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Laparoscopy was introduced more than 100 years ago. However, in some fields its use still meets resistance. Technology such as laparoscopy may help to identify rare and complex disorders, even in very ordinary procedures, such as inguinal hernia repair. This report highlighted the importance of early diagnosis of a complex condition using commonly available technology. To the best of our knowledge, there has not been a similar reported case in such a young patient during laparoscopic inguinal hernia repair.

Background: Unlicensed (UL) and Off-label (OL) prescription of medications is common in paediatrics and does not constitute negligent practice since there is often no approved alternative according to FDA bulary. Aim: The study aimed to determine the current frequency of UL and OL prescriptions in children from one month to 12 years of age in a Paediatric Inpatient Unit (PIU). Methods: This is an observational, prospective study, reviewing the prescriptions of all patients admitted to the PIU in a university hospital in a single week in August 2014 and a single week in January 2015. Results: We included 157 patients of median age 18 months and median length of stay 24 days. There were 1,328 prescription items (average of 8.4 items/patient) and only two patients without UL/OL use. During the winter season (August), 27% of prescriptions were classified as UL and 44.6% as OL, and during summer (January), 29.6% as UL and 45.1% as OL. We identified 188 medications, of which the most prescribed were paracetamol (11%) and dipyrone (9.5%). The most frequent OL classification was regarding drug formulation (15.8%). In the winter week, the most frequent reasons for admission were respiratory (44%), followed by other clinical causes (CC) (17.3%), while in the summer week, they were CC (26.3%), followed by surgical and gastrohepatic (23.7%). Conclusion: The OL prescription of medicines for children in Brazil is in accordance with the international literature. The higher prevalence of OL due to formulation found in this study is related to the use of formulations other than those used by the FDA.

This report describes an adolescent with Mixed Gonadal Dysgenesis and unexpected mosaicism [karyotype 46,X,mar(Y)/ 47,X, mar(Y),+mar(Y)].). Diagnosis with 1 month of age due to atypical genitalia. He presented a right streak gonad, which was removed due to the risk for germ cell tumor, and a left testis with epididymis barely connected and without vas deferens. Left testis maintenance was sufficient for him to undergo spontaneous puberty. The patient was non-responsive to growth hormone. Webbed neck was the only dysmorphic feature. To the best of our knowledge, there were no similar cases reported with spontaneous pubertal progress reported in the literature.

Molecular diagnosis is rarely established in 46,XX testicular (T) disorder of sex development (DSD) individuals with atypical genitalia. The Wilms' tumour factor-1 (WT1) gene is involved in early gonadal development in both sexes. Classically, WT1 deleterious variants are associated with 46,XY disorders of sex development (DSD) because of gonadal dysgenesis. We report a novel frameshift WT1 variant identified in an SRY-negative 46,XX testicular DSD girl born with atypical genitalia. Target massively parallel sequencing involving DSD-related genes identified a novel heterozygous WT1 c.1453_1456del; p.Arg485Glyfs*14 variant located in the fourth zinc finger of the protein which is absent in the population databases. Segregation analysis and microsatellite analysis confirmed the de novo status of the variant that is predicted to be deleterious by in silico tools and to increase WT1 target activation in crystallographic model. This novel and predicted activating frameshift WT1 variant leading to the 46,XX testicular DSD phenotype includes the fourth zinc-finger DNA-binding domain defects in the genetic aetiology of 46,XX DSD.

Ventilator-induced lung injury is well recognized, and appropriate arterial saturation target is unknown, so gentle modes of ventilation and minimizing oxidative stress have been well studied. Our objective was to analyze any association between the oxygen levels at blood sampling and plasma levels of the interleukins IL-6, IL-1β, IL-10, and IL-8 and TNF-αin preterm newborns under mechanical ventilation (MV) in their first two days.Methods. Prospective cohort including neonates with severe respiratory distress. Blood samples were collected right before and 2 hours after invasive MV. For analysis purposes, newborns were separated according to oxygen requirement: low oxygen (≤30%) and high oxygen (>30%) groups. Interleukins were measured using a commercially available kit.Results. 20 neonates (gestational age 32.2 ± 3 weeks) were evaluated. Median O2saturation levels pre-MV were not different in both oxygen groups. In the high oxygen group, IL-6, IL-8, and TNF-αplasma levels increased significantly after two hours under MV.Conclusions. Despite the small sample studied, data showed that there is a relationship between VILI, proinflammatory cytokines, and oxygen-induced lung injury, but a study considering oxidative marker measurements is needed. It seems that less oxygen may keep safer saturation targets playing a less harmful role.

