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The purpose of the study is to test whether NT-proBNP serves as a screening tool for low-risk patent ductus arteriosus and safely avoids routine early echocardiography. This is a prospective observational study in preterm infants ≤32 weeks of gestational age. Infants with ≥5100 pg/ml (positive screening) at 48-72 hours of life received comprehensive echocardiography and were treated according to shunt severity. Infants with NT-proBNP below 5100 pg/ml (negative screening) were managed expectantly. The main outcome was need for ductus treatment within the first 7 days of life. One hundred twenty-five infants were included; 82 had a negative NT-proBNP screening and 43 had a positive NT-proBNP screening. No infant (0%) with a negative screening was treated for ductus while 26 (60.4%) with a positive screening were treated (p < 0.001). NT-proBNP avoided a 65.6% of routine echocardiograms. NT-proBNP had an excellent performance to predict PDA treatment (AUC = 0.967).Conclusion: NT-proBNP at 48-72 hours of life has an excellent performance to detect low risk and avoids unnecessary echocardiograms. This may contribute to optimize PDA management in terms of resource utilization., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Galician newborn screening program for early detection of endocrine and metabolic diseases began in 1978 and was a pioneer in expanded newborn screening in Spain with the incorporation of mass spectrometry in July 2000. As a primary objective, 28 diseases are screened, including those recommended SNS except sickle cell anemia which is in the inclusion phase. In its 20-year history, 404,616 newborns (nb) have been analyzed, identifying 547 cases affected by the diseases included, with a global incidence of 1: 739 newborns and 1: 1.237 of the screened inborn errors of metabolism (IEM) (1:1.580 nb if excluding benign hyperphenylalaninemia-HPA), with an average participation of 99.35%, progressively higher during the analyzed period. Among the pathologies screened, congenital hypothyroidism (1:2.211 nb), cystinuria (1:4.129 nb) and HPA (1:5.699 nb), followed by phenylketonuria and cystic fibrosis (1:10,936 nb) stand out for their incidence. Sixty-six cases of false positives were identified (seventeen of them in relation to maternal pathology) and five false negatives, being the overall PPV and NPV of the program respectively of 89.2% and 99.99%, with a sensitivity of 99.09% and a specificity of 99.98%. The mortality rate of diagnosed CME patients is 1.52%, with eleven cases presenting symptoms prior to the screening result (2%). The intelligence quotient of IEM patients at risk of neurological involvement is normal in more than 95% of cases.

Introduction: Energy deficiency is a cause for myocardial dysfunction during septic shock. In rodents, septic shock decreases the oxidation of long-chain fatty acids and glucose in the myocardium causing energy deficiency. However, the effect of septic shock on myocardial energy metabolites in large animals and human is unknown., Objectives: Investigate the effects of septic shock on myocardial energy metabolites in domestic pigs., Methods: Seventeen female pigs divided into control and lipopolysaccharide (LPS)-induced septic shock groups. Myocardial metabolites were analyzed ex vivo by 1 H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. Gene and protein expression analysis were analyzed by real-time PCR and western blot., Results: Septic shock was associated with an increase in myocardial levels of short- and medium-chain acylcarnitines, lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression. COX-2 and prostaglandin E4 receptor gene expression also increased in the septic myocardium, although the only elevated eicosanoid in the septic animals was thromboxane B2. Myocardial levels of niacin, taurine, glutamate, glutamine, and glutathione were higher, and hypoxanthine levels lower in septic pigs than controls., Conclusions: In pigs, septic shock induced by LPS caused myocardial changes directed to decrease the oxidation of medium- and short-chain fatty acid without an effect on long-chain fatty acid oxidation. The increase in myocardial levels of lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression suggest that septic shock decreases pyruvate dehydrogenase complex activity and glucose oxidation. Homeostasis of niacin, taurine, glutamate, glutamine, glutathione, hypoxanthine and thromboxane B2 is also affected in the septic myocardium.

