Leptin gene polymorphism (rs7799039; G2548A) is associated with changes in serum lipid concentrations during pregnancy: a prospective cohort study.

PURPOSE: Little is known about the effects of leptin and leptin receptor polymorphisms on lipid changes during pregnancy. The aims of this study were to evaluate the associations between the single nucleotide polymorphisms (SNPs) of leptin and leptin receptor genes and the lipid concentrations during pregnancy; and to test whether dietary intake is a mediator in these associations. METHODS: A prospective cohort of 154 pregnant women was followed up in Rio de Janeiro, Brazil during the following gestational periods: 5-13th, 20-26th and 30-36th weeks. HDL-C, total cholesterol (TC) and triglyceride (TG) were measured by the enzymatic colorimetric method, and LDL-C was calculated. DNA was extracted by the phenol-chloroform method, and leptin (G2548A, rs7799039) and leptin receptor SNPs (Q223R; rs1137101 and K109R; rs1137100) were genotyped using real-time PCR. Statistical analyses included linear mixed-effect models. RESULTS: Women with the AA genotype of G2548A polymorphism reported a higher fat and total energy intake and had a higher increase in TG concentration during pregnancy than women with AG or GG genotype. The association between G2548A SNP and TG concentrations was not attenuated by adjusting for total lipid (g) and energy (kcal) intake. We did not observe significant associations between the Q223R and K109R SNPs and the lipid concentrations. CONCLUSIONS: Women homozygous for the A allele of the leptin SNP (G2548A) had a higher increase in TG concentrations per gestational week compared with women with the AG or GG genotype. This is an exploratory and hypothesis-generating study, and the results need confirmation in studies with larger sample sizes.'

Pesquisa Translacional em vitamina A: do ensaio randomizado à intervenção e à avaliação do impacto / Translational Research on vitamin A: from randomized trial to intervention and impact assessment

RESUMO A Pesquisa Translacional é interdisciplinar e está apoiada em três pilares: pesquisa de bancada (básica), leito (aplicações clínicas) e comunidade (aplicações nos sistemas de saúde). O estudo, baseado nos cinco estágios da Pesquisa Translacional, resgatou o histórico da deficiência de vitamina A e da cegueira nutricional no Brasil (T0); o caminho da descoberta científica à escolha da intervenção - suplementação vitamínica (T1); a avaliação da eficácia da intervenção candidata por ensaio randomizado e controlado (T2); a avaliação da implementação e da cobertura na prática (T3); e a avaliação do impacto da intervenção (T4). Para verificar o impacto, aplicou-se a estatística superior de Wald, visando identificar quebras estruturais ao longo da série histórica da mortalidade geral de crianças entre 6 e 59 meses de idade. Para a região Nordeste, que apresentou a maior cobertura programática, o modelo sinalizou três quebras - agosto/1984, junho/1994 e maio/2006 -, nas quais foram estimadas reduções de 10%, 17% e 23%, respectivamente, na ocorrência mensal de óbitos infantis. O processo para a construção do conhecimento sobre a deficiência desta vitamina, a escolha da intervenção, a aplicação deste conhecimento no estabelecimento do Programa Nacional de Suplementação de Vitamina A e a avaliação do seu impacto configuram um exemplo de Pesquisa Translacional em saúde coletiva.

ABSTRACT Translational Research is interdisciplinary and supported by three pillars: bench (basic investigation), bedside (clinical applications) and community (applications in healthcare systems). The study, based on the five stages of translational research, reviewed the history of vitamin A deficiency and nutritional blindness in Brazil (T0); the pathway from scientific discovery to intervention choice - vitamin supplementation (T1); an assessment of the candidate intervention efficacy via randomized controlled trial (T2); the assessment of implementation and coverage in practice (T3) and the intervention impact assessment (T4). To estimate the impact, we applied Wald superior statistics to identify structural breaks along the time series of general mortality of children between 6 and 59 months of age. In the Northeast, region that presents the largest program coverage, the model pointed to three breaks: August/1984, June/1994 and May/2006, in which we estimated reductions of 10%, 17% and 23%, respectively, in the monthly incidence of children´s death. The process to construct knowledge about vitamin A deficiency, the choice of the intervention, the knowledge translation to establish the National Vitamin A Supplementation Program and the evaluation of its impact, constitute an example of translational research in collective health.

