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Background Hereditary fructose intolerance (HFI) is a rare inborn error of fructose metabolism caused by the deficiency of aldolase B. Since treatment consists of a fructose-, sucrose- and sorbitol-restrictive diet for life, patients are at risk of presenting vitamin deficiencies. Although there is no published data on the status of these vitamins in HFI patients, supplementation with vitamin C and folic acid is common. Therefore, the aim of this study was to assess vitamin C and folate status and supplementation practices in a nationwide cohort of HFI patients. Methods Vitamin C and folic acid dietary intake, supplementation and circulating levels were assessed in 32 HFI patients and 32 age- and sex-matched healthy controls. Results Most of the HFI participants presented vitamin C (96.7%) and folate (90%) dietary intake below the recommended population reference intake. Up to 69% received vitamin C and 50% folic acid supplementation. Among HFI patients, 15.6% presented vitamin C and 3.1% folate deficiency. The amount of vitamin C supplementation and plasma levels correlated positively (R = 0.443; p = 0.011). Interestingly, a higher percentage of non-supplemented HFI patients were vitamin C deficient when compared to supplemented HFI patients (30% vs. 9.1%; p = 0.01) and to healthy controls (30% vs. 3.1%; p Conclusions Our results provide evidence for the first time supporting vitamin C supplementation in HFI. There is great heterogeneity in vitamin supplementation practices and, despite follow-up at specialised centres, vitamin C deficiency is common. Further research is warranted to establish optimal doses of vitamin C and the need for folic acid supplementation in HFI.

Financiado para publicación en acceso aberto: Universidade de Vigo/CISUG Evaluation of postnatal exposure to organic pollutants is especially important for suckling infants during breastfeeding, a crucial perinatal growth period when organs and hormonal systems develop. We determined levels of 60 pollutants, including organochlorine pesticides (OCPs), organophosphorus pesticides (OPPs), pyrethroids (PYRs), polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs), and polybrominated diphenyl ethers (PBDEs), in 81 breast milk samples from breastfeeding mothers from Santiago de Compostela (north-western Spain). For most detected organic pollutants, levels were correlated with the season of milk sampling, maternal age at delivery, and place of residence. Dietary consumption habits (eggs, molluscs, and vegetable oils) were also correlated with OCP, OPP, PCB, PBDE and PYR levels. We also assessed the risk to infant health of exposure to organic pollutants in breast milk. PAHs, OCPs, OPPs, and PYRs accounted for almost 95% of the targeted organic pollutants in the samples analysed. Xunta de Galicia | Ref. ED431C 2022/35 Instituto de Salud Carlos III | Ref. RD21/0012

Retinopathy of pre-maturity (ROP) is a retinal disease that causes arrest of vascularization of the retina and can result in retinal detachment and blindness. Current screening protocols may not be sufficiently accurate to identify all at-risk patients. The aim of this study is to validate a method for improved identification of newborns at risk of ROP. We conducted a prospective clinical trial of pre-term newborns

Newborn screening programs are a fundamental tool for secondary prevention or pre-symptomatic detection of certain conditions. The implementation of a newborn screening program requires an evaluation of effectiveness, safety, cost-effectiveness, feasibility and budget impact. Economic evaluation aims to contribute to the sustainability and solvency of health systems, especially when it comes to informing about financing health interventions with public funds. This funding must be justified on the basis of robust evidence of effectiveness, safety, cost-effectiveness, and acceptability. One of the most important limitations when evaluating the cost-effectiveness of a newborn screening program for hereditary disorders or congenital errors of metabolism is the scarcity of scientific evidence that limits the robustness of the economic analysis. Given the low availability of data, the use of expert opinion as a data source is unavoidable to complete the information. However, two main problems make it difficult to synthesize data obtained from various sources: biases and heterogeneity. Moreover, the measurement of quality-adjusted life years (QALYs) in pediatric populations poses serious methodological challenges. In Spain, although there is some heterogeneity in the supply of newborn screening programs between regions, guidelines are being established based on the best available scientific evidence to achieve the homogenization of newborn screening policies and programs at national level.Los programas de cribado neonatal son una herramienta fundamental para la prevención secundaria o detección presintomática de determinadas afecciones. La implantación de un programa de cribado neonatal requiere necesariamente de una evaluación de su efectividad, seguridad, coste-efectividad, factibilidad e impacto presupuestario. La evaluación económica pretende contribuir a la sostenibilidad y solvencia de los sistemas sanitarios, especialmente a la hora de informar sobre la posible financiación, con fondos públicos, de intervenciones sanitarias como el cribado poblacional. Esta financiación debe justificarse en base a pruebas robustas de efectividad, seguridad, coste-efectividad y aceptabilidad. Una de las limitaciones más importantes a la hora de evaluar el coste-efectividad de un programa de cribado neonatal de trastornos hereditarios o de errores congénitos del metabolismo es la escasez de evidencia científica que limita la solidez y robustez del análisis de evaluación económica. Dada la baja disponibilidad de datos, el uso de la opinión de expertos como fuente de datos es inevitable para completar la información necesaria. Sin embargo, dos problemas principales dificultan la síntesis de datos obtenidos de varias fuentes: sesgos y heterogeneidad. Por otro lado, la medición de los años de vida ajustados por calidad (AVAC) en poblaciones pediátricas plantea serios desafíos metodológicos en un análisis de evaluación económica. En España, aunque existe cierta heterogeneidad en la oferta de programas de cribado neonatal entre CC.AA., se están estableciendo directrices basadas en la mejor evidencia científica disponible para conseguir la homogeneización de políticas y programas de cribado neonatal a nivel nacional.

