Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.

Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.

Lactose and Galactose Content in Spanish Cheeses: Usefulness in the Dietary Treatment of Patients with Galactosaemia.

In galactosaemia, a strict galactose-free diet is necessary to prevent or resolve acute symptoms in infants. However, because the body produces up to 10 times more galactose than is found in a galactose-restricted diet, excessively restrictive diets should be avoided in children and adults to prevent nutritional deficiencies. Since cheese is a nutritional source of the calcium necessary for bone health, the latest international guidelines on the management of classical galactosaemia (2017) allow the consumption of cured cheeses with less than 25 mg of galactose/100 g and recommend that each country verifies the adequacy of the cheeses, since most mature cheeses do not always have a lower galactose content. In total, 32 cheese samples were purchased (19 Spanish and 13 international cheeses), and their lactose and galactose contents were analysed using ion chromatography with pulsed amperometric detection (IC-PAD). Five Spanish cheeses contained less than 25 mg of galactose/100 g: García Baquero semi-cured cheese; Hacendado, Gran Reserva and Mahón cured cheeses; and García Baquero Reserva 12-month cured cheese. In addition, eight international cheeses were confirmed as suitable: Comté, Gouda, Gruyere, Maasdam, Parmigiano, Edam, Emmental, and some samples of Cheddar. In addition to the well-known low-galactose Swiss and Dutch cheeses, according to the current results, five Spanish cheeses can be safely consumed. The greater availability of types of cheese favours better bone health in patients with galactosaemia.

Consequences of COVID-19 pandemic over acute bronchiolitis hospitalizations in the center and east of Spain.

INTRODUCTION: Non-pharmaceutical interventions that have been implemented in southern hemisphere countries because of COVID-19 pandemic declaration in March 2020, have evidenced some unexpected changes in the way of spreading of many other viruses. This study as a part of ECEALHBA's Project, reports the consequences of COVID-19 pandemic over 2020-2021 bronchiolitis epidemic period in the Central and Eastern regions of Spain. METHOD: Multicenter, observational, descriptive and ambispective study of admitted infants with the diagnosis of bronchiolitis in 16 Spanish hospitals involved in the investigation project. Five epidemic periods previous to COVID-19 pandemic, from 2015 to 2020, were compared with the current one, 2020-2021, in both a qualitative and quantitative manner. RESULTS: Total of 4643 infants were admitted to the participating hospitals along the study period. Pandemic season hospital admissions for bronchiolitis were 94.1% lower than in pre-pandemic period. December and January were peak months for bronchiolitis admissions during pre-pandemic period, but September was the peak month during pandemic year. There was a progressive decrease of admissions from this moment until the end of the follow-up, in April 2021. Rhinovirus has been the commonest etiology for bronchiolitis in 2020-2021 epidemic period of bronchiolitis. CONCLUSIONS: Some of the non-pharmaceutical interventions initiated because of COVID-19 pandemic are probably related to the dramatic decrease of bronchiolitis cases in 2020-2021 season. It would be rewarding to purpose novel research to clarify how these simple interventions can be useful, close to vaccines and antiviral drugs, to achieve the goal of avoiding the spread of respiratory viruses in pediatric population.

[Consequences of COVID-19 pandemic over acute bronchiolitis hospitalizations in the center and east of Spain]. / Pandemia por COVID-19 y su repercusión sobre las hospitalizaciones por bronquiolitis en el Centro y Este de España.

