Avaliação da sensibilidade médica para o risco de gravidez não planeada

Prémio em Contraceção 2012 da Sociedade Portuguesa de Contraceção

A decrease in dkk1, a Wnt inhibitor, contributes to placental and fetal lipid accumulation in an obesity-prone rat model

Placenta, as the sole transport mechanism between mother and fetus, links the maternal physical state and the immediate and life-long outcomes of the offspring. The present study examined the mechanisms behind the effect of maternal obesity on placental lipid accumulation and metabolism. Pregnant Obese Prone (OP) and Obese Resistant (OR) rat strains were fed a control diet throughout gestation. Placentas were collected on gestational d21 for analysis and frozen placental sections were analyzed for fat accumulation as well as β-Catenin and Dkk1 localization. Additionally, DKK1 was overexpressed in JEG3 trophoblast cells, followed by treatment with NEFA and Oil Red O stain quantification and mRNA analysis to determine the relationship between placental DKK1 and lipid accumulation. Maternal plasma and placental NEFA and TG were elevated in OP dams, and offspring of OP dams were smaller than OR. Placental Dkk1 mRNA content was 4-fold lower in OP placentas, and there was a significant increase in β-Catenin accumulation as well as mRNA content of fat transport and TG synthesis enzymes, including Ppar-delta, Fatp1, Fat/Cd36, Lipin1, and Lipin3. There was significant lipid accumulation within the decidual zones in OP but not OR placentas, and the thickness of the decidual and junctional zones was significantly smaller in OP than OR placentas. Overexpression of DKK1 in JEG3 cells decreased lipid accumulation and the mRNA content of PPAR-Delta, FATP1, FAT/CD36, LIPIN1, and LIPIN3. Our results indicate that Dkk1 may be regulating placental lipid metabolism through Wnt-mediated mechanisms. Additionally, recent studies have suggested that maternal obesity may also program early development of non-alcoholic fatty liver disease (NAFLD), rates of which have correlated with the increase in the obesity epidemic. In the current study, livers of OP offspring had significantly increased TG content (P<0.05) and lipid accumulation when compared to offspring of OR dams. Additionally, hepatic Dkk1 mRNA content was significantly decreased in OP livers when compared to OR (P<0.05), and treating H4IIECR rat hepatocyte cells with NEFA showed that Dkk1 mRNA was also decreased in NEFA-treated cells (P<0.05) that also had lipid accumulation. Chromatin Immunoprecipitation (ChIP) analysis of the Dkk1 promoter in fetal livers showed a pattern of histone modifications associated with decreased gene transcription in OP offspring, which agrees with our gene expression data. These results demonstrate that the hepatic Dkk1 gene is epigenetically regulated via histone modification in neonatal offspring in the current model of gestational obesity, and future studies will be needed to determine whether these changes contribute to excessive hepatic lipid accumulation in offspring of obese dams.

Trombose venosa profunda em idade pediátrica – estudo retrospetivo de 10 anos

Introdução e Objetivos: A trombose venosa profunda (TVP) e o tromboembolismo pulmonar são os componentes do tromboembolismo venoso (TEV) que, embora infrequente, é uma entidade emergente na pediatria. Apresentamos uma casuística cujo objetivo é a avaliação dos aspetos mais relevantes da TVP em idade pediátrica e da sua abordagem terapêutica. Metodologia: Revisão retrospetiva descritiva dos processos dos doentes internados na última década com o diagnóstico de TVP no Serviço de Pediatria da ULSAM. Resultados: Identificaram-se seis doentes, cinco deles do sexo feminino. A mediana de idades foi 17 anos. O edema do membro afetado esteve sempre presente e o segmento venoso mais atingido foi o ileofemoral (2/6). Houve concomitância de pelo menos dois fatores de risco adquiridos em três doentes, sendo o mais frequente o contracetivo oral combinado. Foi excluída trombofilia hereditária em cinco doentes mas ainda aguardamos o resultado do estudo de um doente. O tempo médio de tratamento foi de 9,8 meses. Discussão e Conclusão: A TVP na criança tem sido reconhecida como uma patologia rara, mas importante causa de morbilidade. A maior incidência de TVP foi documentada na adolescência com compromisso do membro inferior, tal como referido na literatura. Verificamos uma conjugação de fatores de risco que, provavelmente, se potenciaram entre si levando à ocorrência do TEV e colocamos a possibilidade do Pediatra se estar a deparar com uma nova realidade anteriormente excluída do atendimento pediátrico. O aumento na incidência desta patologia levanta a questão do acréscimo de risco trombótico nos adolescentes do sexo feminino devido à utilização de contracetivos orais combinados. Salientamos a importância de um consenso nacional no diagnóstico, tratamento e prevenção desta entidade em Pediatria.