New genomic sequencing techniques have shown considerable promise in the field of neonatology, increasing the diagnostic rate and reducing time to diagnosis. However, several obstacles have hindered the incorporation of this technology into routine clinical practice. We prospectively evaluated the diagnostic rate and diagnostic turnaround time achieved in newborns with suspected genetic diseases using a rapid phenotype-driven gene panel (NeoSeq) containing 1870 genes implicated in congenital malformations and neurological and metabolic disorders of early onset (&lt, 2 months of age). Of the 33 newborns recruited, a genomic diagnosis was established for 13 (39.4%) patients (median diagnostic turnaround time, 7.5 days), resulting in clinical management changes in 10 (76.9%) patients. An analysis of 12 previous prospective massive sequencing studies (whole genome (WGS), whole exome (WES), and clinical exome (CES) sequencing) in newborns admitted to neonatal intensive care units (NICUs) with suspected genetic disorders revealed a comparable median diagnostic rate (37.2%), but a higher median diagnostic turnaround time (22.3 days) than that obtained with NeoSeq. Our phenotype-driven gene panel, which is specific for genetic diseases in critically ill newborns is an affordable alternative to WGS and WES that offers comparable diagnostic efficacy, supporting its implementation as a first-tier genetic test in NICUs.

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.El Programa Gallego para la Detección Precoz de Enfermedades Endocrinas y Metabólicas se inició en 1978 y fue pionero en España en el cribado neonatal ampliado con la incorporación de la espectrometría de masas en julio de 2000. Como objetivo primario se criban veintiocho enfermedades, incluyendo las de la cartera básica del Servicio Nacional de Salud excepto la anemia de células falciformes, que está en fase de inclusión. En sus veinte años de trayectoria se analizaron 404.616 recién nacidos (RN), identificando 547 casos afectos de las enfermedades incluidas, con una incidencia global de 1:739 RN vivos y de 1:1.237 RN de las enfermedades metabólicas congénitas (EMC) cribadas (1:1.580 RN excluyendo la hiperfenilalaninemia benigna-HPA), con una participación media del 99,35%, progresivamente creciente durante el período analizado. Entre las patologías cribadas destacan por su incidencia el hipotirodismo congénito (1:2.211 RN), la cistinuria (1:4.129 RN) y la HPA (1:5.699 RN), seguida de fenilcetonuria y fibrosis quística (1:10.936 RN). Se identificaron sesenta y seis casos de falsos positivos (diecisiete de los mismos en relación con patología materna) y cinco falsos negativos, siendo el VPP (valor predictivo positivo) y el VPN (valor predictivo negativo) global del programa del 89,2% y 99,99%, respectivamente, con una sensibilidad de 99,09% y una especificidad del 99,98%. La tasa de mortalidad de los pacientes con EMC diagnosticados fue del 1,52%, presentando once casos sintomatología previa al resultado del cribado (2%). El cociente intelectual de los pacientes con EMC y riesgo de afectación neurológica es normal en más del 95% de los casos.

The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C>T (p.Gln126*) and c.670G>A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient’s fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient’s clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this disease.

