Bakgrund: Graviditetsdiabetes är den vanligaste metabola sjukdomen hos gravida. Sjukdomen ökar drastiskt relaterat till ökat stillasittande. Åtgärder inkluderar kostråd, råd om fysisk aktivitet, stöd att förbättra levnadsvanor samt vid behov insulinbehandling. Trots att forskning visar att fysisk aktivitet har flera positiva effekter på graviditetsdiabetes är mindre än hälften av populationen så fysiskt aktiva som de rekommenderas vara. För att bättre kunna stötta dessa kvinnor i sitt fysiska aktivitetsbeteende behövs mer information om deras kunskap och utfallsförväntningar avseende fysisk aktivitet. Syfte: Att undersöka hur fysiskt aktiva gravida med graviditetsdiabetes är, vilken kunskap och vilka utfallsförväntningar de har avseende fysisk aktivitet vid graviditetsdiabetes samt undersöka eventuella samband mellan kunskap, utfallsförväntningar och fysisk aktivitetsnivå. Metod: Observationsstudie av icke experimentell design genomfördes med webbenkät skapad i Google Forms. Bekvämlighetsurval från specialistmödravården samt sluten Facebook-grupp. Resultat: Majoriteten ägnade mindre än 30 minuter åt fysisk träning en vanlig vecka, uppfyllde inte rekommendationerna för vardagsmotion samt var stillasittande hela dagen. Majoriteten av deltagarna hade mer än häften rätt på kunskapsfrågorna och var säkra på att fysisk aktivitet är hälsosamt. Korrelationsberäkningarna var inte statistiskt signifikanta. Slutsats: Deltagarna hade kunskaper och höga utfallsförväntningar avseende fysisk aktivitet men låg fysisk aktivitetsnivå. Ytterligare forskning krävs för att undersöka eventuell korrelation. / Background: Gestational diabetes mellitus (GDM) is the most common metabolic disease in pregnant women. GDM increases drastically related to sedentary behaviour. Treatment includes dietary advice, advice on physical activity and if necessary, insulin therapy. Objective: The purpose was to examine how physically active women with GDM are, their knowledge and outcome expectations on physical activity during GDM and whether there is any correlation between knowledge, outcome expectations and level of physical activity. Method: Observation study of non-experimental design was performed with a web-based questionnaire created in Google Forms. Study participants from Specialistmödravården at Akademiska sjukhuset Uppsala and a closed Facebook group. Results: The majority devoted less than 30 minutes to physical exercise a regular week, did not meet the recommendations for everyday exercise and were sedentary throughout the day. Most of the participants answered more than half of the questions correctly and were confident that physical activity is healthy. No significant correlations were found. Conclusion: The study participants had knowledge and high outcome expectations regarding physical activity, but their physical activity level was low. Further research on correlations is required.

Introdução: O comprimento telomérico é estudado em vários processos da relação saúdedoença, tais quais estresse oxidativo, processo inflamatório e estresse crônico e parece ser modulado por fatores genéticos e ambientais, além de estar associado a doenças como aterosclerose, doença de Alzheimer, insuficiência cardíaca e disqueratose congênita. Nosso estudo buscou entender a relação entre os telômeros de recém-nascidos e a gestação sob condições adversas. Objetivo: avaliar o impacto da exposição a diferentes ambientes intrauterinos sobre o comprimento de telômeros dos recém-nascidos. Métodos: o comprimento telomérico foi avaliado através do método de qPCR (Razão T/S) de células da mucosa oral de uma amostra conveniência de 239 pares de mãe e recémnascido, divididos nos seguintes grupos de mães: diabéticas (DM) (n=39), hipertensas (HAS) (n=16), tabagistas (n=52), controle (n=99) e mães que tiveram filhos pequenos para a idade gestacional (PIG) (n=33). Resultados: Em todos os grupos observamos uma correlação fraca entre o comprimento telomérico da mãe e da criança (r= 0,229) (p<0,001). Não houve diferença significativa no comprimento telomérico entre os grupos DM, HAS, PIG, Tabaco e Controle. Entretanto, dentro do grupo Tabaco houve diferença significativa numa relação dose-resposta inversa, de maior consumo de cigarro e comprimento telomérico menor, tanto para a mãe (p=0,020) quanto para o recém-nascido (p=0,033). Conclusão: os achados deste estudo sugerem que o uso do tabaco na gestação pode exercer influência negativa sobre o comprimento dos telômeros tanto da mãe quanto do seu filho. / Background: Telomere lenght has been studied in several health-disease processes, such as oxidative stress, inflammatory process and chronic stress. It seems to be influenced by genetic and environmental issues, and it is associated with diseases such as atherosclerosis, Alzheimer's disease, heart failure and congenital dyskeratosis. Our study searched to understand the relationship between newborns telomeres and adverse intrauterine conditions. Objective: to evaluate the impact of exposure to different intrauterine environments on the telomere length of newborns. Methods: the telomere length was evaluated by qPCR (T/S ratio) on oral mucosa cells of a convenience sample of 239 pairs of mother and newborn, divided according to the following groups of mothers: diabetic (DM) (n = 39), hypertensive (HAS) (n = 16), tobacco (n = 52), controls (n = 99) and mothers who had small children for gestational age (SGA) (n = 33). Results: In all groups we observed a weak correlation between the telomere of the mother and the son (r= 0.229) (p <0.001). There was no significant difference in telomere size between DM, HAS, SGAG, Tobacco and Control groups. However, in the Tobacco group there was a significant difference in an inverse dose-response relationship: higher cigarette consumption and lower telomere length, both for the mother (p = 0.020) and for the newborn (p = 0.033). Conclusion: the findings of this study suggest that tobacco use during gestation may induce a negative influence on the telomere length of both the mother and her child.

