Factors associated with linear growth and weight attained in the first year of life in Cruzeiro do Sul, Acre

IObjective: To investigate the associated factors with linear growth and weight attained in the first year of life in the municipality of Cruzeiro do Sul, Acre. Methods: The present study is part of the MINA Study, a population-based birth cohort whose baseline data collection occurred between July 1, 2015 and June 30, 2016, from all hospital admissions for delivery of residents in the municipality, with assessment of sociodemographic and health history information. At 10-15 months, follow-up interviews were conducted to collect data on maternal and infant characteristics, as well as perform an anthropometric evaluation. Outcomes of interest were length for age and body mass index (BMI) for age Z-scores according to the World Health Organization growth standards. From a hierarchical conceptual model with determinants at distal, intermediate and proximal levels and adjustment for the child’s age and sex, multiple linear regression models were fitted for length for age and BMI for age Z-scores, as well as multiple logistic regression models for overweight (BMI for age Z-score >2.0). Results: A total of 772 babies were followed-up at 10-15 months, 52.2% female. At baseline, 39% of participants were beneficiaries of the Bolsa Família Program, 30% reported up to 9 years of schooling, and 31% of the mothers did not attend the minimum recommended number of 6 prenatal appointments. At 26 (SD: 6.6) years of age, mean maternal height was 157.5 cm (SD: 6.0) and 45% were overweight. At birth, mean weight and length for gestational age Zscores were 0.19 (SD: 0.99) and 0.11 (SD: 1.05). During the first year, 2.7% of the children were affected by malaria. Regarding nutritional status, 2.0% of girls and 2.4% of boys were stunted while 6.7% of girls and 6.0% of boys were overweight, with no differences between the sexes. In multiple models for the length for age Z-score, a positive ossociation with wealth index quintiles and maternal height (p for trend 2,0). Resultados: Ao todo, 772 bebês compuseram o seguimento de 10-15 meses, sendo 52,2% do sexo feminino. Na linha de base, 39% das participantes eram beneficiárias do Programa Bolsa Família, 30% reportaram até 9 anos de escolaridade e 31% das mães não recebeu o número mínimo recomendado de 6 consultas pré-natais. Com idade de 26 anos (DP: 6,6), a média de altura materna foi de 157,5 cm (DP: 6,0) e 45% apresentaram excesso de peso. Quanto ao nascimento, as médias de escores-Z de peso e comprimento ao nascer segundo idade gestacional foram 0,19 (DP: 0,99) e 0,11 (DP: 1,05). Ao longo do primeiro ano, 2,7% foram acometidos por malária. Com relação ao estado nutricional, déficit de comprimento para idade esteve presente em 2,0% das meninas e 2,4% dos meninos, enquanto 6,7% das meninas e 6,0% dos meninos apresentaram IMC elevado para idade, sem diferença significante entre sexos. Em análises múltiplas para o índice de comprimento para idade, observou-se associação positiva com quintis de índice de riqueza e altura materna (p de tendência linear <0,01). O incremento de 1 escore-Z de peso e comprimento ao nascer para idade gestacional correspondeu a comprimento para idade 0,17 (IC 95%: 0,07; 0,27) e 0,15 (IC 95%: 0,05; 0,25) escore-Z superior no primeiro ano. Crianças com ocorrência de malária no primeiro ano apresentaram crescimento linear -0,58 (IC 95%: -1,05; -0,11) escore-Z inferior em comparação com aquelas não afetadas. Em análises ajustadas para o índice de IMC para idade, observou-se relação inversa com recebimento do benefício do Programa Bolsa Família (-0,16 escore-Z; IC 95% -0,31; -0,00) e com idade materna (- 0,25 escore-Z; IC 95%: -0,49; -0,02 para bebês de mães com idade ≥30 anos). Constatouse associação positiva com IMC materno e o escore-Z de peso ao nascer (p de tendência linear <0,01). Em modelo múltiplo, a ocorrência de excesso de peso foi positivamente associada com quintis de índice de riqueza (p de tendência linear <0,01). O incremento de uma unidade de escore-Z de peso ao nascer resultou em 37% mais chance de excesso de peso no primeiro ano (IC 95% 1,03; 1,81). Conclusões: Confirmou-se a associação positiva do contexto socioeconômico, de influências intergeracionais e do tamanho ao nascer sobre o crescimento linear e o peso atingido no primeiro ano de vida. Além disso, observou-se impacto relevante e consistentemente negativo da ocorrência de malária sobre o crescimento linear dos bebês. Estratégias sobre fatores potencialmente modificáveis associados ao estado nutricional ao 10-15 meses podem ser particularmente relevantes na perspectiva de janela crítica de oportunidades até os mil dias de vida.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)BV UNIFESP: Teses e dissertaçõe

