Although the association between high maternal alcohol consumption and adverse reproductive outcomes is well established, the effect of lower levels of consumption during pregnancy is unclear; few studies have investigated this exposure. A hospital-based case-control study of small-for-gestational age (SGA) newborns (birth weight below the 10th percentile, according national standards for gestational age and sex) was conducted in Montreal between 1998 and 2000. Controls were born at the same hospital and during the same period with birth weight at or above the 10th percentile. This analysis aims at investigating the effect of low alcohol consumption (0.25 to 3 alcoholic drinks weekly) during pregnancy on the risk of small-for-gestational-age (SGA) birth. Independent effects of wine, beer and spirits and of paternal alcohol consumption before conception were also assessed. The logistic regression analysis showed no significant effect of light maternal drinking during pregnancy on the risk of SGA birth. The association was also studied separately for consumption of wine, beer and spirits, and likewise for paternal alcohol consumption, with similarly negative results.

Diss. (sammanfattning) Stockholm : Karol. inst., 2002. / Härtill 6 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Diversos estudos observaram uma correlação entre doenças na idade adulta e o ambiente durante a vida fetal. O estudo realizado por Barker e colaboradores foi um dos primeiros a relatar a hipótese de um possível envolvimento do ambiente intra-uterino com o desenvolvimento de doenças cardiovasculares, mas os mecanismos responsáveis por esta associação ainda não são totalmente conhecidos. Estudos demonstraram uma associação entre baixo peso ao nascimento com resistência à insulina e intolerância à glicose na vida adulta. Recentemente, verificamos que o consumo de dieta hipossódica, conhecido modelo de resistência à insulina, durante a gestação e lactação está vinculado a menor sensibilidade à insulina na prole adulta. Visto que a presença de resistência à insulina durante a gestação leva a diversas alterações metabólicas na prole adulta, pode-se supor que a sobrecarga de sacarose, um modelo de resistência à insulina, durante a gestação e lactação influencie no desenvolvimento da prole. Assim, o objetivo do presente estudo foi verificar a repercussão da resistência à insulina, durante a gestação sobre a prole adulta. Para tanto, ratas Wistar foram alimentadas com dieta hipo (HO) ou normossódica (NR) suplementadas ou não com sacarose (NR+SAC - 20g/dL) ou maltodextrina (NR+MALTO - 20g/dL) desde a oitava semana de vida até o final da gestação e amamentação. Na prole resultante destes animais foi observado menor peso ao nascimento nos grupos HO, NR+SAC e NR+MALTO. Esta alteração resultou no desenvolvimento de maior insulinemia, pressão arterial e maior captação de glicose na prole de fêmeas das mães do grupo NR+SAC. Os machos apresentaram menor índice de adiposidade e maior expressão gênica renal dos componentes do sistema renina-angiotensina. Tais resultados nos permitem concluir que a sobrecarga de carboidratos durante a gestação e lactação está associada a alterações no peso ao nascimento e no metabolismo da insulina na idade adulta. É possível que a ativação do sistema renina-angiotensina materno induzido pela sobrecarga de carboidrato esteja associada a alterações deste mesmo sistema observado na prole adulta. / Many studies observed a correlation between diseases in adult subjects and the environment during the fetal life. Barker and coworkers hypothesized that there is a possible intrauterine enviroment association with cardiovascular diseases in adulthood. The mechanisms responsible for this association are still not very well known. Recently, we have verified that low-salt diet consumption, a well-known model of insulin resistance, during pregnancy and lactation is associated with a lower insulin sensitivity in the adult offspring. Since insulin resistance during pregnancy leads to many metabolic alterations in the adult offspring, we suppose that sucrose overload during pregnancy and lactation could influence the offspring development. The aim of this study was to verify the effects on adult offspring of insulin resistance during pregnancy and lactation. Female Wistar rats were fed low (LSD) and normal-salt diet (NSD) supplemented or not with sucrose (SUC - 20 g/dL) or maltodextrin (MALTO - 20 g/dL) until the end of pregnancy and lactation. Lower birth weight was observed in offspring of LSD, SUC and MALTO groups. Higher plasma insulin level, blood pressure and glucose uptake was detected in the adult SUC female offspring. SUC male offspring had lower adiposity index and higher gene expression of the renal renin-angiotensin components. These results show that carbohydrate overload during pregnancy and lactation is associated with alterations in birth weight and in insulin metabolism at adult life. It is possible that the maternal renin-angiotensin system activation by the carbohydrate overload is associated with alterations in the same system observed in the adult offspring.