Resumen: Introducción: La taquicardia supraventricular (TSV) es la arritmia más común en el periodo neonatal, sin embargo, su asociación con otros procesos desencadenantes no está bien establecida. El objetivo de este estudio es analizar la posible relación entre TSV neonatal y el reflujo gastroesofágico (RGE), por ser una dolencia relacionada recientemente con las arritmias auriculares. Material y métodos: Se realizó un estudio descriptivo longitudinal retrospectivo de recién nacidos que fueron diagnosticados de TSV en una unidad neonatal de nivel III, durante un período de 5 años, valorando los aspectos morfológicos, la sintomatología asociada y los tratamientos recibidos. Se estudió su asociación con el RGE y la repercusión de este sobre la TSV. Resultados: Dieciocho pacientes (1,2 de cada 1.000 recién nacidos) fueron diagnosticados de TSV. El 50% asociaban RGE con repercusión clínica (p = 0,01) y todos ellos recibieron tratamiento farmacológico. El tiempo medio de control de la TSV sin RGE desde el diagnóstico fue de 6 días (IC 95%: 2,16–9,84, con una mediana de 3) y de 7,6 días cuando estuvieron las 2 dolencias asociadas (IC 95%: 4,14–10,9, mediana de 7) (valor p = 0,024). Conclusiones: Los pacientes con TSV en el período neonatal tienen frecuentemente RGE, y esta asociación genera una mayor dificultad para el control de la taquicardia. El reflujo podría actuar como desencadenante o perpetuante de la arritmia, por eso es importante buscar y tratar el RGE en los recién nacidos con TSV. Abstract: Introduction: Supraventricular tachycardia (SVT) is the most common arrhythmia in the neonatal period, but its association with other triggering processes is not well established. The aim of the study was to analyse the possible relationship between neonatal SVT and gastroesophageal reflux disease (GERD), a condition which was recently linked to atrial arrhythmias. Material and methods: A retrospective longitudinal descriptive study was conducted over a period of 5 years on newborns who were diagnosed with SVT in a level III neonatal unit, assessing morphological aspects, associated symptoms, and treatments received. Its association with GERD and the impact of this on SVT was studied. Results: Eighteen patients (1.2 per 1000 newborns) were diagnosed with SVT. Fifty percent of them were combined with clinically significant GERD (P=.01), and all of them received drug treatment. The average time of control of SVT without GERD since diagnosis was 6 days (95% CI: 2.16-9.84, with a median of 3) and 7.6 days when both pathologies were present (95% CI: 4.14-10.9, with a median of 7) (P=.024). Conclusions: Patients with SVT in the neonatal period frequently have GERD, and this combination leads to more difficulty in controlling the tachycardia. The reflux could act as a trigger or perpetuator of arrhythmia, therefore it is important to find and treat GERD in infants with SVT.

Objective: The objective of this study is to evaluate the preventive effect of oral administration of Lactobacillus fermentum CECT5716 on mastitis incidence in lactating women. Methods: A randomized double-blinded controlled trial that included 625 women was conducted. Women who received preventive dose of antibiotic in the context of delivery were recruited 1–6 days after childbirth and randomly assigned to a group. Probiotic group received 1 capsule/day containing L. fermentum 3 × 109 CFU, control group received 1 placebo capsule/day containing maltodextrin. The intervention period was 16 weeks. The primary outcome of the study was the incidence of clinical mastitis defined as at least two out of the three breast symptoms (pain, redness, and lump) and at least one of fever or flu-like symptoms (shivering, hot sweats, or aches). Results: Two hundred ninety-one women completed 16 weeks of treatment. Sixteen women in the probiotic group developed mastitis versus 30 women in the control group (odds ratio = 0.531; p = 0.058). Incidence rate of mastitis in the probiotic group was significantly lower than that in the control group (IR = 0.130 in the probiotic group versus IR = 0.263 in the control group; p = 0.021). Therefore, the oral administration of L. fermentum CECT5716 during lactation decreased by 51% the incidence rate of clinical mastitis. Staphylococcus spp. load at the end of intervention was significantly lower in breast milk of women in the probiotic group than in breast milk of women in the control group (p = 0.025). Conclusion: Consumption of the probiotic strain L. fermentum CECT5716 might be used during breastfeeding as an efficient strategy to prevent development of lactational mastitis in women. Trial registration: NCT02203877.

The EARS2 nuclear gene encodes mitochondrial glutamyl-tRNA synthetase, a member of the class I family of aminoacyl-tRNA synthetases (aaRSs) that plays a crucial role in mitochondrial protein biosynthesis by catalyzing the charging of glutamate to mitochondrial tRNA(Glu). Pathogenic EARS2 variants have been associated with a rare mitochondrial disorder known as leukoencephalopathy with thalamus and brainstem involvement and high lactate (LTBL). The targeted sequencing of 150 nuclear genes encoding respiratory chain complex subunits and proteins implicated in the oxidative phosphorylation (OXPHOS) function was performed. The oxygen consumption rate (OCR), and the extracellular acidification rate (ECAR), were measured. The enzymatic activities of Complexes I-V were analyzed spectrophotometrically. We describe a patient carrying two heterozygous EARS2 variants, c.376C&gt, T (p.Gln126*) and c.670G&gt, A (p.Gly224Ser), with infantile-onset disease and a severe clinical presentation. We demonstrate a clear defect in mitochondrial function in the patient&rsquo, s fibroblasts, suggesting the molecular mechanism underlying the pathogenicity of these EARS2 variants. Experimental validation using patient-derived fibroblasts allowed an accurate characterization of the disease-causing variants, and by comparing our patient&rsquo, s clinical presentation with that of previously reported cases, new clinical and radiological features of LTBL were identified, expanding the clinical spectrum of this disease.

