Anomalous peroxidase activity of cytochrome c is the primary pathogenic target in Barth syndrome.

Barth syndrome (BTHS) is a life-threatening genetic disorder with unknown pathogenicity caused by mutations in TAFAZZIN (TAZ) that affect remodeling of mitochondrial cardiolipin (CL). TAZ deficiency leads to accumulation of mono-lyso-CL (MLCL), which forms a peroxidase complex with cytochrome c (cyt c) capable of oxidizing polyunsaturated fatty acid-containing lipids. We hypothesized that accumulation of MLCL facilitates formation of anomalous MLCL-cyt c peroxidase complexes and peroxidation of polyunsaturated fatty acid phospholipids as the primary BTHS pathogenic mechanism. Using genetic, biochemical/biophysical, redox lipidomic and computational approaches, we reveal mechanisms of peroxidase-competent MLCL-cyt c complexation and increased phospholipid peroxidation in different TAZ-deficient cells and animal models and in pre-transplant biopsies from hearts of patients with BTHS. A specific mitochondria-targeted anti-peroxidase agent inhibited MLCL-cyt c peroxidase activity, prevented phospholipid peroxidation, improved mitochondrial respiration of TAZ-deficient C2C12 myoblasts and restored exercise endurance in a BTHS Drosophila model. Targeting MLCL-cyt c peroxidase offers therapeutic approaches to BTHS treatment.

Health-related quality of life in paediatric patients with intoxication-type inborn errors of metabolism: Analysis of an international data set.

Acute intoxication-type inborn errors of metabolism (IT-IEM) such as urea cycle disorders and non-acute IT-IEM such as phenylketonuria have a major impact on paediatric patients' life. Patients have to adhere to a strict diet but may face neurocognitive impairment and - in acute diseases - metabolic decompensations nevertheless. Research on the subjective burden of IT-IEM remains sparse. Studies with appropriate sample sizes are needed to make valid statements about health-related quality of life (HrQoL) in children and adolescents with IT-IEM. Six international metabolic centres contributed self-reports and proxy reports of HrQoL (assessed with the Paediatric Quality of Life Inventory) to the final data set (n = 251 patients; age range 2.3-18.8 years). To compare HrQoL of the patient sample with norm data and between acute and non-acute IT-IEM, t tests were conducted. To examine the influence of child age, sex, diagnosis and current dietary treatment on HrQoL, multiple linear regression analyses were conducted. Self-reports and proxy reporst showed significantly lower HrQoL total scores for children with IT-IEM compared to healthy children. Current dietary treatment significantly predicted lower proxy reported total HrQoL. Children with non-acute IT-IEM reported significantly lower psychosocial health and emotional functioning than children with acute IT-IEM. The patient sample showed significantly impaired HrQoL and a diet regimen remains a risk factor for lower HrQoL. Differences in HrQoL between acute and non-acute IT-IEM subgroups indicate that factors beyond symptom severity determine the perception of disease burden. Identifying these factors is of crucial importance to develop and implement appropriate interventions for those in need.

Noncommunicable diseases, risk factors, and protective factors in adults with and without health Insurance. / Doenças Crônicas Não Transmissíveis e fatores de risco e proteção em adultos com ou sem plano de saúde.

This study describes the coverage of health insurance and compares the occurrence of risk factors (RF) and protective factors of noncommunicable diseases in the population with and without health insurancesin Brazilianstate capitals. Data from the telephone survey Vigitel was analyzed. The Poisson regression model was used to estimate the prevalence ratio (PR), comparing RF among those who did or did not have a health insurance. Plan coverage was 49.1%, and the highest prevalences were in Goiania, Vitória, Florianópolis, and Belo Horizonte. Adults over 55 years of age and with higher education were more likely to have an insurance. The population with health insurance hada higher prevalence of protective factors, such as fruit and vegetable consumption (PR = 1.3 95% CI 1.2-1.3), physical activity in their free time (PR = 1.2 (95% CI: 1.2-1.3), mammographies (RP = 1.2 IC95% 1.1-1.3) and pap smears (PR = 1.1 IC95% 1.2-1.3), and lower prevalence of RFs such as smoking (RP = 0.7, 95% CI 0.6-0.8), poor health (RP = 0.8 CI95% 0.6-0.9), obesity (RP = 0.8 IC95% 0.7-0.9), consumption of meat with fat (RP = 0.9 IC95% 0.8-0.9) and whole milk (RP = 0.9 IC95% 0,8-0.9). Regardless of educational level, the population that has health insurancesgenerally has better indicators, such as healthier habits and greater coverage of preventive exams.

