Sociodemographic and reproductive risk factors associated with metabolic syndrome in a population of Brazilian women from the city of Ribeirão Preto: a cross-sectional study

Abstract Objective: To identify sociodemographic and reproductive risk factors associated with MetS in women in their fourth decade of life. Methods: Cohort study conducted on women born from June 1978 to May 1979 in Ribeirão Preto, Brazil. Sociodemographic, clinical, and obstetric data were collected by interview and clinical evaluation. Univariable and multivariable binomial logistic regression models were constructed to identify the risk factors of metabolic syndrome and the adjusted relative risk (RR) was calculated. Results: The cohort included 916 women, and 286 (31.2%) of them have metabolic syndrome. MetS was associated with lack of paid work (RR 1.49; 95% CI 1.14-1.95), marital status of without a partner (RR 1.33; 95% CI 1.03-1.72), low educational level (less than 8 years of schooling [RR 1.72; 95% CI 1.23-2.41], 8 to 12 years of schooling [RR 1.37; 95% CI 1.06-1.76], when compared with more than 12 years of schooling), and teenage pregnancy (RR 2.00; 95% CI 1.45-2.77). There was no association between MetS, and the other covariates studied. Conclusion: Metabolic syndrome in a population of women in the fourth decade of life was associated with lack of employment, lack of a partner, low educational level, and teenage pregnancy.

Serum cytokines in second trimester pregnancy and their relationship with spontaneous preterm births in the Ribeirão Preto and São Luiz cohorts.

OBJECTIVE: To evaluate the association between second trimester plasma cytokine levels in asymptomatic pregnant women and preterm births (PTB) in an attempt to identify a possible predictor of preterm birth. METHODS: The study design was a nested case-control study including women with singleton a gestational age between 20-25(+ 6) weeks from two Brazilian cities. The patients were interviewed, Venous blood samples were collected. The participants were again evaluated at birth. A total of 197 women with PTB comprised the case group. The control group was selected among term births (426 patients). Forty-one cytokines were compared between groups. RESULTS: When only spontaneous PTB were analyzed, GRO, sCD40L and MCP-1 levels were lower in the case group (p < 0.05). Logarithmic transformation was performed for cytokines with discrepant results, which showed increased levels of IL-2 in the group of spontaneous PTB (p < 0.05). In both analyses, the incidence of maternal smoking and of a history of preterm delivery differed significantly between the case and control groups. In multivariate analysis, only serum GRO levels differed between the case and control groups. CONCLUSION: Lower second trimester serum levels of GRO in asymptomatic women are associated with a larger number of PTB. This finding may reflect a deficient maternal inflammatory response.

Preeclampsia and Gestational Hypertension: Biochemical and Antioxidant Features in Vitro Might Help Understand Different Outcomes / Pré-eclâmpsia e hipertensão gestacional: Fatores bioquímicos e antioxidantes in vitro podem auxiliar no entendimento de resultados clínicos distintos

Abstract Objective Gestational hypertension (GH) is characterized by increased blood pressure after the 20th gestational week; the presence of proteinuria and/or signs of end-organ damage indicate preeclampsia (PE). Heme oxygenase-1 (HO-1) is an antioxidant enzyme with an important role in maintaining endothelial function, and induction of HO-1 by certain molecules shows potential in attenuating the condition's effects over endothelial tissue. HO-1 production can also be stimulated by potassium iodide (KI). Therefore, we evaluated the effects of KI over HO-1 expression in human umbilical vein endothelial cells (HUVECs) incubated with plasma from women diagnosed with GH or PE. Methods Human umbilical vein endothelial cells were incubated with a pool of plasma of healthy pregnant women (n = 12), pregnant women diagnosed with GH (n = 10) or preeclamptic women (n = 11)with or without the addition of KI for 24 hours to evaluate its effect on this enzyme expression. Analysis of variance was performed followed by Dunnet's test for multiple comparisons between groups only or between groups with addition of KI (p ≤ 0.05). Results KI solution (1,000 µM) reduced HO-1 in the gestational hypertension group (p = 0.0018) and cytotoxicity in the preeclamptic group (p = 0.0143); treatment with KI reduced plasma cytotoxicity but did not affect the preeclamptic group's HO-1 expression. Conclusion Our findings suggest that KI alleviates oxidative stress leading to decreased HO-1 expression; plasma from preeclamptic women did not induce the enzyme's expression in HUVECs, and we hypothesize that this is possibly due to inhibitory post-transcriptional mechanisms in response to overexpression of this enzyme during early pregnancy.

