Agonista PAN-PPAR (receptores ativadores de proliferação peroxissomal) e alterações hepáticas na prole adulta de camundongos de mães obesas

O objetivo do presente estudo foi avaliar se o Bezafibrato, um agonista PAN-PPAR, é capaz de aliviar a doença não alcoólica do fígado gorduroso (NAFLD) na prole de machos de mães C57BL/6 obesas. Fêmeas virgens foram alimentadas com uma dieta HL (hiperlipídica, 49% de lipídios) ou uma dieta C (controle, 10% de lipídios) por oito semanas antes do acasalamento e durante os períodos de gestação e lactação. A prole de machos foi subdividida em quatro grupos: C (dieta controle para as mães e filhotes); C/BZ (dieta controle para as mães e filhotes com tratamento com Bezafibrato[100mg/Kg]); HL (dieta HL para as mães e dieta controle para os filhotes); e HL/BZ (dieta HL para as mães e dieta controle para os filhotes com tratamento com Bezafibrato [100mg/Kg]). O tratamento com Bezafibrato começou na 12 semana e se manteve por três semanas. Análise do metabolismo, bioquímica, estereológica e por western-blotting foram realizadas. A dieta HL causou um fenótipo de sobrepeso nas mães e acarretou em uma intolerância oral à glicose com aumento da glicemia de jejum. A prole HL apresentou hiperfagia, ganho de massa corporal, altos níveis de triglicerídeo hepático e plasmático, esteatose hepática e aumento da expressão de proteínas lipogênicas concomitante com diminuição do receptor ativador de proliferação peroxissomal alfa (PPARα), que é responsável pela β-oxidação e aumento do receptor ativador de proliferação peroxissomal gama (PPARγ) e do elemento regulador de esterol ligante da proteína 1 (SREBP-1c) proteínas envolvidas na lipogênese hepática. Por outro lado, o tratamento com o Bezafibrato reverteu o quadro da programação metabólica no fígado, com uma melhora dos parâmetros morfológicos, bioquímicos e moleculares do fígado dos animais, com um aumento da ativação de PPARα em associação a uma diminuição do PPARγ e não alterando a expressão de SREBP-1c. Em conclusão, nós demonstramos que o tratamento com Bezafibrato melhora a NAFLD causada pela obesidade materna.

Efeitos intergeracionais da obesidade materna sobre o pâncreas endócrino de camundongos C57BL/6

Objetivo: Avaliar os efeitos da obesidade materna sobre a estrutura do pâncreas e metabolismo de carboidratos no início da vida adulta, com foco na prole da primeira geração (F1) e segunda geração (F2) de progenitoras F0 alimentadas com dieta rica em gordura nos períodos pré-gestacional, durante a gestação e lactação. Métodos: Camundongos C57BL/6 do gênero feminino (F0) foram alimentadas com dieta padrão (SC) ou dieta rica em gordura (HF) durante as oito semanas que antecederam o acasalamento, durante a gestação e lactação para gerar a F1 (F1-SC e F1-HF). As proles geradas receberam dieta SC até o terceiro mês de vida. Aos três meses de idade, fêmeas F1 foram acasaladas para gerar a F2 (F2-SC e F2-HF). Apenas os machos das geração F1 e F2 foram avaliados aos 3 meses de idade. As características metabólicas foram avaliadas pela massa corporal (MC), glicemia de jejum, área sob a curva no teste oral de tolerância a glicose; análise plasmática de insulina, leptina e adiponectina; distribuição e análise morfológica do pâncreas através da imunohistoquímica e imunofluorescência. Resultados: A prole F1-HF teve aumento significativo na massa corporal e glicemia quando comparado à F1-SC. Por outro lado, as proles F2-HF e F2-SC tiveram massas corporais semelhantes. A prole F1-HF e F2-HF mostrou aumento da ingestão de energia, intolerância à glicose, hiperinsulinemia, hiperleptinemia, hipoadiponectinemia, resistência à insulina, aumento da massa pancreática, o aumento da densidade de volume de ilhotas com elevada massa de células alfa e beta, ilhotas hipertrofiadas caracterizadas por uma distribuição alterada de células alfa e beta, e fraca imunoreatividade do pâncreas homeobox duodeno-1 (PDx1). Conclusões: Uma dieta HF materna consumida durante o período pré-concepção e durante toda a gestação e lactação em camundongos promoveu programação metabólica do pâncreas endócrino com pré-disposição ao diabetes mellitus tipo 2 precoce nas proles F1 e F2 do gênero masculino, sugerindo que essas mudanças são intergeracionais.