ABSTRACT Gestational weight gain (GWG) is a normal and expected component of a healthy pregnancy; however, gaining too much or too little weight poses significant risks to maternal and fetal health including fetal under - or overgrowth, downstream obesity, and cardio-metabolic disease. Children born to mothers who exceed the Institute of Medicine GWG recommendations are significantly more likely to have higher birth weights, classify as large for gestational age (LGA) and develop overweight/obesity in infancy, childhood, and adulthood. Furthermore, rapid increases in infant growth weight trajectory, defined by weight-for-length (WFL), as early as six months of life are also associated with obesity in childhood. Energy expenditure and energy intake are known contributors to weight management, have been identified as predictors of excess GWG (eGWG) and are mediators of metabolic dysregulation affecting maternal-fetal health, perhaps independently of eGWG. The ACOG and the Society of Obstetricians and Gynecologists of Canada/Canadian Society for Exercise Physiology (SOGC/CSEP) currently endorse exercising for 30-minute sessions four times a week during the prenatal period. However, the guidelines are currently being reviewed to update recommendations based on more recent literature. A two-arm, parallel group randomized controlled trial (RCT; the Maternal Obesity Management (MOM) trial), was established to mediate GWG and prevent downstream child obesity. Adult pregnant women mean age 32.6 ± 4.4 years, with pre-gravid BMI > 18.5 kg/m2, between 12 and 20 weeks gestation were randomized into one of two groups: lifestyle intervention (n = 41) who received a structured physical activity (PA) and nutrition program in addition to the MOM trial healthy pregnancy handbook, or a standard clinical care control group (n = 35). The intervention took place throughout pregnancy (~ 6 mos.), with postpartum follow-up assessments on mother and child. GWG and PA were objectively measured at three-time points in pregnancy (prior to intervention, second trimester 26-28 weeks, third trimester 36-40 weeks). Offspring WFL was directly measured at 3 and 6 mos postpartum. We hypothesized that women who participated in the lifestyle intervention including regular PA with a structured prenatal exercise class in combination with a nutrition intervention would be more likely to have offspring follow a healthy growth trajectory as measured by offspring WFL z-score between 3 to 6 months of age We assessed and compared PA which was directly measured at three time points throughout the study (baseline, second trimester between 26-28 weeks, and third trimester between 36-40 weeks gestation) using accelerometers and supported by PA recall for activities not captured by the accelerometer. Compliance to exercise classes was recorded by the instructor. Total GWG was calculated in kilograms, by subtracting weight measured at the first prenatal visit from the last visit as part of the study or last prenatal visit, before birth, to capture the full extent of GWG throughout pregnancy. GWG was also evaluated categorically based on being under, meeting, or exceeding the IOM GWG guidelines. Offspring neonatal birth weight was measured in grams as an absolute value and was obtained from antenatal obstetrical records. Infant birth weight was also evaluated categorically as small for gestational age (SGA), average for gestational age (AGA) or large for gestational age (LGA). Infant body length was collected using a tape measure; two measurements were taken to the nearest 0.5 cm and the mean value was taken as true. The tape measure method has been validated against a measuring board which found no statistically significant difference between the two methods. There were no significant differences in GWG between intervention group and control group (mean difference = 0.3 kg, 95% CI, -2.5 – 3.1, p = 0.838). There were also no significant differences in moderate to vigorous physical activity (MVPA) during the second trimester (Z = -0.3408, p = 0.733) and the third trimester of pregnancy (Z = -0.0121, p = 0.9904). However, an increase in light PA from the first study visit in early pregnancy to the second study visit at the end of the second trimester was significantly associated with decreased final GWG in the intervention group, but not in the control group (p = 0.014). Furthermore, a Wilcoxon Rank-Sum Test indicated that the change in weight-for-length z-score from 3 months to 6 months was significantly lower in children born to mothers in the intervention group compared to the children in the control group Ws = 481.00, z = 2.67, p = 0.007. Although GWG did not change, an improved early growth trajectory for offspring born to women engaged in the intervention was observed supporting that early exposures to PA, even light PA, may play a role in downstream child growth and development. Future research should further evaluate optimal tools and counselling techniques that help women make the best possible nutrition and PA choices throughout pregnancy in the best interest of maternal and child health.