Resumo Objetivo A hipertensão gestacional (GH) é caracterizada pelo aumento da pressão sanguínea após a 20ª semana de gestação; a presença de proteinuria e/ou sinais de danos a órgãos como rins, fígado e cérebro indicam pré-eclâmpsia (PE). A heme oxigenase-1 (HO-1) é uma enzima antioxidante com um papel importante na manutenção da função endotelial, e a sua indução por certas moléculas se mostra potencialmente benéfica frente à característica deletéria destas condições sobre o endotélio. Já foi demonstrado anteriormente que a produção de HO-1 pode ser induzida por iodeto de potássio (KI). Portanto, nós avaliamos os efeitos do KI sobre a citotoxicidade e expressão de HO-1 por células de veia de cordão umbilical humano (HUVECs) após incubação com o plasma de mulheres diagnosticadas com GH ou PE. Métodos Células de veia de cordão umbilical humano foram incubadas com pool de plasma de gestantes saudáveis (n = 12), gestantes com GH (n = 10) ou gestantes com PE (n = 11) com ou sem a adição de KI por 24 horas para avaliar a citotoxicidade através da dosagem de lactato desidrogenase e produção de HO-1 por ELISA. Foi realizada ANOVA seguida de teste de Dunnet para múltiplas comparações entre os grupos estudados, considerando significativos valores de p ≤ 0,05. Resultados A solução de KI (1.000 µM) reduziu a produção de HO-1 no grupo GH (p = 0.0018) e a citotoxicidade no grupo PE (p = 0.0143); o tratamento com KI não afetou a produção de HO-1 por HUVECs incubadas com o plasma do grupo PE. Conclusão Nossos achados sugerem que o KI atenua os efeitos do plasma de gestantes com GH ocasionando a diminuição da produção de HO-1; plasma do grupo PE não induziu a produção de HO-1 em HUVECs em comparação ao grupo saudável, e nossa hipótese é a de que tal achado pode ser devido a mecanismos pós-transcricionais em resposta a uma superestimulação da produção de HO-1 nos estágios iniciais da gravidez.

Previous preeclampsia and its association with the future development of cardiovascular diseases: a systematic review and meta-analysis

Preeclampsia is a multifactorial disease. Among these factors, untreated hypertension during pregnancy can result in high morbidity and mortality rates and may also be related to the future development of cardiovascular diseases.Therefore, this systematic review aimed to determine the association of previous preeclampsia with the future development of cardiovascular diseases. Studies on the association between preeclampsia and future cardiovascular diseases published in the last 10 years (2009-2019) were identified from the PubMed/Medline (207 articles), Embase (nine articles), and Cochrane (three articles) databases using the keywords "preeclampsia" and "future cardiovascular diseases", "preeclampsia" and "future heart attack", and "preeclampsia" and "future cardiac disease". After applying the inclusion and exclusion criteria, 15 articles were analyzed by systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The meta-analysis and the determination of the quality of the articles were conducted using RevMan software, version 5.3. Statistically significant differences were observed between the control and previous preeclampsia groups with respect to systolic blood pressure (mean difference [MD] 4.32; 95% confidence interval [95%CI] 3.65, 4.99; p<0.001), diastolic blood pressure (MD): 2.11; 95%CI: 1.68, 2.55; p<0.0001), and insulin level (MD: 2.80; 95% CI: 0.50, 5.11; p<0.001). Body mass index (MD: 2.57, 95%CI: 2.06, 3.07; p=0.0001), total cholesterol (MD: 10.39; 95%CI: 8.91, 11.87; p=0.0001), HDL (MD: 2.83; 95%CI: 2.20, 3.46; p=0.0001), and LDL (MD: 1.77; 95%CI: 0.42, 3.13; p=0.0001) also differed significantly between groups. Thus, the results of the present study showed that women with a history of preeclampsia were more likely to develop cardiovascular disease.

Melatonin and the cardiovascular system in animals: systematic review and meta-analysis

Melatonin, a hormone released by the pineal gland, demonstrates several effects on the cardiovascular system. Herein, we performed a systematic review and meta-analysis to verify the effects of melatonin in an experimental model of myocardial infarction. We performed a systematic review according to PRISMA recommendations and reviewed MEDLINE, Embase, and Cochrane databases. Only articles in English were considered. A systematic review of the literature published between November 2008 and June 2019 was performed. The meta-analysis was conducted using the RevMan 5.3 program provided by the Cochrane Collaboration. In total, 858 articles were identified, of which 13 were included in this review. The main results of this study revealed that melatonin benefits the cardiovascular system by reducing infarct size, improving cardiac function according to echocardiographic and hemodynamic analyses, affords antioxidant effects, improves the rate of apoptosis, decreases lactate dehydrogenase activity, enhances biometric analyses, and improves protein levels, as analyzed by western blotting and quantitative PCR. In the meta-analysis, we observed a statistically significant decrease in infarct size (mean difference [MD], -20.37 [-23.56, -17.18]), no statistical difference in systolic pressure (MD, -1.75 [-5.47, 1.97]), a statistically significant decrease in lactate dehydrogenase in animals in the melatonin group (MD, -4.61 [-6.83, -2.40]), and a statistically significant improvement in the cardiac ejection fraction (MD, -8.12 [-9.56, -6.69]). On analyzing potential bias, we observed that most studies presented a low risk of bias; two parameters were not included in the analysis, and one parameter had a high risk of bias. Melatonin exerts several effects on the cardiovascular system and could be a useful therapeutic target to combat various cardiovascular diseases.