Lifestyle factors, adiposity and cardiometabolic risk factors in South Asian women living in Scotland

South Asians migrating to the Western world have a 3 to 5-fold higher risk of developing type 2 diabetes and double the risk of cardiovascular disease (CVD) than the background population of White European descent, without exhibiting a proportional higher prevalence of conventional cardiometabolic risk factors. Notably, women of South Asian descent are more likely to be diagnosed with type 2 diabetes as they grow older compared with South Asian men and, in addition, they have lost the cardio-protective effects of being females. Despite South Asian women in Western countries being a high risk group for developing future type 2 diabetes and CVD, they have been largely overlooked. The aims of this thesis were to compare lifestyle factors, body composition and cardiometabolic risk factors in healthy South Asian and European women who reside in Scotland, to examine whether ethnicity modifies the associations between modifiable environmental factors and cardiometabolic risks and to assess whether vascular reactivity is altered by ethnicity or other conventional and novel CVD risks. I conducted a cross-sectional study and recruited 92 women of South Asian and 87 women of White European descent without diagnosed diabetes or CVD. Women on hormone replacement therapy or hormonal contraceptives were excluded too. Age and body mass index (BMI) did not differ between the two ethnic groups. Physical activity was assessed and with self-reported questionnaires and objectively with the use of accelerometers. Cardiorespiratory fitness was quantified with the predicted maximal oxygen uptake (VO2 max) during a submaximal test (Chester step test). Body composition was assessed with skinfolds measured at seven body sites, five body circumferences, measurement of abdominal subcutaneous (SAT) and visceral adipose tissue (VAT) with the use of magnetic resonance imaging (MRI) and liver fat with the use MR spectroscopy. Dietary density was assessed with food frequency questionnaires. Vascular response was assessed by measuring the response to acetylcholine and sodium nitroprusside with the use of Laser Doppler Imaging with Iontophoresis (LDI-ION) and the response to shear stress with the use of Peripheral Arterial Tonometry (EndoPAT). The South Asian women exhibited a metabolic profile consistent with the insulin resistant phenotype, characterised by greater levels of fasting insulin, lower levels of high density lipoprotein (HDL) and higher levels of triglycerides (TG) compared with their European counterparts. In addition, the South Asians had greater levels of glycated haemoglobin (HbA1c) for any given level of fasting glucose. The South Asian women engaged less time weekly with moderate to vigorous physical activity (MVPA) and had lower levels of cardiorespiratory fitness for any given level of physical activity than the women of White descent. In addition, they accumulated more fat centrally for any given BMI. Notably, the South Asians had equivalent SAT with the European women but greater VAT and hepatic fat for any given BMI. Dietary density did not differ among the groups. Increasing central adiposity had the largest effect on insulin resistance in both ethic groups compared with physical inactivity or decreased cardiorespiratory fitness. Interestingly, ethnicity modified the association between central adiposity and insulin resistance index with a similar increase in central adiposity having a substantially larger effect on insulin resistance index in the South Asian women than in the Europeans. I subsequently examined whether ethnic specific thresholds are required for lifestyle modifications and demonstrated that South Asian women need to engage with MVPA for around 195 min.week-1 in order to equate their cardiometabolic risk with that of the Europeans exercising 150 min.week-1. In addition, lower thresholds of abdominal adiposity and BMI should apply for the South Asians compared with the conventional thresholds. Although the South Asians displayed an adverse metabolic profile, vascular reactivity measured with both methods did not differ among the two groups. An additional finding was that menopausal women with hot flushing of both ethnic groups showed a paradoxical vascular profile with enhanced skin perfusion (measured with LDI-ION) but decreased reactive hyperaemia index (measured with EndoPAT) compared with asymptomatic menopausal women. The latter association was independent of conventional CVD risk factors. To conclude, South Asian women without overt disease who live in Scotland display an adverse metabolic profile with steeper associations between lifestyle risk factors and adverse cardiometabolic outcomes compared with their White counterparts. Further work in exploring ethnic specific thresholds in lifestyle interventions or in disease diagnosis is warranted.