To describe preventive, diagnostic and therapeutic strategies regarding necrotising enterocolitis in Spain and to identify the strengths, areas of further improvement, and future research lines.Two questionnaires on the management of preterm infants less than 32 weeks, at risk of, or with diagnosed necrotising enterocolitis, were distributed among selected representatives of the surgeons and neonatologists of the Spanish Neonatal Network (SEN1500) participant hospitals with a Paediatric Surgery Department.Percentage of response was 77.1% of contacted surgeons and 88.6% of neonatologists. There is a written protocol on the diagnosis and medical management of necrotising enterocolitis in 52% of the hospitals, and as regards surgical treatment in 33%. There is wide access to donor bank milk and to staff dedicated to breastfeeding promotion (87%). On the contrary, only 52% of the centres perform delayed cord clamping, and probiotics are used in just 23%. The use of abdominal ultrasound is increasing. There are no large differences as regards duration of antibiotic use and bowel rest, whereas there was as regards antibiotic selection, surgical indication, and type of intervention.As regards prevention, delayed cord clamping and extended access to donor milk are two possible aspects of further improvement. The observed discrepancies noted in diagnostic and therapeutic aspects are common in precisely the areas where evidence in the literature is weakest.

Los programas de cribado neonatal son clave en las estrategias de salud pública de una región determinada, establecidas para prevenir los danos ˜ asociados a las enfermedades cribadas. Su importancia se ha intensificado sustancialmente en los últimos anos ˜ debido al creciente número de trastornos en los que diferentes organismos de evaluación han demostrado el beneficio de su detección temprana para el recién nacido. Desde los anos ˜ 60-70 del siglo pasado, muchas regiones implementaron programas de cribado neonatal que hoy en día, al menos en los países desarrollados, son universales, bien establecidos y con excelentes resultados. Sin embargo, aún queda mucho por hacer, principalmente en países en vías de desarrollo de África, Asia y América del Sur. En algunos países europeos, incluida Espana, ˜ la uniformidad entre los paneles de cribado de las diferentes regiones continúa siendo un reto, pues es fuente de desigualdades en materia de salud. Los autores presentan el estado actual de los programas de cribado neonatal en Espana˜ y lo contextualizan en el escenario real europeo y mundial. Newborn screening programs are key players in a country's public health strategies, preventing the burden of care associated with the screened disorders. Its importance has dramatically intensified in recent years due to the increasing number of disorders that fulfil criteria for screening. Since the 1960's, many countries implemented newborn screening programs that are now, at least in developed countries, universal, well established, and with excellent results. Nevertheless, much work is still to be done, mainly in developing countries of Africa, Asia, and South America. In some European countries, including Spain, uniformity of screening panels between different regions is still a challenge, being a source of health inequalities between citizens. The authors will present the current status of newborn screening programs in Spain and integrate it into the current European and world scenario. info:eu-repo/semantics/publishedVersion

Maple syrup urine disease (MSUD) is a rare metabolic disorder with a worldwide prevalence of 1 in every 185,000 live births. However, certain populations display a significant overexpression of the disorder where incidence is reported to be 1 in every 52,541 new-borns. The first-line therapy for MSUD involves a strict dietary leucine restriction and oral supplementation of isoleucine and valine. The dose administered to patients requires strict tailoring according to age, weight and blood levels. In current clinical practice, however, practitioners still have to prepare extemporaneous formulations due to the lack of suitable oral treatments for MSUD. Herein, we evaluate the first time use of 3D printing in a hospital setting for the preparation of personalised therapies with the aim of improving safety and acceptability to isoleucine supplementation in paediatric patients suffering from MSUD. This investigation was a single-centre, prospective crossover experimental study. Four paediatric patients with MSUD (aged 3–16 years) were treated at the Clinic University Hospital in Santiago de Compostela, Spain which is a MSUD reference hospital in Europe. The primary objective was to evaluate isoleucine blood levels after six months of treatment with two types of formulations; conventional capsules prepared by manual compounding and personalised chewable formulations prepared by automated 3D printing. A secondary investigation was to evaluate patient acceptability of 3D printed formulations prepared with different flavours and colours. Isoleucine blood levels in patients were well controlled using both types of formulations, however, the 3D printed therapy showed mean levels closer to the target value and with less variability (200–400 µM). The 3D printed formulations were well accepted by patients regarding flavour and colour. The study demonstrates for the first time that 3D printing offers a feasible, rapid and automated approach to prepare oral tailored-dose therapies in a hospital setting. 3D printing has shown to be an effective manufacturing technology in producing chewable isoleucine printlets as a treatment of MSUD with good acceptability.