RPS Brazilian Birth Cohorts Consortium (Ribeirão Preto, Pelotas and São Luís): history, objectives and methods / Consórcio RPS (Ribeirão Preto, Pelotas e São Luís) de coortes de nascimento brasileiras: história, objetivos e métodos / Consorcio RPS (Ribeirão Preto, Pelotas y São Luís) cohortes brasileñas de nacimiento: historia, objetivos y métodos

Abstract: This paper describes the history, objectives and methods used by the nine Brazilian cohorts of the RPS Brazilian Birth Cohorts Consortium (Ribeirão Preto, Pelotas and São Luís) Common thematic axes are identified and the objectives, baseline periods, follow-up stages and representativity of the population studied are presented. The Consortium includes three birth cohorts from Ribeirão Preto, São Paulo State (1978/1979, 1994 and 2010), four from Pelotas, Rio Grande do Sul State (1982, 1993, 2004 and 2015), and two from São Luís, Maranhão State (1997 and 2010). The cohorts cover three regions of Brazil, from three distinct states, with marked socioeconomic, cultural and infrastructure differences. The cohorts were started at birth, except for the most recent one in each municipality, where mothers were recruited during pregnancy. The instruments for data collection have been refined in order to approach different exposures during the early phases of life and their long-term influence on the health-disease process. The investigators of the nine cohorts carried out perinatal studies and later studied human capital, mental health, nutrition and precursor signs of noncommunicable diseases. A total of 17,636 liveborns were recruited in Ribeirão Preto, 19,669 in Pelotas, and 7,659 in São Luís. In the studies starting during pregnancy, 1,400 pregnant women were interviewed in Ribeirão Preto, 3,199 in Pelotas, and 1,447 in São Luís. Different strategies were employed to reduce losses to follow-up. This research network allows the analysis of the incidence of diseases and the establishment of possible causal relations that might explain the health outcomes of these populations in order to contribute to the development of governmental actions and health policies more consistent with reality.

Resumo: O artigo descreve a história, objetivos e métodos utilizados pelas nove coortes do Consórcio RPS de Coortes de Nascimento. São identificados eixos temáticos comuns, com apresentação dos objetivos, anos de linha de base, fases de seguimento e representatividade das populações de estudo. O Consórcio inclui três coortes de nascimento de Ribeirão Preto, Estado de São Paulo (1978/1979, 1994 e 2010), quatro de Pelotas, Estado do Rio Grande do Sul (1982, 1993, 2004 e 2015) e duas de São Luís, Estado do Maranhão (1997 e 2010). As coortes provêm de três regiões do Brasil, de três estados diferentes, com importantes diferenças socioeconômicas, culturais e de infraestrutura. As coortes foram iniciadas ao nascer dos participantes, exceto a mais recente em cada município, onde as mães foram recrutadas durante a gestação. Os instrumentos para a coleta de dados foram refinados para aproximar diferentes exposições na primeira infância e a influência, a longo prazo, no processo saúde-doença. Os investigadores das nove coortes realizaram estudos perinatais e depois examinaram o capital humano, saúde mental, nutrição e sinais percursores de doenças crônicas. Um total de 17.636 nascidos vivos foram recrutados em Ribeirão Preto, 19.669 em Pelotas e 7.659 em São Luís. Nas coortes que foram iniciadas durante a gestação, foram entrevistadas 1.400 gestantes em Ribeirão Preto, 3.199 em Pelotas e 1.447 em São Luís. Foram utilizadas diferentes estratégias para reduzir as perdas de seguimento. A rede de pesquisa do Consórcio permite analisar a incidência de doenças e identificar possíveis relações causais que podem explicar os desfechos de saúde nessas populações e contribuir para o desenvolvimento de medidas públicas e políticas de saúde que estejam mais de acordo com as respectivas realidades.

Resumen: El trabajo describe la historia, objetivos y métodos usados por nueve cohortes brasileñas del RPS Consorcio de Cohortes de Nacimiento. Se identificaron los ejes temáticos comunes y los objetivos, así como los periodos de referencia, la presentación del estadio de seguimiento y representatividad de la población estudiada. El consorcio incluye tres cohortes de nacimiento de Ribeirão Preto, Estado de São Paulo (1978/1979, 1994 y 2010), cuatro de Pelotas, Estado del Rio Grande do Sul (1982, 1993, 2004 y 2015), y dos de São Luís, Estado del Maranhão (1997 y 2010). Las cohortes cubren tres regiones de Brasil, de tres estados distintos, con marcadas diferencias socioeconómicas, culturales y de infraestructura. Las cohortes comenzaron con el nacimiento, excepto para la más reciente en cada municipio, donde las madres fueron reclutadas durante la gestación. Los instrumentos para la recogida de datos han sido depurados, con el fin de realizar una aproximación a diferentes exposiciones durante las fases tempranas de la vida y su influencia a largo plazo en el proceso de salud-enfermedad. Se incluyeron a los investigadores de las nueve cohortes, donde se llevaron a cabo estudios perinatales, así como los recursos humanos analizados posteriormente, al igual que la salud mental, nutrición y signos precursores de enfermedades no comunicables. Un total de 17.636 nacidos vivos fueron reclutados en Ribeirão Preto, 19.669 en Pelotas, y 7.659 en São Luís. En los estudios que comenzaron durante el embarazo, 1.400 mujeres embarazadas fueron entrevistadas en Ribeirão Preto, 3.199 en Pelotas, y 1.447 en São Luís. Se usaron diferentes estrategias para reducir pérdidas, con el fin de realizar el seguimiento. Esta red de investigación permite el análisis de la incidencia de enfermedades y el establecimiento de posibles relaciones causales que podrían explicar los resultados de salud de estas poblaciones, con el fin de contribuir al desarrollo de acciones gubernamentales y políticas de salud más consistentes con la realidad.