O estudo descreve as coberturas de planos de saúde e compara a ocorrência de fatores de risco (FR) e proteção de Doenças Crônicas Não Transmissíveis, na população com e sem planos de saúde nas capitais brasileiras. Foram analisados dados do inquérito telefônico Vigitel. Foi utilizado o modelo de regressão de Poisson para estimar a razão de prevalência (RP), comparando FR entre quem tem ou não plano de saúde. A cobertura de planos foi de 49,1%, mais elevada em Goiania, Vitória, Florianópolis e Belo Horizonte, entre adultos acima de 55 anos e com maior escolaridade. A população com planos de saúde apresenta prevalências mais elevadas de fatores de proteção como consumo de frutas e hortaliças (RP = 1,3 IC95% 1,2-1,3), prática de atividade física no tempo livre (RP = 1,2 IC95% 1,2-1,3), mamografia (RP = 1,2 IC95% 1,1-1,3) e Papanicolau (RP = 1,1 IC95% 1,2-1,3), e menor prevalência de FR como tabagismo (RP = 0,7 IC95% 0,6-0,8), avaliação de saúde ruim (RP = 0,8 IC95% 0,6-0,9), obesidade (RP = 0,8 IC95% 0,7-0,9), carne com gordura (RP = 0,9 IC95% 0,8-0,9) e leite com gordura (RP = 0,9 IC95% 0,8-0,9). Independentemente da escolaridade, a população que tem planos de saúde apresenta geralmente, melhores indicadores, como hábitos mais saudáveis e maior cobertura de exames preventivos.

Doenças Crônicas Não Transmissíveis e fatores de risco e proteção em adultos com ou sem plano de saúde / Noncommunicable diseases, risk factors, and protective factors in adults with and without health Insurance

Resumo O estudo descreve as coberturas de planos de saúde e compara a ocorrência de fatores de risco (FR) e proteção de Doenças Crônicas Não Transmissíveis, na população com e sem planos de saúde nas capitais brasileiras. Foram analisados dados do inquérito telefônico Vigitel. Foi utilizado o modelo de regressão de Poisson para estimar a razão de prevalência (RP), comparando FR entre quem tem ou não plano de saúde. A cobertura de planos foi de 49,1%, mais elevada em Goiania, Vitória, Florianópolis e Belo Horizonte, entre adultos acima de 55 anos e com maior escolaridade. A população com planos de saúde apresenta prevalências mais elevadas de fatores de proteção como consumo de frutas e hortaliças (RP = 1,3 IC95% 1,2-1,3), prática de atividade física no tempo livre (RP = 1,2 IC95% 1,2-1,3), mamografia (RP = 1,2 IC95% 1,1-1,3) e Papanicolau (RP = 1,1 IC95% 1,2-1,3), e menor prevalência de FR como tabagismo (RP = 0,7 IC95% 0,6-0,8), avaliação de saúde ruim (RP = 0,8 IC95% 0,6-0,9), obesidade (RP = 0,8 IC95% 0,7-0,9), carne com gordura (RP = 0,9 IC95% 0,8-0,9) e leite com gordura (RP = 0,9 IC95% 0,8-0,9). Independentemente da escolaridade, a população que tem planos de saúde apresenta geralmente, melhores indicadores, como hábitos mais saudáveis e maior cobertura de exames preventivos.