Introdução: a adiponectina está envolvida na homeostase energética, através da regulação do metabolismo glicídico e lipídico. Adicionalmente, apresenta propriedades anti-inflamatórias e antiateroscleróticas. Polimorfismos no gene da adiponectina (ADIPOQ) podem modular as concentrações de adiponectina. A influência desses polimorfismos no desenvolvimento da hipertensão gestacional (HAG) e da pré-eclâmpsia (PE) é desconhecida. Objetivo: o objetivo deste trabalho foi analisar a influência dos polimorfismos no gene ADIPOQ sobre o desenvolvimento da hipertensão gestacional e da pré-eclâmpsia. Pacientes e métodos: Foram estudadas 401 gestantes sendo 161 grávidas saudáveis (GS), 113 com HAG e 127 com PE. Os polimorfismos do gene ADIPOQ -11391G>A (rs17300539), -11377C>G (rs266729), 45T>G (rs2241766) e 276G>T (rs1501299) foram genotipados através de discriminação alélica por reação de PCR em tempo real. Os haplótipos foram inferidos através do programa PHASE 2.1. Resultados: não foram observadas diferenças estatisticamente significativas nas freqüências genotípicas e alélicas dos polimorfismos estudados. Na analise dos haplótipos, observamos pequenas diferenças nas freqüências haplotípicas entre os grupos estudados, no entanto, nenhuma destas diferenças foi estatisticamente significativa (P>0,05). Conclusão: Não encontramos nenhuma associação entre as variantes genotípicas e alélicas dos polimorfismos no gene ADIPOQ com o desenvolvimento de hipertensão arterial gestacional e pré-eclâmpsia. / Introduction: adiponectin is involved in energy homeostasis by regulating glucose and lipid metabolism. Additionally, it presents anti-inflammatory and anti-atherosclerotic functions. Polymorphisms in adiponectin gene (ADIPOQ) can modulate the concentrations of adiponectin. The influence of these polymorphisms on the development of gestational hypertension (GH) and preeclampsia (PE) is unknown. Aim: The aim of this work was to examine the influence of polymorphisms in the gene ADIPOQ on the development of gestational hypertension and preeclampsia. Patients and Methods: we studied 401 pregnant women: 161 healthy pregnant (HP), 113 pregnants with gestational hypertension (GH) and 127 pregnants with preeclampsia (PE). Polymorphisms ADIPOQ -11391G>A (rs17300539), - 11377C>G (rs266729), 45T>G (rs2241766) and 276G>T (rs1501299) were genotyped by allelic discrimination by PCR in real time. Haplotypes were inferred using the PHASE 2.1 program. Results: there were no statistically significant differences in allele and genotype frequencies of the polymorphisms studied. In the analysis of haplotypes, we observed small differences in haplotype frequencies between groups, however, none of these differences was statistically significant (P> 0.05). Conclusion: we found no association between the genotypic and allelic variants of the ADIPOQ gene polymorphisms with the development of gestational hypertension and preeclampsia.

A prática de atividade física durante a gestação está relacionada a controle de ganho de peso materno, redução de desenvolvimento de distúrbios metabólicos e síndromes hipertensivas. Está indicada também como intervenção importante no tratamento de Diabetes mellitus, distúrbio metabólico mais comum durante a gravidez. Para a orientação de um adequado programa de exercícios físicos durante o período gestacional, torna-se necessário o conhecimento do conjunto de atividades e do gasto energético de cada paciente durante este período da vida da mulher. O Objetivo do trabalho foi avaliar a taxa de atividade física durante o ciclo gravídico-puerperal e a influência do Índice de Massa Corporal (IMC) em mulheres com ou sem Diabetes Mellitus Gestacional (DMG). As pacientes foram estratificadas de acordo com presença ou ausência de diagnóstico de DMG e IMC pré- concepcional, resultando em quatro grupos com 66 participantes cada (grupo de gestação de risco habitual - GRH com IMC adequado, >=18,5 e <= 24,9 kg/m2, e IMC alterado, >= 25 kg/m e grupo com DMG com IMC adequado, >=18,5 e <= 24,9 kg/m2, e IMC alterado, >= 25 kg/m2). As pacientes selecionadas foram submetidas a análise socioeconômica e foi aplicada a versão validada para o português do Questionário de Atividade Física para Mulheres Grávidas-QAFMG (do inglês Pregnancy Physical Activity Questionnaire-PPAQ) para avaliação do nível de atividade física no período pré-gestacional, no terceiro trimestre da gestação e três meses após o parto, que foram expressos em Equivalente Metabólico da Tarefa (do inglês Metabolic Equivalent of Task-MET). Os resultados mostraram que classificaram-se como de etnia branca 54,55% das entrevistadas no grupo DMG - IMC 0; 63,10% no grupo DMG - IMC 1; 60,24% no grupo GRH- IMC 0; 53,25% no grupo GRH - IMC1; como donas de casa 49,35%; 54,76%; 62,65 e 53,25% nos respectivos grupos. Já em estado civil as porcentagens encontradas foram de 80,52%; 89,29%; 75,90% e 80,52%.A variável escolaridade mostrou que 63,03% das gestantes do grupo DMG de IMC 0, 65,48% das gestantes do grupo DMG - IMC 1, 75,90% das gestantes do 8 grupo GRH e IMC 0 e 72,73% das gestantes do grupo GRH e IMC 1 apresentava entre 8 e 11 anos de estudo. A classe econômica mais predominante em todos os grupos foi a C2 em que a renda familiar é de 1.446,24 reais. (DMG - IMC 0 = 40,26%; DMG - IMC 1 = 31,33%; GRH - IMC 0 = 43,90%; GRH - IMC 1 = 38,96%). Ao comparar as médias dos valores de MET´s encontrados na amostra, notou-se que os valores encontrados na avaliação três meses após o parto (representado pelo tempo 2) foram superiores a 1 (1,10 MET para grupo DMG de IMC adequado e 1,06 MET para IMC alterado e no grupo GRH 1,02 MET de IMC adequado e 1,07 MET de IMC alterado). Já nas análises pré-gestacional (tempo 0) e de terceiro trismestre (tempo 1), os valores foram inferiores a 1 MET. Concluiu-se que o nível de atividade física não foi influenciado pelo diagnóstico de DMG e nem pelo IMC pré- gestacional. No entanto, alterou-se de acordo com a evolução temporal, com aumento da atividade física no período pós-parto. / The practice of physical activity during pregnancy is related to the control of weight gain in the mother\'s part, and the reduced development of metabolic disorders and hypertensive syndromes. It is also indicated as an important intervention in the treatment of Diabetes mellitus, the most common metabolic disorder during pregnancy. In order to achieve an adequate program of physical exercises to be done during the gestational period, it