Circulating HO-1 levels are not associated with plasma sFLT-1 and GTn HMOX1 polymorphism in preeclampsia.

OBJECTIVES: We aimed to assess the plasma HO-1 level and its interrelationship with the plasma sFLT-1 level in preeclamptic and healthy pregnant women with different variants of microsatellite polymorphism (GTn) located in the promoter region of the HMOX-1 gene. METHODS: HO-1 and sFLT-1 were measured by ELISA. HMOX1 genotyping was performed using fragment analysis. RESULTS: We found similar and higher levels of plasma HO-1 and sFLT-1, respectively, in preeclampsia. Similar genotypes and alleles frequencies were found in both groups and the absence of modulation of HO-1 levels by genotypes were observed. CONCLUSION: The plasma HO-1 levels are not increased in preeclampsia women and neither related to sFLT-1 levels and GTn polymorphism.

Circulating Tissue Inhibitor of Metalloproteinase-4 levels are not a Predictor of Preeclampsia in the period between 20 and 25 Weeks of Gestation / Níveis circulantes de inibidor tecidual da metaloproteinase tipo-4 não são um preditor de preeclampsia no período entre 20 e 25 semanas de gestação

Abstract Objective To evaluate whether the circulating level of tissue inhibitor of metalloproteinase- 4 (TIMP-4) in the period between 20 and 25 weeks of gestation is a predictor of preeclampsia. Methods We have performed a case-control study, nested in a prospective study cohort in Ribeirão Preto, in the state of São Paulo, Brazil. Of the 1,400 pregnant women evaluated between 20 and 25 weeks of gestation, 460 delivered in hospitals outside of our institution. Of the 940 pregnant women who completed the protocol, 30 developed preeclampsia. Healthy pregnant women (controls, n = 90) were randomly selected from the remaining 910 participants. From blood samples collected between 20 and 25 weeks of gestation, we performed a screening of 55 angiogenesis-related proteins in 4 cases and 4 controls. The protein TIMP-4 was the most differentially expressed between cases and controls. Therefore, wemeasured this protein in all cases (n = 30) and controls selected (n = 90). Results There were no differences in the plasma TIMP-4 levels of cases compared with controls (1,144 263 versus 1,160 362 pg/mL, respectively; p > 0.05). Conclusion Plasma TIMP-4 levels were not altered at 20 to 25 weeks of gestation, before the manifestation of clinical symptoms; therefore, they are not good predictors of the development of preeclampsia.

Resumo Objetivo Avaliar se o nível de inibidor tecidual de metaloproteinases tipo-4 (TIMP-4, na sigla em inglês) circulante no período entre 20 e 25 semanas de gestação é um preditor de preeclâmpsia. Métodos Foi realizado um estudo caso-controle aninhado em uma coorte de estudo prospectivo em Ribeirão Preto, São Paulo, Brasil. De 1.400 mulheres grávidas avaliadas entre 20 e 25 semanas de gestação, 460 tiveram parto em hospitais fora da nossa instituição. Das 940 gestantes que completaram o protocolo, 30 desenvolveram preeclâmpsia. Gestantes saudáveis (controles, n = 90) foram selecionadas aleatoriamente das 910 participantes restantes. A partir de amostras de sangue coletadas entre 20 e 25 semanas de gestação, foi realizada uma triagem de 55 proteínas relacionadas à angiogênese em 4 casos e 4 controles. A proteína TIMP-4 foi a mais diferentemente expressa entre os casos e os controles; portanto, medimos esta proteína em todos os casos (n = 30) e controles selecionados (n = 90). Resultados Não houve diferenças nos níveis plasmáticos de TIMP-4 nos casos em comparação com os controles (1.144 263 versus 1.160 362 pg/mL, respectivamente; p > 0,05). Conclusão Os níveis plasmáticos de TIMP-4 não foramalterados no período entre 20 e 25 semanas de gestação antes da manifestação dos sintomas clínicos; portanto, não são um bom preditor do desenvolvimento da preeclâmpsia.

Effect of type 2 diabetes mellitus on the pharmacokinetics of metformin in obese pregnant women.