No description available.

Maternal infection during pregnancy is associated with increased risk of both schizophrenia and autism in offspring. Based on this observation, the maternal immune activation mouse model was developed, in which pregnant rodents are treated with immune-activating agents and the brains and behavior of the adult offspring studied. This model has been found to recapitulate a variety of molecular, cellular, and behavioral abnormalities observed in both schizophrenia and autism. However, despite the abundant evidence provided by these studies that prenatal exposure to inflammation alters brain development and function later in life, the molecular mechanisms by which inflammation mediates these effects remains unclear. It has been suggested that other prenatal risk factors for neuropsychiatric disease may alter brain development, in part, via epigenetic mechanisms such as DNA methylation and histone modification. However, a link between inflammation and epigenetic modification in brain has not been established. Therefore, the focus of my thesis was to examine the effect of inflammation on the histone modification, trimethylated histone H3 lysine 4 (H3K4me3), which has been implicated in both normal brain development and in schizophrenia. In Chapter II, I describe experiments examining the effect of a specific, cytokine, interleukin-6 (IL-6), on H3K4me3 in rat forebrain culture. I show that IL-6 treatment results in altered levels of H3K4me3 at multiple gene promoters, frequently in conjunction with altered mRNA expression levels, and demonstrate that a subset of these alterations appear to be dependent on signaling via the signal transducer and activator of transcription 3 (Stat3) pathway. Furthermore, some of the genes affected by IL-6 also showed altered H3K4me3 levels in autism postmortem brain. Though a direct link still remains to be established, this observation suggests that epigenetic changes observed in neuropsychiatric disease may have been induced by prenatal exposure to inflammation. In Chapter III, I describe in vivo experiments employing the maternal immune activation (MIA) mouse model to examine the effects of prenatal inflammation on H3K4me3 in the brain of the offspring, at both fetal and adult stages. I found that immune activation resulted in increased levels of IL-6 protein in fetal brain, working memory deficits in the adult offspring, and subtle changes in H3K4me3 levels in fetal and adult brain. Taken together, these findings demonstrate that an environmental risk factor for schizophrenia and autism—namely, inflammation—is capable of inducing robust and widespread histone modifications in a model of the central nervous system and smaller changes in vivo. This suggests that prenatal exposure to inflammation in human populations may lead to increased susceptibility for neuropsychiatric disorders, in part, by altering chromatin modifications in developing brain.

Background: Migraine headache is a chronic pain condition that affects 20% of women of reproductive age, and is often treated with triptans. Triptans are serotonin 1B, 1D, and 1F receptor agonists that act as vasoconstrictors and inhibitors of the trigeminal cervical complex as well as peripheral neurons; they cross the blood brain barrier and placenta, and as such are plausible neurodevelopmental teratogens. No studies have examined risk of neurodevelopmental problems in children with prenatal triptan exposure. This dissertation had three aims: (1) to examine risk of behavioral problems in children using in the presence of time-varying confounding by concomitant medication use; (2) to examine risk of temperamental, motor, and communication disturbances associated with prenatal triptans exposure, adjusting for unmeasured confounding by migraine type and severity; and (3) to examine changes in neurodevelopment over time associated with prenatal triptan exposure. Methods: This dissertation used data from the Norwegian Mother and Child Cohort Study, a prospective birth cohort including more than 100,000 women recruited during their first prenatal ultrasound visit. Aims 1 and 3 used marginal structural models to assess the risk of (1) neurodevelopmental problems at age 36 months (Aim 1), or (2) change in risk of neurodevelopmental problems from 18 to 36 months (Aim 3) associated with prenatal triptan exposure. Aim 2 used propensity matching and calibration to adjust for unmeasured confounding by migraine type, severity, and attitudes towards medication use in pregnancy. Neurodevelopmental outcome measures included the Child Behavior Checklist (CBCL), the Emotionality, Activity, and Temperament Scale (EAS), and the Ages and Stages Questionnaire (ASQ). Exposure to triptans was ascertained by self-report. Results: Prenatal triptan exposure was associated with greater externalizing behavior problems at 18 and 36 months, as well as greater increases in emotionality and activity from 18 to 36 months. We observed no association between triptan exposure and motor skills or communication problems; triptan use during pregnancy was associated with migraine severity but not migraine type, and adjustment for unmeasured migraine characteristics moved effect estimates towards the null. Conclusions: Prenatal triptan exposure is associated with externalizing-type behaviors and temperament in children, while migraine itself is associated with internalizing-type behaviors and temperament. The use of concomitant medications and the severity of the underlying condition both exerted substantial influence on observed effect estimates, and should be considered in any future studies of triptan medication use in pregnancy.