becomes necessary the knowledge of a set of activities and the energy expenditure of each patient during this period of a woman\'s life. The goal of this study was to evaluate the rate of physical activity during the pregnancy- postpartum cycle and the influence of the Body Mass Index (BMI) in women with or without Gestational Diabetes Mellitus (GDM). Patients were stratified according to the presence or absence of the GDM diagnosis and their preconception BMI, resulting in four groups with 66 participants in each (group of gestational habitual risk - GHR with normal BMI >=18.5 and <= 24.9 kg/m², and with altered BMI, >= 25 kg/m² and group with GDM, with normal BMI, >=18.5 and <= 24.9 kg/m², and with altered BMI, >= 25 kg/m²). The selected patients were submitted to a socioeconomic analysis and to did the Portuguese-validated version of the Pregnancy Physical Activity Questionnaire (PPAQ) to assess the level of physical activity in the pregestational period, in the third trimester of gestation and three months postpartum, which were expressed in Metabolic Equivalent of Task (MET). The results showed that 54.55% of the interviewees in the GDM - BMI 0 group; 63.10% GDM - BMI 1 group; 60.24% in the GHR-BMI 0 group; 53.25% no GHR - BMI 1 group; as housewives 49.35%; 54.76%; 62.65 and 53.25% in the respective groups. Already in civil status as percentages found were of 80.52%; 89.29%; 75.90% and 80.52%. The educational variable showed that 63.03% of the pregnant women in the GDM - BMI 0 group, 65.48% of the pregnant women in the GDM - BMI 1 group, 75.90% of the pregnant women in the GRH - BMI 0 group and 72.73% of the pregnant women in the GHR - BMI 1 group had between 8 and 11 years of study. The most predominant economic class in all groups for a C2 in which the family income is 1.446,24 reais. (GDM - BMI 0 = 40.26%, DMG - BMI 1 = 31.33%, GHR - BMI 0 = 43.90%, GHR - 10 BMI 1 = 38.96%). When comparing as mean values of METs found in the sample, it was observed that the values found in the evaluation three months after childbirth (represented by time 2) were higher than 1 (1.10 MET for adequate BMI of GDM group 1.06 MET for altered BMI and no GHR 1.02 MET for adequate BMI and 1.07 MET for altered BMI). In the pre-gestational analyses (time 0) and the third trimester (time 1), the values lower than 1 MET.It was concluded that the level of physical activity was not influenced by the diagnosis of GDM neither by the pre-gestational BMI. However, it changed according to a temporal development, with increased physical activity in the postpartum period.

INTRODUÇÃO: O Diabetes Gestacional (DG) é qualquer grau de intolerância a carboidratos com início ou diagnóstico na gravidez, com prevalência de 1% a 14% de todas as gestações. Para que complicações provenientes da doença sejam minimizadas, faz-se necessário o adequado controle glicêmico da paciente portadora dessa doença. Modelos experimentais sugerem que reside na musculatura estriada esquelética o principal sítio de resistência à insulina ocorrida durante a gestação. A prática de exercícios resistidos (ER) durante a gestação, embora ainda pouco difundida, é considerada segura, tanto para o feto como para a gestante. A literatura científica, porém, é extremamente escassa em relação à utilização dessa forma de atividade física como coadjuvante no tratamento do DG. OBJETIVOS: O presente estudo teve como objetivo avaliar pacientes com diagnóstico de DG, incluídas em programa de ER realizados com corda elástica, comparando a freqüência de mulheres que usaram insulina no grupo que realizou o programa ao grupo que não se exercitou, e verificar o impacto do programa sobre a adequação do controle glicêmico capilar das gestantes. MÉTODOS: Foi realizado um ensaio clínico randomizado com 62 portadoras de DG que acompanharam o programa de pré-natal da Clínica Obstétrica do Hospital das Clínicas da FMUSP no período entre outubro de 2006 e novembro de 2008. Elas foram alocadas em dois grupos de estudo após o diagnóstico de DG: o grupo de exercícios (GE; n = 31), que praticou ER e o grupo controle (GC; n = 31). Os grupos eram semelhantes em todas as características aferidas no momento da inclusão no estudo. RESULTADOS: Verificou-se redução estatisticamente significativa (p = 0,009) no número de pacientes que necessitou de insulina no GE (n = 07) em comparação ao observado no GC (n= 17). Houve diferença significativa do controle glicêmico entre os grupos. Enquanto o GC atingiu a meta para monitoração glicêmica capilar durante, em média, 43% do período de acompanhamento, o GE o fez por 62% do período de estudo (p = 0,014). Foi verificada também maior freqüência de médias glicêmicas ideais no GE (67,7%) em comparação ao GC (25,8%) (p = 0,001). Não houve diferença significativa (p =0,836) no período (semanas ± DP) entre a inclusão no estudo e o início da terapia com insulina entre o GC (2,00 ± 1,62) e o GE (1,86 ± 1,21), bem como na quantidade de insulina (UI/kg ± DP) utilizada pelas gestantes na comparação entre os grupos (GC: 0,49 ± 0,12; GE: 0,45 ± 0,11; p = 0,398). CONCLUSÕES: A prática de ER por portadoras de DG foi eficiente em diminuir a utilização de insulina, além de melhorar o controle glicêmico dessa população. / INTRODUCTION: Gestational Diabetes (GD) is any degree of intolerance to carbohydrates that begins or is diagnosed in pregnancy, with a prevalence of 1% to 14% of all gestations. So that complications arising from the disease may be minimized, adequate blood sugar control of patients with this disease is necessary. Experimental models suggest that the main area of resistance to insulin occurring during gestation resides in the skeletal muscle. The practice of resistance exercises (RE) during pregnancy, although not widely disseminated, is considered safe for the fetus as well as for the pregnant woman. Scientific literature is extremely scarce with regard to the utilization of this form of physical activity in conjunction with treatment for GD. OBJECTIVES: The object of this study was to evaluate patients with a diagnosis of GD who were included in a program of RE carried out with rubber tubes, comparing the frequency of women who used insulin in the group who participated in the program with the group that did not do the exercises, and to verify the impact of the program on the adequacy of capillary glycemic control of the pregnant women. METHODS: A randomized clinical trial was performed with 62 GD patients who were