Musicoembriologia – qual o impacto no neurodesenvolvimento infantil

Introdução: A musicoembriologia engloba a audição de música durante a gravidez, com o objetivo de melhorar a relação materno-fetal e o neurodesenvolvimento infantil. Contudo, a relação entre estes ainda não está bem estabelecida, pelo que permanece um tema controverso. Objetivo: Rever a evidência disponível sobre o impacto da audição de música durante a gravidez no neurodesenvolvimento infantil. Material e Métodos: Pesquisa de meta-análises (MA), revisões sistemáticas (RS), ensaios clínicos aleatorizados e contro- lados (ECAC), e normas de orientação clinica (NOC), em inglês e português, publicados entre 01/2004 e 04/2014, nas bases de dados Pubmed/Medline, sítios de medicina baseada na evidência e Índex de Revistas Médicas Portuguesas, utilizando os termos MeSH: music; pregnancy; child; neurodevelopment. Para a avaliação dos níveis de evidência (NE) e atribuição de forças de recomendação (FR) foi utilizada a escala SORT (Strength of Recommendation Taxonomy) da American Family Phisician. Resultados: Foram encontrados onze artigos, dos quais quatro foram selecionados: três ECAC e uma RS. Um ECAC (NE 1) mostrou melhoria significativa do comportamento neonatal nas crianças cujas mães ouviram música durante a gravidez. Outro ECAC (NE 2) demonstrou uma melhoria da relação ma- terno-fetal com a musicoembriologia. Outro ECAC (NE3) e a RS (FR B) demonstraram que o ambiente intrauterino é importante no neurodesenvolvimento neonatal, sobretudo no desenvolvi- mento do córtex cerebral motor e neurosensorial. Conclusões: A evidência disponível demonstrou que a au- dição de música durante o período embrionário apresenta benefício no neurodesenvolvimento infantil. (FR B) No entanto os estudos obtidos são em número reduzido e apresentam grande heterogeneidade em termos metodológicos. São necessários mais estudos, com populações controladas e metodologia semelhantes, para a recomendação global desta medida.

Dor abdominal em adolescente

Doente do sexo feminino de 16 anos de idade, recorreu ao serviço de urgência por dor abdominal com duas semanas de evolução localizada à fossa ilíaca esquerda (FIE) associada a obstipação. Negava atividade sexual, referindo último cataménio três semanas antes. Apresentava palpação abdominal dolo- rosa na FIE, sem defesa ou sinais de irritação peritoneal. Estudo analítico inicial e exame sumário de urina normais. Ecografia abdomino-pélvica revelou quisto complexo na região anexial esquerda e ascite de médio volume. Foi doseada a hormona gonadotrofina coriónica sérica que foi positiva (2608 mUI/mL). A ecografia transvaginal revelou quisto simples com área adjacente de aspeto reticular, não evidenciando qualquer imagem de saco gestacional intrauterino. Foi submetida a laparotomia exploradora, constatando-se hemoperitoneu e gravidez ectópica tubar esquerda e efetuada salpingectomia esquerda. Os autores pretendem alertar para uma causa rara de dor abdominal na adolescência, que deverá ser considerada de for- ma a evitar um desfecho potencialmente fatal.