Estudos experimentais feitos em nosso laboratório comprovaram que a inalação de material particulado proveniente da queima de combustíveis fósseis utilizados em siderurgia pelos ratos adultos diminuiu a atividade motora dos animais no campo aberto. Além disso, provamos que os ratos habituaram ao ambiente desse teste, o que significa que a inalação desse tipo de material não provocou variação em termos de aprendizado simples. Uma das causas da alteração no comportamento em relação à motricidade seria o estresse oxidativo causado pelo material particulado no estriado e cerebelo desses animais. Entretanto, em nossa cidade não existem estudos que demonstrem a estreita associação entre inalação de poluentes, estresse oxidativo e alterações comportamentais. Baseados nos nossos trabalhos anteriores e na literatura, nosso objetivo foi investigar se a poluição atmosférica a nível ambiental durante as fases pré e pós-natal alteraria a memória discriminativa de curta-duração e a memória espacial. Além disso, avaliamos o papel do estresse oxidativo como o mecanismo propulsor dessas mudanças de comportamento. Para tal, ratas prenhas foram expostas ao ar filtrado e ao ar não filtrado durante os 21 dias de gestação. Ao final do período de amamentação, os machos foram separados e subdividos em 4 grupos experimentais (n=24): 1) Filtrado: nasceu e viveu em ambiente cujo ar era filtrado, 2) NFF: nasceu em ambiente cujo ar era não filtrado e viveu a partir do 21o dia do pós-natal no ambiente com ar filtrado, 3) FNF: nasceu sob ar filtrado e viveu a partir do 21o dia do pós-natal sob ar não filtrado, 4)NF: nasceu e viveu em ambiente cujo ar era não filtrado. Os animais ficaram expostos a poluição por 150 dias. Os animais foram divididos em 3 lotes: lote 1: n=6 animais por grupo; após anestesia profunda, os animais foram perfundidos com soro fisiológico seguido de paraformaldeído 4%, o encéfalo foi retirado e dissecado em córtex, hipocampo e estriado para análises histológicas por técnicas estereológicas; lote 2: n=12 ratos por grupo; aplicação dos testes comportamentais; um dia após os testes, esses animais foram eutanasiados por decapitação, o encéfalo retirado e dissecado da mesma forma citada anteriormente para análise de estresse oxidativo; lote 3: n=6 animais por grupo; os animais foram decapitados e o sangue troncular coletado para análises de elementos traço tóxicos e essenciais no sangue total. O córtex apresentou lipoperoxidação no grupo NF quando comparado aos outros grupos, assim como uma alta concentração de Cd no sangue. O grupo NFF apresentou uma maior concentração de Cu, Se e Zn no sangue em relação aos demais. Em relação à memória discriminativa de curta-duração, houve uma diminuição no grupo NF em relação aos demais grupos. No hipocampo e estriado, foi observado aumento da lipoperoxidação nos grupos FNF e NF, respectivamente, quando comparado aos outros grupos. Quanto à memória espacial, não houve diferença estatisticamente significativa entre os grupos. Primeiramente, como pudemos observar, o cada estrutura encefálica apresenta uma resposta ao estresse oxidativo. O córtex do grupo NF apresentou aumento de lipoperoxidação. Como se sabe, o Cd é feto tóxico e passa via transplacentária adsorvido ao material particulado inalado pela mãe. No caso do grupo NF, o Cd possivelmente deslocou o Zn do sítio ativo da enzima CuZn superóxido dismutase formando forma inativada da mesma. O Cd, também, forma conjugado com duas moléculas de glutationa reduzida a fim de ser excretado pela bile. Isso reduz a sua capacidade antioxidante. Esse elemento traço desloca o Fe e o Cu dos sítios ativos das suas proteínas de armazenamento, a ferritina e a ceruplasmina, respectivamente. Esses dois elementos ficam livres para catalisar a reação de Fenton cujo produto é o radical hidroxil, extremamente tóxico para o organismo. O grupo NF apresentou uma diminuição na capacidade de discriminar dois objetos diferentes. Provavelmente, o Cd agiu de forma indireta diminuindo a capacidade antioxidante da CuZn superóxido dismutase e da glutationa, além de liberar Fe e Cu e aumentar a produção de radical hidroxil. O aumento da lipoperoxidação causado pelo Cd pode ser o mecanismo responsável pela perda desse tipo de memória. Entretanto, o grupo NFF, cuja exposição à poluição foi na fase pré-natal, não apresentou aumento na lipoperoxidação. Possivelmente, a