following the prenatal program at the Obstetric Clinic of the Hospital of Clinics of FMUSP (Faculty of Medicine from University of Sao Paulo) from October, 2006 to November, 2008. They were divided into two study groups after the diagnosis of GD: the exercise group (EG), who practiced RE, and the control group (CG). The groups were similar in all characteristics assessed at the time of enrollment in the study. RESULTS: A statistically significant reduction (p = 0,009) was verified in the number of patients who needed insulin in the EG (n = 07) in comparison with what was observed in the CG (n = 17). There was a significant difference in glycemic control between the groups. While the CG reached the goal for capillary glycemic monitoring during, on the average, 43% of the follow-up period, the EG reached it for 62% of the study period (p = 0,014). A higher frequency of ideal glicemic mean levels was also verified in the EG (67.7%) in comparison with the CG (25.8%) (p = 0,001). There was no significant difference (p =0,836) in the period (weeks ± SD) between study enrollment and the start of insulin therapy between the CG (2,00 ± 1,62) and the EG (1,86 ± 1,21), nor was there in the amount of insulin (UI/kg ± SD) used by the pregnant women in the comparison between the groups. (CG: 0,49 ± 0,12; EG: 0,45 ± 0,11; p = 0,398). CONCLUSIONS: The practice of RE by pregnant women with GD was efficient to reduce the use of insulin, as well as to improve the glycemic control of this population.

Cannabis sativa (maconha) é a droga ilícita mais conhecida e utilizada em todo o mundo. Recentemente, o uso recreativo da droga por jovens aumentou muito, especialmente entre as gestantes. Estudos indicam que seu uso na gestação causa efeitos fetotóxicos adversos, no entanto, poucos estudos avaliam esses efeitos durante este período crítico sobre o desenvolvimento do sistema imunológico. Neste estudo, avaliamos o impacto da exposição gestacional à fumaça de maconha resultante da queima de cigarros sobre o desenvolvimento do baço e do timo de proles de camundongos BalbC. Utilizamos um modelo que se aproxima das reais condições de uso humano (inalação) sob os aspectos de dose e média exposição. Camundongos fêmeas gestantes (n = 20) foram expostas ao fumo da maconha ou ao ar filtrado (grupo controle) do 5,5° ao 17,5° dia gestacional (DG) por 5 minutos diariamente. Para isso, foi utilizado um aparelho para inalação da fumaça desenvolvido em nosso laboratório, onde os cigarros de maconha (200mg de Cannabis sativa) foram queimados e a fumaça conduzida para a câmara de exposição dos animais (exposição somente inalatória). Os baços e timos das proles foram coletados no 18,5° dia gestacional (DG), 20° e 60° dias pós-natais (DPN) para a realização das análises histológica e histoquímica. Avaliações morfológicas e quantitativas dos órgãos foram realizadas utilizando-se métodos estereológicos e por meio da semi quantificação de fibras do sistema colágeno. Os resultados indicam um aumento no peso corporal dos animais com 60 DPN cujas mães foram expostas ao fumo de Cannabis sativa durante a gravidez. Os machos com 60 DPN expostos apresentaram redução no volume total do timo, assim como em seus principais compartimentos, medula e córtex, onde também foi observado um aumento de fibras do sistema colágeno, quando comparados aos animais controles. Além disso, o baço desses animais também apresentou redução significativa em seu volume, porém não houve redução significativa no volume total da polpa vermelha. Machos e fêmeas com 60 DPN do grupo exposto apresentaram redução no volume total da polpa branca e aumento de fibras do sistema colágeno na região das trabéculas do parênquima do baço. Em suma, a exposição gestacional à maconha causa efeitos fetotóxicos que podem ser observados por alteração no baço e no timo da prole (sendo os efeitos distintos para machos e fêmeas) e estas alterações se tornam mais marcantes com o avanço da idade do animal, com potencial comprometimento da resposta imune nesses indivíduos. / Cannabis sativa (marijuana) is one of the most well-known and used illicit drugs worldwide. Recently, recreational use of that drug among young people has increased greatly, especially among pregnant women. Studies indicate that its use in pregnancy causes adverse fetotoxic effects, however there are few studies evaluating the effects of marijuana use during this critical period on the developing immune system. In this study, we evaluated the impact of gestational exposure to smoke marijuana resulting from burning cigarettes on the spleen and thymus development of BalbC mice offspring. We have used a model that approximates the real conditions of human use (inhalation) under the dose and medium exposure aspects. Pregnant mice (n=20), were exposed to marijuana smoke or filtered air (control group) from 5.5° to 17.5° gestational day (GD) for 5 minutes daily. Thus, we used a smoke inhalation apparatus developed in our laboratory where the marijuana cigarettes (200mg of Cannabis sativa) were burned and conducted to exposure chamber reaching the animals (nose-only exposure). Spleen and thymus of the offspring were collected on the 18.5° gestational day (GD), 20° and 60° postnatal day (PND) for the histological and histochemical analysis. Morphological and quantitative evaluations of these organs were performed using stereological methods and semi quantification of collagen fibers. The results indicate an increase in the mice body weight at PND 60 whose mothers were exposed to Cannabis sativa smoke during pregnancy. The PND 60 males from exposed group showed lower thymus total volume, as well as its main compartments such as medulla and cortex, where collagen fibers was also observed, when compared with males from the control group. Also, the spleen of these animals also presented a significant reduction, however no significant reduction was showed in the total volume of the red pulp. In addition, males and females from the exposed group at PND 60 presented reduction in total volume in the white pulp and increased of collagen fibers in the trabeculae region of the spleen. In summary, gestational exposure to marijuana causes fetotoxic effects that can be observed due to alteration in the spleen and thymus of the offspring (the effects being different for males and females), and these changes being marked with the advancement of the age, with potential impairment of the immune response in these individuals.