Abstract This study describes the coverage of health insurance and compares the occurrence of risk factors (RF) and protective factors of noncommunicable diseases in the population with and without health insurancesin Brazilianstate capitals. Data from the telephone survey Vigitel was analyzed. The Poisson regression model was used to estimate the prevalence ratio (PR), comparing RF among those who did or did not have a health insurance. Plan coverage was 49.1%, and the highest prevalences were in Goiania, Vitória, Florianópolis, and Belo Horizonte. Adults over 55 years of age and with higher education were more likely to have an insurance. The population with health insurance hada higher prevalence of protective factors, such as fruit and vegetable consumption (PR = 1.3 95% CI 1.2-1.3), physical activity in their free time (PR = 1.2 (95% CI: 1.2-1.3), mammographies (RP = 1.2 IC95% 1.1-1.3) and pap smears (PR = 1.1 IC95% 1.2-1.3), and lower prevalence of RFs such as smoking (RP = 0.7, 95% CI 0.6-0.8), poor health (RP = 0.8 CI95% 0.6-0.9), obesity (RP = 0.8 IC95% 0.7-0.9), consumption of meat with fat (RP = 0.9 IC95% 0.8-0.9) and whole milk (RP = 0.9 IC95% 0,8-0.9). Regardless of educational level, the population that has health insurancesgenerally has better indicators, such as healthier habits and greater coverage of preventive exams.

Genotype-phenotype correlations and BH4 estimated responsiveness in patients with phenylketonuria from Rio de Janeiro, Southeast Brazil.

BACKGROUND: Genetic heterogeneity and compound heterozygosis give rise to a continuous spectrum of phenylalanine hydroxylase deficiency and metabolic phenotypes in phenylketonuria (PKU). The most used parameters for evaluating phenotype in PKU are pretreatment phenylalanine (Phe) levels, tolerance for dietary Phe, and Phe overloading test. Phenotype can vary from a "classic" (severe) form to mild hyperphenylalaninemia, which does not require dietary treatment. A subset of patients is responsive to treatment by the cofactor tetrahydrobiopterin (BH4 ). Genotypes of PKU patients from Rio de Janeiro, Brazil, were compared to predicted and observed phenotypes. Genotype-based estimations of responsiveness to BH4 were also conducted. METHODS: Phenotype was defined by pretreatment Phe levels. A standard prediction system based on arbitrary assigned values was employed to measure genotype-phenotype concordance. Patients were also estimated as BH4 -responders according to the responsiveness previously reported for their mutations and genotypes. RESULTS: A 48.3% concordance rate between genotype-predicted and observed phenotypes was found. When the predicted phenotypes included those reported at the BIOPKU database, the concordance rate reached 77%. A total of 18 genotypes from 30 patients (29.4%) were estimated as of potential or probable BH4 responsiveness. Inconsistencies were observed in genotypic combinations including the common "moderate" mutations p.R261Q, p.V388M, and p.I65T and the mild mutations p.L48S, p.R68S, and p.L249F. CONCLUSION: The high discordance rate between genotype-predicted and observed metabolic phenotypes in this study seems to be due partially to the high frequency of the so-called "moderate" common mutations, p.R261Q, p.V388M, and p.I65T, which are reported to be associated to erratic or more severe than expected metabolic phenotypes. Although our results of BH4 estimated responsiveness must be regarded as tentative, it should be emphasized that genotyping and genotype-phenotype association studies are important in selecting patients to be offered a BH4 overload test, especially in low-resource settings like Brazil.

Trends in risk and protective factors for non-communicable diseases in the population with health insurance in Brazil from 2008 to 2015. / Tendências de fatores de risco e proteção de doenças crônicas não transmissíveis na população com planos de saúde no Brasil de 2008 a 2015.