INTRODUCTION: Non-pharmaceutical interventions that have been implemented in southern hemisphere countries because of COVID-19 pandemic declaration in March 2020, have evidenced some unexpected changes in the way of spreading of many other viruses. This study as a part of ECEALHBA's Project, reports the consequences of COVID-19 pandemic over 2020-2021 bronchiolitis epidemic period in the Central and Eastern regions of Spain. METHOD: Multicenter, observational, descriptive and ambispective study of admitted infants with the diagnosis of bronchiolitis in 16 Spanish hospitals involved in the investigation project. Five epidemic periods previous to COVID-19 pandemic, from 2015 to 2020, were compared with the current one, 2020-2021, in both a qualitative and quantitative manner. RESULTS: Total of 4643 infants were admitted to the participating hospitals along the study period. Pandemic season hospital admissions for bronchiolitis were 94.1% lower than in pre-pandemic period. December and January were peak months for bronchiolitis admissions during pre-pandemic period, but September was the peak month during pandemic year. There was a progressive decrease of admissions from this moment until the end of the follow up, in April 2021. Rhinovirus has been the commonest etiology for bronchiolitis in 2020-2021 epidemic period of bronchiolitis. CONCLUSIONS: Some of the non-pharmaceutical interventions initiated because of COVID-19 pandemic are probably related to the dramatic decrease of bronchiolitis cases in 2020-2021 season. It would be rewarding to purpose novel research to clarify how these simple interventions can be useful, close to vaccines and antiviral drugs, to achieve the goal of avoiding the spread of respiratory viruses in pediatric population.

Usefulness of complementary test in the study of patients with chronic abdominal pain.

INTRODUCTION: Chronic abdominal pain (CAP) in children is a symptom that frequently leads to a visit to the paediatrician, which affects family life and occasionally requires the need to perform diagnostic studies (DS). The objective was to carry out a qualitative, quantitative, and economic analysis on the tests requested. MATERIAL AND METHODS: An observational, prospective and multicentre study was conducted that included children between 4-15 years old affected by CAP. The difference between organic and functional disorders was taken into account. The following variables were collected: history, warning signs and symptoms, DS, and the cost of these. RESULTS: The study included 235 children with CAP (Age; mean 9.7 ± 2.7 SD). The large majority (79%) were functional disorders and 21% organic disorders. Almost half of the patients had some warning sign or symptom, but urinary symptoms were only associated with organic disorders. The abdominal ultrasound, faecal parasites, breath test, and endoscopy were the most associated with organic disorders. There was a difference between the costs of the DS according to each centre. The total economic cost was 52,490.80 euros, with 195 euros per patient for functional disorders and 306 euros for organic disorders. CONCLUSION: Signs and symptoms of alarm in CAP were very frequent, but had low discriminative capacity. The abdominal ultrasound and faecal parasites are innocuous DS, and could be useful as a first level study. The endoscopy and the breath test were the most discriminative of organic disease. The economic cost of DS arising from the diagnosis of exclusion in CAP was high.

[Diagnosis of celiac disease in clinical practice: present and future]. / Diagnóstico de enfermedad celiaca en la práctica clínica: presente y futuro.

INTRODUCTION: European guidelines for the diagnosis of celiac disease (CD) have been updated in 2020. The primary objective was to review the compliance with the diagnostic criteria for CD, according to ESPGHAN 2012. Secondarily, to describe the clinical characteristics of the patients and to assess the changes that would be implied by the application of the new 2020 criteria. PATIENTS AND METHODS: Retrospective multicenter study in which 10 centers participated. Patients from 0 to 16 years old with a new diagnosis of CD in 2018-2019 were included. Clinical, serological variables and the performance of intestinal biopsy (IB) were collected. RESULTS: 163 patients were included (57% female) with a median age of 7.6 years (SD 4.4). The form of presentation was: 47.8% classical, 30.7% no classical and 21.5% asymptomatic, with differences depending on age. Total IgA and anti-transglutaminase IgA antibodies were performed in all centers as the first diagnostic step. IgA anti-endomysial antibodies (EMA) were performed in 80%, and HLA haplotype in 95%. Of the total, 78 cases (47.9%) met criteria for not performing intestinal biopsy (IB). IB was indicated in the remaining 85 patients, but was not performed in 29 cases (17.8%). The performance of IB was lower in the secondary hospitals than in the tertiary ones (p < 0.05). If we applied the ESPGHAN 2020 criteria, we would disregard the HLA study, and 21 more patients would not have required IB (going from 47.9% to 60.7% of the total). CONCLUSIONS: Discrepancies are observed in the application of the ESPGHAN 2012 diagnostic criteria due to the different accessibility to EMA and endoscopic IB in secondary centers. With the ESPGHAN-2020 criteria, around 60% of patients will be able to be diagnosed without IB, provided that the determination of EMA is ensured.