Evidence synthesis is considered a corner stone of modern health care and clinical practice. Systematic reviews of randomised trials, when undertaken with meta-analysis provide summary estimates on the effectiveness of interventions. However, the findings of meta-analysis are often limited by the selective reporting of primary studies, and the variations in population, intervention and outcomes. Furthermore, difficulties in disentangling the study and individual level associations in meta-analysis make them susceptible to ecological fallacy, and may lead to incorrect conclusions. Meta-analysis using Individual Participant Data (IPD) has the potential to overcome many of the above limitations, by using raw trial data. Access to IPD minimises problems from incomplete or incorrect reporting of trial outcomes, by verifying reported results, and by standardising the definition of outcomes where possible. Importantly, this allows detecting any variation in the effects of interventions according to characteristics of the participants. Amalgamated individual datasets assembled to address the effectiveness question, can be further used to explore secondary objectives such as the relationship between surrogate and clinical outcomes. This maximises the use of available clinical data, and addresses the problem of research waste. In this thesis, I evaluated the effects of diet and physical activity based interventions in pregnancy on maternal and offspring outcomes using both study-level and IPD meta-analyses, and assessed the differential effects of interventions on outcomes according to mother's BMI pre or in early pregnancy. I reviewed the variation in outcomes reported in this field, and developed composite outcomes for IPD meta-analysis. I also evaluated the relationship between weight gain in pregnancy and clinical outcomes in pregnancy using the IPD meta-analysis methodology. Aims The aim of this thesis was to evaluate the effects of diet and physical activity based interventions in pregnancy on clinical outcomes using standard and advance methods of evidence synthesis; assess the variation in outcomes and their clinical importance in a trial with those interventions and examine the relationship between gestational weight gain and important clinical outcomes. Methods Delphi methodology, systematic reviews of literature, and meta-analyses using study-level and individual participant data of randomised controlled trials (RCTs). Results Composite outcomes Developed composite outcomes comprise of four maternal (gestational diabetes, hypertensive disorders in pregnancy, preterm birth, caesarean section) and four offspring outcomes (stillbirth, small for gestational age, large for gestational age, and admission to neonatal intensive care unit). The components to assess maternal composite outcome were available in two-thirds (66.7%, 24/36) and for offspring composite in half (50%, 18/36) of the studies in the IPD meta-analysis. The effect of interventions was not statistically significant neither on the maternal nor on the offspring composite - Odds Ratio (OR) 0.90 (95% CI 0.79, 1.03) and OR 0.94 (95% CI 0.83, 1.08), respectively. The direction of the pooled effect was consistent between the composite and its components for the maternal composite and variable for the offspring outcomes. 6 Effects of diet and physical activity based interventions The IPD meta-analysis of 36 RCTs (>12 500 women) showed a significant effect of diet and physical activity based interventions in pregnancy in reducing gestational weight gain (Mean Difference -0.70 kg, 95% CI -0.92, -0.48) and chance of caesarean section delivery (OR 0.91, 95% CI 0.83, 0.99) in comparison to routine antenatal care. There was no effect of the interventions on any of the offspring complications. Incorporation of outcome data unavailable on study-level returned more modest magnitude of the summary estimates in comparison to effects obtained using study-level data of trials that shared IPD. The addition of study-level data from non-IPD trials changed the magnitude and the statistical significance of the summary effects on GDM - from OR 0.89 with only IPD (95% CI 0.72, 1.10; 27 studies, 9 427 women) to OR 0.76 (95% CI 0.65, 0.89; 59 studies, 16 885 women). It has also changed the funnel plot structure in the meta-analysis for gestational weight gain (Egger's test p = 0.04 with only IPD to p= 0.61). The IPD meta-analysis shows that the effects of diet and physical activity based interventions on the maternal and the offspring outcomes did not differ by women's BMI status. While the study-level meta-regression indicated that the interventions might reduce gestational weight gain stronger for the obese women - coefficient -0.22 (95% CI -0.33, -0.11) for each 10% change in the proportion of women in the obese class. Outcomes in trials with diet and physical activity based interventions 66 primary publications from trials with diet and physical activity based interventions in pregnancy reported 142 outcomes. Half of those outcomes appeared in the publications once (72/142). 'Critically important' outcomes are reported less often in comparison to 'non-critical' ones (15.5%, 22/142 vs 68.3%, 97/142). The overall quality of outcome reporting varied between trials with the least frequently provided information on the methods to improve the quality of outcome measures (33.3%, 22/66 publications). 