ResumoObjetivo: Apresentar um novo ramo da ciência, denominado origens desenvolvimentistas da saúde e doença (DOHaD), abordando conceitos, métodos de estudo, aspectos éticos e perspectivas para essa área do conhecimento. Fontes dos dados:Revisão não sistemática da literatura biomédica, com o intuito de obter referências históricas e atualizadas relacionadas com o tema em discussão. Síntese dos dados:Estudos recentes demonstram associações entre agravos ocorridos em fases iniciais do desenvolvimento somático e a amplificação do risco para doenças crônicas ao longo da vida, tais como obesidade, diabetes e doenças cardiovasculares. Diferentes modelos foram propostos na tentativa de melhor explicar essas associações, como a teoria do fenótipo poupador, a programação, as respostas adaptativas preditivas e o conceito de concordância ou contraste. Alguns dos possíveis mecanismos envolvidos nesses processos são: efeitos do ambiente sobre a expressão gênica, através de mecanismos epigenéticos; efeitos de sinais hormonais transmitidos ao feto através da placenta ou ao recém-nascido através da lactação. Conclusões:O DOHaD agrega informações advindas de várias áreas do conhecimento, propondo novas metodologias de investigação no sentido de esclarecer a influência de eventos adversos ocorridos em fases precoces do desenvolvimento humano sobre o padrão de saúde e doença ao longo da vida. Esse novo campo da ciência propõe novos modelos de causalidade e mecanismos envolvidos no surgimento e desenvolvimento de doenças crônicas. Os resultados dessas investigações poderão resultar em impacto significativo na prevenção de doenças crônicas, bem como na promoção de saúde em diferentes fases da vida.J Pediatr (Rio J). 2007;83(6):494-504: DOHaD, programação, hipótese de Barker. AbstractObjective: To present a new branch of scientific knowledge, known as the developmental origins of health and disease (DOHaD), covering its concepts, study methods and ethical considerations in addition to the prospects for this area of knowledge. Sources:A non-systematic review of the biomedical literature intended to identify historical and current references related to the subject under discussion. Summary of the findings:Recent studies demonstrate associations between aggressions suffered during the initial phases of somatic development and amplified risk of chronic diseases throughout life, such as obesity, diabetes and cardiovascular diseases. A variety of models have been proposed in attempts to better explain these associations, such as the thrifty phenotype, programming and predictive adaptive response theories and the concept of match or mismatch. Some of the mechanisms possibly involved in these processes are: effects of the environment on gene expression, through epigenetic mechanisms; effects of hormonal signals transmitted to the fetus via the placenta or the newborn via lactation.Conclusions: DOHaD draws together information originating from many different areas of knowledge, proposing new investigative methodologies to elucidate the influe...

ObjectiveThis population-based birth cohort study examined whether normal weight obesity is associated with metabolic disorders in young adults in a middle-income country undergoing rapid nutrition transition.Design and MethodsThe sample involved 1,222 males and females from the 1978/79 Ribeirão Preto birth cohort, Brazil, aged 23–25 years. NWO was defined as body mass index (BMI) within the normal range (18.5–24.9 kg/m2) and the sum of subscapular and triceps skinfolds above the sex-specific 90th percentiles of the study sample. It was also defined as normal BMI and % BF (body fat) >23% in men and >30% in women. Insulin resistance (IR), insulin sensitivity and secretion were based on the Homeostasis Model Assessment (HOMA) model.ResultsIn logistic models, after adjusting for age, sex and skin colour, NWO was significantly associated with Metabolic Syndrome (MS) according to the Joint Interim Statement (JIS) definition (Odds Ratio OR = 6.83; 95% Confidence Interval CI 2.84–16.47). NWO was also associated with HOMA2-IR (OR = 3.81; 95%CI 1.57–9.28), low insulin sensitivity (OR = 3.89; 95%CI 2.39–6.33), and high insulin secretion (OR = 2.17; 95%CI 1.24–3.80). Significant associations between NWO and some components of the MS were also detected: high waist circumference (OR = 8.46; 95%CI 5.09–14.04), low High Density Lipoprotein cholesterol (OR = 1.65; 95%CI 1.11–2.47) and high triglyceride levels (OR = 1.93; 95%CI 1.02–3.64). Most estimates changed little after further adjustment for early and adult life variables.ConclusionsNWO was associated with MS and IR, suggesting that clinical assessment of excess body fat in normal-BMI individuals should begin early in life even in middle-income countries.