Newborn screening programs are key players in a country’s public health strategies, preventing the burden of care associated with the screened disorders. Its importance has dramatically intensified in recent years due to the increasing number of disorders that fulfil criteria for screening. Since the 1960s, many countries implemented newborn screening programs that are now, at least in developed countries, universal, well established, and with excellent results. Nevertheless, much work is still to be done, mainly in developing countries of Africa, Asia, and South America. In some European countries, including Spain, uniformity of screening panels between different regions is still a challenge, being a source of health inequalities between citizens. The authors will present the current status of newborn screening programs in Spain and integrate it into the current European and world scenario. Resumen: Los programas de cribado neonatal (PCN) son clave en las estrategias de salud pública de una región determinada, establecidas para prevenir los daños asociados a las patologías cribadas. Su importancia se ha intensificado sustancialmente en los últimos años debido al creciente número de trastornos en los que diferentes organismos de evaluación han demostrado el beneficio de su detección temprana para el recién nacido. Desde los años 60-70 del siglo pasado, muchas regiones implementaron de PNC que hoy en día, al menos en los países desarrollados, son universales, bien establecidos y con excelentes resultados. Sin embargo, aún queda mucho por hacer, principalmente en países en vías de desarrollo de África, Asia y América del Sur. En algunos países europeos, incluida España, una mayor uniformidad entre los paneles de cribado de las diferentes regiones continúa siendo un reto, pues conduce a desigualdades en materia de salud. Los autores presentan el estado actual de los PCN en España y lo contextualizan en el escenario real europeo y mundial.

Hereditary multiple intestinal atresia associated with severe combined immunodeficiency (MIA-SCID) is a very rare disease caused by deleterious mutations in the tetratricopeptide repeat domain-containing protein 7A gene TTC7A. It is characterized by intestinal obstruction, sepsis, and a poor prognosis. Insights into phenotype-genotype correlations could help to guide genetic counseling and increase our knowledge of the natural history of this disease.We report the case of a newborn in which his fetal magnetic resonance imaging showed jejunal atresia and microcolon and an abdominal x-ray at birth confirmed intestinal obstruction. The clinical course was complicated by multiple episodes of sepsis, and laboratory investigations showed SCID. The genetic analysis identified a homozygous c.53344_53347 mutation in the TTC7A gene compatible with MIA-SCID syndrome. The patient required 3 operations because of new intestinal atresias in the first months of life. She underwent bone marrow transplantation at 8 months of age but died of liver failure secondary to graft-versus-host disease.Immunologic assessment and genetic screening for TTC7A mutations are important in patients with MIA. Greater knowledge of the functions of the TTC7A protein will have important therapeutic implications for patients with MIA-SCID syndrome.

Actualmente todos los ninos se benefician de una exploracion de salud que se lleva a cabo en los primeros dias de vida mediante la llamada prueba del talon o cribado metabolico neonatal. Muy a menudo los pediatras, otros especialistas y todo el personal sanitario tienen que dar una respuesta a los resultados del cribado. El abanico de necesarias explicaciones es muy amplio: desde comunicar sencillamente lo que significa un resultado dentro de los limites de la normalidad, una peticion de repeticion una muestra o dar respuesta a una emergencia. En ocasiones el medico tendra que dar una indicacion rapida a una situacion desafiante en la que una investigacion o la instauracion de un tratamiento adecuado son esenciales para una buena evolucion. En todas estas situaciones es cuando podra apreciarse hasta que punto resultara util tener este Manual clinico del cribado metabolico al alcance de la mano, que ahora se presenta en una nueva edicion corregida, actualizada y aumentada