Early determinants of linear growth and weight attained in the first year of life in a malaria endemic region.

We investigated linear growth and weight attained among 772 children at 10-15 months of age in the first population-based birth cohort in the Brazilian Amazon. Sociodemographic, maternal and birth characteristics were collected in interviews soon after birth at baseline. Anthropometric evaluation was conducted at 10-15 months. Multiple linear regression models were fitted for length-for-age (LAZ) and body mass index (BMI)-for-age Z scores (BAZ), considering a hierarchical conceptual framework with determinants at distal, intermediate and proximal levels, with adjustment for the child's sex and age. Mean LAZ and BAZ were 0.31 (SD: 1.13) and 0.35 (SD: 1.06), respectively. Overall, 2.2% of children were stunted and 6.6% overweight. Among socioeconomic factors, household wealth index was positively associated with LAZ (p for trend = 0.01), while children whose families received assistance from the Bolsa Família conditional cash transfer program were 0.16 Z score thinner (95% CI: -0.31, -0.00). Maternal height and BMI were positively associated with both LAZ and BAZ at 10-15 months of age (p for trend <0.001). Child's size at birth was positively related with LAZ (p<0.001 for both birth weight and length). BAZ was 0.34 (95% CI: 0.24, 0.44) higher, but 0.11 lower (95% CI: -0.21, -0.02), for each increase in 1 Z score of birth weight and length, respectively. Children with at least one reported malaria episode within the first year of life were 0.58 (95% CI: -1.05, -0.11) Z score shorter. Socioeconomic and intergenerational factors were consistently associated with LAZ and BAZ at 10-15 months of age. The occurrence of malaria was detrimental to linear growth. In a malaria endemic region, reduction of inequalities and disease burden over the first 1,000 days of life is essential for taking advantage of a critical window of opportunity that can redirect child growth trajectories toward better health and nutrition conditions in the long term

NOTCH1 mutations are associated with high CD49d expression in chronic lymphocytic leukemia: Link between the NOTCH1 and the NF-κ B pathways

In chronic lymphocytic leukemia (CLL), stabilizing mutations of NOTCH1, affecting up to 10-15% of cases, have been associated to poor prognosis, disease progression and refractoriness to chemotherapy. NOTCH1 mutations are significantly overrepresented in trisomy 12 CLL, a disease subset frequently expressing CD49d, the α4 chain of the very-late-activation-4 integrin, a well-known key regulator of microenviromental interactions, and negative prognosticator in CLL. In the present study, by analysing a wide cohort of 1180 CLL, we observed a very strong association between the presence of NOTCH1 mutations and the expression of CD49d (P&lt;0.0001), occurring also outside the trisomy 12 CLL subset. Using both the MEC-1 CLL-like cells stably transfected with the NOTCH1 intracellular domain and primary CLL cells bearing a mutated or wild-type NOTCH1 gene configuration, we provide evidence that triggering of the NOTCH1 pathway resulted in a positive CD49d expression regulation, which was driven by a NOTCH1-dependent activation of nuclear factot-κB (NF-κB). Consistently, pharmacological inhibition of the NOTCH1 and/or of the NF-κB pathways resulted in impaired NF-κB nuclear translocation with consequent down-modulation of CD49d expression. Altogether, our data link for the first time NOTCH1 mutations to CD49d expression regulation through the involvement of the NF-κB pathway in CLL