BACKGROUND AND OBJECTIVE: The use of metformin throughout gestation by women with polycystic ovary syndrome (PCOS) and type 2 diabetes mellitus (T2DM) significantly reduces the number of first-trimester spontaneous abortions and the rate of occurrence of gestational diabetes and hypertensive syndromes. Metformin is taken up into renal tubular cells by organic cation transport 2 (OCT2) and eliminated unchanged into the urine. The objective of this study was to analyse the influence of T2DM on the pharmacokinetics of metformin in obese pregnant women and in a control group of non-diabetic obese pregnant women with PCOS. METHODS: Eight non-diabetic obese pregnant women with PCOS and nine obese pregnant women with T2DM taking oral metformin 850 mg every 12 h were evaluated throughout gestation. Serial blood samples were collected over a 12-h period during the third trimester of pregnancy. Steady-state plasma concentrations of metformin were determined by high-performance liquid chromatography with a UV detector. The pharmacokinetic results of the two groups, reported as median and 25th and 75th percentile, were compared statistically using the Mann-Whitney test, with the level of significance set at p < 0.05. RESULTS: The pharmacokinetic parameters detected for PCOS versus T2DM patients, reported as median, were, respectively: elimination half-life 3.75 versus 4.00 h; time to maximum concentration 2.00 versus 3.00 h; maximum concentration 1.42 versus 1.21 µg/mL; mean concentration 0.53 versus 0.56 µg/mL; area under the plasma concentration-time curve from time zero to 12 h 6.42 versus 6.73 µg·h/mL; apparent total oral clearance 105.39 versus 98.38 L/h; apparent volume of distribution after oral administration 550.51 versus 490.98 L; and fluctuation (maximum-minimum concentration variation) of 179.56 versus 181.73 %. No significant differences in pharmacokinetic parameters were observed between the groups. CONCLUSION: T2DM in the presence of insulin use does not influence the pharmacokinetics of metformin in pregnant patients, demonstrating the absence of a need to increase the dose, and consequently does not influence the OCT2-mediated transport in pregnant women with PCOS.

Oclusão traqueal para fetos com hérnia diafragmática esquerda grave isolada: um estudo experimental controlado não randomizado / Tracheal occlusion for fetuses with severe isolated left-sided diaphragmatic hernia: a nonrandomized controlled experimental study

OBJETIVO: Comparar a sobrevida pós-natal de fetos com hérnia diafragmática congênita esquerda grave isolada, os quais foram submetidos à oclusão traqueal, com a de controles não randomizados contemporâneos. MÉTODOS: Estudo experimental não randomizado e controlado, conduzido de abril de 2007 a setembro de 2011. Fetos portadores de hérnia diafragmática congênita esquerda isolada com herniação hepática e relação pulmão/cabeça <1,0, que foram submetidos à oclusão traqueal (grupo de estudo) ou conduta expectante (controles não randomizados contemporâneos), foram comparados quanto à relação pulmão/cabeça e ao observado/esperado da relação pulmão/cabeça no diagnóstico, à idade gestacional por ocasião do parto e sobrevida neonatal com alta do berçário. A evolução da relação pulmão/cabeça e do observado/esperado da relação pulmão/cabeça depois da oclusão traqueal foi descrita. Testes de Fisher, Mann-Whitney e Wilcoxon foram usados na análise estatística. RESULTADOS: Não houve diferenças significativas entre o grupo de estudo (n=28) e o Controle (n=13) quanto à relação pulmão/cabeça (p=0,7) e ao observado/esperado da relação pulmão/cabeça (p=0,5), no momento do diagnóstico, nem à idade gestacional no parto (p=0,146). A sobrevida com alta do berçário foi maior (p=0,012) no grupo da oclusão traqueal (10/28=35,7 por cento) do que no Grupo Controle (0/13=0,0 por cento). Houve aumento da relação pulmão/cabeça (p<0,001) e do observado/esperado da relação pulmão/cabeça (p<0,001) entre o momento do diagnóstico da hérnia diafragmática congênita [relação pulmão/cabeça: 0,8 (0,4-0,9); observado/esperado da relação pulmão/cabeça: 27,0 (15,3-45,0)] e um dia antes da retirada do balão traqueal [relação pulmão/cabeça: 1,2 (0,5-1,8); observado/esperado da relação pulmão/cabeça: 40,0 (17,5-60,0)]. CONCLUSÕES: Houve melhora significativa na sobrevida pós-natal com alta do berçário de fetos com hérnia diafragmática congênita esquerda isolada grave, que foram submetidos à oclusão traqueal em relação a controles não randomizados contemporâneos.

PURPOSE: To compare postnatal survival to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion, with that of nonrandomized contemporaneous controls. METHODS: Experimental nonrandomized controlled study, performed from April 2007 to September 2011. Fetuses with severe isolated left-sided congenital diaphragmatic hernia with liver herniation into the chest and lung area-to-head circumference ratio <1.0, who underwent tracheal occlusion (study group) or expectant management (non-randomized contemporaneous controls), were compared in terms of lung area-to-head circumference ratio and observed/expected lung area-to-head circumference ratio (observed/expected lung area-to-head circumference ratio) at the time of diagnosis, gestational age at birth, and survival to hospital discharge. Modifications in lung area-to-head circumference ratio and o/e lung area-to-head circumference ratio after tracheal occlusion were also analyzed. Fisher's exact test, Mann-Whitney's or Wilcoxon's tests were used for the comparisons. RESULTS: There were no significant differences between the Study Group (TO=28) and Controls (n=13) in terms of the lung area-to-head circumference ratio (p=0.709) and the observed/expected lung area-to-head circumference ratio (p=0.5) at the time of diagnosis and gestational age at birth (p=0.146). The survival to hospital discharge was higher (p=0.012) in the tracheal occlusion group (10/28=35.7 percent) than in controls (0/13=0.0 percent). There was a significant increase in lung area-to-head circumference ratio (p<0.001) and observed/expected lung area-to-head circumference ratio (p<0.001) between the diagnosis of the congenital diaphragmatic hernia [lung area-to-head circumference ratio: 0.80 (0.40-0.94); observed/expected lung area-to-head circumference ratio: 27.0 (15.3-45.0)], and the day before retrieval of the balloon [lung area-to-head circumference ratio: 1.2 (0.50-1.80); observed/expected lung area-to-head circumference ratio: 40.0 (17.5-60.0)]. CONCLUSIONS: There was a significant improvement in the survival rate to hospital discharge of fetuses with severe isolated left-sided congenital diaphragmatic hernia, who underwent tracheal occlusion in comparison to nonrandomized contemporaneous controls.