The intestinal microbiome is a unique ecosystem that influences metabolism in humans. Experimental evidence indicates that intestinal microbiota can transfer an obese phenotype from humans to mice. Since mothers transmit intestinal microbiota to their offspring during labor, we hypothesized that among vaginal deliveries, maternal body mass index is associated with neonatal gut microbiota composition. We report the association of maternal pre-pregnancy body mass index on stool microbiota from 74 neonates, 18 born vaginally (5 to overweight or obese mothers) and 56 by elective C-section (26 to overweight or obese mothers). Compared to neonates delivered vaginally to normal weight mothers, neonates born to overweight or obese mothers had a distinct gut microbiota community structure (weighted UniFrac distance PERMANOVA, p < 0.001), enriched in Bacteroides and depleted in Enterococcus, Acinetobacter, Pseudomonas, and Hydrogenophilus. We show that these microbial signatures are predicted to result in functional differences in metabolic signaling and energy regulation. In contrast, among elective Cesarean deliveries, maternal body mass index was not associated with neonatal gut microbiota community structure (weighted UniFrac distance PERMANOVA, p = 0.628). Our findings indicate that excess maternal pre-pregnancy weight is associated with differences in neonatal acquisition of microbiota during vaginal delivery, but not Cesarean delivery. These differences may translate to altered maintenance of metabolic health in the offspring.

We hypothesize that increasing rates of cesarean delivery may play a role in the obesity epidemic worldwide.

Rationale: It remains unclear whether premature birth, in the absence of neonatal respiratory disease, results in abnormal growth and development of the lung. We previously reported that a group of healthy infants born at 32-34 weeks' gestation and without respiratory complications had decreased forced expiratory flows and normal forced vital capacities at 2 months of age. Objectives: Our current study evaluated whether these healthy infants born prematurely exhibited improvement or ''catch-up'' in their lung function during the second year of life. Methods: Longitudinal measurements of forced expiratory flows by the raised volume rapid thoracic compression technique were obtained in the first and the second years of life for infants born prematurely at 32.7 (range, 30-34) weeks' gestation (n 5 26) and infants born at full term (n 5 24). Measurements and Main Results:Healthy infants born prematurely demonstrate decreased forced expiratory flows and normal forced vital capacities in the first and second years of life. In addition, the increases in lung function with growth were similar to full-term infants. Conclusions: Persistently reduced flows in the presence of normal forced vital capacity and the absence of catch-up growth in airway function suggest that premature birth is associated with altered lung development.

Intrauterine growth restriction (IUGR) is associated with metabolic disorders in adulthood. In rats, an early adverse environment alters food preferences in adult life. We investigated whether IUGR is associated with spontaneous macronutrient preferences in humans. Two thousand sixty-three participants from a Brazilian birth cohort were evaluated at 24 y of age using a food frequency questionnaire, physical examination, anthropometric measurements, and biochemical assays (glucose, insulin, cholesterol, and triglycerides). IUGR was defined by the birth weight ratio (BWR ϭ birth weight/mean weight for gestational age). Individuals were classified as non growth restricted (BWR Ն0.85), moderately growth restricted (0.85 Ͼ BWR Ն 0.75), and severely growth restricted (BWR Ͻ0.75). Severe IUGR women consumed a greater carbohydrate to protein ratio, even after controlling for social variables. There was a continuous association between growth restriction and later carbohydrate to protein ratio consumption in women. Women from both IUGR groups had a larger waist to hip ratio (WHR). The prevalence of metabolic syndrome was comparable between the groups. IUGR women preferred carbohydrates to protein in their regular diet, suggesting that spontaneous food choices may precede the appearance and contribute to the risk for metabolic diseases in this group. (Pediatr Res 65: 215-220, 2009) S tudies have shown that low birth weight, a marker for adverse fetal conditions, is associated with metabolic disorders in adulthood, predicting insulin resistance and type 2 diabetes (1), hypertension (2), obesity (3) and cardiovascular disease (4), especially in cases where there is evidence of postnatal body weight catch-up during childhood. Thus, feeding patterns and accelerated weight gain during the postnatal period are crucial mediators of the risk for subsequent obesity, cardiovascular disease (5), and insulin resistance (6).The developing organism may use the maternal intrauterine environment's hormonal milieu as a signal to indicate conditions that will exist in the postnatal environment (7) to favor the adaptation to the environment in which it will develop. Therefore, for a fetus reared in a stressful environment with possible shortage of nutrients, metabolic and neurochemical patterns would be adjusted very early during development favoring energy storage for the individual's survival.Studies in animals propose that altered eating and exercise behaviors precede the development of obesity and insulin resistance (8 -10). Exposure to a high fat diet further exacerbates the metabolic and cardiovascular abnormalities in these animals (8). In our previous studies in rats (11,12), we demonstrated that early life experience affects sweet food intake later in life. These findings would indicate that adverse perinatal events in humans could affect an individual's voluntary food choices for palatable foods, influencing the risk for metabolic diseases in adult life. We tested this hypothesis in a birth cohort followed to adulthood i...

CRD42015020838.

The hypothesis of similarity between the extreme degrees of social distribution, translated by maternal education level in relation to the proportion of low birth weight, was not confirmed.