Polymorphisms in the leptin (rs7799039) gene are associated with an increased risk of excessive gestational weight gain but not with leptin concentration during pregnancy.

Single nucleotide polymorphisms (SNPs) in leptin (LEP) and leptin receptor (LEPR) have been shown to be linked to obesity-related metabolic markers and phenotype. Therefore, we hypothesized that the LEP-rs7799039 and LEPR-rs1137101 SNPs are related to the risk of pre-pregnancy overweight/obesity (body mass index ≥25 kg/m2) as well as to excessive gestational weight gain (GWG) and high concentrations of leptin throughout pregnancy. We investigated a prospective cohort of 147 Brazilian pregnant women through weeks 5-13, 20-26, and 30-36 of gestation. Genetic variants of LEP and LEPR were analyzed by real-time polymerase chain reaction and leptin by enzyme-linked immunosorbent assay. Statistical analyses included multiple linear regression, linear mixed effects, and Poisson regression models. Genotype AA carriers for the LEP-rs7799039 gene maintained a lower body weight throughout pregnancy compared with those with genotypes GG or GA + GG (ßAAvsGG = -7.91 kg; 95% confidence interval [CI], -14.21 to -1.61; P = .01; and ßAAvsGA + GG = -7.66 kg; 95% CI, -14.07 to -1.25; P = .02). The A allele was significantly associated with an increased risk for excessive GWG (relative riskLEP-GAvsGG, 2.16; 95% CI, 1.23-3.80; and relative riskLEP-AAvsGG, 2.37; 95% CI, 1.04-5.39). Neither the LEP-rs7799039 nor LEPR-rs1137101 SNP was significantly associated with pre-pregnancy overweight/obesity risk and leptin concentrations during pregnancy. In conclusion, our results indicate that women who had the AA genotype for LEP-rs7799039 displayed a lower body weight throughout pregnancy compared with GG or GA + GG carriers. LEP-rs7799039 was significantly associated with an increased risk for excessive GWG, but the results do not support significant associations of the LEP-rs7799039 and LEPR-rs1137101 polymorphisms with pre-pregnancy overweight/obesity risk and leptin concentrations throughout pregnancy.

Association of the FTO (rs9939609) and MC4R (rs17782313) gene polymorphisms with maternal body weight during pregnancy.

OBJECTIVE: The fat mass and obesity (FTO) and melanocortin-4 receptor (MC4R) genes have been consistently associated with the risk for obesity, but few studies have examined the association of the obesity risk alleles with gestational outcomes. The aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) of the FTO (rs9939609) and MC4R (rs17782313) genes with changes in maternal body weight during pregnancy. METHODS: A sample of 136 pregnant women were followed in a prospective cohort at 5 to 13, 20 to 26, and 30 to 36 wk gestation and 30 to 45 d postpartum. SNPs were analyzed by real-time polymerase chain reaction. Associations between polymorphisms and the outcomes were investigated through longitudinal linear mixed-effects models, multiple linear regression models, and Poisson regression models. RESULTS: An SNP in the FTO (rs9939609) gene but not in the MC4R (rs17782313) gene was significantly associated with prepregnancy body mass index (BMI) ≥25 kg/m(2) (relative riskFTO = 2.1; 95% confidence interval [CI], 1.4-3.1). SNPs were not statistically associated with excessive gestational weight gain (GWG) or postpartum weight retention (PPWR). For the FTO (rs9939609) gene, women with the AA genotype were heavier in the body weight trajectory of pregnancy, but not when their weight had been adjusted for prepregnancy BMI (ßFTO = 0.5 kg; 95% CI, -1.9 to 3). These women started pregnancy heavier but gained less weight (FTO*gestational age = -0.1; 95% CI, -0.2 to 0.03) compared with those who had at least one T allele. CONCLUSIONS: The FTO (rs9939609) AA genotype is positively associated with prepregnancy excessive weight. We found no evidence of a significant effect of the MC4R (rs17782313) or the FTO (rs9939609) gene polymorphisms on the GWG and PPWR.