espanolObjetivo: determinar las diferencias a lo largo de los tres anos en el manejo de las vias centrales de bebes prematuros menores de 1.500 gramos. Metodo: estudio descriptivo longitudinal retrospectivo en bebes de Resultados: se estudiaron 120 bebes, siendo la media de edad gestacional de 29,8 semanas y el peso medio al nacimiento de 1.148 gramos. En 62 bebes (51,6%) se inserto una via central, siendo la de primera eleccion la via umbilical, con un tiempo medio de permanencia de seis dias, seguido del PICC, con una permanencia media de ocho dias y de localizacion mas habitual en el miembro superior, seguida del miembro inferior y la cabeza. La causa mas comun de retirada de la via central fue la electiva, debido a la finalizacion del tratamiento, y la contaminacion mas frecuente el Estafilococo epidermidis. En el periodo de estudio se encontro una leve disminucion, estadisticamente significativa (p= 0,033). Conclusiones: el acceso vascular central se muestra como la principal via de manejo del gran prematuro menor de 1.000 gramos de peso, siendo la via umbilical la de primera eleccion, seguido del PICC. Aproximadamente la mitad de los bebes tuvo una via central. EnglishObjective: to determine any differences in the management of central lines in preterm babies weighing less than 1,500 grams, during a 3-year period. Method: a descriptive longitudinal retrospective study in babies Results: the study included 120 babies, with a mean gestational age of 29.8 weeks and 1,148 grams as mean weight at birth; 62 babies (51.6%) had a central line inserted, with umbilical access as first choice, for a mean period of six days, followed by peripheral catheterization, for a mean period of eight days, and the most frequent location was upper limb, followed by lower limb and head. The most frequent cause for removal of the central line was elective, due to treatment completion, and the most frequent contamination was by Staphylococcus Epidermidis. During the period of the study, a mild reduction was found, which was statistically significant (p= 0.033). Conclusions: central vascular access appears as the main pathway for management in preterm babies weighing less than 1,000 grams, with umbilical access as first choice, followed by peripheral catheterization. Approximately half of male and female babies had a central line inserted.

Large for gestational age (LGA) newborns have an increased risk of obesity, insulin resistance, and metabolic syndrome. Acylcarnitine profiles in obese children and adults are characterized by increased levels of C3, C5, and certain medium-chain (C12) and long-chain (C14:1 and C16) acylcarnitines. C2 is also increased in insulin-resistant states. In this 1-year observational study of 2514 newborns (246 LGA newborns, 250 small for gestational age (GA) newborns, and 2018 appropriate for GA newborns), we analyzed and compared postnatal acylcarnitine profiles in LGA newborns with profiles described for obese individuals. Acylcarnitine analysis was performed by tandem mass spectrometry on dried-blood spots collected on day 3 of life. LGA newborns had higher levels of total short-chain acylcarnitines (p

Introduction: Supraventricular tachycardia (SVT) is the most common arrhythmia in the neonatal period, but its association with other triggering processes is not well established. The aim of the study was to analyse the possible relationship between neonatal SVT and gastroesophageal reflux disease (GERD), a condition which was recently linked to atrial arrhythmias. Material and methods: A retrospective longitudinal descriptive study was conducted over a period of 5 years on newborns who were diagnosed with SVT in a level III neonatal unit, assessing morphological aspects, associated symptoms, and treatments received. Its association with GERD and the impact of this on SVT was studied. Results: Eighteen patients (1.2 per 1000 newborns) were diagnosed with SVT. Fifty percent of them were combined with clinically significant GERD (P = .01), and all of them received drug treatment. The average time of control of SVT without GERD since diagnosis was 6 days (95% CI: 2.16–9.84, with a median of 3) and 7.6 days when both pathologies were present (95% CI: 4.14–10.9, with a median of 7) (P = .024). Conclusions: Patients with SVT in the neonatal period frequently have GERD, and this combination leads to more difficulty in controlling the tachycardia. The reflux could act as a trigger or perpetuator of arrhythmia, therefore it is important to find and treat GERD in infants with SVT. Resumen: Introducción: La taquicardia supraventricular (TSV) es la arritmia más común en el periodo neonatal, sin embargo, su asociación con otros procesos desencadenantes no está bien establecida. El objetivo de este estudio es analizar la posible relación entre TSV neonatal y el reflujo gastroesofágico (RGE), por ser una dolencia relacionada recientemente con las arritmias auriculares. Material y métodos: Se realizó un estudio descriptivo longitudinal retrospectivo de recién nacidos que fueron diagnosticados de TSV en una unidad neonatal de nivel III, durante un período de 5 años, valorando los aspectos morfológicos, la sintomatología asociada y los tratamientos recibidos. Se estudió su asociación con el RGE y la repercusión de este sobre la TSV. Resultados: Dieciocho pacientes (1,2 de cada 1.000 recién nacidos) fueron diagnosticados de TSV. El 50% asociaban RGE con repercusión clínica (p = 0,01) y todos ellos recibieron tratamiento farmacológico. El tiempo medio de control de la TSV sin RGE desde el diagnóstico fue de 6 días (IC 95%: 2,16–9,84, con una mediana de 3) y de 7,6 días cuando estuvieron las 2 dolencias asociadas (IC 95%: 4,14–10,9, mediana de 7) (valor p = 0,024). Conclusiones: Los pacientes con TSV en el período neonatal tienen frecuentemente RGE, y esta asociación genera una mayor dificultad para el control de la taquicardia. El reflujo podría actuar como desencadenante o perpetuante de la arritmia, por eso es importante buscar y tratar el RGE en los recién nacidos con TSV.