Predictors of Response to Exclusive Enteral Nutrition in Newly Diagnosed Crohn´s Disease in Children: PRESENCE Study from SEGHNP.

Exclusive enteral nutrition (EEN) has been shown to be more effective than corticosteroids in achieving mucosal healing in children with Crohn´s disease (CD) without the adverse effects of these drugs. The aims of this study were to determine the efficacy of EEN in terms of inducing clinical remission in children newly diagnosed with CD, to describe the predictive factors of response to EEN and the need for treatment with biological agents during the first 12 months of the disease. We conducted an observational retrospective multicentre study that included paediatric patients newly diagnosed with CD between 2014-2016 who underwent EEN. Two hundred and twenty-two patients (140 males) from 35 paediatric centres were included, with a mean age at diagnosis of 11.6 ± 2.5 years. The median EEN duration was 8 weeks (IQR 6.6-8.5), and 184 of the patients (83%) achieved clinical remission (weighted paediatric Crohn's Disease activity index [wPCDAI] < 12.5). Faecal calprotectin (FC) levels (µg/g) decreased significantly after EEN (830 [IQR 500-1800] to 256 [IQR 120-585] p < 0.0001). Patients with wPCDAI ≤ 57.5, FC < 500 µg/g, CRP >15 mg/L and ileal involvement tended to respond better to EEN. EEN administered for 6-8 weeks is effective for inducing clinical remission. Due to the high response rate in our series, EEN should be used as the first-line therapy in luminal paediatric Crohn's disease regardless of the location of disease and disease activity.

Assessment of nutritional status and bone health in neurologically impaired children: a challenge in pediatric clinical practice.

INTRODUCTION: Introduction: neurologically impaired children frequently experience nutritional disorders and bone health complications. Our aim was firstly to analyze a method to interpret bone mineral density (BMD) accurately in neurologically impaired children. Secondly, to determine its relationship with the nutritional status and micronutrient levels in order to identify which factors are associated with low BMD. Methods: a observational multicenter study was conducted in children with moderate-to-severe neurological impairment. Data collected included: medical records, anthropometric measures, hematologic and biochemical evaluation. BMD was measured with Dual-energy X-ray absorptiometry and z-scores were calculated adjusting for sex and chronological age. Secondly, BMD z-scores were calculated applying height age (age at which the child's height would be in 2nd percentile) instead of chronological age. Results: fifty-two children were included (aged 4-16 years). Seventeen patients (32.7%) received feeding by gastrostomy tube. Height and BMI z-score were below 2SD in 64% and 31% of patients respectively, with normal mid upper arm circumference and skinfold thickness measurements. Low vitamin-D levels were found in 42% of cases. 50% of patients evidenced low BMD when calculated for chronological age, whereas only 34.5% showed BMD z-score <-2 when calculated for height age. No correlation was observed between BMD and vitamin-D levels, weight and height z-scores or age when BMD was calculated applying height age. Conclusions: the prevalence of low BMD is high in neurologically impaired children, and it is probably multifactorial. In these children, we suggest adjusting BMD for height age, in order not to over diagnose low BMD.

INTRODUCCIÓN: Introducción: los niños con afectación neurológica con frecuencia presentan trastornos nutricionales y complicaciones óseas. Nuestro objetivo fue, en primer lugar, analizar un método para interpretar la densidad mineral ósea (DMO) de forma adecuada en estos pacientes. En segundo lugar, determinar la relación de la DMO con el estado nutricional y los niveles de micronutrientes, para determinar qué factores se asocian con baja DMO. Métodos: estudio observacional multicéntrico, se incluyeron niños con afectación neurológica moderada-severa. Se recogieron datos clínicos, medidas antropométricas y una evaluación hematológica y bioquímica. La DMO fue evaluada mediante densitometría, y se calcularon los z-scores según la edad y sexo. En segundo lugar, se recalcularon los z-scores de DMO para la edad talla (edad en la cual la talla del niño se encontraría en el percentil 2) en vez de la edad cronológica. Resultados: se incluyeron 52 niños (4-16 años). Diecisiete pacientes (32,7%) recibían alimentación por gastrostomía. Los z-scores de peso y talla estaban por debajo de 2 desviaciones estándar (DE) en el 64% y 31% de los pacientes respectivamente, con normalidad de las mediciones de perímetro braquial y pliegues tricipital y subescapular. Los niveles de vitamina D estaban bajos en el 42% de los casos. La mitad de los pacientes tenían baja DMO cuando se calculó para la edad cronológica, mientras que solo el 34,5% presentaron DMO por debajo de 2 DE cuando se calculó para la edad talla. No observamos correlación entre z-scores de DMO calculados para la edad talla y los niveles de vitamina D, la edad o los z-scores de peso y talla. Conclusiones: la prevalencia de baja DMO es alta en niños con discapacidad neurológica, y probablemente es multifactorial. En estos niños, sugerimos ajustar DMO para la edad talla, para evitar sobrediagnosticar baja DMO.

