou responsável pela criança foram realizadas no hospital para os casos e no domicílio para os controles utilizando-se questionário semelhante. A análise dos dados foi conduzida com três grupos distintos: Grupo 1 - todos os subtipos de LLA, entrevistas com as mães ou outros responsáveis pelas crianças; Grupo 2 - todos os subtipos de LLA, entrevistas com as mães; Grupo 3 - LLA de precursores B, entrevistas com as mães. Para estimar o risco de LLA associado com as variáveis relacionadas a infecções e características maternas odds ratios (OR) e intervalos com 95 por cento de confiança (IC 95 por cento ) foram calculados por meio de análise de regressão logística multivariada não condicional. Três modelos de regressão logística foram conduzidos: a) com ajuste por sexo e idade da criança; b) com ajuste por sexo, idade da criança e escolaridade materna; c) com ajuste por todas potenciais variáveis de confusão via stepwise forward selection. Resultados. Os resultados correspondentes ao Grupo 3 e Modelo 3 de análise revelaram proteção para LLA em crianças com histórico de episódios de gripe (categoria frequentemente versus não OR = 0,27; IC 95 por cento 0,15-0,48), episódios de dor no ouvido (categoria raramente versus não OR = 0,48; IC 95 por cento 0,25-0,90), frequência à creche (categoria mais de 24 meses versus nunca OR = 0,37; IC 95 por cento 0,17-0,77), e contato com cães no primeiro ano de vida (categoria sim versus não OR = 0,76; IC 95 por cento 0,45-1,27). Foi observado tênue aumento do risco de LLA em crianças com mães que referiram consumo de álcool no passado (OR = 1,29; IC 95 por cento 0,62-2,68) e ainda bebe (OR = 1,53; IC 95 por cento 0,97-2,41) em comparação àquelas cujas mães referiram nunca ter consumido álcool. Baixo nível educacional das mães foi associado com aumento do risco de LLA em crianças (categoria 0 a 4 anos versus 12 e mais OR = 2,71; IC 95 por cento 1,26-5,81). Conclusões. Os resultados mostraram que exposição a infecções na infância, frequência à creche e contato com cães no primeiro ano de vida exercem papel protetor para LLA, por outro lado, o consumo de álcool e o baixo nível educacional das mães aumentaram o risco de LLA em crianças / Introduction. The etiology of acute lymphoblastic leukemia (ALL), the most common cancer in childhood, is not completely known. Objective. To examine the association of childhood infections and mother characteristics with ALL in children living in São Paulo. Methods. Case-control study with 241 cases recruited in eight hospitals in the state of São Paulo and diagnosed with ALL from January 2003 to February 2009. The 598 controls were selected from the São Paulo Birth Registry. Interviews with the mother or guardian were conducted in the hospital for cases and at home for controls through a similar questionnaire. Data analysis was performed in three distinct groups: Group 1 - all subtypes of ALL, interviews conducted with the mother or other childs guardian; Group 2 - all subtypes of ALL, interviews conducted with the mother; Group 3 - precursor B ALL, interviews conducted with the mother. In order to estimate the risk of ALL associated with variables related to infections and mother characteristics odds ratios (OR) and 95 per cent confidence interval (95 per cent CI) were calculated by unconditional multivariate logistic regression. Three logistic regression models were conducted: a) with adjustment for sex and age of child; b) with adjustment for sex, age of child and maternal education; c) adjusted for all potential confounders through stepwise forward selection. Results. The results corresponding to Group 3 and Model 3 revealed protection for ALL in children with episodes of influenza (category often versus no OR = 0.27; 95 per cent CI 0.15-0.48), episodes of earache (category rarely versus no OR = 0.48; 95 per cent CI 0.25-0.90), daycare attendance (category over 24 months versus never OR = 0.37; 95 per cent CI 0.17-0.77), and contact with dogs in the first year of life (category yes versus no OR = 0.76; 95 per cent CI 0,45-1.27). Slight increase was observed in the risk of ALL in children with mothers who reported alcohol consumption in the past (OR = 1.29; 95 per cent CI 0.62-2.68) and still drink (OR = 1.53; 95 per cent CI 0.97-2.41) compared to those whose mothers reported never having consumed alcohol. Low educational level of the mothers was associated with increased risk of ALL in children (category 0-4 years versus 12 and over OR = 2.71; 95 per cent CI 1.26-5.81). Conclusions. The results provided evidences that exposure to infections in the childhood, daycare attendance and contact with dogs in the first year of life have a protective role in ALL, on the other hand, alcohol consumption and low education level of mothers increase the risk of ALL in children