Background/Aims: Hypernatremic dehydration in term neonates is associated with inadequate fluid intake, usually related to insufficient lactation. The use of hypotonic fluids is appropriate to dilute serum sodium (SNa), but cerebral edema may develop when it happens abruptly. Our objective was to clarify how to correct hypernatremic dehydration properly. Methods: The following databases were searched, limited to studies published until January 31st, 2016: Clinical Trials, MEDLINE/PubMed, EMBASE, LILACS, and the Cochrane Library. We included open-label trials, nonrandomized controlled trials, or prospective and retrospective case series evaluating relevant outcomes. Information regarding the way of administering the treatment, type of fluid used, rates of complications and outcomes, as well as the rate of SNa reduction were collected. Results: Searches yielded 771 articles: 64 had the full text reviewed and 9 were included. No randomized clinical trials or systematic reviews focusing on treatment of hypernatremic dehydration and its outcomes were found. We found a scarcity of high quality studies and great methodology heterogeneity. Conclusions: More severe hypernatremia is at greater risk of causing severe adverse effects of treatment. There is no consensus about the optimal rate of SNa drop in this population, but a slower correction appears to be safer. Questions as when parenteral fluids are indicated remain unanswered.

Mucopolysaccharidosis type I (MPS I) is a storage disorder caused by the deficiency of the lysosomal enzyme α-L-iduronidase. MPS I has a chronic progressive evolution with multisystemic symptomatology and wide clinical variability, with its main manifestations in the skeletal, respiratory, cardiac and neurological systems. Until recently, therapeutic options for MPS I were limited to hematopoietic stem cell transplantation for severe cases, and palliative care. Laronidase (Aldurazyme®, BioMarin/Genzyme, CA, USA), a synthetic variant of the human α-L-iduronidase, is a specific treatment for MPS I. Enzyme replacement therapy with intravenous infusion of laronidase aims to reduce and/or prevent the accumulation of glycosaminoglycans (dermatan and heparan sulfate), which is probably the most important, although possibly not the only, cause of the clinical manifestations of MPS I. This article reviews the data published to date on the clinical indications and user experience of laronidase in patients with MPS I.

Epidemiological research points to the high prevalence of psychiatric disorders among insomniacs. We carried out a cross-sectional study with medical students with the aim of evaluating the association between insomnia and suspicion of psychiatric disorder; 302 medical students were included (184 males and 118 females; mean age = 20.47±1.89 years). The main association was tested by logistic regression analysis. The overall prevalence of positivity in a screening test for psychiatric disorder was 22.19%; and of insomnia, 28.15%. Difficulty initiating sleep (OR=3.45), difficulty maintaining sleep (OR=7.61), falling asleep later (OR=1.99) and waking up earlier (OR=1.91) were associated with suspicion of psychiatric disorder. As a group, the variables difficulty initiating sleep, difficulty maintaining sleep, falling asleep after 11 pm, and waking up before 6 am presented an odds ratio of 5.96 for positivity in the screening for psychiatric disorder. Furthermore, difficulty maintaining sleep (OR=2.24) was associated with "being female," and falling asleep later (OR=0.43) was associated with "being male". These results underscore the importance of determining in what cases difficulty sleeping may have severe clinical repercussions or affect performance. Estudos epidemiológicos têm mostrado alta prevalência de transtorno psiquiátrico em pessoas com insônia. Realizamos estudo transversal em amostra de estudantes de medicina, com o objetivo de avaliar a associação entre insônia e positividade na triagem para transtorno psiquiátrico; 302 estudantes foram incluídos (184 homens e 118 mulheres; média da idade = 20.47±1,89 anos). A associação foi testada através da análise de regressão logística. A prevalência de teste positivo na triagem para transtorno psiquiátrico foi 22,19%; e de insônia, 28,15%. Dificuldade para iniciar o sono (OR=3,45), dificuldade para manter o sono (OR=7,61), dormir tarde (OR=1,99) e levantar cedo (OR=1,91) foram as variáveis associadas à possibilidade de transtorno psiquiátrico. Quando consideradas em conjunto, as variáveis "dificuldade em iniciar o sono", "dificuldade em manter o sono", "dormir após 23 h" e "acordar antes das 6 h" apresentaram razão de chance de 5,96 para positividade na triagem para transtorno psiquiátrico. Além disso, dificuldade em manter o sono (OR=2,24) foi associada ao sexo feminino; e dormir tarde (OR=0,43), ao sexo masculino. Esses resultados enfatizam a importância de determinar em que caso a dificuldade com o sono pode ter repercussões clínicas severas ou afetar o desempenho.