OBJECTIVE: To analyze trends in risk and protective factors for non-communicable diseases (NCD) and access to preventive tests in the population with health insurance in Brazilian state capitals between 2008 and 2015. METHODS: This is a cross-sectional study that analyzed data collected from the Surveillance of Risk and Protective Factors for non-communicable diseases (NCD) Telephone Survey (Sistema Nacional de Vigilância de Doenças Crônicas por Inquérito Telefônico - Vigitel) on adults aged 18 years and older. We analyzed trends in NCD indicators among health insurance users in approximately 30 thousand interviews done between 2008 and 2015. We used the simple linear regression model to calculate the trends. RESULTS: Health insurance users showed an increase in the prevalence of protective factors such as fruit and vegetable consumption, and physical activity in leisure time. Also, there was a decrease in risk factors such as smoking and soft drink consumption, increase in mammography coverage, and a drop in smoking prevalence. However, overweight, obesity, and diabetes increased. CONCLUSION: There are differences according to gender, and, in general, women accumulate more protective factors and men, more risk factors.

OBJETIVO: Analisar as tendências de fatores de risco e proteção de doenças crônicas não transmissíveis (DCNT) e do acesso a exames preventivos na população com planos de saúde nas capitais brasileiras entre 2008 e 2015. MÉTODOS: Trata-se de estudo transversal, analisando dados coletados do Sistema Nacional de Vigilância de Doenças Crônicas por Inquérito Telefônico (Vigitel), de adultos com 18 anos e mais. Foram analisadas tendências de indicadores de DCNT entre os usuários de planos de saúde, em cerca de 30 mil entrevistas a cada ano, entre 2008 e 2015. Utilizou-se o modelo de regressão linear simples para o cálculo das tendências. RESULTADOS: Usuários de planos de saúde apresentaram aumento das prevalências de fatores de proteção como o consumo de frutas e legumes e atividade física no lazer; houve redução de fatores de risco como tabagismo, consumo de refrigerantes, aumento na cobertura de mamografia e declínio na prevalência do tabagismo. Entretanto, ocorreu aumento do excesso de peso, obesidade e diabetes. CONCLUSÃO: Existem diferenças segundo sexo, e em geral as mulheres acumulam mais fatores de proteção e homens, mais fatores de risco.

Behavioral and Emotional Problems in Early-Treated Brazilian Children and Adolescents with Phenylketonuria.

BACKGROUND Phenylketonuria (PKU) is an inborn error of metabolism caused by mutations in the phenylalanine hydroxylase (PAH) gene. When untreated, PKU leads to a significant intellectual deficiency. Although early initiation of dietary therapy allows normal cognitive development, low adherence to treatment may result in neuropsychological deficits, including attention problems. This study was performed to evaluate emotional and behavioral problems in early-treated children and adolescents with PKU using the Child Behavior Checklist - CBCL/6-18 answered by parents. MATERIAL AND METHODS The study included 36 PKU patients. The mean scores of internalizing, externalizing, and total problems, syndrome scales, and DSM-IV-oriented scales of patients were compared with those of controls. An analysis to evaluate the importance of adherence to treatment and presence of intellectual disability was also performed. RESULTS There were no significant differences between patients and controls for almost all CBCL/6-18 scales, with the exception of the Attention Problem Scale - CBCL-APS. The mean (±SD) of the CBCL-APS scores of patients (7.86±5.33) was considerably higher than the mean of the controls (6.07±4.37; p=0.016), but not different from the mean of a matched control subsample (6.69±4.46; p=0.316). The difference between the mean of the scores of DSM-IV/ADHD scale of patients (6.72±4.07) and controls (5.73±3.56; p=0.102) was not significant. Non-adherence to treatment and intellectual disability had a negative impact on both CBCL-APS and DSM-IV/ADHD scale scores. CONCLUSIONS Our findings indicate a significant prevalence of parents' complaints of attention problems and hyperactivity in non-adherent to treatment and intellectually low performing patients with PKU.

Mutation analysis of the PAH gene in phenylketonuria patients from Rio de Janeiro, Southeast Brazil.