PURPOSE: The purpose of this study was to assess factors associated with the development of drug resistant tuberculosis in Ethiopia. DESIGN: A quantitative case-control study was conducted to determine if there were any significant differences in prevalence of pre-defined factors between cases and controls. METHODS: Cases were patients with drug resistant tuberculosis who had a confirmed diagnosis by culture drug-susceptibility or gene expert tests. Successfully treated, tuberculosis symptom free patients who had been on first-line tuberculosis treatment and who were registered as cured or treatment completed were taken as controls. An equal number of cases (N=181) and controls (N=181) was selected using a systematic random sampling method and was used in the study. A structured questionnaire developed by the researcher was used to collect data. Odds ratio and multiple logistic regression were used to quantify the strength of association between dependent and independent variables. RESULTS: The development of drug resistant tuberculosis was significantly associated with two or more previous episodes of tuberculosis illness (adjusted odds ratio (AOR): 14.84; 95% CI 8.90 –24.75), previous first-line tuberculosis treatment not directly observed by a health worker for 7 to 8 weeks (AOR: 13.41; 95% CI 8.06 – 22.29) and previous first-line tuberculosis treatment outcome of failure (AOR: 39.19; 95% CI 12.05 -127.46). Interruption of first-line tuberculosis treatment for one day or more (AOR = 4.28; 95% CI 2.76 – 6.64) and history of treatment in the first-line tuberculosis treatment category for previously treated patients (AOR: 3.70; 95% CI 2.40 – 5.72) were also significantly associated with the development of drug resistant tuberculosis in the current study. CONCLUSION: Patients with a history of previous first-line tuberculosis treatment, patients who interrupted previous first-line tuberculosis treatment and patients with previous first-line tuberculosis treatment outcome of failure were at high risk of developing drug resistant tuberculosis. Therefore, the full course of first-line tuberculosis treatment should be given, following the Directly Observed Treatment (DOT) guide. Patients with recurrent tuberculosis and unfavourable first-line tuberculosis treatment outcome should be tested for drug susceptibility. / Health Studies / D. Litt. et Phil. (Health Studies)

Le carcinome hépatocellulaire (CHC) est, dans le monde, le 5ème cancer le plus fréquent pour les hommes et le 7ème pour les femmes. En Europe, la France a un taux élevé à 7,8/100 000 habitants en 2018 (10 624 nouveaux cas estimés). Malgré les progrès, le pronostic du CHC est encore très sombre : il est la 4ème cause de mortalité par cancer au niveau mondial, avec une médiane de survie de 10 à 11 mois.Le CHC se développe dans 80% des cas sur une cirrhose due à une intoxication alcoolique chronique, une infection virale B ou C, ou plus rarement une pathologie métabolique. Les patients atteints de cirrhose ont un risque très élevé de développer un cancer mais également d’autres complications infectieuses liées à des processus d’inflammation chronique du foie. Il est donc indispensable d’identifier les facteurs intervenant dans le risque de complications et en particulier de CHC dans cette population pour mettre en place des actions préventives adaptées. L’alimentation est une source importante de composés bioactifs, en particulier pro- et anti-inflammatoires et représente un facteur modifiable potentiel. Les facteurs nutritionnels liés à la carcinogenèse hépatique sont donc encore mal définis. De plus, ces études ne sont pas toujours transposables dans une population aux habitudes alimentaires occidentales, et surtout n’ont pas été réalisées chez des patients atteints de cirrhose, pourtant les plus à risque de développer un CHC mais qui ont sans doute une alimentation spécifique.L’étude cas-témoin "CiRCE" (investigateur principal : Pr