Objective: To assess whether early NT-ProBNP can identify the need for echocardiographic assessment of hemodynamically significant patent ductus arteriosus (HsPDA) in preterm infants., Study Design: Prospective observational study of infants with a gestational age ≤32 weeks. Echocardiographic assessment and NT-proBNP measurement were performed at 48-96 h. ROC curves were generated to assess optimal cutoffs to detect HsPDA and predict the need for treatment., Results: Eighty-five patients were included. HsPDA was present in 28 infants (37.6%), and 22 (25.8%) received treatment. The optimal NT-proBNP cutoff for the detection of HsPDA was 5099 pg/mL (sensitivity 94%, specificity 82%, area under the curve 0.941, P < 0.001). Only 1 child with NT-proBNP levels <5099 pg/mL was ultimately treated for PDA. NT-proBNP screening could have avoided 45 of 85 routine echocardiograms (53%)., Conclusion: NT-proBNP screening at 48-96 h of life may identify preterm infants at low risk for HsPDA, improving PDA management.

Clinical practice guidelines are an important tool for improving healthcare. In recent years there has been accumulating evidence on the impact of nutritional supplementation with probiotics in the very low birth weight infants. With no uniformity in microorganisms and strains used. The Spanish Neonatology Society (SENeo), through its Nutrition and Metabolism Group has undertaken to develop recommendations that will be useful as a guide for the neonatologist in this field., (Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

The effectiveness of antenatal corticosteroid therapy for foetal lung maturation in pre-term infants is well known, but there is uncertainty about the time that the treatment remains effective. A descriptive, longitudinal study was conducted to determine whether the need for surfactant administration was determined by the time-lapse between corticosteroids administration and delivery, and when repeating the doses of maternal corticosteroids should be considered. A total of 91 premature infants ≤32 weeks and/or ≤1,500 g (limit 34+6 weeks) whose mothers had received a complete course of corticosteroids were included. In patients at 27-34+6 weeks, we found that the longer the time elapsed between delivery and administration of corticosteroids, most likely were the babies to require treatment with surfactant (P=.027). The resulting ROC curve determined an 8-days cut-off after which repeating a dose of corticosteroids should be assessed., (Copyright © 2013 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data., Methods: Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications., Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood)., Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

Following current recommendations for preventing retinopathy of prematurity (ROP) involves screening a large number of patients. We performed a prospective study to establish a useful screening system for ROP prediction and we have determined that measuring serum levels of IGF1 at week three and the presence of sepsis have a high predictive value for the subsequent development of ROP. A total of 145 premature newborn, with birthweight <1500 g and/or <32 weeks gestational age, were enrolled. 26.9% of them showed some form of retinopathy. A significant association was found between the development of retinopathy and each of the following variables: early gestational age, low birthweight, requiring mechanical ventilation, oxygen treatment, intracranial haemorrhage, sepsis during the first three weeks, bronchopulmonary dysplasia, the need for erythrocyte transfusion, erythropoietin treatment, and low levels of serum IGF1 in the third week. A multiple logistic regression analysis was used to obtain curves for the probability of developing ROP, based on the main factors linked with ROP, namely serum levels of IGF1 and presence of sepsis. Such preclinical screening has the ability to identify patients with high-risk of developing retinopathy and should lead to better prediction for ROP, while at the same time optimising the use of clinical resources, both human and material.

Introduction: Excess methionine can cause central nervous system disorders such as diffuse cerebral edema and disorders of myelin., Patients and Method: A retrospective and prospective (ambispective) observational study in preterm newborns admitted to our hospital over a period of 15 months and who had hypermethioninemia in neonatal screening tests by tandem mass spectrometry. The progress of these infants was monitored during the first year of life, assessing their methionine levels, diet, somatometric parameters and neurodevelopment., Results: From a study population of 187 preterm infants, 16 of them showed isolated hypermethioninemia. Weight and feeding the babies with a special formula enriched with methionine is related to an increased number of cases of transient isolated hypermethioninemia (62.6% received a higher contribution of methionine than 97mg/kg/day). We also found a statistically significant correlation between the days that patients received the formula and the time it takes to normalize the levels of methionine in plasma (R 0.791, p=0.000). There was no correlation between the methionine peak reached in plasma and the score on the Brunet Lézine test, at the corrected age of 6 months., Conclusions: This study highlights the importance amino acid supplements, particularly methionine, in premature infants' formulas due to the impact they may have on neurological development., (2009 Asociación Española de Pediatría. Published by Elsevier Espana. All rights reserved.)