In preterm infants, the need for intubation and mechanical ventilation is associated with ventilator-induced lung injuries and subsequent bronchopulmonary dysplasia. The aim of the present review was to improve the understanding of the mechanisms of injury that involve cytokine-mediated inflammation to contribute to the development of new preventive strategies. Relevant articles were retrieved from the PubMed database using the search terms "ventilator-induced lung injury preterm", "continuous positive airway pressure", "preterm", and "bronchopulmonary dysplasia". The resulting data and other relevant information were divided into several topics to ensure a thorough, critical view of ventilation-induced lung injury and its consequences in preterm infants. The role of pro-inflammatory cytokines (particularly interleukins 6 and 8 and tumor necrosis factor alpha) as mediators of lung injury was assessed. Evidence from studies conducted with animals and human newborns is described. This evidence shows that brief periods of mechanical ventilation is sufficient to induce the release of pro-inflammatory cytokines. Other forms of mechanical and non-invasive ventilation were also analyzed as protective alternatives to conventional mechanical ventilation. It was concluded that non-invasive ventilation, intubation followed by early surfactant administration and quick extubation for nasal continuous positive airway pressure, and strategies that regulate tidal volume and avoid volutrauma (such as volume guarantee ventilation) protect against ventilator-induced lung injury in preterm infants.

OBJECTIVE To analyze the frequency of unlicensed (UL) and off-label (OL) prescriptions in neonates admitted to the neonatal intensive care unit of a tertiary care hospital and to determine their association with patients' severity. METHODS Observational cohort study including drugs prescribed during hospitalization of neonates over a 6-week period between July and August 2011. The drugs were classified as UL and OL for dose, frequency, presentation, age group, or indication, according to an electronic list of drugs approved by the Food and Drug Administration. Patients were followed until hospital discharge or 31 days of hospitalization, with daily records of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS We identified 318 prescription items for 61 patients (average of five items/patient); there were only 13 patients with appropriate use of medications (21%). A prevalence of 7.5% was identified for UL prescriptions and 27.7% for OL, and the most prevalent OL use was that related to age group - 19.5%. Fifty-seven medications were computed - one patient received 10 UL/OL drugs during hospitalization. The prevalence of OL uses was higher in preterm infants < 35 weeks and in those with higher severity scores (p = 0.00). CONCLUSIONS The prevalence of neonates exposed to UL/OL drugs during hospitalization was high, especially for those with higher NTISS scores. Although there is general appreciation that neonates, especially preterm infants, have a high rate of drug use, an assessment including different cultures and countries is still needed to prioritize areas for future research in the pharmacotherapy of this vulnerable population.

Jaundice is a physiological phenomenon; however, severe hyperbilirubinemia occurs in only 5 to 6% of the healthy newborn population. It has been suggested that genetic variation could enhance the risk of hyperbilirubinemia when coexpressed with other icterogenic conditions.The study included newborns with a gestational age of greater than 35 wk and weights greater than 2,000 g with indications for phototherapy. The polymorphisms from UGT1A1 (rs8175347), SLCO1B1 (rs4149056 and rs2306283), and SLCO1B3 (rs17680137 and rs2117032) were analyzed by capillary electrophoresis and hydrolysis probes.A total of 167 hyperbilirubinemic infants and 247 control subjects were enrolled. The gender, ABO incompatibility, birth weight, and gestational age differed between the groups, but the allelic and genotypic frequency of the polymorphisms from SLCO1B genes did not. In logistic regression, the ABO incompatibility, gestational age, and polymorphic T allele of rs2117032 remained in the model. The presence of this polymorphism seemed to provide protection from hyperbilirubinemia. The individuals who were homozygous for the G allele of rs2306283 and who were glucose 6-phosphate-dehydrogenase deficient were more frequent among the cases.Although genetic variation accounts for a good part of this condition, the association between different polymorphisms and environmental factors has yet to be explained.