Hillon) offre l’opportunité de travailler sur les facteurs de risques environnementaux, nutritionnels et métaboliques du CHC chez des patients cirrhotiques, toute étiologie confondue. Cette étude est coordonnée par l’équipe EPICAD du centre de Recherche Inserm UMR 1231 « Lipides, Nutrition Cancer » avec le soutien du Centre d’Investigation Clinique Inserm1432/CHU de Dijon. Six centres hospitaliers (Besançon, Dijon, Metz, Nancy, Reims, Strasbourg) ont inclus entre 2008 et 2012 des malades atteints de cirrhose compliquée de CHC (428 cas) ou non compliquée de CHC (760 témoins). En plus du recueil standardisé de données cliniques, et d’une collection biologique, un questionnaire alimentaire a permis l’estimation de la consommation de 208 aliments, boissons et plats.La comparaison des cas et des témoins permet d’étudier le risque de CHC chez des patients atteints de cirrhose. L’ensemble de ces données constitue une base de travail très riche pour une thèse d’Université dans l’objectif de préciser le rôle des facteurs alimentaires dans la survenue de complications chez des patients atteints de cirrhose, en particulier la survenue d’un CHC. Plusieurs approches ont été abordées :1/ par aliments permettant de confirmer les hypothèses du WCRF/AICR mais chez des patients atteints de cirrhose2/ par profils de consommation alimentaire définis à priori permettant une approche plus intégrée de l’alimentation.3/Utilisation du Diet Inflammatory Index conçu pour estimer le potentiel inflammatoire de l’alimentation.4/ Focus les lipidesCes résultats qui manquaient encore dans la littérature pourraient amener à des recommandations nutritionnelles spécifiques à cette population de patients bien particulière et très à risque de complications graves et en particulier de CHC. / Hepatocellular Carcinoma (HCC) is worldwide the 5th most common diagnosed cancer in men and the 7th in women and the 4th cause of cancer death with a median survival between 10 and 11 months. The incidence rate in France is relatively high (7.8/100 000 with 10 624 estimated new cases in 2018). HCC prognosis is very poor due to the difficulty to diagnose it at an early stage. Around 80% of HCC occur in the setting of cirrhosis, mainly caused by alcoholism, chronic infections with HBV and HCV or metabolic syndrome. Cirrhotic patients have a high-risk to develop chronic inflammation or other liver complications that can progress toward cancer. Thus, it is important to identify the risk factors of these complications, and mainly HCC, in this specific population in order to define preventive tools.Diet is composed of several bioactive components and represents a modifiable factor with preventive potential. Associations between dietary factors and HCC risk have been little investigated and results were conflicting. It has been suggested that some foods, such as fruit, vegetables, fish and white meat, have a protective effect, whereas red and processed meat seem to be associated with an elevated risk of HCC. Strong evidence exists only for the relationship between liver carcinogenesis and coffee consumption. The previous results require confirmation especially in occidental countries and in such a high-risk population suffering from cirrhosis, for which food choices may differ.The French multicenter case-control study CiRCE (main investigator: Pr Hillon) was conducted to identify the environmental, nutritional and metabolic risk factors of developing HCC in cirrhotic patients with different etiologies. This study is coordinated by the EPICAD team from the National Institute for Health and Medical Research Inserm UMR1231 “Lipid Nutrition Cancer” with the collaboration of the Clinical Investigation Center of Dijon CHU. Between June 2008 and December 2012, cirrhotic patients with HCC (428 cases) or without HCC (760 controls) were recruited in six academic hospitals of the North-East of France (Besancon, Dijon, Metz, Nancy, Reims and Strasbourg). In addition to clinical data, every patient has to fill a diet history questionnaire that included 208 food items. A biobank has been also constituted.The comparisons between cases and controls allow investigating the HCC risk in cirrhotic patients.All these data are of great interest to investigate the relationships between dietary and metabolic factors and the risk of HCC or occurrence of complications in cirrhotic patients.