Avaliação de políticas públicas de segurança alimentar e combate à fome no período 1995-2002. 3 - o Programa Nacional de Controle da Deficiência de Vitamina A / Evaluation of public policies to promote food security and the fight against hunger, 1995-2002. 3 - the Brazilian National Program to Control Vitamin A Deficiency

A distribuição de vitamina A em Dias Nacionais de Vacinação ocorre desde 1983; o Brasil foi pioneiro nesse tipo de intervenção. O estudo avaliou o programa no período de 1995-2002 na perspectiva de estrutura-processo-resultado. A metodologia envolveu pesquisa documental, entrevistas com gestores e estudo de caso em 44 municípios da Bahia, resultando em 1.344 questionários domiciliares. Em relação à estrutura, o programa operou sem instrumento normativo a partir de 1998, decorrente da extinção do Instituto Nacional de Alimentação e Nutrição. Melhorias nos processos de aquisição e distribuição do suplemento impactaram positivamente na sua cobertura; em 2002, foram distribuídas 3,5 milhões de cápsulas (cobertura 72 por cento). Nas 2.546 crianças estudadas na Bahia, não houve regularidade na distribuição e a cobertura anual variou de 8 por cento a 26 por cento. As limitações de tempo e recursos humanos, informadas pelos gestores, corroboram a hipótese de que essa estratégia não contribui para esclarecer a população sobre a importância da vitamina. Os achados mostram ser necessária a articulação sistemática entre esferas de governo para que o programa seja executado e monitorado em sua plenitude.

Vitamin A supplements have been distributed during National Immunization Days since 1983, and Brazil has been a pioneer in this kind of strategy. The current study evaluated the National Program from 1995 to 2002, from a structure-process-results perspective. The methodology involved document research, interviews with health services managers, and a case study in 44 municipalities in Bahia State, resulting in 1,344 household interviews. In relation to structure, from 1998 on the program operated without a normative instrument due to the extinction of the National Institute of Nutrition. Improvements in the processes of vitamin supply procurement and distribution had a positive impact on coverage, reaching 3.5 million capsules in 2002 (72 percent coverage). For the 2,546 children studied in Bahia, vitamin A distribution was irregular, with annual coverage varying from 8 percent to 26 percent. Program managers reported time constraints and insufficient human resources, consistent with the hypothesis that this type of strategy does not help inform the population about the importance of vitamin A. These findings point to the need for systematic linkage between different levels of government in order to fully implement and monitor the program.

[Evaluation of public policies to promote food security and the fight against hunger, 1995-2002. 3--the Brazilian National Program to Control Vitamin A Deficiency]. / Avaliação de políticas públicas de segurança alimentar e combate à fome no período 1995-2002. 3--o Programa Nacional de Controle da Deficiência de Vitamina A.

Vitamin A supplements have been distributed during National Immunization Days since 1983, and Brazil has been a pioneer in this kind of strategy. The current study evaluated the National Program from 1995 to 2002, from a structure-process-results perspective. The methodology involved document research, interviews with health services managers, and a case study in 44 municipalities in Bahia State, resulting in 1,344 household interviews. In relation to structure, from 1998 on the program operated without a normative instrument due to the extinction of the National Institute of Nutrition. Improvements in the processes of vitamin supply procurement and distribution had a positive impact on coverage, reaching 3.5 million capsules in 2002 (72% coverage). For the 2,546 children studied in Bahia, vitamin A distribution was irregular, with annual coverage varying from 8% to 26%. Program managers reported time constraints and insufficient human resources, consistent with the hypothesis that this type of strategy does not help inform the population about the importance of vitamin A. These findings point to the need for systematic linkage between different levels of government in order to fully implement and monitor the program.

