Refining the phenotype of SINO syndrome: A comprehensive cohort report of 14 novel cases.

PURPOSE: Spastic paraplegia, intellectual disability, nystagmus, and obesity syndrome (SINO) is a rare autosomal dominant condition caused by heterozygous variants in KIDINS220. A total of 12 individuals are reported, comprising 8 with SINO and 4 with an autosomal recessive condition attributed to biallelic KIDINS220 variants. METHODS: In our international cohort, we have included 14 individuals, carrying 13 novel pathogenic KIDINS220 variants in heterozygous form. We assessed the clinical and molecular data of our cohort and previously reported individuals and, based on functional experiments, reached a better understanding of the pathogenesis behind the KIDINS220-related disease. RESULTS: Using fetal tissue and in vitro assays, we demonstrate that the variants generate KIDINS220 truncated forms that mislocalize in punctate intracellular structures, with decreased levels of the full-length protein, suggesting a trans-dominant negative effect. A total of 92% had their diagnosis within 3 years, with symptoms of developmental delay, spasticity, hypotonia, lack of eye contact, and nystagmus. We identified a KIDINS220 variant associated with fetal hydrocephalus and show that 58% of examined individuals present brain ventricular dilatation. We extend the phenotypic spectrum of SINO syndrome to behavioral manifestations not previously highlighted. CONCLUSION: Our study provides further insights into the clinical spectrum, etiology, and predicted functional impact of KIDINS220 variants.

Blood-Biomarkers for Glucose Metabolism in Preterm Infants.

This was an exploratory, prospective, longitudinal, cohort study that aimed to establish "healthy" reference levels related to growth parameters and glucose metabolites in preterm infants. This was conducted to further investigate growth and metabolic disturbances potentially related to neonatal illness. The study sample consisted of 108 preterm infants born before 32 weeks in 2018-2019 in the Capital Region of Denmark. Repetitive blood samples were acquired at the neonatal wards, while clinical data were obtained from the regional hospital medical record system. Thirty-four "healthy" preterm infants (31%) were identified. The "ill" infants were divided into four subgroups dependent on gestational age and small for gestational age. Reference levels for the growth parameters and metabolic biomarkers glucose, albumin, and adiponectin, and two glucose control indicators, glycated albumin and fructosamine, were determined for the "healthy" and "ill" subgroups. The "ill" extremely preterm infants had increased glucose levels (mean difference 0.71 mmol/L, 95% CI 0.23; 1.18 mmol/L) and glycated albumin (corrected; %) (mean difference 0.92 mmol/L, 95% CI 0.38 mmol/L;1.47 mmol/L) compared to the "healthy" infants. In "ill" extremely preterm infants and "ill" very preterm infants born small for gestational age, levels of biomarkers containing proteins were decreased. In the "Ill" extremely preterm infants and infants born small for gestational age, postnatal growth was continuously decreased throughout the postconceptional period. The short-term glucose-control indicator, glycated albumin (corrected; %), reflected well the high glucose levels due to its correction for the depleted plasma-protein pool.

Switch from intravenous-to-oral antibiotics in neonatal probable and proven early-onset infection: a prospective population-based real-life multicentre cohort study.

OBJECTIVE: To evaluate the implementation of switch from intravenous-to-oral antibiotic therapy with amoxicillin in neonates with early-onset infection (EOI). DESIGN, SETTING AND PATIENTS: A population-based multicentre cohort study. All term-born neonates with EOI were prospectively included between 1 December 2018 to 30 November 2020. INTERVENTION: Intravenous-to-oral switch antibiotic therapy in clinically stable neonates. MAIN OUTCOME MEASURES: The primary outcome was readmission due to infection. Secondary outcomes were days of hospitalisation and antibiotic use in the pre-implementation versus post implementation period. RESULTS: During 2 years, 835 neonates commenced antibiotics for EOI (1.5% (95% CI 1.4% to 1.6%)) of all term live births). Of those, 554 (66%) underwent a full course of treatment. There were 23 episodes of culture-proven infection (0.42 per 1000 term live births (95% CI 0.27 to 0.63)). A total of 478 of 531 (90%) neonates with probable infection underwent switch therapy. None was readmitted due to infection. The median duration of hospitalisation was 3.0 days (IQR 2.5-3.5) and 7.4 days (IQR 7.0-7.5) in the switch and intravenous therapy groups, respectively. According to antibiotic surveillance data, 1.2% underwent a full course of treatment following implementation of oral switch therapy (2019-2020), compared with 1.2% before (2017-2018). CONCLUSION: In clinical practice, switch therapy was safe and used in 9 of 10 neonates with probable EOI. Knowledge of the safety of antibiotic de-escalation is important as home-based oral therapy ameliorates the treatment burden for neonates, caregivers and healthcare systems. Despite the ease of oral administration, implementation of switch therapy did not increase the overall use of antibiotics.