Women empowerment and the current use of long acting and permanent contraceptive: Evidence from 2010 Malawi Demographic and Health Survey

Background Both contraceptive use and fertility rates are high fertility in Malawi. Status of women remains low and is believed to affect reproductive health decisions including use of Long Acting and Permanent Contraceptives Method (LAPCM). Objective This study seeks to examine the relationship between women empowerment and LAPCM. A measure of women’s empowerment is derived from the women’s responses to questions on the number of household decisions in which the respondent participates, employment status, type of earnings, women’s control over cash earnings and level of education. Methods The study is based on a sub sample of 5,948 married women from the 2010 Malawi Demographic and Health Survey. Data was analysed using descriptive statistics, Chi-square and multinomial logistic regression models (α=5%). Results The prevalence of current use of LAPCM was 20.0% and increases with increasing empowerment level (p<0.001). Mean age and empowerment score of women who are currently using LAPCM were 38.53±6.2 years and 6.80±2.9 respectively. Urban women (22.2%) were more currently using LAPCM than rural women (19.4%) p<0.001. Women who belong to Seven Day Adventists/Baptist were 1.51(C.I=1.058-2.153; p=0.023) more likely and Muslims were 0.58(C.I=0.410-0.809; p=0.001) less likely to currently use LAPCM than Catholic women. Being in the richest wealth quintile (OR=1.91; C.I=1.362-2.665; p<0.001) promotes current use of LAPCM than poorest. The likelihood of currently using LAPCM was higher among women who have access to FP programmes on media and increases consistently with increasing women empowerment level even when other potential confounding variables were used as control. Conclusion In Malawi, LAPCM is still underutilized and more than half of the women are not adequately empowered. Women empowerment, wealth quintile and access to FP programmes are key factors influencing the use of LAPCM. Programmes that address these determinants are urgently needed in Malawi.

Validación de curvas antropométricas de crecimiento intrauterino: Hospital Vicente Corral, Cuenca, Ecuador, 2013

Se realizó un estudio transversal en el Hospital Vicente Corral de Cuenca (Ecuador) en febrero-agosto de 2013, para la valoración de las curvas intrauterino del Centro Latinoamericano de Atención Perinatal (CLAP), Olsen, Alarcón-Pittaluga, Lubchenco-Bataglia y Babson-Benda con el objetivo de identificar el patrón antropométrico de crecimiento fetal más adecuado para la clasificación de los recién nacidos hasta que el Ecuador cuente con patrones propios. La muestra se conformó con neonatos, cuyas madres eran menores de 21 años. Se incluyó a niños nacidos vivos, con edad gestacional entre 22 y 42 semanas cumplidas y que contaron con todas las medidas antropométricas. Se excluyó a niños con malformaciones congénitas mayores. Se valoraron la sensibilidad, especificidad e índice kappa de Cohen de las curvas antropométricas estudiadas según las variables peso, talla, perímetro cefálico y sexo del recién nacido. Las curvas del CLAP (36.6-43.5%) y de Olsen (37.0-40.9%) identificaron porcentajes similares de PEG15. Las curvas de Babson-Benda detectaron muy pocos PEG (1.3-2.8%). Para la variable peso: las curvas de Olsen presentaron alta sensibilidad (81.8-97.6%), muy altas especificidad (91.8-97.5%) e índice kappa (0.807-0.873). Las curvas de Alarcón-Pittaluga tuvieron muy buena sensibilidad (98.2-99.5%); buena especificidad (74.9-77.9%) e índice kappa (0.707-0.717). Las curvas de Lubchenco-Bataglia presentaron baja sensibilidad (40.0-42.8%), muy buena especificidad (99.3-100.0%) y moderado índice kappa (0.449-458). Las curvas de Babson-Benda presentaron muy baja sensibilidad (3.5-6.4%), muy buena especificidad (100.0%) y pobre índice kappa (0.044-0.072). Se concluye que se deben utilizar las curvas antropométricas de Olsen hasta que el Ecuador cuente con curvas propias. No se recomienda utilizar las curvas de Babson-Benda ni de Lubchenco-Bataglia.