BACKGROUND: Phenylketonuria (PKU) is an autosomal recessive disease resulting from mutations in the PAH gene. Most of the patients are compound heterozygotes, and genotype is a major factor in determining the phenotypic variability of PKU. More than 1,000 variants have been described in the PAH gene. Rio de Janeiro's population has a predominance of Iberian, followed by African and Amerindian ancestries. It is expected that most PKU variants in this Brazilian state have originated in the Iberian Peninsula. However, rare European, African or pathogenic variants that are characteristic of the admixed population of the state might also be found. METHODS: A total of 102 patients were included in this study. Genomic DNA was isolated from dried blood spots. Sanger sequencing was used for PAH gene variant identification. Deletions and duplications were also screened using MLPA analysis. Haplotypes were also determined. RESULTS: Nine (8.8%) homozygous and 93 (91.2%) compound heterozygous patients were found. The spectrum included 37 causative mutations. Missense, nonsense, and splicing pathogenic variants corresponded to 63.7%, 2.9%, and 22.6% of the mutant alleles, respectively. Large (1.5%), and small deletions, inframe (5.4%) and with frameshift (3.9%), comprised the remainder. The most frequent pathogenic variants were: p.V388M (12.7%), p.R261Q (11.8%), IVS10-11G>A (10.3%), IVS2+5G>C (6.4%), p.S349P (6.4%), p.R252W (5.4%), p.I65T (4.4%), p.T323del (4.4%), and p.P281L (3.4%). One novel variant was detected: c.934G>T (p.G312C) [rs763115697]. CONCLUSION: The three most frequent pathogenic variants in our study (34.8% of the alleles) were also the most common in other Brazilian states, Portugal, and Spain (p.V388M, p.R261Q, IVS10-11G>A), corroborating that the Iberian Peninsula is the major source of PAH mutations in Rio de Janeiro. Pathogenic variants that have other geographical origins, such IVS2+5G>C, p.G352Vfs*48, and IVS12+1G>A were also detected. Genetic drift and founder effect may have also played a role in the mutation spectrum we observed.

Tendências de fatores de risco e proteção de doenças crônicas não transmissíveis na população com planos de saúde no Brasil de 2008 a 2015 / Trends in risk and protective factors for non-communicable diseases in the population with health insurance in Brazil from 2008 to 2015

RESUMO: Objetivo: Analisar as tendências de fatores de risco e proteção de doenças crônicas não transmissíveis (DCNT) e do acesso a exames preventivos na população com planos de saúde nas capitais brasileiras entre 2008 e 2015. Métodos: Trata-se de estudo transversal, analisando dados coletados do Sistema Nacional de Vigilância de Doenças Crônicas por Inquérito Telefônico (Vigitel), de adultos com 18 anos e mais. Foram analisadas tendências de indicadores de DCNT entre os usuários de planos de saúde, em cerca de 30 mil entrevistas a cada ano, entre 2008 e 2015. Utilizou-se o modelo de regressão linear simples para o cálculo das tendências. Resultados: Usuários de planos de saúde apresentaram aumento das prevalências de fatores de proteção como o consumo de frutas e legumes e atividade física no lazer; houve redução de fatores de risco como tabagismo, consumo de refrigerantes, aumento na cobertura de mamografia e declínio na prevalência do tabagismo. Entretanto, ocorreu aumento do excesso de peso, obesidade e diabetes. Conclusão: Existem diferenças segundo sexo, e em geral as mulheres acumulam mais fatores de proteção e homens, mais fatores de risco.

