Kidney and urogenital abnormalities in Down syndrome: a meta-analysis.

BACKGROUND: Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature.  METHODS: A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. RESULTS: Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78-16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15-7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. CONCLUSIONS: This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Febrile Seizures: A Systematic Review of Different Guidelines.

BACKGROUND: Febrile seizures (FS) are the most common neurological disorder in pediatric age. FS affect 2% to 12% of children and result from a complex interplay of genetic and environmental factors. Effective management and unambiguous recommendations are crucial for allocating health care resources efficiently and ensuring cost-effectiveness in treating FS. METHODS: This systematic review compares existing guidelines to provide insights into FS management. Seven guidelines published between 1991 and 2021, from Japan, United Kingdom, United States, Mexico, India, and Italy, were included. Data extraction covered definitions, diagnostic criteria, hospital admission criteria, diagnostic tests, management, and prophylaxis recommendations. RESULTS: Hospital admission criteria varied but typically included age <18 months and complex FS. Neuroimaging and lumbar puncture recommendations varied, with most guidelines suggesting limited use. Pharmacologic prophylaxis was generally discouraged for simple FS but considered only for high-risk cases, due to the benign nature of FS and the potential side effects of antiseizure medications. CONCLUSIONS: Guidelines on FS exhibit similarities and differences, highlighting the need for standardized management and improved parental education to enhance clinical outcomes and reduce economic and social costs associated with FS. Future research should focus on creating updated international guidelines and ensuring their practical implementation.

Salivary fatty acids in humans: a comprehensive literature review.

Fatty acids (FAs) exert diverse biological functions in humans, influencing physiological responses and, ultimately, health and disease risk. The analysis of FAs in human samples has significant implications and attracts interest in diagnostics and research. The standard method for assessing FA profiles involves the collection of blood samples, which can be inconvenient, invasive, and potentially painful, particularly for young individuals outside hospital settings. Saliva emerged as a promising alternative for evaluating FA profiles in both clinical and research settings. However, to the best of our knowledge, an updated synthesis of the related evidence is unavailable. This comprehensive review aims to summarize data on FA analysis and highlight the potential of the use of salivary FAs as a biomarker in health and disease. Over the past decade, there has been a growing interest in studying salivary FAs in chronic diseases, and more recently, researchers have explored the prognostic value of FAs in acute conditions to check the availability of a non-invasive sampling methodology. A deeper understanding of salivary FAs could have relevant implications both for healthy individuals and patients, particularly in elucidating the correlation between the dietary lipidic content and salivary FA level, Finally, it is crucial to address the standardization of the methods as the sampling, processing, and analysis of saliva are heterogeneous among studies, and limited correlation between blood FAs and salivary FAs is available.

Cardiovascular risk and inflammation in a population with autoimmune diseases: a narrative review.

Juvenile Systemic Connective Tissue Diseases (JSCTD) are a heterogeneous group of chronic autoimmune diseases, associated with dyslipidemia and increased cardiovascular risk are related. Studies from the last 10 years, from 2013 to 2022, on lipid profiles in JSCTD were collected. Different studies on lipid profiles in children affected by JSCTD were selected, because the aim is to analyze the cardiovascular risk and the possibility of atherosclerosis in these patients in whom, sometimes, corticosteroid therapies and immunosuppressants increase the state of dyslipidemia. Several studies have shown that autoimmune diseases with an inflammatory substrate also share abnormalities in lipid profile and increased cardiovascular risk. Specifically, associations have been found between Juvenile Systemic Connective Tissue Diseases and elevated triglycerides, TC-C (Total Cholesterol), LDL-C (Low-Density Lipoprotein), low HDL-C (High-Density Lipoprotein), and increased risk of developing diseases such as myocardial infarction, peripheral vascular disease, pulmonary and arterial hypertension, and atrial fibrillation. Supplementation with alpha-linolenic acid (ALA) on the other hand has also been analyzed with positive results in reducing inflammatory parameters, such as IL-6 (Interleukin-6), CRP (C-reactive protein), and fasting glucose, in subjects with dyslipidemia. These observations suggest that supplementation with ALA, an omega-3 precursor, may positively modulate both the inflammatory status and dyslipidemic conditions in patients with autoimmune disorders.

Clinical and laboratory parameters associated with febrile seizure recurrence within the first 24†h: a ten-year cohort study.