Factors Associated With Changes in Magnesium Levels in Asymptomatic Neonates: A Longitudinal Analysis

Background: Neonates and infants with hypomagnesemia present with seizures and psychomotor delay. Objectives: The present study evaluated the changes in magnesium (Mg) levels and factors associated with these in the first three days of life. Materials and Methods: We monitored 50 clinically asymptomatic neonates; they were not given any magnesium supplements even if they had hypomagnesemia at baseline. The variables analysed were: serum Mg; gestational age; birth weight; length; and the ponderal index. We used random effects (RE) models for longitudinal analysis of these data. Results: The mean standard deviation (SD) gestational age was 36.3 (3.6) weeks and the mean (SD) weight was 2604.2 (754.4) grams. About 31% of the neonates had hypomagnesemia (< 1.6 mg/dL) on day one; however, all had normal magnesium levels by day three of life (P < 0.001). At birth, after adjusting for intrauterine growth retardation status (IUGR), serum Mg levels were lower by 0.0097 mg/dL (95% CI: -0.019 to -0.0003) per 100 grams increase in weight of the neonate. After adjusting for IUGR status, the mean increase in the serum Mg levels was 0.14 mg/dL (95% confidence intervals [CI]: 0.10 to 0.18) per day. The per-day increase in magnesium levels was significantly higher in low birth weight babies (0.10, 95% CI: 0.01 to 0.18) compared with normal birth weight babies. Conclusions: Asymptomatic neonates may have a high prevalence of hypomagnesemia; however, the levels become normal without any magnesium supplementation. Even though regular monitoring of magnesium levels is useful, no supplements are required - particularly in clinically asymptomatic neonates.

Estudo sobre a migração transuterina e a razão sexual de conceptos em bovinos da raça Nelore (Bos taurus indicus)

Dissertação (mestrado)—Universidade de Brasília, Faculdade de Agronomia e Medicina Veterinária, 2016.

Early-life markers of atherosclerosis using aortic and carotid intima-media thickness: an assessment of methods to account for child size

Background.—Distinguishing pathological from physiological relationships between vessel size and aortic intima-media thickness (aIMT) is an important challenge, especially in growing children. We examined the relationship between childhood vessel diameter and aIMT and assessed common analytic approaches used to address this relationship.Methods.—We analyzed aIMT in two population-derived cohorts; 6-week-old infants and 19-year-olds. We simulated datasets in which we assumed a simple physiological relationship between vessel diameter and aIMT, and then superimposed possible pathological effects on aIMT; (a) intrauterine growth retardation, (b) macrosomia and (c) both intrauterine growth retardation and macrosomia. Using simulated datasets and cohorts, we evaluated analytic strategies including those in which the relationship between vessel diameter and aIMT was (a) ignored, (b) adjusted for by dividing aIMT by weight, or (c) adjusted for using varying regression techniques.Results.—aIMT was found to increase in proportion to vessel diameter in both cohorts (138 μm/mm at 6 weeks and 52 μm/mm at 19 years of age). Simply dividing aIMT by weight produced negative associations with weight across all datasets. By contrast, adjusting for vessel diameter as a covariate enabled accurate distinction of the direction of the association between aIMT and weight in all simulated datasets. These results were replicated in the cohort studies for both aIMT and carotid intima-media thickness.Conclusion.—There is a physiological relationship between vessel diameter and aIMT. Simply dividing aIMT by weight may lead to incorrect assumptions regarding the relationship between weight and aIMT. However, the physiological relationship is appropriately estimated by including vessel diameter as a covariate in regression.

Epigenetic regulation of neurodevelopmental genes in response to in utero exposure to phthalate plastic chemicals: how can we delineate causal effects?

