Rastreio Universal da Audição Neonatal um Pequeno Teste para o Audiologista , um Grande Passo para a Humanidade?

O Rastreio Universal da Audição Neonatal tem sido um objectivo que várias gerações de audiologistas, otorrinolaringologistas e pediatras tem tentado ao longo dos anos. Os autores fazem uma revisão dos principais métodos utilizados para a avaliação da audição dos recém-nascidos, bem como das dificuldades encontradas e limitações da sua utilização. Desde o inicio da década de noventa vêm a ser implementados verdadeiros métodos de detecção precoce e universal da surdez infantil, utilizando métodos fisiológicos tais como os potenciais evocados auditivos e as otoemissões acústicas (c1ássicos e automáticos). São descritos os artigos mais importantes que fundamentam a necessidade de diagnóstico e intervenção precoces na surdez sensorioneural, com vista a melhorar a aquisição e desenvolvimento da fala e da competência linguística, o que permite uma melhor integração da criança, independentemente do seu grau de surdez. São também enunciadas as directivas do "European Consensus Development on Neonatal Hearing Screening" e do "Joint Comitee on Infant Hearing".

Rastreio Neonatal de Hemoglobinopatias numa População Residente em Portugal

The primary objective of newborn screening of hemoglobinopathies is the early identification of infants with sickle cell disease, as they are at increased clinical risk. Other goals include the identification of other types of clinically significant hemoglobinopathies and the detection of heterozygous carriers followed by the screening and counselling of family members. We performed a pilot study for the neonatal screening of hemoglobinopathies in 400 samples of cord blood taken from a maternity in Lisbon. We did not find any newborn with sickle cell disease. Six samples were from sickle cell heterozygotes, the respective families were studied and informed. We looked for the presence of alpha-thalassemia at birth in 100 consecutive samples of cord blood, by the presence of Hb Bart's, abnormal red blood cell indices and alpha-globin genotype. The results show an incidence of 10% of alpha-thalassemia (-alpha) carriers and 4% of triple alpha-globin gene carriers. The authors discuss the feasibility of neonatal screening of hemoglobinopathies in a Portuguese-speaking population consisting of a low prevalence of Hb S trait autoclonous group and a high prevalence immigrant minority

Spectrum and Frequency of GJB2 Mutations in a Cohort of 264 Portuguese Nonsyndromic Sensorineural Hearing Loss Patients

OBJECTIVE: To assess the spectrum and prevalence of mutations in the GJB2 gene in Portuguese nonsyndromic sensorineural hearing loss (NSSHL) patients. DESIGN: Sequencing of the coding region, basal promoter, exon 1, and donor splice site of the GJB2 gene; screening for the presence of the two common GJB6 deletions. STUDY SAMPLE: A cohort of 264 Portuguese NSSHL patients. RESULTS: At least one out of 21 different GJB2 variants was identified in 80 (30.2%) of the 264 patients analysed. Two mutant alleles were found in 53 (20%) of these probands, of which 83% (44/53) harboured at least one c.35delG allele. Twenty-seven (10.2%) of the probands harboured only one mutant allele. Subsequent analysis revealed that the GJB6 deletion del(GJB6-D13S1854) was present in at least 7.4% (2/27) of the patients carrying only one mutant GJB2 allele. Overall, one in five (55/264) of the patients were diagnosed as having DFNB1-related NSSHL, of which the vast majority (53/55) harboured only GJB2 mutations. CONCLUSIONS: This study provides clear demonstration that mutations in the GJB2 gene are an important cause of NSSHL in Portugal, thus representing a valuable indicator as regards therapeutical and rehabilitation options, as well as genetic counseling of these patients and their families.

Polymerase Chain Reaction Screening for Fungemia and/or Invasive Fungal Infections in Patients with Hematologic Malignancies

