Análise da amplitude da resposta das emissões otoacústicas e das latências das ondas do PEATE, como possíveis indicadores de comprometimento das células ciliadas cocleares e nervo auditivo, em lactentes com asfixia

Pós-graduação em Bases Gerais da Cirurgia - FMB

Birth prevalence and characteristics of congenital toxoplasmosis in Sergipe, North-east Brazil

Objectives To estimate, by neonatal screening, the birth prevalence of congenital toxoplasmosis among live-born infants in Sergipe state, Brazil, and to investigate the clinical features of affected infants. Methods Dried blood spot specimens obtained from 15 204 neonates were assayed for the presence of anti-T. gondii IgM antibodies. Duplicate retesting was done in infants with positive and borderline results. Confirmatory testing in peripheral blood samples consisted of testing for anti-T. gondii IgG and IgM in infants and mothers. Those with possible congenital toxoplasmosis were evaluated and followed up to a median age of 20 months. Congenital infection was confirmed in the presence of persisting anti-T. gondii IgG antibodies beyond 12 months of age. All infants with confirmed infection were treated with pyrimethamine, sulfadiazine and folinic acid for 1 year. Results Fifty-three infants had detectable IgM in dried blood spot specimens. Confirmatory testing was reactive in 39/50, of which, 38 completed follow-up. Six of 15 204 newborns were diagnosed with congenital toxoplasmosis, resulting in an estimated birth prevalence of four per 10 000 [CI 95% 1.48.0]. Four infants (67%) showed signs of congenital toxoplasmosis in their first year of life; three (75%) had retinochoroidal scars, and one had cerebral calcifications. Two infants remained asymptomatic until 20 months of age. Conclusions The birth prevalence of congenital toxoplasmosis is high in the Brazilian state of Sergipe, with most of the infants showing ocular lesions. Preventive measures are strongly warranted.

Questionnaire for monitoring auditory and language development in the first year of life

Purpose: To validate a monitoring questionnaire about hearing and language development applied by community health agents in the first year of life. Methods: Seventy six community health agents, previously trained on infant hearing health, administered a questionnaire to the families of 304 children with ages from 0 to 1 year. The questionnaire contains questions regarding hearing and language development and, for all age groups, the question “Does your child hear well?” was presented. The validity of the questionnaire was assessed by analyzing false positive and false negative rates of the identified children. A double-blind study was conducted so that all children assessed by the questionnaire were submitted to hearing evaluation performed by audiologists. Results: Four children (1.32%) were diagnosed with sensorineural hearing loss (two unilateral), and 69 (22.7%) with conductive hearing loss. The monitoring questionnaire showed specificity of 96% and sensitivity of 67%, with a false-negative rate of 33% for not identifying the unilateral hearing loss, and a false-positive rate of 4%. Conclusion: The questionnaire used has shown to be feasible and relevant to actions of the community health agents of the Family Health Strategy program, with high specificity and moderate sensitivity. The use of the validated instrument should be considered to complement Newborn Hearing Screening Programs, in order to identify late onset or acquired hearing loss.

Monitoramento de crianças com indicadores de risco para a deficiência auditiva

Purpose: to describe the proposal of monitoring children in the first year of life, who were not identified in the newborn hearing screening program but had risk factors for hearing loss. Method: the study included 258 risk children who had obtained the result “pass” in the Universal Newborn Hearing Screening Program of Hospital Santa Isabel – Bauru/SP, from June to November 2008. It was applied by the telephone, a validated questionnaire in a previous study, containing questions about hearing and language. For each question there were two possible answers: “yes” or “no” and we considered “failure” to obtain at least one “no” answer. With such result, the child was scheduled to perform an immediate hearing evaluation. Results: the questionnaire was applied with 169 families; with the others, there was no contact. From the total, 164 (97,04%) obtained “passed” and five (2,96%) “failed”. Between these five children, only three showed up for hearing evaluation and one had no disorders; two presented conductive hearing loss. It was observed distinct prevalence among the risk factors and there was no relation (p>0,05) of the risk factors with the evasion in the monitoring process. Conclusion: the monitoring through a questionnaire applied by telephone proved to be feasible, however, it is necessary to develop strategies to support their execution.