Introduction: We assessed clinical and laboratory parameters associated with early recurrence of febrile seizure in patients presenting at the Emergency Department with a first episode. Methods: Case series of patients admitted to the emergency department with the first episode of febrile seizure for ten consecutive years. Exclusion criteria were focal features and prolonged duration (>15 min). Results: We included 693 patients, 284 (41%) female. Median age of 20 (IQR 15-27) months. Fifty-two (8%) patients had a recurrence within 24 h. At univariate analysis, patients with recurrent seizures had higher use of antipyretics (88% vs. 74%, P = 0.03, OR 2.6, 95% CI: 1.1-7.7), higher median maximal body temperature (39.3 °C, IQR 38.9-39.9, vs. 38.9, IQR 38.4-39.3, P < 0.001, OR 2.3, 95% CI: 1.5-2.6) and presented with a lower proportion of respiratory tract infections (54% vs. 70%, P = 0.02) compared to patients without recurrence. A maximal body temperature equal to or higher than 39 °C was associated with a higher recurrence (11% vs. 4%, P < 0.001, OR 2.9, 95% CI: 1.6-5.6). Hyponatremia was not associated with a risk of recurrence. The multivariate analysis confirmed a direct association with body temperature (OR 2.3, 95% CI: 1.5-3.7, P < 0.001), and an inverse association with respiratory tract infections (OR 0.4, 95% CI: 0.2-0.9, P = 0.01), while antipyretic use was not correlated (OR 1.9, 95% CI: 0.8-5.2, P = 0.2). Conclusions: High body temperature and respiratory tract infections were (directly and inversely) associated with recurrences. Consideration of these conditions might help for anticipating the probability of recurrence.

Risk factors and scores for prediction of coronary artery aneurysms in Kawasaki disease: a European monocentric study.

BACKGROUND: Japanese Kawasaki disease (KD) risk scores cannot be adopted in non-Japanese patients. In North American populations a baseline coronary artery Z-score > 2 and the Son score are associated with coronary artery aneurysms (CAAs) at 4 and 8 weeks from disease onset. In European populations, the Kawanet and Kawanet-echo scores are associated with intravenous immunoglobulin resistance. This study aims to evaluate the association between KD risk scores and baseline coronary artery Z-scores with CAAs at one, two, and six months in a European population. METHODS: Historical cohort study of all the children diagnosed with KD in a tertiary care hospital in Milan, Italy, between 1st January 2015 and 31st May 2021. Univariate and multivariate (adjusting for age and corticosteroid therapy) logistic regression analyses were used to study the association between the risk scores, a baseline Z-score ≥ 2 and ≥ 2.5 with CAAs. RESULTS: Eighty-nine patients were diagnosed with KD at our Centre, and 12 were excluded based on the exclusion criteria. We included 77 patients, 51 (66%) males, and 26 (34%) females, with a median age at presentation of 27 months (IQR 13-46). A baseline Z-score ≥ 2 was correlated with CAAs at one and two-month follow-ups (odds ratio (OR) 10, 95% confidence interval (CI) 2-72, and OR 18, CI 3-357) but not at six-month follow-up. The Son score showed an association with one and two-month follow-up CAAs (OR 3, CI 1.3-7, and OR 3, CI 1.3-8) but not with a six-month follow-up. CONCLUSIONS: Patients with a baseline Z-score ≥ 2 are at higher risk for CAAs in the long term. The Son score should be tested in larger European samples. Further studies should keep the observational periods longer than 8 weeks from KD onset.

A systematic review and meta-analysis on nutritional and dietary interventions for the treatment of acute respiratory infection in pediatric patients: An EAACI taskforce.

Acute respiratory infections are a major cause of morbidity and mortality in children worldwide. Dietary and nutritional interventions, including minerals and vitamin supplementation, have been explored as potential treatments for these infections. However, the evidence on their efficacy is limited and inconclusive. This systematic review and meta-analysis aim to provide a comprehensive summary of the available evidence on the effectiveness of dietary and nutritional interventions for treating acute respiratory tract infections in children. A systematic review was conducted according to the PRISMA 2020 guidelines in April 2022 and updated in April 2023. Clinical trials focusing on dietary or nutritional interventions, including supplementations, in children with acute respiratory tract infections were included. The selection of interventions and outcomes was based on biological plausibility. Data were extracted using a standardized form, and the risk of bias was assessed using the Cochrane Risk of Bias Tool. Meta-analysis was performed using random-effect models. A total of 50 studies were included in the review. Four trials were conducted in low, 32 in lower-middle, 12 in upper-middle, and only two in high-income countries. The studies evaluated various dietary interventions, including zinc, vitamin A, vitamin E, vitamin D, and probiotics. The results of individual studies on the efficacy of these interventions were mixed, with some showing positive effects on clinical outcomes such as duration of symptoms, while others showed no significant impact. Meta-analysis was conducted for zinc supplementation in children with pneumonia, and the pooled results suggested a potential limited benefit in terms of reduced hospital length of stay but not time to recovery. Meta-analyses on vitamin D did not show any effect in children with pneumonia. This systematic review fills a critical gap in the literature by synthesizing the available evidence on the efficacy and safety of nutritional or dietary interventions for acute respiratory tract infections in children. The findings indicate no dietary or nutritional intervention can currently be recommended for the routine treatment of respiratory tract infections in children based on single supplement studies. The metanalysis suggests that zinc supplementation might have a beneficial effect on length of hospitalization in children with pneumonia. New studies are needed to establish more conclusive evidence for pediatric acute respiratory diseases especially for children living in a context of high-income countries.