INTRODUCTION: Invasive fungal infections (IFIs) are a life-threatening complication in patients with hematologic malignancies, mainly in acute leukemia patients, following chemotherapy. IFI incidence is increasing, and associated mortality remains high due to unreliable diagnosis. Antifungal drugs are often limited by inadequate antimicrobial spectrum and side effects. Thus, the detection of circulating fungal DNA has been advocated as a rapid, more sensitive diagnostic tool. PATIENTS AND METHODS: Between June 01 and January 03, weekly blood samples (1,311) were screened from 193 patients undergoing intensive myelosuppressive or immunosuppressive therapy. IFI cases were classified according to European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria. Fungal DNA was extracted from whole blood and amplified using polymerase chain reaction (PCR) published primers that bind to the conserved regions of the fungal 18S rRNA gene sequence. In our study, two or more consecutive positive samples were always associated with fungal disease. RESULTS: PCR screening predicted the development of IFI to be 17 days (median). This test had a specificity of 91.1% and a sensitivity of 75%. IFI incidence was 7.8%. DISCUSSION: Therefore, our results confirm the potential usefulness of PCR serial screening and the clinical applicability in everyday routine. PCR screening offers a noninvasive repeatable aid to the diagnosis of IFI.

Diagnóstico Neonatal de Síndrome de Prader-Willi

A síndrome de Prader-Willi tem uma prevalência aproximada de 1:25000 nascimentos. No período neonatal há hipotonia severa, atraso de crescimento e dificuldade alimentar que persistem durante o primeiro ano de vida. O quadro clínico inicial contrasta com a bulimia que se evidencia mais tarde e que, não controlada, pode conduzir à obesidade mórbida. Descrevem-se as características clínicas, o diagnóstico genético e os cuidados específicos a ter na promoção da saúde a propósito de cinco crianças com síndrome de Prader Willi, cujo diagnóstico foi feito no período neonatal.

Specificity and Sensitivity of Screening for Anti-HLA Antibodies in Kidney Allograft Dysfunction

BACKGROUND: Prospective testing for posttransplant circulating anti-HLA antibodies seems to be a critical noninvasive tool, but confirmatory data are lacking. MATERIALS AND METHODS: Over the last 3 years, peritubular capillary (PTC) C4d deposition was prospectively sought by an immunofluorescence technique applied to frozen tissue in biopsies obtained for allograft dysfunction. Screening for circulating anti-HLA class I/II alloantibodies (AlloAb) by the flow cytometric test was performed simultaneously. RESULTS: We evaluated 132 sets of biopsies and simultaneous serum samples. PTC C4d deposition was demonstrated in 15.9% (21/132) of biopsies. Circulating anti-HLA I/II AlloAb were detected in 25% (33/132) of serum samples. Employing receiver-operator characteristic (ROC) curves for all C4d-positive biopsies, screening for AlloAb showed a global specificity of 82% and sensitivity of 61.9%. When this analysis was restricted to biopsies obtained in the first month posttransplantation, the sensitivity increased to 81.8%, but the specificity decreased to 76.9%. After the first month posttransplantation, we observed sensitivity of 40.0% and a specificity of 86.4%. In the first month posttransplantation, all patients with a diagnosis of acute antibody-mediated rejection displayed circulating anti-HLA class I/II, but not always at the same time as the C4d-positive biopsy. CONCLUSIONS: In the first month posttransplantation, prospective monitoring of anti-HLA antibodies may be useful. The high sensitivity allows the identification of patients at risk, affording an earlier diagnosis of antibody-mediated rejection. After the first month, the test can be used to evaluate allograft dysfunction episodes, since positivity is highly suggestive of an antibody-mediated process.

Vólvulo Intestinal en el Periodo Neonatal: 8 Años de Experiencia en un Hospital Pediátrico Terciario

Análise dos casos de volvo intestinal ocorridos no período neonatal nos últimos 8 anos (2002 a 2010). Material e métodos: Foram estudados os recém-nascidos admitidos na UCIN cujo diagnóstico de saída foi volvo intestinal. Foram estudados os seguintes parâmetros: idade gestacional e pós-natal, apresentação clínica e imagiológica, intervenção cirúrgica e resultados. Resultados: Foram identificados 15 doentes 7 dos quais no último ano do estudo. Sete RN eram pré-termo (PT) ou ex pré-termo. A mediana de peso ao nascer foi de 2665g (660-3900); 4 RN eram muito baixo peso. A mediana de idade de início dos sintomas foi 7 dias; em 5 RN a doença teve início nas primeiras 24 horas de vida; em 3 destes, o volvo ocorreu in utero. Sinais e sintomas: grande distensão abdominal-12; resíduo gástrico bilioso-11; alterações da parede abdominal-5; dejecções com sangue-4; instabilidade hemodinâmica-6. Imagiologia: grande distensão de ansas, sem ar ectópico- 10 doentes; ausência de ar no abdómen-4; trânsito intestinal contrastado sugestivo de malrotação e volvo-3; ecografia e Doppler abdominal com sinal de “whirlpool”-2. Todos foram submetidos a cirurgia de urgência, sendo o volvo confirmado intraoperatoriamente; foi necessária ressecção intestinal em 9 doentes; 3 ficaram com síndrome do intestino curto; registou-se um óbito por falência multi-orgânica no período pós-operatório. Conclusão: Foi encontrado um elevado número de casos de volvo intestinal em RN pré-termo ou ex pré-termo, de volvo in utero e de elevada ocorrência de casos no último ano do estudo. Resíduo gástrico bilioso e distensão abdominal foram os sintomas mais frequentes de volvo e devem ser tomados em consideração no diagnóstico diferencial com outras situações cirúrgicas abdominais. As sequelas são potencialmente graves.