New approach in the diagnosis and therapy of hyperphenylalaninemia

Background. Phenylketonuria is the most prevalent inborn error of aminoacid metabolism. Is an autosomal recessive disorder. It results from mutations in the phenylalanine hydroxilase (PAH) gene. Phenotypes can vary from mild hyperphenylalaninemia to a severe phenylketonuria wich, if untreated, results in severe mental retardation. Thanks to neonatal screening programmes, early detection and promp dietetic intervention (phenylalanine restricted diet lifelong) has allowed to avoid neurocognitive complications. Recently, a new therapy is become widely used: the oral supplementation with the PAH cofactor (BH4), wich can alleviate the diet burden. Genotype-phenotype correlation is a reliable tool to predict metabolic phenotype in order to establish a better tailored diet and to assess the potential responsiveness to BH4 therapy. Aim Molecular analysis of the PAH gene, evaluation of genotype-phenotype correlation and prediction of BH4 responsiveness in a group of HPA patients living in Emilia Romagna. Patients and methods. We studied 48 patients affected by PAH deficiency in regular follow-up to our Metabolic Centre. We performed the molecular analysis of these patients using genomic DNA extracted from peripheral blood samples Results. We obtained a full genotipic characterization of 46 patients. We found 87 mutant alleles and 35 different mutations, being the most frequent IVS10-11 G>A (19.3%), R261Q (9.1%), R158Q (9.1%), R408Q (6.8%) and A403V (5.7%), including 2 new ones (L287, N223Y) ever described previously. Notably, we found 15 mutations already identified in BH4-responsive patients, according to the literature. We found 42 different genotipic combinations, most of them in single patients and involving a BH4-responsive mutation. Conclusion. BH4 responsiveness is shown by a consistent number of PAH deficient hyperphenylalaninemic patients. This treatment, combined with a less restricted diet or as monotherapy, can reduce nutritional complications and improve the quality of life of these patients.

Lethal respiratory failure and mild primary hypothyroidism in a term girl with a de novo heterozygous mutation in the TITF1/NKX2.1 gene

CONTEXT: Thyroid transcription factor 1 (TITF1/NKX2.1) is expressed in the thyroid, lung, ventral forebrain, and pituitary. In the lung, TITF1/NKX2.1 activates the expression of genes critical for lung development and function. Titf/Nkx2.1(-/-) mice have pituitary and thyroid aplasia but also impairment of pulmonary branching. Humans with heterozygous TITF1/NKX2.1 mutations present with various combinations of primary hypothyroidism, respiratory distress, and neurological disorders. OBJECTIVE: The objective of the study was to report clinical and molecular studies of the first patient with lethal neonatal respiratory distress from a novel heterozygous TITF1/NKX2.1 mutation. Participant: This girl, the first child of healthy nonconsanguineous French-Canadian parents, was born at 41 wk. Birth weight was 3,460 g and Apgar scores were normal. Soon after birth, she developed acute respiratory failure with pulmonary hypertension. At neonatal screening on the second day of life, TSH was 31 mU/liter (N <15) and total T(4) 245 nmol/liter (N = 120-350). Despite mechanical ventilation, thyroxine, surfactant, and pulmonary vasodilators, the patient died on the 40th day. RESULTS: Histopathology revealed pulmonary tissue with low alveolar counts. The thyroid was normal. Sequencing of the patient's lymphocyte DNA revealed a novel heterozygous TITF1/NKX2.1 mutation (I207F). This mutation was not found in either parent. In vitro, the mutant TITF-1 had reduced DNA binding and transactivation capacity. CONCLUSION: This is the first reported case of a heterozygous TITF1/NKX2.1 mutation leading to neonatal death from respiratory failure. The association of severe unexplained respiratory distress in a term neonate with mild primary hypothyroidism is the clue that led to the diagnosis.