Metformin pharmacokinetics in nondiabetic pregnant women with polycystic ovary syndrome.

BACKGROUND: The use of metformin throughout gestation by pregnant women with polycystic ovary syndrome (PCOS) significantly reduces the number of first trimester spontaneous abortions and the rate of occurrence of gestational diabetes. OBJECTIVE: The objective of this study was to investigate the pharmacokinetics and the placental transfer of metformin in pregnant women with PCOS. PATIENTS AND METHODS: Eight pregnant women with PCOS taking 850 mg metformin every 12 h during the third trimester of pregnancy were evaluated. Maternal blood samples were collected at steady state during the dose interval (0-12 h). Maternal and umbilical cord blood samples were also obtained at delivery. Metformin plasma concentrations were analyzed by high-performance liquid chromatography, and pharmacokinetic parameters were determined using a non-compartmental model. Data are reported as median and minimum and maximum values. RESULTS: Metformin pharmacokinetic parameters were: t(½), 3.8 (2.8-5.4) h; t(max), 2.0 (0.5-3.0) h; C(max), 1.4 (0.5-2.1) mg/L; C(mean), 0.5 (0.2-0.9) mg/L; AUC(0-12), 6.4 (1.1-9.2) mg h/L; Cl/f, 105 (60-274) L/h; Vd/f, 551 (385-1173) L; median fluctuation, 89 (79-95)%. Umbilical/maternal metformin plasma concentration ratios were 0.7 (0.4-1.3). CONCLUSION: Metformin oral clearance (Cl/f) had increased in our patients relative to nonpregnant healthy volunteers or diabetic patients. Therefore, lower plasma metformin concentrations were observed for nondiabetic pregnant women with PCOS. Future studies should be conducted to demonstrate the therapeutic efficacy of metformin during pregnancy. Caution is warranted as umbilical/maternal metformin plasma concentrations ratios of around 0.7 require metformin dosage adjustment.

[Fetal cardiac rhabdomyoma: analysis of five cases]. / Rabdomiomas cardíacos fetais: análise de cinco casos.

PURPOSE: to analyze the differential diagnosis, follow-up and therapeutic approach in five cases of primary cardiac tumors diagnosed during the prenatal period. METHODS: during the period from January 1997 to December 2008, 7989 pregnant women were submitted to morphological ultrasound due to the presence of risk factors for fetal malformations. Fetuses with hyperechogenic intracardiac masses larger than 1 mm diagnosed by ultrasound evaluation of the fetal heart, were selected for study. The differential diagnosis between the different tumor types was made on the basis of the ultrasound characteristics of the masses. RESULTS: five fetuses with hiperechogenic intracardiac masses were diagnosed, corresponding to a 0.06% prevalence rate. Gestational age ranged from 28 to 36 weeks (mean: 31), and maternal age ranged from 23 to 45 years (mean: 34.2). The most frequent location of the masses was the left ventricle (100%). Echographically, all masses were single or multiple, hyperechogenic, homogeneous and well delimited, compatible with a diagnosis of rhabomyoma. In cases in which the diameters of the masses were less than 20 mm, an expectant conduct was followed and no complications occurred during the prenatal period. One case with a huge tumor presented arrhythmia and cardiac insufficiency during the 35 gestational weeks, and the interruption of pregnancy was indicated. Tuberous sclerosis was associated in four cases (80%) and the diagnosis was confirmed during the postnatal follow-up. CONCLUSIONS: fetal morphological ultrasonography is the main form of early detection of primary cardiac tumors. The fetal cardiac evaluation is of fundamental importance for the differential morphological characterization of cardiac masses and for the evaluation of cardiac function. Rhabdomyomas are the most common type of fetal tumor. An expectant pre and postnatal conduct is followed, with a low risk of complications and with the possibility of spontaneous regression in most cases. Postnatal clinical follow-up is mandatory due to the high frequency of associated tuberous sclerosis.

Rabdomiomas cardíacos fetais: análise de cinco casos / Fetal cardiac rhabdomyoma: analysis of five cases