Perinatal Bacterial Infection: Screenning of Vertical Transmitted Infections

Perinatal bacterial infection may be caused by any microorganism colonizing the vaginal tract. Neonatologists and paediatricians are especially concerned about group B Stretpococcus (GBS). However, Enterobactereacea, mainly E.coli and Proteus, are also responsible for infection. GBS screening may be accomplished in over 90% of pregnant women. In our maternity in 2007-2008, 85% of the mothers had been screened. Screening and prophylaxis were responsible for a decreasing incidence of neonatal infection - from 0.6/1000 to 0.15/1000 live births in Portugal, from 2002 to 2007. However there are some difficulties related to screening. In the second Portuguese study 16/57 NB with early-onset infection (28%) were born to “negative” mothers. Several factors illustrate how difficult is to draw national screening policies: a wide range of carrier’s state rate throughout a country - in Portugal from 12% to 30%. The success of any screening policy may also be affected by additional technical and organizational problems. In countries where home delivery is a tradition or a trend intrapartum GBS prophylaxis requires a very well organized assistance.. Moreover factors usually accepted as protective are not so effective. In the Portuguese study 24/57 infected newborns (42%) were delivery by caesarean section. Another subject deals with the workload in the postnatal ward generated by deficient compliance to the guidelines a problem not confirm by a study of our group. Decreasing the importance of GBS, highlight the importance of E. coli in perinatal infection. From the 16 340 registrations of the National Registry 1676 were newborns with mother-related infection. Applying the same reasoning to E.coli as to GBS and Listeria monocytogenes – that is considering all of them are of maternal origin - 6.7% of these infections were due to E. coli, 4.6% to SGB and 0.5% to Listeria monocytogenes. In conclusion screening and prophylaxis may be not the best way to prevent all GBS neonatal infections but by now it is the only available procedure. The other bacteria continue to demand a high suspicion level and immediate intervention.

Rastreio Neonatal Sistemático de Infecção por CMV

O virus citomegálico humano (HCMV) é a principal causa de infecção congénita. Estima-se que em Portugal se situe entre 0,7% e 1%. O registo nacional de casos de infecção congénita por CMV realizado pela UVP/SPP entre 2006 e 2011, encontrou uma incidência de 0.074/1000 nados vivos. Atendendo a que este é um registo de RN sintomáticos e que estes correspondem a 10% dos infectados, teremos cerca de 0,7/1000 RN infectados por ano em Portugal, um valor semelhante ao encontrado no Reino Unido e Irlanda. Uma revisão americana usando exclusivamente população de RN infectados diagnosticados em estudos de rastreio universal e englobando 117 986 RN, concluiu que a incidência da infecção foi de 0,7% e a percentagem de crianças sintomáticas foi de 12,7% das quais 40 a 58% vieram a ter sequelas permanentes; das crianças assintomáticas 13,5% vieram a desenvolver sequelas permanentes. A surdez neurosensorial é considerada a sequela mais frequente contudo há grande desconhecimento sobre as sequelas visuais. A correcção precoce da surdez melhora muito o prognóstico da criança pelo que um diagnóstico precoce é essencial. O rastreio auditivo neonatal detecta apenas cerca de 50% destas crianças uma vez que a surdez é evolutiva podendo manifestar-se mais tarde. O rastreio pós natal de infecção congénita assintomática seria de grande utilidade mas não está ainda determinado qual a melhor estratégia para atingir tal objectivo. A utilização dos cartões de Guthrie para este fim parece ser uma boa solução mas alguns estudos questionam a sensibilidade da técnica. O custo de um programa deste tipo em Portugal poderia rondar os 19 milhões de euros anuais contabilizando apenas o preço de uma PCR por RN. Obviamente que muitos resultados teriam que ser repetidos ou confirmados por cultura, o que agravaria mais o orçamento. Na ausência de metodologia de rastreio com sensibilidade adequada para detectar infecções assintomáticas, o meio mais correcto de diagnosticar surdez na criança terá que se basear na clínica e na sensibilização dos pais para a detecção precoce de défice auditivo. A intervenção terapêutica adequada melhorará em muito a função mas outras terapêuticas, nomeadamente antivírica, não estão aprovadas nos RN assintomáticos.