Integration of adult patients with phenylketonuria into professional life: long-term follow-up of 27 patients in a single centre in Switzerland

BACKGROUND Neonatal screening and treatment of phenylketonuria (PKU) prevent the development of neurocognitive impairment. The degree of dysfunction may be related to metabolic control and responsible for a hampered school career. METHODS This was a retrospective study from a single metabolic unit of a Swiss University Hospital. The time point of diagnosis and all Phenylalanin (Phe) concentrations during the follow-up were recorded. The primary outcome was integration into professional life defined as no professional studies versus accomplished apprenticeship versus high school diploma/university. Phe levels were correlated with professional outcome. The control group consisted of the patients' healthy parents and siblings. RESULTS A total of 27 patients (13 females, 14 males) were included in the study. The mean (SD) follow-up period was 25.1 (7.6) years. The control group consisted of 57 subjects. Overall, 23 patients were diagnosed by neonatal screening, and 4 patients were diagnosed later. All 4 were in the non-professional study group. Compared with the controls there were significantly more patients in the non-professional study group (26% vs 9%, p <0.05) and significantly less in the accomplished apprenticeship group (59% vs 82%; p <0.04). After exclusion of the patients with late diagnosis no significant differences were found with regard to the professional integration between patients and controls. Significant differences in Phe-levels between the three groups could be documented between 2-10 years of age with the highest levels in the non-professional study followed by the accomplished apprenticeship and the high school diploma group (p <0.01). CONCLUSION Patients who are diagnosed by neonatal screening and are consequently cared for are able to accomplish an apprenticeship or a high school diploma.

DISTRIBUTION OF NEONATAL HYPOTHYROIDISM IN TEXAS (SCREENING)

The State of Texas began mandatory screening for neonatal hypothyroidism in February 1980. The data from the first three years of the program's operation were compiled and incidence rates were calculated. Incidence rates include summary rates for the Texas population as well as specific rates by sex, race, geographic area, and month of the year.^ Differences in incidence rates were studied to determine whether these differences may be attributed to bias in data collection, or bias due to differences in blood thyroxine levels associated with sex, race, or geographic location.^ An attempt was made to definitively identify the type of neonatal hypothyroidism for each case from Harris County. Incidence rates were used to study relationships between specific diagnoses and race and sex. ^

Measuring parent satisfaction with a neonatal hearing screening program

The primary aim of the present study was to investigate parent satisfaction with a neonatal hearing screening program through use of a valid and reliable questionnaire developed for this purpose (Parent Satisfaction Questionnaire with Neonatal Hearing Screening Program; PSQ-NHSP). Eighty parents whose children had received hearing screening participated in this study. High levels of satisfaction were reported with more than 90% of parents satisfied with all aspects of the program. The PSQ-NHSP was analyzed for validity and reliability and demonstrated excellent internal consistency reliability (sigma = 0.94) and excellent test-retest reliability (rho = 0.97). Content validity of the PSQ-NHSP was partially established by reviewing available literature on parent satisfaction studies in other pediatric health-care service programs. Construct validity of the PSQ-NHSP was indicated by a significant positive relationship between overall satisfaction and the three specific dimensions in the questionnaire. The satisfaction questionnaire was found to be a useful instrument for identifying service shortfalls, and routine use of the PSQ-NHSP in other neonatal hearing screening programs is recommended.