Sobrepeso e obesidade na gravidez: marcadores bioquímicos e resultados maternos e perinatais

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Efeito Diabetes mellitus gestacional na modulação de genes relacionados ao metabolismo mitocondrial e a implicação na predisposiçao do recém-nascido à obesidade

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Obesidade e sobre peso pré-gestacionais: prevalência e principais complicações maternas

Objetive: The goal of this review is to present up-to-date information on the prevalence of overweight and obesity and to discuss the evidence regarding the impact of these conditions on the health of mother.Data Collection Method: We conducted a search for articles in the Medline, PubMed and Scielo databases covering the past 5 years, and reviewed the bibliographical references contained in the articles selected. Articles were selected by subjective evaluation in terms of methodology, sample size and year of publication. Summary of evidence: Current information points to a high and growing prevalence of overweight and obesity. We found strong evidence linking excess weight before pregnancy with the development of pregnancy-induced hypertension, gestational diabetes, pregnancy at 41 weeks or over, thromboembolism, cesarean section and puerperal infection. Conclusions: Excess weight in the pre-pregnancy is one of the most important risk factors of maternal health, whose importance increases because it is a modifiable risk factor. The obese pregnant woman should be considered at high risk and it is recommended that women be with the weight as close to normal as possible before conception.

Maternal support for autonomy : relationships with persistence for children with Down syndrome and typically developing children

Maternal behaviors and child mastery behaviors were examined in 25 children with Down syndrome and 43 typically developing children matched for mental age (24–36 months). During a shared problem-solving task, there were no group differences in maternal directiveness or support for autonomy, and mothers in the two groups used similar verbal strategies when helping their child. There were also no group differences in child mastery behaviors, measured as persistence with two optimally challenging tasks. However, the two groups differed in the relationships of maternal style with child persistence. Children with Down syndrome whose mothers were more supportive of their autonomy in the shared task displayed greater persistence when working independently on a challenging puzzle, while children of highly directive mothers displayed lower levels of persistence. For typically developing children, persistence was unrelated to maternal style, suggesting that mother behaviors may have different causes or consequences in the two groups.

Maternal age and paternal age are associated with distinct childhood behavioural outcomes in a general population birth cohort

Abstract Background Recent studies show that advanced paternal age (APA) is associated with an increased risk of neurodevelopmental disorders such as autism, bipolar disorder and schizophrenia. A body of evidence also suggests that individuals who develop schizophrenia show subtle deviations in a range of behavioural domains during their childhood. The aim of the study was to examine the relationship between paternal and maternal ages and selected behavioural measures in children using a large birth cohort. Method Participants were singleton children (n = 21,753) drawn from the US Collaborative Perinatal Project. The outcome measures were assessed at 7 years. The main analyses examined the relationship between parental age and behavioural measures when adjusted for a range of potentially confounding variables, including age of the other parent, maternal race, socio-economic measures, sex, gestation length, maternal marital status, parental mental illness, and child's age-at-testing. Results Advanced paternal age was associated with a significantly increased risk of adverse ‘externalizing’ behaviours at age seven years. For every five year increase in paternal age, the odds of higher ‘externalizing’ behaviours was increased by 12% (OR = 1.12; 95% CI = 1.03, 1.21, p < 0.0001). The relationship persisted after adjusting for potential confounding factors. ‘Internalizing’ behavioural outcome was not associated with advanced paternal age. In contrast, advanced maternal age was significantly protective against adverse ‘externalizing’ behavioural outcomes, but associated with an increased risk of adverse ‘internalizing’ behavioural outcomes. Discussion The offspring of older fathers show a distinctly different pattern of behaviours compared to the offspring of older mothers. The diverse socio-cultural and biologically-mediated factors that underpin these findings remain to be clarified. In light of secular trends related to delayed parenthood, the mechanisms underlying these findings warrant closer scrutiny.