Introduction: Glutaric Acidaemia type I (GA-I) is an autosomal recessive progressive neurodegenerative inborn error of metabolism caused by deficient activity of the enzyme glutaryl-CoA dehydrogenase (GCDH). In most cases, the diagnosis is established biochemically by the detection of glutaric acid and 3-hydroxy glutaric acid in urine and glutarylcarnitine in plasma. Patients excreting small amounts of glutaric acid may be overlooked., Objective: To investigate the value of expanded newborn screening by adding the measurement of urine glutarylcarnitine to conventional chromatography-mass spectrometry (GC-MS) in the diagnosis of GA-1., Material and Methods: We report clinical and biochemical data in 5 GA-I patients diagnosed in our Hospital. Details regarding biochemical diagnosis are emphasised and the absence or presence of symptoms was correlated with neuroimaging findings, age at diagnosis and treatment., Results: Two patients showed high glutarylcarnitine levels in plasma and were identified by routine newborn GC-MS screening. Following early appropriate treatment they are asymptomatic 6 years later. Two patients with delayed diagnosis displayed neurological sequels in spite of treatment. The remaining patient, who presented with encephalopathic episode at age 8 months showed normal glutarylcarnitine levels in routine plasma GC-MS but high urine glutarylcarnitine levels in a retrospectively screened urine sample from the newborn period., Conclusions: Early treatment seems to positively influence the clinical evolution of GA-I patients. Thus, improving the identification of GA-I represents an important diagnostic challenge. The urinary excretion of glutarylcarnitine is a specific biochemical marker of GA-I and allows the identification of patients without glutaric aciduria and with normal plasma acylcarnitine profiles.

Introduction: Maple syrup urine disease (MSUD) is a rare autosomal recessive disorder caused by an inherited deficiency of branched chain alpha-ketoacid dehydrogenase activity. Accumulation of the amino acids leucine, isoleucine, valine and alloisoleucine and their metabolic products in cells and biological fluids results in severe brain dysfunction., Patients and Methods: We present three cases of MSUD diagnosed in Galicia since 2000, the year in which the Extended Newborn Screening Program by tandem mass spectrometry was started in this region. One of the patients was diagnosed on the basis of early clinical presentation and the others by neonatal screening. Enzymatic and molecular studies confirmed two classic cases of MSUD and an intermediate variant. We describe the clinical and biochemical details at confirmation of diagnosis and the long-term outcome of the three patients. Throughout follow-up, all the patients maintained adequate leucine levels, which were near the normal range (mean levels: 220, 177 and 252 micromol/L, respectively). Several moderate metabolic decompensations were observed but leucine levels only occasionally exceeded 1000 micromol/L (one day in two patients). IQ tests were performed in all patients and scores were within the normal range. In view of our results, we believe the following measures are essential to improve the prognosis of MSUD: inclusion of this disease in Expanded Neonatal Screening Programs with early samples (at 2-3 days of life); aggressive treatment in the initial phase and during acute decompensations; strict metabolic control to prevent crises, monitoring of branched-chain amino acids (dried blood spot sample), and maintenance of long term plasma leucine levels below 300 micromol/L.

In order to investigate effects produced by external cranial irradiation on neuroendocrine systems. GH secretion (elicited by oral clonidine and by GRF-29 as iv bolus) and TSH and PRL responses to an iv bolus of TRH were evaluated in children previously irradiated for LLA (n-7) or medulloblastoma (n-3). Growth velocity was also periodically evaluated. Three years after radiotherapy, while a normal GH response to clonidine challenge was observed in 60% of cases, growth velocity was impaired in 83.3% of them. GH release induced by GRF-29 was normal in another 60% of patients. Either basal TSH values or its' response to TRH were significantly increased in the three medulloblastomas, in spite of clinical and biochemical euthyroid status of these patients. Our data indicate that cranial radiotherapy produces functional neuroendocrine alterations; specificity and degree of these are dependent on the dose received. Therefore, to allow a suitable replacement hormonal therapy as soon as possible, this type of patients need a periodic evaluation of their endocrine status.