[Greater vigilance in medication for children and adolescent is warranted in Denmark].

Only 30% of medication used for children and adolescents and 10% of the medication used for neonates has been evaluated for use in these populations. Infants and children differ from adults regarding pharmacodynamic and -kinetics, but they also differ from each other due to e.g. age, weight, and body composition, as we argue in this review. There is only limited knowledge within this area leading to the use of off-label, extemporaneous and unlicensed medication. Greater national vigilance in medication for children and adolescent is warranted to secure better and safer medicine for newborns, infants, children and adolescents.

Development of one paediatric and one neonatal formulary list in hospital settings.

AIMS: The aim of this study is to describe the stepwise process towards creating two formulary lists: one for paediatric and one for neonatal patients covering common diseases in hospital settings. METHODS: This study presents the concept for developing a formulary list, namely how to: (1) organize the editorial board, (2) procure drug consumption data and database management, including information on labelling status, dosing options, excipients and problematic adverse events, current guidelines, evidence and price, (3) develop the first edition for the formulary list and formulary manual, and (4) to establish a paediatric sub-committee within the Regional Drug and Therapeutic Committee to maintain and continually develop the two formularies. RESULTS: The total number of drugs was 411 ATC level 5, which covers 1097 unique item numbers prior to the paediatric formulary list, of which 263 item numbers were included in the final list. In neonates, 201 drugs ATC level 5 were evaluated, covering 348 unique item numbers, of which 104 item numbers were included in the final neonatal formulary list. Eighty-eight percent of the included drugs in the paediatric formulary were licensed to children (not specified by age group), 2% were unlicensed in Denmark, and 7% were extemporaneous preparations. For neonates, the percentage was 48%, 4% and 16%, correspondingly. CONCLUSION: The process is time-consuming as studies are lacking and age-appropriate dosage forms and concentrations differ amongst countries. Nevertheless, the process should be somewhat similar between countries, albeit different drugs may be selected for the final formulary lists.

A Randomized Trial of Low-Flow Oxygen versus Nasal Continuous Positive Airway Pressure in Preterm Infants.

BACKGROUND: Nasal continuous positive airway pressure (nCPAP) stabilizes the residual volume and may decrease the risk of 'atelectotrauma', potentially promoting lung development in neonates. OBJECTIVES: To assess whether replacing nCPAP by low-flow O2 by nasal cannula affects lung function expressed as the arterial/alveolar oxygen tension ratio (a/A pO2 ratio) on postnatal day 28. METHODS: Preterm infants (birth weight <1,500 g and gestational age, GA >26 + 0 weeks) stable on nCPAP between postnatal days 4 and 7 were randomized to nCPAP or low-flow O2 by nasal cannula (<0.2 liters/min). Study criteria defined how to wean/restart respiratory support or change from low-flow O2 to nCPAP and vice versa. Transcutaneous monitoring was used for the assessment of the a/A pO2 ratio on day 28 using a head box for all infants for accurate measurement and to eliminate possible effects from nCPAP or low-flow O2 on oxygen requirement. RESULTS: We enrolled 52 infants (nCPAP group n = 30 and low-flow O2 group n = 22). The a/A pO2 ratio at 28 days was 0.43 ± 0.17 (nCPAP group) versus 0.48 ± 0.18 (p = 0.36). The duration of nCPAP was 16.4 (low-flow group) versus 41.1 days (nCPAP group), p < 0.001. There was no difference between groups in the fraction needing any respiratory support at 36 weeks' corrected age, length of stay, weight at discharge, and relative weight gain. CONCLUSIONS: Replacing nCPAP by low-flow O2 in preterm infants with GA >26 weeks at the end of the first week of life did not seem to affect the a/A pO2 ratio or weight gain negatively. Thus, prolonged nCPAP seems not to have a positive effect on lung function at 28 days of life and replacement by low-flow O2 could reduce the cost of equipment and increase the ease of nursing.

[Multiple mini interviews before the occupation of main training posts in paediatrics]. / Multiple miniinterview før besættelse af pædiatriske hoveduddannelsesstillinger er gennemførlige.

Interviews are mandatory in Denmark when selecting doctors for training positions. We used multiple mini interviews (MMI) at four recruitment rounds for the main training posts in paediatrics. In total, 125 candidates were evaluated and assessed by CV and MMI (4-5 stations). Reliability for individual stations in MMI assessed by Cronbach's alpha was adequate (0.63-0.92). The overall reliability assessed by G-theory was lower, suggesting that different skills were tested. The acceptability was high. Our experiences with MMI suggest good feasibility and reliability. An increasing number of stations may improve the overall reliability.