Maternal anxiety and attention problems in children at 5 and 14 years

Objective: This study examines the association between maternal anxiety from pregnancy to 5 years and child attention problems at 5 and 14 years. Method: Birth cohort of 3,982 individuals born in Brisbane between 1981 and 1983 are assessed. Self-reported measures of maternal anxiety are assessed at four time points. Maternal reports of child attention problems using Achenbach’s Child Behavior Checklist are assessed at 5 and 14 years. Results: Children of mothers experiencing anxiety during or after pregnancy are at greater risk of experiencing attention problems at 5 and 14 years. After adjusting for maternal age and child’s gender, antenatal anxiety is strongly associated with persistent attention problems (OR = 3.65, 95% CI = 2.19, 6.07). Children with chronically anxious mothers are 5.67 (95% CI = 3.56, 9.03) times more likely to have persistent attention problems. These associations remain consistent after adjusting for potential confounders. Conclusions: Maternal anxiety appears to increase the rate of child attention problems and identifies a need for treatment programs to have a dual focus—the mother and her child. (J. of Att. Dis. 2009; XX(X) 1-XX)

Maternal reminiscing style during early childhood predicts the age of adolescents' earliest memories

Individual differences in parental reminiscing style are hypothesized to have long-lasting effects on children’s autobiographical memory development, including the age of their earliest memories. This study represents the first prospective test of this hypothesis. Conversations about past events between 17 mother–child dyads were recorded on multiple occasions between the children’s 2nd and 4th birthdays. When these children were aged 12–13 years, they were interviewed about their early memories. Adolescents whose mothers used a greater ratio of elaborations to repetitions during the early childhood conversations had earlier memories than adolescents whose mothers used a smaller ratio of elaborations to repetitions. This finding is consistent with the hypothesis that past-event conversations during early childhood have long-lasting effects on autobiographical memory.

To work or not to work? Child development and maternal labor supply

We estimate the effect of early child development on maternal labor force participation. Mothers of poorly developing children may remain at home to care for their children. Alternatively, mothers may enter the labor force to pay for additional educational and health resources. Which action dominates is the empirical question we answer in this paper. We control for the potential endogeneity of child development by using an instrumental variables approach, uniquely exploiting exogenous variation in child development associated with child handedness. We find that a one unit increase in poor child development decreases maternal labor force participation by approximately 10 percentage points.

Maternal feeding practices and feeding behaviors of Australian children aged 12 to 36 months

Objectives To explore parents' perceptions of the eating behaviors and related feeding practices of their young children. Methods Mothers (N=740) of children aged 12 to 36 months and born in South Australia were randomly selected by birth date in four 6-month age bands from a centralized statewide database and invited to complete a postal questionnaire. Results Valid completed questionnaires were returned for 374 children (51% response rate; 54% female). Although mothers generally reported being confident and happy in feeding their children, 23% often worried that they gave their child the right amount of food. Based on a checklist of 36 specified items, 15% of children consumed no vegetables in the previous 24 hours, 11% no fruit and for a further 8% juice was the only fruit. Of 12 specified high fat/sugar foods and drinks, 11% of children consumed none, 20% one, 26% two, and 43% three or more. Six of eight child-feeding practices that promote healthy eating behaviors were undertaken by 75% parents 'often' or 'all of the time'. However, 8 of 11 practices that do not promote healthy eating were undertaken by a third of mothers at least ‘sometimes’. Conclusions In this representative sample, dietary quality issues emerge early and inappropriate feeding practices are prevalent thus identifying the need for very early interventions that promote healthy food preferences and positive feeding practices. Such programs should focus not just on the 'what', but also the 'how' of early feeding, including the feeding relationship and processes appropriate to developmental stage. Key words: Maternal feeding practices, infants, obesity