The use of high-flow nasal cannula (HFNC) therapy as respiratory support for preterm infants has increased rapidly worldwide. The evidence available for the use of HFNC is as an alternative to nasal continuous positive airway pressure (CPAP) and in particular to prevent postextubation failure. We report a case of tension pneumocephalus in a preterm infant as a complication during HFNC ventilation. Significant neurological impairment was detected and support was eventually withdrawn. Few cases of pneumocephalus as a complication of positive airway pressure have been reported in the neonatal period, and they all have been related to CPAP. This report reinforces the need to be aware of this rare but possible complication during HFNC therapy, as timely diagnosis and treatment can prevent neurological sequelae. We also stress the importance of paying close attention to flow rate, nasal cannula size and insertion, and mouth position, and of regularly checking insertion depth.

Supplemental Digital Content is available in the text, In patients with phenylketonuria (PKU) compliant to diet greater tendency to overweight and higher inflammatory biomarkers levels than controls were reported. Although this could lead to atherogenesis, the elastic properties of large arteries in PKU patients have never been assessed. The aim of this study was to assess arterial stiffness measured by applanation tonometry in PKU patients compared to healthy controls. We carried out a cross-sectional study in 41 PKU patients (range age: 6–50 years old) and 41 age- and gender-matched healthy controls. Evaluated data included pharmacological treatment with sapropterin, clinical, and biochemical parameters. Aortic stiffness was assessed noninvasively by applanation tonometry measuring central blood pressure, aortic augmentation index (Aix@HR75), augmentation pressure (AP), and pulse wave velocity (PWV). We found higher PWV in classic PKU patients (6.60 m/second vs 5.26 m/second; P: .044). Percentage of PKU patients with PWV above 90 percentile was higher than controls (14.63% vs 2.32%; P: .048). A positive relationship was observed between the annual Phe median and PWV (r: 0.496; P: .012). PKU subjects with lower Phe tolerance showed more body weight (67.6 kg vs 56.8 kg; P: .012) and more PWV than those with higher Phe tolerance (6.55 m/second vs 5.42 m/second; P: .044). Our data show increased aortic stiffness in PKU patients, measured by applanation tonometry, when compared to healthy controls. Higher Phe levels are associated with a bigger PWV increase, which is not present in those subjects compliant to diet or under sapropterin treatment. These results could have marked effects in both research and clinical daily practice for a proper evaluation of cardiovascular risk in PKU subjects.

The mucopolysaccharidoses (MPSs) are underdiagnosed but they are evaluated in few newborn screening programs, probably due to the many challenges remaining, such as the identification of late-onset phenotypes. Systematic screening at the onset of clinical symptoms could help to early identify patients who may benefit from specific treatments. The aim of this prospective study was to assess a novel selective screening program, the FIND project, targeting patients aged 0 to 16 years with clinical manifestations of MPS. The project was designed to increase awareness of these diseases among pediatricians and allow early diagnosis. From July 2014 to June 2016, glycosaminoglycan (GAG) levels normalized to creatinine levels were determined in urine-impregnated analytical paper submitted by pediatricians who had patients with clinical signs and/or symptoms compatible with MPS. When high GAG concentrations were detected, a new liquid urine sample was requested to confirm and identify the GAG present. When a specific form of MPS was suspected, enzyme activity was analyzed using blood-impregnated paper to determine MPS type (I, IIIB, IIIC, IVA, IVB, VI, or VII). Age-specific reference values for GAG were previously established using 145 urine samples from healthy children. GAG levels were normal in 147 (81.7%) of the 180 initial samples received. A liquid sample was requested for the other 33 cases (18.3%); GAG levels were normal in 13 of these and slightly elevated in 12, although the electrophoresis study showed no evidence of MPS. Elevated levels with corresponding low enzymatic activity were confirmed in 8 cases. The mean time from onset of clinical symptoms to detection of MPS was 22 months, and just 2 cases were detected at the beginning of the project were detected with 35 and 71 months of evolution of clinical symptoms. Our screening strategy for MPS had a sensitivity of 100%, a specificity of 85%, and a positive predictive value of 24%. The FIND project is a useful and cost-effective screening method for increasing awareness of MPS among pediatricians and enabling the detection of MPS at onset of clinical symptoms.