Avaliação de políticas públicas de segurança alimentar e combate à fome no período 1995-2002: 2 - Programa de Alimentação do Trabalhador / Evaluation of Brazilian public policies to promote food security and fight hunger, 1995-2002: 2 - the Workers' Nutrition Program

O estudo avaliou o Programa de Alimentação do Trabalhador (PAT) entre 1995 e 2002, sob a ótica da estrutura-processo-resultado. A metodologia consistiu em pesquisa documental e estudo de caso em 45 municípios na Bahia, resultando em 2.389 questionários domiciliares. Em termos de estrutura analisou-se a evolução normativa do programa até 2002. Quanto ao atendimento das necessidades nutricionais dos trabalhadores, o programa passou de uma insuficiente adequação calórica nos anos 80 para uma associação positiva entre sobrepeso e trabalho em empresa com PAT. Na Bahia a cobertura foi insuficiente entre os 5.120 adultos maiores de 20 anos investigados. Houve diferença significativa no acesso a benefícios alimentares entre trabalhadores do interior (26,1 por cento) e da capital (6,1 por cento). Contudo, a focalização foi adequada: todos os beneficiados no interior e 92,4 por cento na capital tinham renda menor que cinco salários mínimos. Faz-se necessária uma maior divulgação do PAT junto à população alvo, de forma a conscientizar os trabalhadores sobre os seus direitos e as ações desenvolvidas pelo Programa.

This study evaluated the Workers' Nutrition Program in Brazil from 1995 to 2002, from a structure-process-results perspective. The methodology involved documental research and a case study in 45 municipalities in the State of Bahia, resulting in 2,389 household interviews. In relation to structure, we analyzed the program's normative evolution until 2002. As for nutritional recommendations, the program shifted from insufficient calorie supply in the 1980s to a positive association between overweight and employment in companies adopting the Workers' Nutrition Program. In Bahia, overall program coverage was insufficient among the 5,120 adults 20 years or older who were interviewed. A significant difference was observed in access to food benefits among workers in the interior of the State (6.1 percent) as compared to the State capital, Salvador (26.1 percent). However, targeting was adequate: all workers benefiting from the program in the interior and 92.4 percent of those in Salvador earned less than five times the minimum wage (approximately U$950/month). It is necessary to improve the program's coverage in the target population in order to raise workers' awareness about their rights and the actions developed by the program.

[Evaluation of Brazilian public policies to promote food security and fight hunger, 1995-2002. 2 - the Workers' Nutrition Program]. / Avaliação de políticas públicas de segurança alimentar e combate à fome no período 1995-2002: 2 - Programa de Alimentação do Trabalhador.

This study evaluated the Workers' Nutrition Program in Brazil from 1995 to 2002, from a structure-process-results perspective. The methodology involved documental research and a case study in 45 municipalities in the State of Bahia, resulting in 2,389 household interviews. In relation to structure, we analyzed the program's normative evolution until 2002. As for nutritional recommendations, the program shifted from insufficient calorie supply in the 1980s to a positive association between overweight and employment in companies adopting the Workers' Nutrition Program. In Bahia, overall program coverage was insufficient among the 5,120 adults 20 years or older who were interviewed. A significant difference was observed in access to food benefits among workers in the interior of the State (6.1%) as compared to the State capital, Salvador (26.1%). However, targeting was adequate: all workers benefiting from the program in the interior and 92.4% of those in Salvador earned less than five times the minimum wage (approximately US dollars 950/month). It is necessary to improve the program's coverage in the target population in order to raise workers' awareness about their rights and the actions developed by the program.

Panorama das ações de controle da deficiência de vitamina A no Brasil / Overview of actions to control vitamin A deficiency of in Brazil