No description available.

No description available.

Semiparametric modeling is a combination of the parametric and nonparametric models in which some functions follow a known form and some others follow an unknown form. In this dissertation we made contributions to semiparametric modeling for matched case-crossover data. In matched case-crossover studies, it is generally accepted that the covariates on which a case and associated controls are matched cannot exert a confounding effect on independent predictors included in the conditional logistic regression model. Any stratum effect is removed by the conditioning on the fixed number of sets of the case and controls in the stratum. However, some matching covariates such as time, and/or spatial location often play an important role as an effect modification. Failure to include them makes incorrect statistical estimation, prediction and inference. Hence in this dissertation, we propose several approaches that will allow the inclusion of time and spatial location as well as other effect modifications such as heterogeneous subpopulations among the data. To address modification due to time, three methods are developed: the first is a parametric approach, the second is a semiparametric penalized approach and the third is a semiparametric Bayesian approach. We demonstrate the advantage of the one stage semiparametric approaches using both a simulation study and an epidemiological example of a 1-4 bi-directional case-crossover study of childhood aseptic meningitis with drinking water turbidity. To address modifications due to time and spatial location, two methods are developed: the first one is a semiparametric spatial-temporal varying coefficient model for a small number of locations. The second method is a semiparametric spatial-temporal varying coefficient model, and is appropriate when the number of locations among the subjects is medium to large. We demonstrate the accuracy of these approaches by using simulation studies, and when appropriate, an epidemiological example of a 1-4 bi-directional case-crossover study. Finally, to explore further effect modifications by heterogeneous subpopulations among strata we propose a nonparametric Bayesian approach constructed with Dirichlet process priors, which clusters subpopulations and assesses heterogeneity. We demonstrate the accuracy of our approach using a simulation study, as well a an example of a 1-4 bi-directional case-crossover study. / Ph. D.

Idiopathic normal pressure hydrocephalus (INPH) is a dementia treatable by insertion of a cerebrospinal fluid shunt. It has been suggested that INPH has similar pathophysiological mechanisms as cerebrovascular disease, but the vascular risk factor (VRF) profile of INPH patients has not been assessed using a modern epidemiological approach. The cognitive symptoms of INPH resemble the symptoms of depression, but the prevalence of depression among INPH patients is unknown. In addition, few studies investigate the impact of shunting on the quality of life (QoL), and no study has investigated the impact of comorbidity on QoL in INPH patients. The objective of this dissertation was to present the VRF profile of INPH and to investigate the hypothesis that INPH may be a subgroup of vascular dementia. Additional objectives were to assess the prevalence of depression in INPH patients and to investigate the impact of shunting and comorbidities on QoL in INPH. In the first cohort, the prevalence of possible INPH was assessed through clinical and radiological examinations in patients with a transient ischemic attack (TIA), consecutively admitted to the same hospital during 2006-2008. In the second cohort, VRFs, vascular disease and QoL were analysed in INPH patients consecutively shunted 2008-2010 in five out of six neurosurgical centres in Sweden. Patients remaining after inclusion (n=176, within the age-span 60-85 years and not having dementia) were compared to population-based age- and gender-matched controls (n=368, same inclusion criteria as for the INPH patients). Assessed VRFs were: hypertension, diabetes, obesity, hyperlipidemia, psychosocial factors (stress and depression), smoking, alcohol intake, physical activity and, dietary pattern. Cardiovascular, cerebrovascular and peripheral vascular disease as well as QoL were also assessed. Parameters were assessed through questionnaires, clinical examinations, measurements, ECG and, blood samples. In the first cohort, 4% of the TIA patients had clinically and radiologically verified INPH. In the second cohort, VRFs were