Achieving the millennium development goals for health - Cost effectiveness analysis of strategies for. maternal and neonatal health in developing countries

Objective To determine the costs and benefits of interventions for maternal and newborn health to assess the appropriateness of current strategies and guide future plans to attain the millennium development goals. Design Cost effectiveness analysis. Setting Two regions classified by the World Health Organization according to their epidemiological grouping: Afr-E, those countries in sub-Saharan Africa with very high adult and high child mortality, and Sear-D, comprising countries in South East Asia with high adult and high child mortality. Data sources Effectiveness data from several sources, including trials, observational studies, and expert opinion. For resource inputs, quantifies came from WHO guidelines, literature, and expert opinion, and prices from the WHO choosing interventions that are cost effective database. Main outcome measures Cost per disability adjusted life year (DALY) averted in year 2000 international dollars. Results The most cost effective mix of interventions was similar in Afr-E and Sear-D. These were the community based newborn care package, followed by antenatal care (tetanus toxoid, screening for pre-eclampsia, screening and treatment of asymptomatic bacteriuria and syphilis); skilled attendance at birth, offering first level maternal and neonatal care around childbirth; and emergency obstetric and neonatal care around and after birth. Screening and treatment of maternal syphilis, community based management of neonatal pneumonia, and steroids given during the antenatal period were relatively less cost effective in Sear-D. Scaling up all of the included interventions to 95% coverage would halve neonatal and maternal deaths. Conclusion Preventive interventions at the community level for newborn babies and at the primary care level for mothers and newborn babies are extremely cost effective, but the millennium development goals for maternal and child health will not be achieved without universal access to clinical services as well.

Rastreio neonatal dos défices do ciclo da ureia em Portugal

Os défices do ciclo da ureia são um grupo de doenças hereditárias do metabolismo caracterizadas fundamentalmente por uma acumulação de amónia. Clinicamente o espectro é muito alargado, com formas de apresentação no período neonatal até situações mais moderadas de apresentação tardia em adultos. O tratamento é fundamentalmente de base nutricional e traduz-se numa redução significativa da mortalidade e morbilidade. Com a introdução da espectrometria de massa nos laboratórios de rastreio neonatal em meados dos anos 90, passou a ser possível quantificar alguns intermediários do ciclo, o que associado à existência de um intervalo livre e um tratamento eficaz, permitiu o rastreio de algumas das doenças deste grupo. Em 2004 iniciou-se em Portugal o rastreio dos défices do ciclo da ureia, tendo-se rastreado até ao presente, 988 687 recém-nascidos e identificado 19 casos positivos. Recentes desenvolvimentos técnicos vieram possibilitar a quantificação de novos marcadores, mais concretamente do ácido orótico, o que abre a possibilidade de rastrear o défice em ornitina transcarbamilase, o défice do ciclo da ureia mais frequente. Os autores apresentam a situação atual do rastreio dos défices do ciclo da ureia e as perspetivas em virtude dos novos desenvolvimentos técnicos.

Rastreio neonatal da homocistinúria clássica revela uma elevada frequência da deficiência em MAT I/III na Península Ibérica

A homocistinúria devida à deficiência da enzima cistationina -sintetase ou “homocistinúria clássica” é uma doença metabólica rara (1/344 000 RN), de transmissão autossómica recessiva e caracterizada por elevada heterogeneidade clínica, que frequentemente contribui para o diagnóstico tardio. Existe tratamento efetivo, se instituído antes de se instalarem sintomas irreversíveis, pelo que tem sido incluída num número considerável de programas de rastreio neonatal. O rastreio baseia-se na determinação dos níveis plasmáticos de metionina, por espectrometria de massa em tandem (ms/ms), mas conduz à identificação de muitos casos falsos-positivos, portadores de uma condição com significado clínico não completamente esclarecido, a deficiência em metionina adenosiltransferase (MAT I/III). Ambas as condições são rastreadas na Galiza e em Portugal desde 2000 e 2004, respetivamente. Desde então, foram identificados três doentes com homocistinúria clássica e 44 doentes com deficiência em MAT I/III. Uma forma dominante, e aparentemente benigna, desta última condição, associada à mutação p.R264H, parece ser muito frequente na Península Ibérica. A implementação de um teste de segunda linha, consistindo na determinação da homocisteína total, permitiria reduzir consideravelmente o número de RN identificados com deficiência em MAT I/III e melhorar a especificidade e valor positivo preditivo do rastreio da homocistinúria clássica.