ABSTRACT: Objective: To analyze trends in risk and protective factors for non-communicable diseases (NCD) and access to preventive tests in the population with health insurance in Brazilian state capitals between 2008 and 2015. Methods: This is a cross-sectional study that analyzed data collected from the Surveillance of Risk and Protective Factors for non-communicable diseases (NCD) Telephone Survey (Sistema Nacional de Vigilância de Doenças Crônicas por Inquérito Telefônico - Vigitel) on adults aged 18 years and older. We analyzed trends in NCD indicators among health insurance users in approximately 30 thousand interviews done between 2008 and 2015. We used the simple linear regression model to calculate the trends. Results: Health insurance users showed an increase in the prevalence of protective factors such as fruit and vegetable consumption, and physical activity in leisure time. Also, there was a decrease in risk factors such as smoking and soft drink consumption, increase in mammography coverage, and a drop in smoking prevalence. However, overweight, obesity, and diabetes increased. Conclusion: There are differences according to gender, and, in general, women accumulate more protective factors and men, more risk factors.

Adaptation of alpha-fetoprotein and intact human chorionic gonadotropin fluoroimmunometric assays to dried blood spots.

BACKGROUND: Although dried blood spots (DBS) are very convenient for massive screening, there are very few examples of their application in maternal serum screening of Down's syndrome and neural tube defects. For large-scale mass population screening in Brazil, a continental country, DBS would be fairly recommended. As there are no easily available commercial assays of AFP and hCG in DBS, the Wallac Delfia fluoroimmunometric assays intended for these biochemical markers were adapted to DBS. METHODS: Serum specimens and DBS obtained from 116 pregnant women were analyzed by conventional methodology and by the adapted assays, respectively. Precision (within-run and between-run), recovery and detection limits studies were conducted RESULTS: The non-linear regression fit of the levels of AFP and hCG in DBS by gestational age in days was described. There was a strong statistically significant correlation between the levels of these analytes in serum specimens and in DBS. For both analytes, the precision variances were compared to those presented by the manufacturer for serum samples. CONCLUSION: It is feasible to use these DBS adapted assays in maternal serum screening programs.

Inibina-A no soro materno no segundo trimestre gestacional: um novo marcador bioquímico de síndrome de Down / Second-trimester maternal serum inhibin-A: a new biochemical marker of Down's syndrome

As inibinas säo hormônios glicoproteícos que durante a gravidez, säo sintetizados, principalmente, pela placenta. A inibina-A é a principal forma dimérica circulante durante este período. Este hormônio vem sendo incluído no teste combinado de rastreamento da síndrome de Down por marcadores bioquímicos de soro materno, por aumentar a taxa de detecçäo. Nosso estudo abrangeu a dosagem de inibina-A em 160 amostras de soro materno utilizando-se um ensaio imunoenzimático do tipo sanduíche, de média sensibilidade. Verificamos que os níveis de inibina-A säo constantes ao longo do segundo trimestre gestacional, como já havia constatado por outros autores anteriormente. Encontramos uma correlaçäo positiva entre os níveis de inibina-A e os de Beta-hcg (p=0,0001). O peso materno e a inibina-A sérica mostraram uma correlaçäo negativa (p=0,0023). Näo foi observada correlaçäo estatisticamente signicativa dos valores de inibina-A com níveis de AFP e uE3. Nossos dados foram comparados com aqueles encontrados na literatura médica. Este estudo nos permitirá incluir mais este marcador em nosso esquema de rastreamento pré-natal de síndrome de Down

Triploidia fetal associada à diminuiçäo da subunidade ß e do estriol näo-conjugado no soro materno / Fetal triploidy associated with low levels of unconjugated estriol and beta-subunit in maternal serum

Relatamos um caso de triploidia fetal näo-molar detectada na 20ª semana gestacional por cordocentese realizada em razäo de estudo ultra-sonográfico que revelou retardo do crescimento intra-uterino e grave oligoidrâmnio. Na 19ª semana foram verificados acentuada diminuiçäo da subunidade beta livre da gonadotrofina coriônica humana e do estriol näo-conjugado e níveis de alfa-fetoproteína normais, apontando para um risco aumentado de síndrome de Edwards. Houve morte fetal um dia após a cordocentese e a resoluçäo do caso foi por parto vaginal induzido com misoprostol e ocitocina, sob analgesia peridual. Estudo cromossômico das células sangüíneas fetais revelou o cariótipo 69, XXX. O grave retardo do crescimento intra-uterino, a macrocefalia, constatada no estudo anatomopatológico do feto, e os níveis muito baixos de hCG e de estriol näo-conjugado sugerem um caso de triploidia por diginia, fertilizaçäo de um óvulo diplóide por um espermatozóide haplóide.