To evaluate the correlation between glucose-6-phosphate-dehydrogenase (G6PD) deficiency and neonatal jaundice.Prospective, observational case-control study was conducted on 490 newborns admitted to Hospital de Clínicas de Porto Alegre for phototherapy, who all experienced 35 or more weeks of gestation, from March to December 2007. Enzymatic screening of G6PD activity was performed, followed by PCR.There was prevalence of 4.6% and a boy-girl ratio of 3:1 in jaundiced newborns. No jaundiced neonate with ABO incompatibility presented G6PD deficiency, and no Mediterranean mutation was found. A higher proportion of deficiency was observed in Afro-descendants. There was no association with UGT1A1 variants.G6PD deficiency is not related to severe hyperbilirubinemia and considering the high miscegenation in this area of Brazil, other gene interactions should be investigated.

Mucopolysaccharidosis type II (MPS II) is an X-linked recessive disease caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase, leading to progressive accumulation of glycosaminoglycans in nearly all cell types, tissues and organs. Enzyme replacement therapy reduces the storage of these substances in the lysosomes. Oxidative stress is related to the pathophysiology of many disorders, including inborn errors of metabolism. Oxidative damage to protein and lipid has been described in MPS types I and III. The aim of this study was to analyze DNA damage, as determined by the alkaline comet assay using silver staining, in peripheral leukocytes from MPS II patients before treatment and during the first six months of enzyme replacement therapy. We also correlated DNA damage with lipid and protein oxidative damages, analyzed by plasma malondialdehyde levels and carbonyl group content, respectively. We found a significant increase in lipid and protein damage in MPS II patients before treatment when compared to controls. Also, our results showed greater DNA damage in terms of damage index (DI) in pretreatment MPS II patients (DI = 18.0 ± 2.4) when compared to controls (DI = 66.0 ± 2.0). Enzyme replacement therapy led to a significant decrease in levels of malondialdehyde and DNA damage when compared to pretreatment, but did not reach control values. Significant positive correlations between DNA damage and malondialdehyde levels, as well as carbonyl group content, were observed. Our findings indicate that MPS II patients are subject to DNA damage and that enzyme replacement therapy is able to protect against this process.

Mucopolysaccharidosis VI is caused by accumulation of the glycosaminoglycan dermatan sulfate in all tissues due to decreased activity of the enzyme arylsulfatase B. Patients exhibit multisystemic signs and symptoms in a chronic and progressive manner, especially with changes in the skeleton, cardiopulmonary system, cornea, skin, liver, spleen and meninges. Patients usually have normal intelligence. In the past, treatment of mucopolysaccharidoses was limited to palliative medical care. The outcome for affected patients improved with the introduction of new technologies as hematopoietic stem cell transplantation, relegated to specific situations after enzyme replacement therapy (ERT) became available. The specific ERT for MPS VI, galsulfase (Naglazyme®, Biomarin Pharmaceutical) was approved in 2005 by FDA and in 2006 by EMEA, and three clinical studies including 56 patients have evaluated the efficacy and safety. Long-term follow up data with patients treated up to 5 years showed that ERT is well tolerated and associated with sustained improvements in the patients' clinical condition. Intrathecal ERT may be considered in situations of high neurosurgical risk but still it is experimental in humans, as is intra-articular ERT. It is possible that the full impact of this therapy will only be demonstrated when patients are identified and treated soon after birth, as it was shown that early introduction of ERT produced immune tolerance and improved enzyme effectiveness in the cat model. New insights on the pathophysiology of MPS disorders are leading to alternative therapeutic approaches, as gene therapy, inflammatory response modulators and substrate reduction therapy.

The purpose of this trial is to investigate the relationship between dietary calcium content and incidence of preeclampsia, comparing diet calcium content in normotensive and preeclampsia patients. Dietary calcium was measured by a dietary interview conducted at the day after delivery.This is a prospective cross-sectional study involving 1092 patients who delivered at Hospital de Clínicas de Porto Alegre - Brazil.The average diet calcium content in the studied population was 1038 mg. The average calcium intake in the normotensive group was 1057 mg, in chronic hypertension group was 962 mg, in transient hypertension group was 963 mg, in mild preeclampsia was 902 mg and in severe preeclampsia group was 755 mg. The results of this study show that pregnant women who develop severe preeclampsia have a significant lower diet calcium intake when compared to normotensive women (P = 0.018).The results of the present study can provide the foundations for prospective trials, including randomised clinical trials involving only patients with a low content of calcium in their diet.