alta concentração dos elementos traço essenciais, Cu, Zn e Se aumentou a atividade das enzimas CuZn superóxidodismutase e glutationa peroxidase, respectivamente, o que evitou danos oxidativos durante o período intra-uterino. O grupo FNF apresentou aumento de lipoperoxidação no hipocampo, mas não houve diferença na memória espacial testada com o labirinto de Morris modificado. Portanto, considerando todos os achados, concluímos que, possivelmente, o aumento da lipoperoxidação causado indiretamente pelo Cd pode ser um dos mecanismos responsáveis pela perda da capacidade da memória discriminativa de curta-duração. Além disso, os elementos traço essenciais exercem uma proteção via aumento das defesas antioxidantes dos animais que nasceram em ambiente poluído e, após 21 dias de vida, foram transferidos para o ambiente com o ar filtrado, o que demonstra, provavelmente, a existência de mecanismos antioxidantes de adaptação em ambientes inóspitos como forma de proteção contra o agente agressor durante o desenvolvimento do embrião. / Experimental studies done at our laboratory demonstrated that the inhalation of residual oil fly ash by the adult rats decreased motor activity of the animals in the open-field test. Additionaly, we showed that rats which inhalated residual oil fly ash preserved its habituation capacity. In this study, oxidative stress in striatum and cerebellum might be the cause of motor activity alterations. However, there were any studies about air pollution and behavioral alterations in Porto Alegre. Based on our previous works and in the literature, our objective was to investigate if the exposure to air pollution during intrauterine and lactation periods would damage the short term discriminative and spatial memories and if the mechanisms would be dependent of oxidants. For such, female pregnant rats were exposed to the filtered air and to the non filtered air during the 21 days of gestation. At the end of the breast-feeding period, the males were separate and divided in 4 experimental groups (n =24): 1) Filtered (F): - pre and post-natal exposure until adulthood in filtered air; 2) non filtered/filtered air (NFF): pre-natal period in non-filtered air until PND21 and post-natal in filtered air until adulthood; 3) filtered air/non-filtered air (FNF): pre-natal period in filtered air until PND 21 and post-natal period in non-filtered air until adulthood; 4) non filtered air (NF): pre and post-natal periods in non-filtered air.The animals were exposed the pollution for 150 days. The animals were divided in 3 lots: lot 1: n=6 animals per group; after anesthesia, the animals were perfused with saline solution following by paraformaldehyde 4%, the brain was removed and dissected in cortex, hippocampus and striatum for histological analyses by stereological techniques; lot 2: n=12 rats per group; submitted to behavioral tests; one day after the tests, those animals were euthanized by decapitation, the brain was removed and dissected in the same way mentioned previously for oxidative stress analysis; lot 3: 6 animals per group; the animals were decapitated and the troncular blood was collected to analyze the toxic and the essential trace elements. The cortex presented lipoperoxidation in NF group when compared to other groups, as well as a high concentration of Cd in the blood. The group NFF presented higher blood concentration of Cu, Se and Zn when compared to other groups. There was a decrease in the discriminative capacity in the group NF when compared to other groups. In the hippocampus and striatum, increases of lipidperoxidation were observed in the groups FNF and NF, respectively, when compared to other groups. Spatial memory of all groups was preserved. We observed the each brain structure reacts in a different way to oxidative stress. The NF cortex group presented an increased of lipidperoxidation. In this group, there was higher Cd blood concentration, which passes through placenta and it is fetotoxic. It might be possible that Cd dislocated Zn of the active site of CuZn superóxido dismutase resulting in inactive forms of this enzyme. The Cd also depletes reduced glutathione. Moreover, Cd may dislocate the Fe and Cu from its storage proteins to react with oxygen peroxide increasing the hydroxyl radical production by Fenton reaction. The group NF presented a decrease in the capacity to discriminate