7 Gestational weight gain and pregnancy outcomes IPD from 4 429 pregnant women randomised to the control arms of RCTs with diet and physical activity based interventions were available for the analysis. Women who most often exceeded the IOM recommendation belonged to the overweight (51.5%, 641/ 1 245 women) and the obese groups (44.5%, 695/ 1 562 women) while women with normal BMI most often gained below the recommended amounts (40%, 649/1 622 women). Each kilogram of gestational weight gain within the IOM ranges was not link with a change in the chances of preterm birth, caesarean section, or birth of LGA and SGA infant. Not achieving of the recommended weight was associated with the decreasing chance of giving birth to LGA infant with each kilogram below the lower limit among the obese women (OR 0.80, 95% CI 0.65, 0.99). Each kilogram of weight gain above the upper limit was associated with an increase in the chance of caesarean section (adjusted 1.04, 95% CI 1.01, 1.08) and delivering LGA infant (adjusted 1.08, 95% CI 1.05, 1.12) regardless on women's BMI status. Conclusions Diet and physical activity based interventions in pregnancy moderately reduced gestational weight gain and decrease the odds of caesarean delivery. Overall, IPD meta-analysis improved the robustness of the evidence synthesis of RCTs with diet and physical activity based interventions. However, more attention is needed for the data-related issues in IPD meta-analysis as the purported benefits of the method are not always practically realised. The use of the composite outcomes was hampered by the variable availability of important clinical outcomes. The introduction of minimal core outcome set would facilitate the comparison of the wide range of the evaluated interventions and improve implementation of the composite outcomes. Gestational weight gain was found to be associated with the odds of delivering LGA infant and caesarean section. Future research should aim to collect and report a minimal set of outcomes, and ensure better reporting of study conduct and its findings.

Introdução: O exercício físico como parte do tratamento do diabetes mellitus gestacional (DMG) pode ajudar na manutenção das concentrações da glicemia de jejum. Objetivos: Conduzir uma revisão sistemática, com metanálise de ensaios clínicos randomizados, para avaliar o efeito do exercício supervisionado e estruturado ou o efeito do aconselhamento de atividade física, em mulheres com DMG, e comparar ao pré-natal usual para o controle da glicemia. Métodos: Os estudos elegíveis foram identificados a partir das bases de dados MEDLINE, EMBASE, Web of Science, Scopus e SportDiscus até 4 de Junho de 2015. Os dados foram extraídos de ensaios clínicos randomizados que compararam o pré-natal usual ao pré-natal usual somado ao exercício supervisionado e estruturado (pelo menos uma vez na semana) ou ao aconselhamento de atividade física, pelas quais os valores de glicemia de jejum pré e pós-intervenção estavam disponíveis. A metanálise de efeitos randômicos foi conduzida para a diferença entre as médias pós-intervenção da glicemia de jejum. Resultados: Foram encontradas 664 publicações, nas quais 82 foram avaliadas pela elegibilidade e oito foram incluídas na análise final. O efeito total do exercício nas concentrações absolutas da glicemia de jejum não foi significativamente diferente (P = 0,11) comparado ao pré-natal usual. Entretanto, o aconselhamento de atividade física comparado ao pré-natal usual demonstrou uma redução significativa nas concentrações da glicemia de jejum (diferença da média ponderada -3,88 mg/dL, 95% CI-7,33 a -0,42; I2, 48%; P para heterogeneidade < 0,15). Conclusão: O exercício supervisionado ou o aconselhamento de atividade física em mulheres com DMG não foi significativamente diferente comparado ao pré-natal usual nas concentrações de glicemia de jejum. Visto que o pré-natal usual inclui algum tipo de recomendação de atividade física, estes resultados não são surpreendentes. O aconselhamento de atividade física com o pré-natal usual inclui modificações da dieta que podem motivar as mulheres com DMG a serem mais ativas e aderentes ao aconselhamento nutricional, enquanto que o exercício estruturado pode ser mais difícil de atingir. / Background: Exercise as part of the treatment for gestational diabetes mellitus (GDM) may help maintain fasting glucose concentrations. Objective: A systematic review with meta-analysis was performed to evaluate the effect of weekly-supervised exercise or physical activity (PA) counseling in GDM women compared to standard care (SC) on glycemic control. Methods: Eligible trials were identified from MEDLINE, EMBASE, Web of Science, Scopus and SportDiscus up to 4 June 2015. Data were retrieved from randomized controlled trials comparing SC with SC plus weekly-supervised (at least once a week) prenatal exercise or PA counseling for which fasting blood glucose (FBG) values pre and post intervention were available. Random-effects meta-analysis was conducted for mean difference in FBG post exercise intervention. Results: Our search yielded 664 publications of which 82 were assessed for eligibility. Eight were analyzed and all were included in the meta-analysis. The overall effect of exercise on absolute FBG concentrations was not different (P=0.11) compared to SC. However, PA counseling versus SC showed a significant reduction in the absolute FBG concentrations (weighted mean difference -3.88 mg/dL, 95% CI-7.33 to -0.42; I2, 48%; P for heterogeneity<0.15). Conclusions: Supervised exercise or PA counseling in GDM women was not significantly different compared to SC on FBG concentrations. Since SC includes some type of PA recommendation, these results are not surprising. PA counseling with SC including dietary modifications may help motivate GDM women to be more active and adherent to nutrition advice, while structured exercise may be more difficult to achieve.