overrepresented among the INPH patients compared with the controls. The VRFs independently associated with INPH were: hyperlipidemia (Odds ratio (OR): 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), obesity (OR: 5.4, 95%CI: 2.5-11.8) and, psychosocial factors (OR: 5.3, 95%CI: 3.2-8.9). When adding the VRFs that were overrepresented in INPH, although not independently (physical inactivity and hypertension), these six VRFs accounted for 24% of the INPH cases in the elderly population (population attributable risk %: 24). Depression was overrepresented in shunted INPH patients compared to the controls (46% vs. 13%, p<0.001) and the main predictor for low QoL was a coexisting depression (p<0.001). In conclusion, the results of the INPH-CRasH study are consistent with a vascular pathophysiological component of INPH and indicate that INPH may be subgroup of vascular dementia. In clinical care and research, a complete risk factor analysis as well as screening for depression and a measurement for quality of life should be included in the work-up of INPH patients. The effect of targeted interventions against modifiable VRFs and anti-depressant treatment in INPH patients should be evaluated. / Idiopatisk normaltryckshydrocefalus (INPH, från engelskans ”idiopathic normal pressure hydrocephalus”) är en neurokirurgiskt behandlingsbar demens. Behandlingen är att operera in en shunt som dränerar cerebrospinalvätska från ventriklarna. Det har föreslagits att INPH skulle kunna orsakas av liknande patofysiologiska mekanismer som vid cerebrovaskulär sjukdom, men den vaskulära riskfaktorprofilen hos INPH-patienter har aldrig undersökts i en modern epidemiologisk studie. De kognitiva symtomen vid INPH påminner om symtomen vid depression, men prevalensen av depression hos INPH-patienter är okänd. Få studier undersöker hur shuntning påverkar livskvalitet och ingen studie har undersökt hur komorbiditet påverkar livskvaliteten vid INPH. Syftet med den här avhandlingen var att undersöka den vaskulära riskfaktorprofilen hos INPH-patienter samt att utforska hypotesen att INPH skulle kunna vara en undergrupp till vaskulär demens. Ytterligare ett syfte med avhandlingen var att undersöka hur många INPH-patienter som har depression samt undersöka hur shunting och komorbiditet påverkar livskvalitet vid INPH. I den första kohorten undersöktes kliniska och radiologiska fynd som tydde på INPH hos de patienter som blivit diagnostiserade med en TIA (från engelskans: transient ischemic attack) 2006-2008 på Norrlands Universitetssjukhus i Umeå. I den andra kohorten undersöktes konsekutivt shuntade INPH-patienter 2008-2010 från fem av sex neurokirurgiska kliniker i Sverige. De patienter som inkluderades i studien (n=176, ålder: 60-85 år, ej dementa) jämfördes med köns- och åldersmatchade kontroller från normalpopulationen (n=368, samma inklusionskriterier som för INPH-patienterna). De riskfaktorer som undersöktes var: hypertension, hyperlipidemi, diabetes, fetma, psykosociala faktorer (stress och depression), rökning, alkohol, fysisk aktivitet och diet. Även kardiovaskulära och cerebrovaskulära sjukdomar undersöktes, liksom perifer vaskulär sjukdom samt livskvalitet. Datainsamling skedde genom frågeformulär, kliniska undersökningar, mätningar, EKG och blodprov. I den första kohorten hade 4% av TIA-patienterna kliniskt och radiologiskt verifierad INPH. I den andra kohorten var vaskulära riskfaktorer överrepresenterade hos INPH-patienterna jämfört med iv normalpopulationen. Hyperlipidemi (OR: 2.4, 95%CI: 1.4-4.0), diabetes (OR: 2.2, 95%CI: 1.2-3.9), fetma (OR: 5.4, 95%CI: 2.5-11.8) och psykosociala faktorer (OR: 5.3, 95%CI: 3.2-8.9) var associerade med INPH oberoende av kön, ålder och de andra riskfaktorerna. Hypertension och fysisk inaktivitet var också associerade med INPH, dock inte oberoende av övriga riskfaktorer. Sammanlagd PAR% (från engelskans: population attributable risk %) för de här sex riskfaktorerna var 24%. INPH-patienterna hade depression i högre utsträckning än kontrollerna (46% vs. 13%, p<0.001), och depression var den viktigaste prediktorn för låg livskvalitet. Resultaten tyder på att vaskulär sjukdom och vaskulära riskfaktorer är involverade i den patofysiologiska mekanismen vid INPH. INPH kan vara en undergrupp till vaskulär demens. En fullständig riskfaktoranalys och screening för depression bör ingå i den preoperativa utvärderingen såväl som i forskning på INPH-patienter, och ett mått på livskvalitet bör införas. Effekten av riktade insatser mot såväl vaskulära riskfaktorer som depression vid INPH bör utvärderas.