Maternal administration of erythromycin fails to eradicate intrauterine ureaplasma infection in an ovine model

Erythromycin is the standard antibiotic used for treatment of Ureaplasma species during 3 pregnancy; however, maternally administered erythromycin may be ineffective at eliminating 4 intra-amniotic ureaplasma infections. We asked if erythromycin would eradicate intra-amniotic 5 ureaplasma infections in pregnant sheep. At 50 days of gestation (d, term=150d) pregnant ewes 6 received intra-amniotic injections of erythromycin-sensitive U. parvum serovar 3 (n=16) or 10B 7 medium (n=16). At 100d, amniocentesis was performed; five fetal losses (ureaplasma group: 8 n=4; 10B group: n=1) had occurred by this time. Remaining ewes were allocated into treatment 9 subgroups: medium only (M, n=7); medium and erythromycin (M/E, n=8); ureaplasma only (Up, 10 n=6) or ureaplasma and erythromycin (Up/E, n=6). Erythromycin was administered intra11 muscularly (500 mg), eight-hourly for four days (100d-104d). Amniotic fluid samples were 12 collected at 105d. At 125d preterm fetuses were surgically delivered and specimens were 13 collected for culture and histology. Erythromycin was quantified in amniotic fluid by liquid 14 chromatography-mass spectrometry. Ureaplasmas were isolated from the amniotic fluid, 15 chorioamnion and fetal lung of animals from the Up and Up/E groups, however, the numbers of 16 U. parvum recovered were not different between these groups. Inflammation in the 17 chorioamnion, cord and fetal lung was increased in ureaplasma-exposed animals compared to 18 controls, but was not different between the Up and Up/E groups. Erythromycin was detected in 19 amniotic fluid samples, although concentrations were low (<10-76 ng/mL). This study 20 demonstrates that maternally administered erythromycin does not eradicate chronic, intra- amniotic ureaplasma infections or improve fetal outcomes in an ovine model, potentially due to 22 the poor placental passage of erythromycin.

Observational assessment and maternal reports of motivation in children and adolescents with Down Syndrome

Despite a lack of consistent empirical evidence, there has been an ongoing assumption that intellectual disability is associated with reduced levels of motivation. The participants in this study were 33 children with Down syndrome ages 10–15 years and 33 typically developing 3–8-year-old children. Motivation was measured through observational assessments of curiosity, preference for challenge, and persistence, as well as maternal reports. There were no significant group differences on motivation tasks, but mothers of children with Down syndrome rated their children significantly lower on motivation than did parents of typically developing children. There were some intriguing group differences in the pattern of correlations among observations and parent reports. The findings challenge long-held views that individuals with intellectual disability are invariably deficient in motivation.

Maternal exposure to ambient temperature and the risk of preterm birth and stillbirth in Brisbane, Australia

Almost 10% of all births are preterm and 2.2% are stillbirths globally. Recent research has suggested that environmental factors may be a contributory cause to these adverse birth outcomes. The authors examined the relationship between ambient temperature and preterm birth and stillbirth in Brisbane, Australia between 2005 and 2009 (n = 101,870). They used a Cox proportional hazard model with live birth and stillbirth as competing risks. They also examined if there were periods of the pregnancy where exposure to high temperatures had a greater effect. Exposure to higher ambient temperatures during pregnancy increased the risk of stillbirth. The hazard ratio for stillbirth was 0.3 at 12 °C relative to the reference temperature at 21 °C. The temperature effect was greatest for fetuses of less than 36 weeks of gestation. There was an association between higher temperature and shorter gestation, as the hazard ratio for live birth was 0.96 at 15 °C and 1.02 at 25 °C. This effect was greatest at later gestational ages. The results provide strong evidence of an association between increased temperature and increased risk of stillbirth and shorter gestations.