OBJETIVO: Este trabalho propõe-se a descrever a trajetória da implantação das ações de controle da deficiência de vitamina A no Brasil. MÉTODOS: Trata-se de estudo baseado em dados secundários, obtidos nos registros, documentos técnicos e relatórios oficiais do Instituto Nacional de Alimentação e Nutrição, autarquia do Ministério da Saúde extinta em 1997, da Coordenação Geral da Política Nacional de Alimentação e Nutrição do Ministério da Saúde, e informações obtidas com informantes-chaves, empregando a abordagem multidimensional alicerçada na tríade: estrutura-processo-resultado. RESULTADOS: O Brasil foi pioneiro na iniciativa de introduzir a distribuição de vitamina A nas campanhas nacionais de imunização, estratégia posteriormente preconizada pela Organização Mundial da Saúde e pelo Fundo das Nações Unidas para a Infância. Desde 1983, o Ministério da Saúde utiliza megadoses de vitamina A, como uma das ações para combater a deficiência deste micronutriente. O percentual de cobertura da população alvo (crianças de 6 a 59 meses) tem aumentado, alcançando 72 por cento e 68 por cento, nos anos de 2002 e 2003, respectivamente. Essas coberturas são semelhantes às registradas nos 40 países que adotam esta estratégia. Desde 2001 o programa foi ampliado para beneficiar puérperas, no pós-parto imediato. CONCLUSÃO: Foram modestos os avanços obtidos até o ano de 1992, fato que pode ser explicado pela falta de regularidade na distribuição das cápsulas de vitamina A. A partir de 1994, o programa manteve certa constância, porém persiste a necessidade de promover ações mais consolidadas nos serviços de saúde com maior alcance social, para além da distribuição rotineira dessas cápsulas.

OBJECTIVE: This manuscript aims to describe the implementation of actions to control vitamin A deficiency in Brazil. METHODS: The study was based on secondary data obtained from official reports and technical documents from the former Instituto Nacional de Alimentação e Nutrição (inactivated in 1997), from the Coordenação Geral da Política Nacional de Alimentação e Nutrição, Ministry of Health and information obtained from key informants employing the multidimensional approach based on the triad: structure-process-result. RESULTS: Brazil was pioneer in taking the initiative of linking vitamin A distribution to the National Immunization Days, a strategy that later on was recommended by the World Health Organization and the United Nations Children's Fund. Since 1983, vitamin A megadoses are employed as a strategy to fight this micronutrient deficiency by the Ministério da Saúde. Coverage of the target population (children 6-59 months old) is steadily increasing, reaching 72 percent and 68 percent in the years 2002 and 2003 respectively. These coverage rates are similar to those reported in the 40 countries that have also adopted this strategy. Since 2001 the program was extended to lactating women, in the immediate post-partum period. CONCLUSION: The program achievements until 1992 were very modest, fact that could be explained by the irregularity of vitamin A capsule distribution. From 1994 on the distribution was more constant, but the need to promote more integrated actions in the health services, as well as far reaching social actions, beyond the routine distribution of vitamin A capsules, still remains.

[Prevalence of hypovitaminosis A among preschool children from northeastern Brazil, 1998]. / Prevalência da hipovitaminose A em pré-escolares no Estado de Sergipe, 1998.

OBJECTIVE: To determine the prevalence of vitamin A deficiency in a population-based sample. METHODS: This was a cross-sectional study conducted in the State of Sergipe, northeastern Brazil, in May and June, 1998. It involved 607 children aged 6 to 60 months. The information was obtained by means of interviews with the persons responsible for these children, in their homes. Blood samples were collected via venous puncture and serum retinol assays were carried out by means of high performance liquid chromatography (HPLC). In simultaneous analyses of the study variables, p<0.05 was accepted for testing statistically significant associations. RESULTS: A mean serum retinol value of 0.87 micromol/l (+/- 0.38) was found among the children investigated. The prevalence of levels considered low (0.35 to 0.69 micromol/l) was 22.5% and the prevalence of levels considered deficient (<0.35 micromol/l) was 9.6%. Inadequate serum retinol levels were therefore seen in 32.1% of the children. The serum retinol level showed an association with per capita family income and the weight/age indicator. No statistically significant association was found for serum retinol level in relation to the child's age and sex, or the mother's variables. CONCLUSION: Vitamin A deficiency among preschool children is an important public health problem. Hypovitaminosis A is mainly related to low per capita family income and low infant weight.