La maladie de Crohn (MC) pédiatrique a des conséquences majeures sur la qualité de vie des patients atteints (troubles de croissance, absentéisme scolaire, etc). L’étiologie de la MC est inconnue. La théorie de l’hygiène (TH) stipule que les conditions de vie sanitaires des pays industrialisés préviennent l’exposition antigénique et empêchent le développement de la tolérance immunitaire chez les enfants. Ceci mènerait à une réaction excessive du système immunitaire lors d’expositions subséquentes et engendrerait le développement de maladies inflammatoires chroniques telles la MC. Objectif: Analyser l’association entre la fréquence, la temporalité et le type d’infections infantiles (indicateurs d’environnements pourvus d’antigènes) et le risque de MC pédiatrique. Une étude cas-témoin fût réalisée, les cas de MC provenant d’un centre hospitalier tertiaire montréalais. Les témoins, provenant des registres de la Régie d’assurance maladie du Québec (RAMQ), furent appariés aux cas selon leur âge, sexe et lieu de résidence. L’exposition aux infections fût déterminée grâce aux codes de diagnostic ICD-9 inscrits dans la base de données de la RAMQ. Un modèle de régression logistique conditionnelle fût construit afin d’analyser l’association entre infections et MC. Des ratios de cotes (RC) et intervalles de confiance à 95% (IC 95%) furent calculés. Résultats: 409 cas et 1621 témoins furent recrutés. Les résultats de l’analyse suggèrent un effet protecteur des infections infantiles sur le risque de MC (RC: 0,67 [IC: 0,48-0,93], p=0,018), plus particulièrement au cours des 5 premières années de vie (RC: 0.74 [IC: 0,57-0,96], p=0,025). Les infections rénales et urinaires, ainsi que les infections des voies orales et du système nerveux central (virale), semblent particulièrement associées à l’effet protecteur. Les résultats de l’étude appuient la théorie de l’hygiène: l’exposition aux infections infantiles pourrait réduire le risque de MC pédiatrique. / Crohn’s disease (CD) poses specific challenges in the paediatric population (growth failure, depression, etc). The environmental contributors to CD aetiology remain largely unknown. There are suggestions that sanitary living conditions prevailing in developed countries prevent antigen exposure and impede the development of immunological tolerance amongst children, resulting in abnormally heightened immunological responses with subsequent exposures (hygiene hypothesis). Evidence for the hygiene hypothesis in CD aetiology remains unclear. Objectives: To assess the role of the frequency, timing and type of childhood infections (measures of antigen exposure) on the risk of paediatric CD. A case-control study was carried out. Confirmed cases of CD were recruited from a tertiary care paediatric hospital. Controls matched to the cases on calendar age, gender, and area of residence, were selected using the provincial health insurance files. Infection exposure was ascertained using ICD-9 diagnostic codes provided by the provincial insurer’s administrative databases. Conditional logistic regression analysis was used to assess the relationship between childhood infections and CD. Odds ratios (OR) and corresponding 95% confidence intervals (95% CI) were estimated. 409 cases and 1621 controls were recruited. A diagnosis of infection was associated with reduced risks for paediatric CD (OR=0.67, 95% CI:[0.48-0.93], p=0.018), attributable to infection exposures primarily during the first 5 years since birth [OR=0.74, 95% CI=0.57-0.96, p=0.025]. Infections affecting the kidney and urinary tract, oral tract and viral CNS infections, were most significantly associated with protective effects. Our study provides support for the hygiene hypothesis in CD whereby exposure to infections in early childhood could potentially reduce risks for CD.