Diabetes mellitus gestacional (DMG) é uma condição cada vez mais frequente na população, uma vez que os novos critérios adotados consideram menores valores de glicemia para diagnóstico e cada vez mais mulheres iniciam a gestação com excesso de peso, fator de risco para DMG. Cerca de 50% das mulheres que tiveram DMG irão desenvolver diabetes mellitus tipo 2 (DM2) entre 5 e 10 anos após o parto. Uma das intervenções utilizada para prevenção do DM2 é o aleitamento materno (AM). Entretanto, são escassas as informações sobre AM em mulheres que tiveram DMG. Sendo assim, o objetivo deste estudo é avaliar o aleitamento materno em mulheres que tiveram diabetes gestacional e os fatores associados à não iniciação. Trata-se de um estudo de coorte, com dados da linha de base e seguimento de um estudo maior, LINDA-Brasil, realizado nas cidades de Porto Alegre (RS), Pelotas (RS) e Fortaleza (CE), de março de 2013 a dezembro de 2016. Gestantes com DMG foram arroladas em serviços de pré-natal de alto risco. Foram coletados dados demográficos, sócio-econômicos, de estilo de vida e contato. O seguimento foi realizado por ligações telefônicas e foram coletadas informações do parto, dados do recém-nascido e amamentação. Essas ligações foram realizadas um mês após o recrutamento e dois meses após o parto. A descrição dos dados foi apresentada através de frequências relativas e absolutas ou média e desvio padrão. Análise de Regressão de Poisson foi utilizada para estimar o risco relativo de não ter iniciado aleitamento materno. Todas as participantes assinaram termo de consentimento livre e esclarecido. Foram incluídas 2523 mulheres. A média de idade foi 31,3 (±6,3) anos, sendo a maioria branca (49,5%), com ensino médio completo (38,3%) e renda entre 1 e 2 salários mínimos (39,9%). Não ter amamentado o último bebê (RR = 3,82; IC95%: 1,86 – 7,84), fumo durante a gestação (RR = 2,09; IC95%: 1,17 – 3,75), bebê com problemas ao nascer (RR = 3,11; IC95%: 1,90 – 5,12), prematuridade (RR = 1,60; IC95%: 1,09 – 2,57), consumo de bebidas adoçadas (RR = 1,10; IC95%: 1,02 – 1,19) e não ter intenção de amamentar o bebê (RR = 4,75; IC95%: 1,92 – 11,72) foram relacionadas à não iniciação ao aleitamento materno. Experiências anteriores, problemas com o bebê e comportamento materno, como fumo na gestação, consumo de bebidas adoçadas e não ter intenção de amamentar são fatores associados à não iniciação ao aleitamento materno em mulheres que tiveram diabetes mellitus gestacional. / Gestational diabetes mellitus (GDM) is an increasingly frequent condition in the population, since the new criteria adopted consider lower values of glycemia for diagnosis, and more and more women are starting gestation with excess weight, a risk factor for GDM. About 50% of women who have GDM will develop type 2 diabetes mellitus (DM2) between 5 and 10 years after giving birth. One of the interventions used to prevent DM2 is breastfeeding. However, there is little information on AM in women who have GDM. Therefore, the objective of this study is to evaluate breastfeeding in women who had gestational diabetes and factors associated with non-initiation. This is a cohort study, with baseline data and follow-up of a larger study, LINDA-Brasil, conducted in the cities of Porto Alegre (RS), Pelotas (RS) and Fortaleza (CE), March 2013 To December 2016. Pregnant women with DMG were enrolled in high-risk prenatal services. Demographic, socio-economic, lifestyle and contact data were collected. Follow-up was performed by telephone calls and information was collected on birth, newborn data and breastfeeding. These calls were made one month after enrollment and 2 months after delivery. The data description was presented through relative and absolute frequencies or mean and standard deviation. Poisson regression analysis was used to estimate the relative risk of not having started breastfeeding. All participants signed a free and informed consent form. A total of 2523 women were included. The mean age was 31.3 (± 6.3) years, the majority of whom were white (49.5%), with a high school education (38.3%) and income between 1 and 2 minimum wages (39.9% ). Not having breastfed the last baby (RR = 3.82, 95% CI: 1.86 - 7.84), smoking during pregnancy (RR = 2.09, 95% CI: 1.17 - 3.75), baby with (RR = 3.11, 95% CI: 1.90 - 5.12), prematurity (RR = 1.60, 95% CI: 1.09 - 2.57), consumption of sweetened beverages (RR = 1 , 10; 95% CI: 1.02 - 1.19) and did not intend to breastfeed the baby (RR = 4.75, 95% CI: 1.92 - 11.72) were related to non - initiation to breastfeeding. Previous experiences, problems with the baby and maternal behavior, such as smoking during pregnancy, consumption of sweetened beverages and no intention to breastfeed are factors associated with not initiating breastfeeding in women who have had gestational diabetes mellitus.