Prevalência da hipovitaminose A em pré-escolares no Estado de Sergipe, 1998 / Prevalence of hypovitaminosis A among preschool children from northeastern Brazil, 1998

OBJETIVO: Determinar a prevalência da deficiência de vitamina A em uma amostra de base populacional de crianças. MÉTODOS: Trata-se de um estudo de corte transversal realizado de maio a junho de 1998, no Estado de Sergipe, envolvendo 607 crianças de seis a 60 meses de idade. As informações foram obtidas por meio de entrevistas domiciliares com os responsáveis pelas crianças. A coleta de sangue foi realizada por venipuntura e a dosagem do retinol sérico pelo método da cromatografia líquida de alta resolução. Para a análise simultânea das variáveis do estudo, aceitou-se o valor de p<0,05 para testar as associações de significância estatística. RESULTADOS: Encontrou-se um valor médio de retinol sérico de 0,87 µmol/l (±0,38) entre as crianças investigadas. A prevalência de níveis considerados baixos (0,35 a 0,69 µmol/l) foi de 22,5 por cento e de níveis considerados deficientes (<0,35 µmol/l), de 9,6 por cento, resultando em 32,1 por cento de crianças com níveis inadequados de retinol sérico. A distribuição de retinol sérico se mostrou associada com a renda per capita e o indicador peso/idade. Não foi encontrada associação estatisticamente significante com idade e sexo das crianças e com as variáveis maternas. CONCLUSAO: A deficiência de vitamina A das crianças pré-escolares constitui um importante problema de saúde pública. A hipovitaminose-A está relacionada principalmente à baixa renda per capita da família e baixo peso infantil.

Tolerância à aplicaçäo de megadores de vitamina A associada à vacinaçäo em crianças no Nordeste do Brasil / Tolerance of vitamin A application associated with mass immunization of children in Northeast Brazil

Um estudo de seguimento foi desenvolvido em duas localidades do semi-árido do estado da Bahia, Nordeste do Brasil, com o objetivo de identificar a ocorrência e a natureza de possíveis efeitos adversos agudos em conseqüência da suplementaçäo com megadoses de vitamina A (100.000 e 200.000 UI) oferecida junto com imunizaçäo em massa, a crianças de seis a 59 meses de idade. A amostra do estudo foi composta por 852 crianças; 416 do município de Teofilândia integraram o grupo que recebeu a vitamina A com as vacinas e 436 crianças de Santa Bárbara foram incluídas no grupo que recebeu somente a vacina. Nas 24 horas que antecederam a vacinaçäo, as crianças dos dois grupos referiram similar freqüência de diarréia, febre e vômito; a anorexia foi mais prevalente em Teofilândia e persistiu durante todo o período de seguimento. Os resultados sugerem que nenhum efeito adverso agudo, em especial diarréia, vômito, febre ou anorexia, esteve associado à ingestäo da vitamina A combinada à vacinaçäo em massa, particularmente à Sabin, DPT e anti-sarampo.

Hipovitaminose A em crianças de áreas rurais do semi-árido baiano / Vitamin A deficiency in children of rural zones, Northeast region of Brazil

Avalia a distribuiçäo e a magnitude da deficiência de vitamina A e o consumo dietético de 161 crianças de 6 a 72 meses de idade, de áreas rurais do Município de Cansançäo-BA, Brasil. Os níveis de retinol sérico foram medidos pelo método espectrofotométrico (Bessey-Lowry modificado por Araújo e Flores, 1978). A média do retinol sérico distribuiu-se homogeneamente entre as diferentes faixas etárias. Níveis inadequados de retinol sérico (deficiente<10,0µg/dl e baixos<20,0µg/dl) foram detectados em 44,7 por cento das crianças, caracterizando a deficiência como problema de saúde pública. Os níveis de retinol sérico näo mostraram associaçäo estatisticamente significante com sexo e idade das crianças, contudo as menores de 24 meses apresentaram prevalência mais alta de níveis inadequados. A principal fonte de vitamina A, disponível para essas crianças, é representada pelos carotenóides, em especial beta-caroteno. Foi observada maior diversificaçäo no consumo dos alimentos de conteúdos moderado e baixo em vitamina A no grupo de 24 a 72 meses de idade, sem contudo assegurar níveis adequados de retinol sérico para este grupo etário