Introdução: A leucemia linfoblástica aguda (LLA) é a neoplasia pediátrica com maior incidência no mundo. Sua etiologia é resultante de múltiplas interações entre herança genética e exposição a agentes ambientais potencialmente carcinogênicos nos períodos pré-natal, nascimento e pós-natal. O parto cesáreo tem sido apontado como fator de risco para LLA em crianças. No Brasil, país com altas taxas de cesariana, são poucos os estudos que avaliaram a associação de cesariana com LLA na infância. Objetivos: Investigar a associação de cesariana e condições pré-natal e pós-natal com LLA em crianças nascidas no estado de São Paulo. Métodos: Estudo caso-controle de base populacional. Os casos de LLA, crianças nascidas no estado de São Paulo a partir de 1999, foram recrutados em oito hospitais de 2003 a 2009. Os controles foram emparelhados com os casos por sexo, idade e cidade de nascimento. As informações utilizadas nesse estudo foram obtidas em entrevistas com as mães ou responsáveis pelas crianças por meio de questionário estruturado. Informações adicionais foram adquiridas no banco de Declarações de Nascidos Vivos (DNV), que integra o Sistema de Informações de Nascidos Vivos (SINASC) da Secretaria Municipal de Saúde de São Paulo e do Ministério da Saúde. Após o linkage probabilístico dos bancos de dados, a amostra final comporta 133 casos e 459 controles, relação de 3,4 controles por caso. Análises de regressão logística não condicional e condicional foram conduzidas para estimar a associação entre cesariana, condições pré-natal e pós-natal e LLA, com estimava dos odds ratios (OR) e respectivos intervalos de 95% de confiança (IC 95%). Três modelos de regressão logística foram elaborados: 1) ajuste por idade e sexo da criança, idade e escolaridade da mãe; 2) ajuste pelas variáveis anteriores, mais raça e número de consultas; 3) ajuste por todas as variáveis anteriores e a inclusão de idade gestacional e peso ao nascer. Resultados: A análise de regressão logística não condicional, com base no Modelo 2, revelou discreto risco de LLA na exposição à cesariana (OR=1,10; IC95% 0,71-1,70), proteção na condição de mãe com 12 ou mais anos de escolaridade (OR=0,46; IC95% 0,24-0,89) e idade da criança de 6 a 8 anos no diagnóstico (OR=0,30; IC95% 0,13-0,67). Resultados similares foram observados na análise de regressão logística condicional no Modelo 2: cesariana (OR=1,18; IC95% 0,69-2,00), mães com 12 ou mais anos de escolaridade (OR=0,56; IC95% 0,25-1,24). Conclusões: Há uma tênue associação entre cesariana e LLA na infância, sem significância estatística. Alta escolaridade da mãe e crianças na faixa etária entre 6 e 8 anos foram fatores de proteção para LLA. Crianças com síndrome de Down apresentaram seis vezes o risco de LLA. Os resultados obtidos por análise regressão logística condicional foram similares aos da regressão logística não condicional. / Introduction: Acute lymphoblastic leukemia (ALL) is the most common pediatric neoplasia worldwide. Its etiology results from multiple interactions between genetic inheritance and exposure to potentially carcinogenic environmental agents during the prenatal, birth, and postnatal periods. Cesarean section has been identified as a risk factor for ALL in children. In Brazil, a country with high Cesarean section rates, few studies have evaluated the association of Cesarean section with ALL in childhood. Objectives: To investigate the association of Cesarean section, prenatal and postnatal conditions with ALL in children born in the state of São Paulo. Methods: Population-based case-control study. The cases of ALL, children born in the state of São Paulo from 1999, were recruited in eight hospitals from 2003 to 2009. Controls were matched with cases by sex, age and city of birth. The information used in this study were obtained through interviews with mothers or guardians of the children, using a structured questionnaire. Additional information were get from the Live Births Database, stored in the Live Birth Information System at the São Paulo Municipal Health Department and at the Brazilian Ministry of Health. After the databases probabilistic linkage, the final sample entails 133 cases and 459 controls, 3.4 controls per case ratio. Non-conditional and conditional logistic regression analyzes were conducted to estimate the