Long-lasting effects of COVID-19 pandemic on hospitalizations and severity of bronchiolitis.

Bronchiolitis is a common cause of hospitalization in infants. The long-lasting impact of hygiene and social behavior changes during the pandemic on this disease is debated. We investigated the prevalence of hospitalized cases, clinical severity, and underlying risk factors before and during pandemic. The study was conducted in 27 hospitals in Italy and included infants hospitalized for bronchiolitis during the following four periods: July 2018-March 2019, July 2020-March 2021, July 2021-March 2022, and July 2022-March 2023. Data on demographics, neonatal gestational age, breastfeeding history, underlying chronic diseases, presence of older siblings, etiologic agents, clinical course and outcome were collected. A total of 5330 patients were included in the study. Compared to 2018-19 (n = 1618), the number of hospitalizations decreased in 2020-21 (n = 121). A gradual increase was observed in 2021-22 (n = 1577) and 2022-23 (n = 2014). A higher disease severity (need and length of O2-supplementation, need for non-invasive ventilation, hospital stay) occurred in the 2021-22 and, especially, the 2022-23 periods compared to 2018-19. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity.   Conclusions: Compared to adults, COVID-19 in infants is often asymptomatic or mildly symptomatic and rarely results in hospitalization. This study indicates that the pandemic has indirectly induced an increased burden of bronchiolitis among hospitalized infants. This shift, which is not explained by the recognized risk factors, suggests the existence of higher infant vulnerability during the last two seasons. What is known: • The pandemic led to a change in epidemiology of respiratory diseases • Large data on severity of bronchiolitis and underlying risk factors before and during COVID-19 pandemic are scarce What is new: • Compared to pre-pandemic period, hospitalizations for bronchiolitis decreased in 2020-21 and gradually increased in 2021-22 and 2022-23 • Compared to pre-pandemic period, higher disease burden occurred in 2021-22 and, especially, in 2022-23. This tendency persisted after adjusting for risk factors associated with bronchiolitis severity • The interplay among viruses, preventive measures, and the infant health deserves to be further investigated.

Complementary Feeding Practices: Recommendations of Pediatricians for Infants with and without Allergy Risk.

AIM: To investigate the routine guidance provided by pediatricians concerning the timing of complementary feeding (CF) for both healthy infants and those at a heightened risk of allergies. METHODS: A total of 233 pediatricians participated in an anonymous online survey that included questions about demographics and recommendations for CF. Specifically, they provided guidance on the types of foods, preparation methods, supplements, time intervals for introducing new foods to infants at low and high allergy risk, and delayed food introductions for high-risk cases. RESULTS: The respondents advised introducing certain foods at specific ages: fruits, starchy non-gluten grains, vegetables, olive oil, and meat were appropriate at 6 months; gluten-rich grains at 7 months; yogurt, hard-boiled eggs, and legumes at 8 months; fish at 8.5 months; and nuts at 9 months. Pediatricians, especially those with less than 15 years of practice, often introduced egg, seafood, gluten-rich grains, legumes, and nuts earlier for high-risk infants. Parenthood and male gender were associated with the earlier introduction of eggs and grains. CONCLUSIONS: Greek pediatricians follow a structured food introduction schedule for CF in infants. Interestingly, they tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants. Key Notes: Despite recent evidence-based indications on healthy complementary feeding strategies for infants, discrepancies persist among pediatricians regarding food choices and the order and timing of food introduction, both for healthy infants and those at risk of allergy. Guidance on complementary feeding by pediatricians is influenced by their individual characteristics. Pediatricians tend to delay the introduction of common food allergens and recommend longer intervals between introducing new foods, particularly for high-risk infants.

Validation of Indirect Calorimetry in Children Undergoing Single-Limb Non-Invasive Ventilation: A Proof of Concept, Cross-Over Study.