Feto portador de síndrome de Turner e tetralogia de Fallot associadas à elevaçäo de alfafetoproteína materna / Fetal Turner syndrome and tetralogy de Fallot associated with elevated maternal serum alpha-fetoprotein levels

A síndrome de Turner fetal e suas complicações, a hidropisia e o higroma cístico, podem produzir alteração dos marcadores bioquímicos de soro materno inicialmente utilizados no rastreamento de síndrome de Down e de defeitos de tubo neural (DTN). Os autores relatam o caso de uma gestante de 37 anos, que foi rastreada para síndrome de'Down e DTN no início do 2§ trimestre. Foi constatado aumento da alfafetoproteína de soro materno (MSAFP) e o rastreamento foi considerado positivo para DTN. Foi realizado exame ultra-sonográfico tridimensional, que não demonstrou nenhuma anormalidade fetal ou placentária, caracterizando o caso como elevação idiopática de MSAFP. No 3§ trimestre, a gravidez evoluiu com acentuada oligoidrâmnia e alteração do fluxo uteroplacentário, obrigando à instituição de terapia com corticosteróides e parto cesáreo na 34§ semana gestacional. O concepto do sexo feminino foi encaminhado à UTI neonatal, onde foram diagnosticadas tetralogia de Fallot e síndrome de Turner. Esse caso incentivou os autores a rever a literatura sobre marcadores bioquímicos de soro materno na síndrome de Turner e nas malformações cardíacas congênitas. Ao final, propõe-se um protocolo para elevação idiopática de MSAFP.

Marcadores bioquímicos utilizados em rastreamento pré-natal de síndrome de down e defeitos de tubo neural no segundo trimestre de gestaçäo: medianas de um grupo brasileiro de gestantes / Second trimester serum markeres in antenatal screening of down`s syndrome and neural tube defects: medians from a group of brasilian pregnant women

Foram realizadas, dosagens de marcadores bioquímicos - utilizados no rastreamento de síndrome de Down (SD) e defeitos de tubo neural (DTN) - em amostras de soro materno do segundo trimestre de gravidez, entre a 14ª e a 20ª semana gestacional (SG). Estes marcadores foram a alfafetoptoteína (AFP), o estriol näo conjugado (uE3) e a subunidade beta livre da gonadotrofina coriônica humana (beta-hCG livre). Foram excluídos das análises os resultados de soro materno de gestaçöes que vieram dar à luz conceptos com síndrome de Down, outros defeitos cromossomiais e defeitos de tubo neural. Os níveis de AFP e de uE, mostraram uma curva ascendente, enquanto os de beta-hCG livre apresentaram uma curva descendente ao longo do período analisado, concordando com os dados da literatura. As medianas (observadas) destes três marcadores bioquímicos de soro materno foram obtidoas para cada SG completa, e as equaçöes de regressäo das medianas foram fornecidas por software específico. Comparou-se as medianas regressadas com as publicaçöes em trabalo europeus (França, Itália e Reino Unido) e na bula do kit de origem finlandesa (Delfia, Wallac oy), utilizado nos ensaios bioquímicos. Foram analisadas as possíveis causas das diferenças encontradas, com ênfase nas questöes metodológicas e nas diferenças entre as populaçöes investigadas, especialmente em relaçäo a peso materno, peso o nascer, etnia e tabagismo. As medianas "brasileiras", assim obtidas, podem ser encaradas como o primeiro passo no estabelecimento de valores normativos nacionais, independentes dos publicados em tabelas de risco da literatura estrangeira