[Epstein-Barr virus primary infection in healthy children]. / Primoinfección por el virus de Epstein-Barr en niños sanos.

INTRODUCTION: The aim of this study is to assess epidemiological, clinical and laboratory characteristics of primary infection by Epstein-Barr virus (EBV) in children without previous diagnosis of any immune disease and its relationship with clinical presentation. PATIENTS AND METHODS: A retrospective study was conducted on all children from 0 to 15 years with IgM against viral capsid of EBV positive or indeterminate during a 22 month period. Epidemiological, clinical and laboratory data were analysed and compared between typical (mononucleosis syndrome) and non-typical clinical symptoms. RESULTS: The study included a total of 103 children, with a median age of 7 years (3-12.5 years). Almost two-thirds (63%) of patients had typical clinical signs, with a mononucleosis syndrome, and 37% had a non-typical presentation. The non-typical clinical group had a lower age (P=.03) and took less antibiotic than the typical clinical group (P=.015). From laboratory studies, there were no differences between the groups, except in RCP, which was higher in typical clinical group (P=.04). Heterophile antibodies were positive in 33% of patients. An indeterminate IgM against viral capsid was present in 20% of the patients, and most of them had an oligosymptomatic or atypical presentation. An IgM positive for other viruses was found in 21%, and 3 of them were suspicious of false positive for EBV. CONCLUSIONS: In the studied population, a primary infection due to EBV is common in younger ages, and they have usually an oligosymptomatic clinical presentation. A very low percentage of positive heterophile antibodies were found. Cases with indeterminate IgM against viral capsid are more frequent in the non-typical clinical group. Co-infection with other viruses is common.

[Anti-tissue transglutaminase antibodies not related to gluten intake]. / Anticuerpos antitransglutaminasa no relacionados con la ingesta de gluten.

INTRODUCTION: Anti-tissue transglutaminase antibodies (tTG) have high specificity for coeliac disease (CD). However, positive anti-tTG antibodies have been described in non-coeliac patients. Aim To assess positive anti-tTG antibodies not related to gluten intake. PATIENTS AND METHODS: Retrospective review and follow up conducted on patients with suspected CD (increase anti-tTG levels and gastrointestinal symptoms) but with atypical serology results, positive anti-tTG with gluten free diet and a decrease in anti-tTG levels despite gluten intake. RESULTS: A total of 9 cases were reviewed in which 5 cases had Marsh 3 involvement in the initial biopsy, and were diagnosed with CD (Group A). They began a gluten free diet and also a cow's milk protein (CMP) free diet because of their nutritional status. When CMP was re-introduced, anti-tTG increased, and returned to normal after the CMP was withdrawn again. The other 4 patients had a normal initial biopsy (Group B). Gluten was not removed from their diet, but they started a CMP free diet because a non IgE mediated CMP allergy was suspected. Symptoms disappeared, and anti-tTG was normal after CMP free diet with gluten intake. All the patients had susceptibility haplotype HLA DQ2/DQ8. CONCLUSIONS: CMP ingestion after an exclusion diet can induce an increase in anti-tTG in some coeliac subjects. CMP can produce this immune response if there were no gluten transgressions. This response has also been observed in non-IgE mediated CMP allergy patients with the susceptibility haplotype HLA DQ2/DQ8.