BACKGROUND: The accurate assessment of resting energy expenditure (REE) is essential for personalized nutrition, particularly in critically ill children. Indirect calorimetry (IC) is the gold standard for measuring REE. This methodology is based on the measurement of oxygen consumption (VO2) and carbon dioxide production (VCO2). These parameters are integrated into the Weir equation to calculate REE. Additionally, IC facilitates the determination of the respiratory quotient (RQ), offering valuable insights into a patient's carbohydrate and lipid consumption. IC validation is limited to spontaneously breathing and mechanically ventilated patients, but it is not validated in patients undergoing non-invasive ventilation (NIV). This study investigates the application of IC during NIV-CPAP (continuous positive airway pressure) and NIV-PS (pressure support). METHODS: This study was conducted in the Pediatric Intensive Care Unit of IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, between 2019 and 2021. Children < 6 years weaning from NIV were enrolled. IC was performed during spontaneous breathing (SB), NIV-CPAP, and NIV-PS in each patient. A Bland-Altman analysis was employed to compare REE, VO2, VCO2, and RQ measured by IC. RESULTS: Fourteen patients (median age 7 (4; 18) months, median weight 7.7 (5.5; 9.7) kg) were enrolled. The REE, VO2, VCO2, and RQ did not differ significantly between the groups. The Limits of Agreement (LoA) and bias of REE indicated good agreement between SB and NIV-CPAP (LoA +28.2, -19.4 kcal/kg/day; bias +4.4 kcal/kg/day), and between SB and NIV-PS (LoA -22.2, +23.1 kcal/kg/day; bias 0.4 kcal/kg/day). CONCLUSIONS: These preliminary findings support the accuracy of IC in children undergoing NIV. Further validation in a larger cohort is warranted.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

The debate continues on the best age to stop breastfeeding.

The ongoing debate on the optimal duration of breastfeeding in high-income countries is challenging. The decision to continue breastfeeding beyond the introduction of solids according to WHO indications involves multifaceted considerations, such as nutritional needs, psychological factors and cultural influences, given the growing number of immigrants. The impact on maternal health, sleep routines and family dynamics should be carefully weighed too. CONCLUSION: Next studies should investigate associations of different modalities and periods of breastfeeding with physical and neurodevelopmental outcomes, including psychological aspects. A personalised and gradual approach is suggested, guided by informed decisions and a supportive network.

Novel insect-based child nutrition: the position of the nutritional committee of the Italian society of pediatric gastroenterology, hepatology and nutrition (SIGENP).

BACKGROUND: The European Union (EU) approved the placement on European market of insect-based novel foods. Those foods were defined safe for the consumption for all European population, including children. MAIN BODY: The nutrition committee of the Italian society of Paediatric Hepatology and Nutrition (SIGENP) performed literature research to understand benefits and risk of those use of those NF for Italian children. A special attention was reserved to the European Food Safety Agency (EFSA) reports upon which those novel insect-based were approved. CONCLUSIONS: Based on the current knowledge, despite a possible ecological advantage, the group of expert suggests additional researches before pronouncing on a possible use for children diet, because of insufficient evidence on nutritional benefits and possible food allergies.

Why do mothers mix milk feed their infants? Results from a systematic review.

CONTEXT: Combining or supplementing breastfeeding with formula feeding, also called mixed milk feeding (MMF), is a common infant feeding practice. However, there is no well-established MMF evidence-base for informing and guiding parents. A better understanding of the reasons why mothers practice MMF may facilitate identification of efficient strategies for supporting exclusive breastfeeding, and/or opportunities to prolong breastfeeding, at least partially. OBJECTIVE: An updated systematic literature review was undertaken with the primary aim of gaining a deeper understanding of the reasons why mothers choose MMF. DATA SOURCES: Six databases were searched for relevant articles published in English from January 2012 to January 2022. DATA EXTRACTION: Two reviewers independently performed the screenings and data extraction, and any differences were resolved by a third reviewer. Data from 138 articles were included, 90 of which contained data on MMF reasons/drivers, and 60 contained data on infant age and/or maternal demographic factors associated with MMF. DATA ANALYSIS: A total of 13 different unique MMF drivers/reasons were identified and categorized according to whether the drivers/reasons related to perceived choice, necessity, or pressure. Risk of bias was evaluated using the Quality Assessment Tool of Diverse Studies and the JBI Systematic Reviews tool. Several different terms were used to describe and classify MMF across the studies. The most commonly reported reasons for MMF were related to a perception of necessity (39% of drivers, eg, concerns about infant's hunger/perceived breast milk insufficiency or breastfeeding difficulties), followed by drivers associated with perceived choice (34%; eg, having more flexibility) and perceived pressure (25%; eg, returning to work or healthcare professionals' advice). This was particularly true for infants aged 3 months or younger. CONCLUSION: The key global drivers for MMF and their distribution across infant age and regions were identified and described, providing opportunities for the provision of optimal breastfeeding support. A unified definition of MMF is needed in order to enable more comparable and standardized research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no. CRD42022304253.

The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications.

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, ß-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.