Accumulating evidence, from animal models and human observational studies, implicates the in utero (and early postnatal) environment in the 'programming' of risk for a variety of adverse outcomes and health trajectories. The modern environment is replete with man-made compounds such as plastic product chemicals (PPC), including phenols and phthalates. Evidence from several human cohorts implicates exposure to these chemicals in adverse offspring neurodevelopment, though a direct causal relationship has not been firmly established. In this review we consider a potential causal pathway that encompasses epigenetic human variation, and how we might test this mechanistic hypothesis in human studies. In the first part of this report we outline how PPCs induce epigenetic change, focusing on the brain derived neurotrophic factor (BDNF) gene, a key regulator of neurodevelopment. Further, we discuss the role of the epigenetics of BDNF and other genes in neurodevelopment and the emerging human evidence of an association between phthalate exposure and adverse offspring neurodevelopment. We discuss aspects of epidemiological and molecular study design and analysis that could be employed to strengthen the level of human evidence to infer causality. We undertake this using an exemplar recent research example: maternal prenatal smoking, linked to methylation change at the aryl hydrocarbon receptor repressor (AHRR) gene at birth, now shown to mediate some of the effects of maternal smoking on birth weight. Characterizing the relationship between the modern environment and the human molecular pathways underpinning its impact on early development is paramount to understanding the public health significance of modern day chemical exposures.

Infant adiposity at birth and early postnatal weight gain predict increased aortic intima-media thickness at 6 weeks of age: a population-derived cohort study

Infant body composition and postnatal weight gain have been implicated in the development of adult obesity and cardiovascular disease, but there are limited prospective data regarding the association between infant adiposity, postnatal growth and early cardiovascular parameters. Increased aortic intima-media thickness (aortic IMT) is an intermediate phenotype of early atherosclerosis. The aim of the present study was to investigate the relationship between weight and adiposity at birth, postnatal growth and aortic IMT. The Barwon Infant Study (n=1074 mother-infant pairs) is a population-derived birth cohort. Infant weight and other anthropometry were measured at birth and 6 weeks of age. Aortic IMT was measured by trans-abdominal ultrasound at 6 weeks of age (n=835). After adjustment for aortic size and other factors, markers of adiposity including increased birth weight (β=19.9 μm/kg, 95%CI 11.1, 28.6; P<0.001) and birth skinfold thickness (β=6.9 μm/mm, 95%CI 3.3, 10.5; P<0.001) were associated with aortic IMT at 6 weeks. The association between birth skinfold thickness and aortic IMT was independent of birth weight. In addition, greater postnatal weight gain was associated with increased aortic IMT, independent of birth weight and age at time of scan (β=11.3 μm/kg increase, 95%CI 2.2, 20.3; P=0.01). Increased infant weight and adiposity at birth, as well as increased early weight gain, were positively associated with aortic IMT. Excessive accumulation of adiposity during gestation and early infancy may have adverse effects on cardiovascular risk.

Milk: milk of monotremes and marsupials

Lactation has evolved from an ancient reproductive strategy which appears to have been present long before the evolution of extantmammals. The ability to lactate is a feature only found among mammals and involves a facet of maternal care where mothers secretea nutrient-rich milk which is delivered to the young by the mammary gland. Evolutionary studies indicate that lactation was establishedprior to divergence of extant mammalian lineages. It also seems that lactation evolved long before gestation in utero. Secretionsof ancestral mammary glands may have had antimicrobial properties that protected either eggs or hatchlings and organiccomponents that supplemented offspring nutrition. Over the course of evolution, lactation became a highly efficient, effectiveand adaptable means of providing maternal care for neonates. The evolution of a placenta in eutherian mammals resulted inmore extensive intrauterine development of an embryo and the ability to lactate after birth became a critical part of the reproductivestrategy of mammalian species. Following development of highly nutritious milks, evolution produced diversity in milk compositionand function, quantity of milk output, length of lactation, length of intervals between nursing and contributions of lactation tooffspring nutrition.