OBJETIVO: Avaliar a extensão do uso de medicamentos não apropriados para crianças em prescrições de uma unidade de tratamento intensivo pediátrica (UTIP) terciária, de acordo com os padrões estabelecidos pela FDA. MÉTODOS: Estudo transversal, observacional, baseado na avaliação das prescrições de todos os pacientes admitidos na UTIP do Hospital de Clínicas de Porto Alegre, no período de seis semanas consecutivas. Foram considerados idade, sexo, peso, doença prévia, motivo de admissão na UTIP, e PIM (pediatric index of mortality) dos pacientes, e todos os medicamentos prescritos e suas indicações, com as respectivas apresentações, doses, freqüências e vias de administração. O critério de adequação na prescrição dos medicamentos seguiu a classificação de aprovação da FDA, baseada no catálogo de informações de medicamentos USP DI 2001, em três faixas etárias pediátricas. RESULTADOS: Os dados foram obtidos nos meses de julho e agosto de 2002, em diferentes dias, de seis semanas consecutivas, baseados nas prescrições de 51 pacientes em 54 admissões de UTIP. A mediana de idade dos pacientes foi 10,5 meses, sendo 61% do sexo masculino. Dois terços (65%) dos pacientes apresentavam doença prévia, e 87% das admissões ocorreram por motivos clínicos, sendo 57% por causas respiratórias. Foram registrados 747 itens de prescrição, com prevalências de 10,5% para medicamentos não aprovados e 49,5% para medicamentos não padronizados. A distribuição das prevalências de prescrição, tanto pela faixa etária quanto pelo nível de gravidade dos pacientes na admissão (de acordo com as categorias de risco do PIM), nas três classes de medicamentos, não mostrou diferença estatística entre os grupos. CONCLUSÃO: A alta prevalência de prescrições com medicamentos não apropriados para crianças confirma, também no nosso meio, o uso inadequado e inadvertido de medicamentos não testados ou de apresentações não padronizadas para crianças em UTIP. Isso aponta para a necessidade de estimular a realização de estudos sobre qualidade, eficácia e segurança de medicamentos para uso pediátrico. OBJECTIVE: To assess the extent of use of drugs not recommended for children in prescriptions issued in a tertiary pediatric intensive care unit (PICU), according to FDA standards. METHODS: Observational cross-sectional study. The prescriptions issued to all patients admitted to the PICU at Hospital de Clínicas de Porto Alegre, Brazil, over a six-week period were assessed. Patients' age, sex, weight, prior disease, reason for admission to the PICU and pediatric index of mortality (PIM) were recorded, as were all drugs prescribed, their indications, presentations, doses, frequencies and means of administration. Adequacy for prescription of drugs in three pediatric age ranges was defined according to USA Food and Drug Administration (FDA) approval classification, based on the USP DI 2001 drug reference database. RESULTS: Data were obtained in the months of July and August 2002, on different days, for six consecutive weeks, based on prescriptions issued to 51 patients in 54 admissions to the PICU. Median patient age was 10.5 months; 61% of patients were male. Two thirds of patients (65%) presented prior disease. 87% of admissions were due to clinical reasons, of which 57% were respiratory complaints. A total of 747 prescription items were registered, with prevalence of 10.5% for non-approved uses and 49.5% for off-label uses. No statistically significant difference was found in the distribution of prevalence of irregular prescription either by the three age ranges or by level of severity of disease at admission (according to PIM risk categories). CONCLUSION: The high prevalence of prescription of drugs not recommended for children confirms, in the Brazilian context, the inadequate and inadvertent use of drugs either not approved or off-label for PICU use. This demonstrates the need to encourage further studies on the quality, effectiveness and safety of drugs for pediatric use.

Background and Aims It is known that unlicensed medicines (unapproved) or used other way than directed in the label (off-label use) are widely prescribed in children. In the NICU, the severity of the patient justifies this type of prescription, evoking the risk-benefit ratio. We aimed to analyze the exposure to unapproved or off-label drugs in NICU in a tertiary university hospital in southern Brazil. Method A descriptive cohort of drugs prescribed during hospitalization for 129 patients within 6 weeks. The drugs were classified as non-approved, and off-label for the dose, frequency, presentation, age or indication, according to FDA-approved e-lary. Results We identified 318 items of prescriptions for 61 patients - an average of 5 items/patient, 68 patients without medication. Prevalence of 7.5% for unapproved drugs and 27.7% for off-label, and the more prevalent off-label use was regarding to age - 19.5%. It was computed 57 medications - one patient used 10 off-label drugs during hospitalization. The prevalence of off-label uses was higher in infants < 35 weeks (p=0.00). Sepsis, malformation and extreme prematurity were the main causes to prescribe an off-label medication (p=0.00). Conclusion Neonates exposed to off-label drugs in NICU had more severe disease, and because it is known that newborns, especially premies, use many drugs, it is necessary to prioritize research in the pharmacotherapy of this population so vulnerable.