Peritubular Capillaries C4d Deposits in Renal Allograft Biopsies and Anti HLA I/II Alloantibodies Screening. Incidence and Clinical Importance

Aim: To characterise clinically the patients with C4d in peritubular capillaries deposits (C4dPTCD) and/or circulating anti-HLA class I/II alloantibodies. To determine the correlation between positive C4dPTCD and circulating anti-HLA class I/II alloantibodies during episodes of graft dysfunction. Subjects and Methods: C4d staining was performed in biopsies with available frozen tissue obtained between January 2004 and December 2006. The study was prospective from March 2005, when a serum sample was obtained at the time of biopsy to detect circulating anti-HLA class I/II alloantibodies. Results: We studied 109 biopsies in 86 cadaver renal transplant patients. Sixteen of these (14.7%) presented diffuse positive C4dPTCD. There was a 13.5% rate of +C4dPTCD incidence within the first six months of transplantation and 16% after six months (p>0.05). Half of the +C4dPTCD in the first six months was associated with acute humoral rejection. After six months, the majority of +C4dPTCD (n=7/8) was present in biopsies with evidence of interstitial fibrosis/tubular atrophy and/or transplant glomerulopathy. The C4dPTCD was more frequent in patients with positive anti-HCV antibodies(p<0.0001), a previous renal transplant (p=0.007), and with a panel reactivity antibody (PRA) ≥ 50%(p=0.0098). The anti-HCV+ patients had longer time on dialysis (p=0.0019) and higher PRA(p=0.005). Circulating anti-HLA I/II alloantibodies were screened in 46 serum samples. They were positive in 10.9% of samples, all obtained after six months post transplant. Circulating alloantibodies were absent in 92.5% of the C4d negative biopsies. Conclusion: We found an association between the presence of C4dPTCD and 2nd transplant recipients,higher PRA and the presence of anti-HCV antibodies. The presence of HCV antibodies is not a risk factor for C4dPTCD per se, but appears to reflect longer time on dialysis and presensitisation. In renal dysfunction a negative alloantibody screening is associated with a reduced risk of C4dPTCD (<10%).

Mucoviscidose com Sintomatologia Respiratória no Período Neonatal

Descreve-se um caso de mucoviscidose com sintomatologia respiratória iniciada no período neonatal, associada a insuficiência pancreática invulgarmente precoce, o estudo da genética molecular revelou que, ao nível do gene CFTR, foi identificado na doente um composto genético das mutações FS08 e GS42X Realça-se a raridade desta forma de apresentação sendo no entanto lícito admitir-se esta entidade nosológica no diagnóstico diferencial da sindroma de dificuldade respiratória no recém-nascido. Discute-se a patogénese e alguns aspectos particulares da terapêutica instituida, os quais tem sido importantes para a melhoria da expectativa de vida de doentes com esta patologia.

Incontinentia Pigmenti in the Neonatal Period

Incontinentia pigmenti (IP) is a rare multisystem disease, X linked dominant disorder. As all X linked dominant diseases, it is usually male-lethal. Female newborn admitted to the neonatal intensive care unit on the fi rst day of life was diagnosed as having probable herpetic infection with vesicular skin lesions distributed on upper right limb and inferior limbs. Family history showed that her 22-year-old mother had hypopigmented lesions on the lower limbs and her 13-month-old sister had hyperpigmented lesions on the trunk and limbs. In newborns, herpes infection emerges as the principal diagnosis of vesicular rash, due to the importance of precocious diagnosis and treatment. Other hypothesis must be considered in a newborn with vesicobullous rash, such as IP.