association between cesarean section, pre- and postnatal conditions, and ALL with estimation of odds ratios (OR) and respective 95% confidence intervals (95% CI). Three models of logistic regression were elaborated: 1) adjustment by age and sex of the child, age and schooling of the mother; 2) adjustment for the previous variables, more race and number of queries; 3) adjustment for all previous variables and the inclusion of gestational age and birth weight. Results: The nonconditional logistic regression analysis, based on Model 2, revealed a slight risk of ALL on cesarean section exposure (OR = 1.10, 95% CI 0.71-1.70), protection on the condition of mothers with 12 or more years of schooling (OR = 0.46, 95% CI 0.24-0.89), and age of child from 6 to 8 years at diagnosis (OR = 0.30, 95% CI, 0.13-0, 67). In the conditional logistic regression analysis in Model 2, similar results were observed: cesarean (OR = 1.18, 95% CI 0.69-2.00), mothers with 12 or more years of schooling (OR = 0.56, 95% CI, 0.25-1.24). Conclusions: There is a weak association between cesarean section and ALL in childhood, with no statistical significance. Mother with high education level and children in the age range between 6 and 8 years were protective factors for ALL. Children with Down syndrome had a six-fold risk of ALL. The results obtained by conditional logistic regression analysis were similar to those of non-conditional logistic regression.

Em virtude da importância dos recém-nascidos de muito baixo peso (RNMBP) na constituição da morbidade e mortalidade infantil realizou-se estudo para identificar os fatores de risco associados ao seu nascimento e avaliar os cuidados recebidos durante a internação e os índices de mortalidade. Método. Estudo de caso-controle, abrangendo 200 recém-nascidos(RN) com peso entre 500 e 1499g(casos) e 400 RN com peso entre 3000 e 3999g (controles), no período de março de 1998 a dezembro de 2004. Foram estudadas variáveis maternas sócio-econômicas e educacionais e variáveis da gestação e do parto. Foi utilizada a análise univariada e multivariada, adotando-se um nível de significância de 5 por cento . Resultados. A percentagem de mortalidade dos RNMBP foi de 32,5 por cento , sendo o limite de viabilidade de 600g de peso e 26 semanas de idade gestacional. As principais causas básicas de óbito foram a hipertensão materna (35,3 por cento ), as infecções maternas(18,5 por cento ) e a prematuridade (18,5 por cento ) e a principal causa imediata de óbito foi a infecção(52,3 por cento ). As variáveis que estiveram relacionadas com o nascimento de RNMBP foram a idade materna igual ou acima de 35 anos, a ausência de pré-natal, as doenças na gestação, a hipertensão materna, a internação durante a gestação e a história de um filho anterior de baixo peso ao nascer. Conclusão. Muitos nascimentos de RNMBP ocorreram por causas evitáveis relacionadas com a freqüência e qualidade do pré-natal / Objective. Due to the importance of very low birth weight (VLBW) in the make up of infant morbidity and mortality, a study was performed to identify risk factors associated with their birth, and to evaluate care received while in hospital and mortality rates. Method. A case-control study, covering 200 newborns (NB) weighing between 500 and 1499g (cases) and 400 NB weighing between 3000 to 3999g (controls) during the period from March 1998 to December 2004. Maternal socioeconomic and educational variables were studied besides variables on pregnancy and delivery. Simple and multiple analysis was used, adopting a 5 per cent level of significance. Results. The mortality percentage of VLBW was 32.5 per cent , and the limit of viability was a weight of 600g and 26 weeks of gestational age. The main basic causes of death were maternal hypertension (35.3 per cent ), maternal infections (18.5 per cent ) and prematurity (18.5 per cent ), and the main immediate cause of death was infection (52.3 per cent ). The variables that were related to the birth of VLBW were maternal age equal to or above 35 years, lack of prenatal examination, diseases in pregnancy, maternal hypertension, hospitalization during pregnancy, and the history of a previous low birth weight child. Conclusion. Many VLBW births occurred due to unavoidable reasons related to the frequency and quality of pre-natal care