Mucopolysaccharidosis type III (MPS III, Sanfilippo syndrome) is a lysosomal storage disorder, caused by a deficiency in one of the four enzymes involved in the catabolism of glycosaminoglycan heparan sulfate. It is characterized by progressive cognitive decline and severe hyperactivity, with relatively mild somatic features. This review focuses on clinical features, diagnosis, treatment, and follow-up of MPS III, and provides information about supplementary tests and differential diagnosis. Given that few reviews of MPS III have been published, several studies were compiled to establish diagnostic recommendations. Quantitative urinary glycosaminoglycan analysis is strongly recommended, and measurement of disaccharides, heparin cofactor II-thrombin complex and gangliosides is also used. Enzyme activity of the different enzymes in blood serum, leukocytes or fibroblasts, and mutational analysis for SGSH, NAGLU, HGSNAT or GNS genes are required to confirm diagnosis and differentiate four subtypes of MPS III. Although there is no global consensus for treatment, enzyme replacement therapy and gene therapy can provide appropriate results. In this regard, recent publications on treatment and follow-up are discussed.

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 (, SCOPUS: ar.j, info:eu-repo/semantics/published

Background Umbilical cord hemangioma is very rare and may not be detected prenatally. However, it should be considered in differential diagnosis with other umbilical masses because it can cause significant morbidity. Methods We report the case of a newborn referred with suspected omphalitis and umbilical hernia. Results Physical examination showed an irreducible umbilical tumor, the size of olive, with dubious secretion. The initial suspected diagnosis was urachal or omphalomesenteric duct remnants. Abdominal ultrasound and magnetic resonance imaging showed an umbilical and a mesenteric mass. Tumor markers were negative. A definitive diagnosis of umbilical cord and intestinal hemangioma was established after surgical excision and histologic examination of the umbilical mass. Propranolol was prescribed due to the extent of the intestinal lesion. Conclusion This report highlights the diagnostic challenges of hemangiomas in unusual locations. Apart from the rarity of these tumors, few tests are available to guide diagnosis, and surgery and histologic examination are generally required for a definitive diagnosis. Finally, it is essential to rule out associated malformations and hemangiomas in other locations.

To evaluate clinical, biochemical and genetic findings of two series of patients with biotinidase deficiency.Fifteen cases detected through newborn screening and six through selective screening for hearing loss or metabolic disease.No patient detected by neonatal screening had symptoms and only one case with partial biotinidase activity developed myoclonic seizures that resolved with biotin. More common mutations found among this group were p.D444H and the double mutation [p.D444H;p.A171T]. However, neurological and hearing manifestations predominated among the six symptomatic cases and mutations p.L32fs, p.G34fs, p.T401I, p.D444H, p.T532M and the novel one p.L466fs were identified. Patients with profound biotinidase deficiency and/or clinical signs were treated with pharmacological doses of biotin (10-30mg daily).Biotinidase deficiency must be included in the newborn screening programmes in order to begin early treatment even in partial forms. Different mutations found in both series of patients suggest that routine genetic procedure of the BTD gene by direct sequencing might be useful to assign patients to the partial or profound form of the disease.

Homocystinuria due to cystathionine beta-synthase (CBS) deficiency has been extensively studied, but to date, no spectrum of CBS mutations of Spanish homocystinuric patients has been reported. Here we present a mutation analysis of thirteen Spanish and three Portuguese unrelated homocystinuric patients. Ten mutations were found to account for the thirty-two mutant alleles and five of these (C275Y, L338P, S349N, R379Q, and L456P) are reported here for the first time. All five novel mutations were found to affect evolutionarily conserved residues suggesting that they may impair enzyme function. Interestingly, neither of the two common CBS mutations, I278T and G307S, was detected in this series, and no patient was found to respond to pyrodoxine. Enzyme activities in cultured fibroblasts from 10 of the patients were assayed, and they ranged from 0 to 13 % of controls analyzed in parallel. The T191M mutation (which has only ever been reported once before in a Spanish patient) accounted for 50% of the mutant alleles. Comparison of the clinical data of seven patients homozygous for T191M indicated that this genotype is a poor predictor of the phenotype. A common haplotype was identified in all the T191M chromosomes of Spanish origin, while a different one was present in the four T191M chromosomes from Portuguese patients.