Background and aims: Neonatal jaundice seems a benign condition but babies must be monitored in order to identify those who are at higher risk of encephalopathy. Abnormalities in hepatic conjugation of bilirubin were proposed in those cases - polymorphisms of the hepatic enzyme UGT1A1. Herein, we estimated the frequency of alleles and of genotypes of the promoter region of UGT1A1 gene in newborns and evaluated its association with severe hyperbilirubinemia. Methods: Case-control study, including all neonates who were in phototherapy at NICU/HCPA from March to December 2007, born > 35w of gestational age and weight > 2000g. Controls were neonates not jaundiced. Informed consent form applied. PCR performed and analyzed in GeneMapper® program. Results (490 NBs included): There were 7 of the 10 possible UGT1A1 genotypes identified; those related to Gilbert's syndrome were in 16%. Prevalence of polymorphic genotypes in icteric patients was 13.5% and in normal patients was 18.2%, p=0.08. In 86.6% of white neonates - lowrisk genotypes, 13.4%, Gilbert's genotypes, while among blacks, 34% showed the latter genotypes, and 76%, low-risk (p=0.001). Conclusions: In the present sample the presence of polymorphic variants of UGT1A1 could not be associated to severe hyperbilirubinemia. Variants showed allelic prevalence and frequencies similar to those observed in other populations, with a highlight to the genotypes of higher risk in blacks and mulattos. Possibly due to the high miscegenation found in our state, other factors and genic interactions should be sought in order to explain severe neonatal hyperbilirubinemia, including the study of other polymorphisms.

Background and Aims The Neonatal Therapeutic Intervention Scoring System (NTISS) is an index of intensity of use of technologies with significant association to mortality risk. We intended to analyze this score use in the NICU of a university hospital, correlating with mortality. Method It was a prospective cohort including 129 newborns admitted to NICU during a 6-week-period. Patients were followed for up to 31 days, with daily calculation of NTISS. Demographic data were all obtained by review of medical records, under informed consent. For statistical analysis It was used the x² and Mann-Whitney tests. Results The most frequent cause of hospitalization was neonatal jaundice (35%), followed by early respiratory dysfunction (16%) and prematurity (13%), the mean hospital stay was 10 days. The median NTISS was 6 on the first day and remained stable in the next days. Only 4 patients died during the study - with a first day NTISS median of 28 vs 6 (p = 0.002). This behavior continued until the seventh day and SNAPPEII score also showed this kind of tendency. Patients with extreme prematurity, congenital malformation or early respiratory dysfunction that remained hospitalized until 31 days exhibited NTISS values greater than the median until the 27th day of admission. Conclusion The NTISS, at least in the first week of hospitalization, was higher in patients who die, as a predictor of mortality in this sample. The NTISS remained high under conditions known to be severe for a long period of hospitalization, which may affect heath costs.

Background and aims: IEM are genetic diseases the majority with recessive inheritance and varied clinical presentation that turn diagnosis into a challenge. Especially in developing countries, knowledge of IEM by health professionals is restricted. In order to overcome this problem, an Information Service on IEM (SIEM) was created in Brazil, being a pioneering service in Latin America. SIEM is operating in the Genetics Service of HCPA since October 2001, helping physicians to diagnose suspected patients as a toll-free service. For each consultation a follow-up is conducted and the case is considered “concluded” after its diagnosis is confirmed and classified as metabolic disease or not. Some cases remain undiagnosed. This study aims to compare investigational strategies in infants admitted to ICU under 1y-old, in order to emphasize personal investigation and remote advisement in diagnosis. Methods: Cross-sectional study of 3 groups of children suspected to present an IEM, to be developed in 24 months, enrolling patients of NICU or PICU of HCPA, or suspected cases that consulted to SIEM, or even suspected cases which their biological samples were sent to IEM Laboratory of HCPA. Results: We did not find any paper comparing investigational strategies, that's why this study is important. Giugliani et al, in 1991, diagnosed IEM in 8% of suspected samples and Sanseverino studied ICU suspected patients confirming 13%. Unpublished data from SIEM showed a prevalence of 16%. Conclusions: we estimate to study 225 for each group to find a difference of at least 8% between SIEM cases and laboratory cases.