OBJETIVO: analisar o diagnóstico, evolução e conduta terapêutica em cinco casos de tumores cardíacos primários diagnosticados no período pré-natal. MÉTODOS: no período de Janeiro 1997 a Dezembro 2008, 7.989 gestantes foram submetidas à avaliação ultrassonográfica morfológica fetal devido à presença de fatores de risco para malformações fetais. Foram selecionados os casos com massas hipercogênicas intracardíaca maiores que 1 mm diagnosticados na avaliação ultrassonográfica do coração fetal. O diagnóstico diferencial dos tumores foi realizado segundo as características ultrassonográficas das massas. RESULTADOS: em cinco fetos foram diagnosticadas massas hiperecogênicas intracardíaca correspondendo a uma taxa de prevalência de 0,06 por cento. A idade gestacional variou entre a 28ª e a 36ª semanas (média=31) e a idade materna variou de 23 a 45 anos (média=34,2). A localização mais frequente das massas foi o ventrículo esquerdo (100 por cento). Ecograficamente, todas as massas eram hipercogênicas, homogêneas, únicas ou múltiplas e bem delimitadas, compatíveis com diagnóstico de um rabdomioma. Nos casos em que os diâmetros das massas foram menores que 20 mm, a conduta foi expectante e não houve complicações no período pré-natal. Um caso com tumor de grande volume apresentou arritmia e insuficiência cardíaca na 35ª semana de gestação, sendo indicada a interrupção da gestação. Em 80 por cento dos casos foi observada associação com esclerose tuberosa no seguimento pós-natal. A regressão dos tumores cardíacos ocorreu em três casos (60 por cento) durante um seguimento médio de três anos. Todos os recém-nascidos eram do sexo masculino e sem antecedentes familiares de esclerose tuberosa. CONCLUSÕES: a avaliação ultrassonográfica morfológica fetal é a principal forma de detecção precoce dos tumores cardíacos primários. A avaliação cardíaca fetal é fundamental para a caracterização morfológica diferencial das massas cardíacas e para avaliação funcional cardíaca...

PURPOSE: to analyze the differential diagnosis, follow-up and therapeutic approach in five cases of primary cardiac tumors diagnosed during the prenatal period. METHODS: during the period from January 1997 to December 2008, 7989 pregnant women were submitted to morphological ultrasound due to the presence of risk factors for fetal malformations. Fetuses with hyperechogenic intracardiac masses larger than 1 mm diagnosed by ultrasound evaluation of the fetal heart, were selected for study. The differential diagnosis between the different tumor types was made on the basis of the ultrasound characteristics of the masses. RESULTS: five fetuses with hiperechogenic intracardiac masses were diagnosed, corresponding to a 0.06 percent prevalence rate. Gestational age ranged from 28 to 36 weeks (mean: 31), and maternal age ranged from 23 to 45 years (mean: 34,2). The most frequent location of the masses was the left ventricle (100 percent). Echographically, all masses were single or multiple, hyperechogenic, homogeneous and well delimited, compatible with a diagnosis of rhabomyoma. In cases in which the diameters of the masses were less than 20 mm, an expectant conduct was followed and no complications occurred during the prenatal period. One case with a huge tumor presented arrhythmia and cardiac insufficiency during the 35 gestational weeks, and the interruption of pregnancy was indicated. Tuberous sclerosis was associated in four cases (80 percent) and the diagnosis was confirmed during the postnatal follow-up. CONCLUSIONS: fetal morphological ultrasonography is the main form of early detection of primary cardiac tumors. The fetal cardiac evaluation is of fundamental importance for the differential morphological characterization of cardiac masses and for the evaluation of cardiac function. Rhabdomyomas are the most common type of fetal tumor. An expectant pre and postnatal conduct is followed, with a low risk of complications and with the possibility of spontaneous...

Infecção urinária na gravidez: [revisão] / Urinary tract infection in pregnancy: [review]

Vários fatores tornam a infecção do trato urinário (ITU) uma relevante complicação do período gestacional, agravando tanto o prognóstico materno quanto o prognóstico perinatal. Durante muitos anos, a gravidez foi vista como fator predisponente a todas as formas de ITU. Hoje, sabe-se que ela, como evento isolado, não é responsável por maior incidência de ITU; as mudanças anatômicas e fisiológicas impostas ao trato urinário pela gravidez predispõem à transformação de mulheres bacteriúricas assintomáticas (BA) em gestantes com ITU sintomáticas. A BA acomete entre 2 e 10 por cento de todas as gestantes, das quais aproximadamente 30 por cento desenvolverão pielonefrite, se não tratadas adequadamente. No entanto, observa-se incompreensível resistência dos pré-natalistas à identificação da BA neste período. Seu diagnóstico é microbiológico e baseia-se em duas uroculturas apresentando mais que 10(5) colônias/mL de urina, identificando-se o mesmo germe. Seu tratamento é facilitado, visto que pode ser baseado no antibiograma, não havendo fundamentação científica de que o pré-estabelecimento de esquemas terapêuticos seja uma medida adequada. Para o tratamento da pielonefrite, não é possível aguardar o resultado da cultura e o conhecimento prévio do perfil de resistência dos antibacterianos disponíveis para uso em gestantes seria a melhor medida. Outra variável importante é utilizar um antibiótico bactericida, endovenoso na fase aguda da infecção e com possibilidades de ser administrado via oral após a melhora clínica da paciente, em seu domicílio. Em nosso meio, a droga que melhor atende a todas estas demandas é a cefuroxima, utilizada por um período de 10-14 dias. As cefalosporinas de terceira geração não existem na forma oral, carreando o inconveniente de tratamento parenteral em sua totalidade. Em decorrência dos efeitos colaterais, considera-se inadequado o uso de aminoglicosídeos em gestantes. Apesar das inconsistentes insinuações de contra-indicações...