two different objects. Cd may act in an indirect way reducing the antioxidant capacity of CuZn superxidodismutase and of the glutathione and increasing the hydroxyl radical production. Lipoperoxidation in NF cortex caused by the Cd may be one of the mechanisms which explain the loss of discriminative capacity. However, the group NFF, whose air pollution exposure was in the pre-natal period, did not present increase of lipidperoxidation. The higher concentrations of essential trace elements (Cu, Se and Zn) may protect this group against oxidative stress. These elements are cofactor of antioxidants enzymes, superoxidodismutase and glutathione peroxidase and increased its activities during the intra-uterine exposure to air pollution. The group FNF presented lipidperoxidation increase in the hippocampus, but there was no difference in the spatial memory tested with Morris\' maze. Therefore, considering our data, we suggested that the increase of lipidperoxidation caused indirectly by Cd, which was adsorbed in particulate matter surface, may be one of the mechanisms which explain the loss of short-term discriminative memory

JUSTIFICATIVA E OBJETIVOS: Condições adversas no ambiente pré-natal e primeiros anos de vida são independentemente associados com risco aumentado de doença cardiovascular. A hipótese aceita atualmente para essa associação é a de que agravos, principalmente nutricionais, ocorridos durante a gestação alteram a organização de órgãos e sistemas, que ao serem solicitados na vida adulta, teriam menor capacidade funcional. Com base nessa premissa, o trabalho tem o objetivo de estudar a relação entre o peso ao nascer, crescimento no primeiro ano de vida e fatores de risco para doença cardiovascular e aterosclerose subclínica em adultos do Centro de Saúde-Escola (CSE) \"Prof. Samuel B. Pessoa\" da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Em 2009, 88 adultos jovens com idade entre 20-31 anos, seguidos desde o início da vida no CSE, foram submetidos ao diagnóstico de aterosclerose subclínica. Informações relacionadas às características sociodemográficas, dados antropométricos, medidas da pressão arterial, perfil metabólico, e avaliação da aterosclerose subclínica pela ultrassonografia e métodos gráficos foram obtidas dos adultos, e estudadas de acordo com 2 pontos de corte em relação ao peso de nascimento (< 2.500 gramas; e, > 3.500 gramas) e ganho de peso no primeiro ano de vida. Os pesos foram obtidos dos registros de prontuários. Os achados atuais dos adultos foram analisados em relação às condições de nascimento e ao ganho de peso no primeiro ano de vida. Para realização das análises estatísticas foram realizadas regressões multivariadas. RESULTADOS: Baixo peso ao nascer, menor de 2.500 gramas (g) foi negativamente correlacionado com a relação cintura-quadril (RCQ) elevada, segundo coeficiente de regressão (CR) igual a -0,323, IC 95% [-0,571, -0,075] p < 0,05, níveis de pressão arterial diastólica (CR=-4,744, IC 95% [-9,017,-0,470] p < 0,05), HDL-colesterol reduzido (CR=-0,272, IC 95% [-0,516, -0,029] p < 0,05), e frequência da espessura da média-íntima (EMI) média da carótida esquerda (CE) acima do p75 (CR=-0,242, IC 95% [-0,476,-0,008] p < 0,05). Peso ao nascer maior do que 3.500 g foi positivamente associado com IMC (CR=2,832, IC 95% [0,433, 5,233] p < 0,05), IMC >= 25,0 kg/m2, (CR=0,317, IC 95% [0,782, 0,557] p < 0.05), cintura abdominal elevada (CR=0,284, IC 95% [0,054, 0,513] p < 0,05), RCQ elevada (CR=0,280, IC 95% [0,054, 0,505] p < 0,05), glicemia de jejum (CR=3,808, IC 95% [0,558, 7,058] p < 0,05), MEGA mínima (CR=4,354, IC 95% [0,821, 7,888] p < 0,05), MEGA máxima (CR=7,095, IC 95% [0,608, 13,583] p < 0,05), tamanho do lobo direito do fígado (CR=6,896, IC 95% [1,946, 11,847] p < 0,01), e com a frequência do lobo direito do fígado acima do p75 (CR=0,361, IC 95% [0,169, 0,552] p < 0,01). Ganho de peso no primeiro ano de vida menor que: a diferença entre o peso com 12 meses de idade e o peso de nascimento no p50 das curvas da Organização Mundial da Saúde, foi considerado inadequado, sendo negativamente correlacionado com EMI média da CE (CR=-0,046, IC 95% [-0,086, -0,006] p < 0,05), frequência da EMI média da CE acima do p75 (CR=-0,253, IC 95% [-0,487, -0,018] p < 0,05), EMI da (CE+CD)/2, com CR=-0,038, IC 95% [-0,073, -0,002] p < 0,05, e com a frequência da EMI (CE+CD)/2 acima do p75 (CR=-0,241, IC 95% [-0,442, -0,041] p < 0,05). CONCLUSÕES: Adultos com pesos de nascimento menores do que 2.500 g. e maiores do que 3.500 g. e com ganho de peso insuficiente no primeiro ano de vida apresentaram diferentes fenótipos metabólicos, mas todos relacionados com fatores de risco aumentados para doença cardiovascular e aterosclerose subclínica, quando comparados com aqueles que nasceram com peso adequado e com ganho de peso suficiente no primeiro ano de vida / BACKGROUND AND OBJECTIVES: Adverse conditions in the prenatal environment and in the first years of life are independently associated with increased risk for cardiovascular disease. The currently accepted hypothesis for this association is the one that states that alterations occurred during pregnancy, mainly nutritional ones, affect the organization of organs and systems that would have a lower functional capacity when needed during adult life. This paper aims to study the relationship between weight at birth, growth in the first year of life and risk factors for cardiovascular disease and subclinical atherosclerosis subclinical atherosclerosis in adults of the \"Prof. Samuel B. Pessoa\" Health Center-School (CSE) from the Medical School of the University of São Paulo. METHODS: In the year of 2009, 88 young adults aged between 20 and 31, followed since the beginning of their lives in the CSE, were submitted to the diagnosis of subclinical atherosclerosis. Their sociodemographic qualities, anthropometric data, blood pressure measurements, metabolic profile, evaluation of subclinical atherosclerosis by ultrasound and graphical methods were collected. These pieces of information were later studied according to their birth weight (< 2,500 grams and > 3,500 grams) and to the gain of weight during their first year of life. Weights were obtained from the registrations of their medical records. The current findings in the adults were analysed in relation to their conditions of birth and weight gain in the first year of life. Multivariate regressions were performed in order to obtain the statistical analyses. RESULTS: Low birth weight, less than 2,500 grams (g) was negatively correlated with higher waist-to-hip ratio (WHR), according to regression coefficient (RC) equal to -0.323, 95% CI [-0.571, -0.075] p < 0.05, diastolic blood pressure (RC=-4.744, 95% CI [-9.017, -0.470] p < 0.05), reduced HDL cholesterol (RC=-0.272, 95% CI [-0.516, - 0.029] p < 0.05), and the frequency of the intima-media thickness (IMT) of the left carotid artery average above 75th p (RC=-0.242 95% CI [-0.476, -0.008] p < 0.05). Birth weight greater than 3,500g was positively associated with BMI (RC=2.832, 95% CI [0.433, 5.233] p < 0.05), BMI >= 25.0 kg/m2, (RC=0.317, 95% CI [0.782, 0.557] p < 0.05), waist circumference elevated (RC=0.284, 95% CI [0.054, 0.513] p < 0.05), WHR elevated (RC=0.280, 95% CI [0.054, 0.505] p < 0.05), fasting glucose (RC=3.809, 95% CI [0.559, 7.058] p < 0.05), minimum subcutaneous adipose tissue (SAT) with RC=4.354, 95% CI [0.821, 7.888] p < 0.05), maximum SAT (RC=7.095, 95% CI [0.608, 13.583] p < 0.05), size right lobe of the liver (RC=6.896, 95% CI [1.946, 11.847] p < 0.01), and the frequency of the right lobe of the liver above the 75th percentile (RC=0.361, 95% CI [0.169, 0.552] p < 0.01). Weight gain in the first year of life was considered inadequate when it was lower than the difference between the weight at 12 months of age and birth weight at the 50th percentile curves of the World Health Organization (WHO), and negatively correlated with media IMT of left carotid (RC=-0.046, 95% CI [-0.086, -0.006] p < 0.05, frequency of media IMT of left carotid above the 75th percentile (RC=-0.253, 95% CI [-0.487, -0.018] p < 0.05), media IMT(left carotid + right carotid)/2 com RC=-0.038, 95% CI [-0.073, -0.002] p < 0.05, and the frequency of the media IMT (left carotid + right carotid)/2 above the 75th percentile (RC=-0.241, 95% CI [-0.442,-0.041] p < 0.05). CONCLUSIONS: Adults with weight at birth lower than 2,500 g and higher than 3,500 g and with insufficient weight gain in the first year of life have showed different metabolic phenotypes, but all related to increased risk factors for cardiovascular disease and subclinical atherosclerosis when compared to those who were born with appropriate weight and who have gained enough weight during the first year of life