Several factors cause urinary tract infection (UTI) to be a relevant complication of the gestational period, aggravating both the maternal and perinatal prognosis. For many years, pregnancy has been considered to be a factor predisposing to all forms of UTI. Today, it is known that pregnancy, as an isolated event, is not responsible for a higher incidence of UTI, but that the anatomical and physiological changes imposed on the urinary tract by pregnancy predispose women with asymptomatic bacteriuria (AB) to become pregnant women with symptomatic UTI. AB affects 2 to 10 percent of all pregnant women and approximately 30 percent of these will develop pyelonephritis if not properly treated. However, a difficult to understand resistance against the identification of AB during this period is observed among prenatalists. The diagnosis of UTI is microbiological and it is based on two urine cultures presenting more than 10(5) colonies/mL urine of the same germ. Treatment is facilitated by the fact that it is based on an antibiogram, with no scientific foundation for the notion that a pre-established therapeutic scheme is an adequate measure. For the treatment of pyelonephritis, it is not possible to wait for the result of culture and previous knowledge of the resistance profile of the antibacterial agents available for the treatment of pregnant women would be the best measure. Another important variable is the use of an intravenous bactericidal antibiotic during the acute phase, with the possibility of oral administration at home after clinical improvement of the patient. At our hospital, the drug that best satisfies all of these requirements is cefuroxime, administered for 10-14 days. Third-generation cephalosporins do not exist in the oral form, all of them involving the inconvenience of parenteral administration. In view of their side effects, aminoglycosides are considered to be inadequate for administration to pregnant women. The inconsistent...

Rastreamento e diagnóstico ecocardiográfico das arritmias e cardiopatias congênitas fetais / Screening and echocardiographic diagnosis of arrhythmias and congenital heart diseases in the fetus

OBJETIVO: analisar os resultados obtidos em programa de rastreamento e diagnóstico de arritmias e cardiopatias congênitas centrado em uma unidade terciária e determinar a importância do diagnóstico precoce na evolução fetal e neonatal. MÉTODOS: foram analisados os resultados da avaliação cardíaca fetal efetuada em 1159 gestantes em dois níveis diferentes. Nível I: uso da ultra-sonografia morfológica com o objetivo de rastrear a presença de alteração cardíaca, sem estabelecer um diagnóstico diferencial. Nível II: por ecocardiograma fetal com o objetivo de diagnosticar as cardiopatias fetais existentes. Os resultados da detecção de arritmias bem como da avaliação das alterações estruturais foram comparados, sendo estabelecidas a sensibilidade e a especificidade para ambos os níveis no pré-natal, ao exame pós-natal ou à necropsia. A concordância entre ambos os níveis foi calculada pelo índice kappa. RESULTADOS: as arritmias detectadas no nível I foram confirmadas em todos os casos e não houve falso-negativos, sendo que em cinco pacientes houve necessidade de tratamento intra-útero. A detecção das alterações estruturais obtidas no nível I teve sensibilidade de 72 por cento e especificidade de 98 por cento, com 28 por cento de falso-positivos. No nível II estes parâmetros foram, respectivamente, de 100 e 99 por cento. De acordo com o coeficiente kappa de 57 por cento, um grau de concordância de categoria moderada foi observado entre ambos os níveis. Das cardiopatias congênitas da nossa série 51 por cento necessitaram intervenção farmacológica ou invasiva no período neonatal. CONCLUSÃO: o estudo ultra-sonográfico obstétrico é fundamental no rastreamento das alterações cardíacas fetais. O ecocardiograma fetal apresentou alto índice de sensibilidade e especificidade no diagnóstico das arritmias e cardiopatias congênitas, possibilitando o tratamento precoce das alterações graves.

Tratamento da endometrite puerperal com antibioticoterapia parenteral exclusiva / Treatment of puerperal endometritis using a regimen with exclusive parenteral antibiotics

OBJETIVO: analisar a efetividade e segurança da antibioticoterapia parenteral hospitalar exclusiva para tratamento da endometrite puerperal, em população de baixo nível socioeconômico. MÉTODOS: estudo clínico prospectivo, que avaliou 21 puérperas com diagnóstico de endometrite puerperal, cujas gestações foram resolvidas em hospital universitário por cesárea (52,4 por cento) ou parto normal (47,6). A amostra caracterizou-se por baixo nível socioeconômico e de escolaridade. Foram submetidas ao regime de antibioticoterapia parenteral exclusiva, apenas durante o período de internação (grupo ATP-EX). Os resultados foram comparados com aqueles obtidos de série histórica do mesmo serviço (20 casos) submetidas a antibioticoterapia parenteral hospitalar, complementada por terapia via oral ambulatorial (grupo ATP+VO). As pacientes foram avaliadas clinicamente em retornos periódicos visando identificar casos de recidivas e complicações infecciosas. RESULTADOS: uma paciente do grupo ATP+VO necessitou de reinternação no 6º dia após a alta por recrudescência da endometrite. Não foi observada nenhuma complicação entre as pacientes do grupo ATP-EX. CONCLUSAO: para o tratamento de endometrite puerperal, não foi observado benefício adicional com a adição da antibioticoterapia oral complementar após a alta. Os resultados com o uso da antibioticoterapia parenteral exclusiva durante a internação indicam que esse esquema pode ser utilizado com segurança em população de baixo nível socioeconômico