Unintended PG administration (34 mg/kg/24 h) for a maximum of 48 h seems to be tolerated in (pre)term neonates and does not affect short-term postnatal adaptations. Further studies on PG disposition and the level of safe exposure to PG, including long-term safety data in neonates are needed.

No abstract

• Gastrointestinal complications arise early in the course of the disease and have a severe impact on the quality of life of the patients. What is New: • This review is a concise summary of the current literature on gastrointestinal complications of cystic fibrosis. • We focused on clinical presentation and diagnostic investigations and provide a comprehensive resume of the current treatment options.

International audienc

Background and aims: Following the results of the paediatric early versus late parenteral nutrition in critical illness (PEPaNIC) multicentre, randomised, controlled trial, the new ESPGHAN/ESPEN/ESPR/ CSPEN and ESPNIC guidelines recommend to consider withholding parenteral macronutrients for 1 week, while providing micronutrients, in critically ill children if enteral nutrition is insufficient. Critically ill children are suspected to be vulnerable to micronutrient deficiencies due to inadequate enteral nutrition, increased body's demands and excessive losses. Hitherto, micronutrient requirements in PICU are estimated based on recommended daily intakes for healthy children and expert opinion. We aimed to provide an overview of the current practice of micronutrient administration and practical considerations in the three participating centres of the PEPaNIC study, and compare these therapies with the recommendations in the new ESPGHAN/ESPEN/ESPR/CSPEN guidelines. Methods: We describe the current composition and preparation of the prescribed parenteral micronutrients (consisting of vitamins, trace elements and electrolytes) in the three centres (Leuven, Rotterdam and Edmonton) that participated in the PEPaNIC RCT, and compare this per micronutrient with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines recommendations. Results: The three centres use a different micronutrient supplementation protocol during the first week of critical illness in children, with substantial differences regarding the amounts administered. Leuven administers commercial vitamins, trace elements and electrolytes in separate infusions both in 4 h. Rotterdam provides commercial vitamins and trace elements simultaneously via 8-h infusion and electrolytes continuously over 24 h. Lastly, Edmonton administers commercial vitamins and institutionally prepared trace elements solutions in 1 h and electrolytes on demand. Comparison with the ESPGHAN/ESPEN/ESPR/CSPEN guidelines yields in differences between the recommendations and the administered amounts, which are most substantial for vitamins. Conclusion:The practice of intravenous micronutrient administration differs substantially between the three PEPaNIC centres and in comparison with the current guideline recommendations. This deviation is at least partially explained by the inability to provide all recommended amounts with the currently available commercial products and by the lack of strong evidence supporting these recommendations.

To attain effective and safe pharmacotherapy in neonates, caregivers have to consider both the clinical characteristics of the newborn and the pharmacokinetic estimates of a given compound during prescription and administration. Overall, clearance in neonates is low when compared to other pediatric subpopulations. Despite this overall low clearance, there is already extensive between individual variability in clearance in early life. As a consequence, neonates are in urgent need of tailored drug product development that considers the need for both low and flexible dosing to maintain dose accuracy. During the development of such formulations tailored for neonates, there is also a need for guidance on excipient exposure. The available knowledge on the safety or toxicity of excipients is limited and difficult to retrieve, but there are initiatives (e.g. Safety and Toxicity of Excipients for Pediatrics [STEP] database initiative) to improve the present situation. In addition, population focussed studies on aspects of clinical pharmacology of excipients in neonates should be conducted. The propylene glycol research project and the European Study for Neonatal Excipient Exposure (ESNEE) initiative illustrate its feasibility. Finally, until tailored formulations make it to the market, compounding practices for drug formulations in neonates should be evaluated to guarantee correct dosing, product stability, safety and to support pharmacists in their daily practice.

Introduction: Acute on Chronic Liver Failure (ACLF) is defined as an acute deterioration of pre-existing chronic liver disease related to a precipitating event with increased mortality at 3 months due to multisystem organ failure. Children with Intestinal Failure Associated Liver Disease (IFALD) are at particular risk of ACLF as they often face a long waiting time for appropriate sized liver small bowel transplant donors and are not able to be categorised as super urgent. We aimed to characterise ACLF in children with IFALD. Methods: All BCH patients from 2000-2020 with IFALD determined to be in ACLF utilising European Foundation for Study of Chronic Liver Failure (EASL CLIF) criteria were included. Descriptive statistics was presented as median (range) and CLIF C ACLF score calculated to predict 28-day mortality. Results: 6 children with IFALD were included. 3 patients had Gastroschisis, 2 Necrotising Enterocolitis (NEC) and 1 total colonic Hirschsprung's. Median age at ACLF onset was 1 year (0.8-2). ACLF triggers were sepsis in 5 and GI bleed in 1. Bilirubin at time of ACLF onset was 600 umol/L (506-870), Creatinine 30 umol/L (14-124), Prothrombin time 22 (15-35), Grade 3,4 hepatic encephalopathy (2/6), ventilation (2/6) and CLIF C ACLF score 31 (28-49). There was 100% mortality (n=6) between 2000-2012. Median time from ACLF admission to death was 29 days (6-60). Transplant listing occurred in 4, 3 pre ACLF with a median of 17 days (10-120) and 1 7 days post ACLF. 2 children were thought to be too unwell to list. Discussion: Children with IFALD are vulnerable to develop ACLF, particularly from triggering factors e.g. line sepsis. Children presenting with ACLF had end stage IFALD and median time to death was short, with not enough time for rescue transplantation. The decrease in ACLF episodes in last decade may be related to less incidence of IFALD due to advances in parenteral nutrition. Conclusion:Children with end stage IFALD can be at risk of developing ACLF especially following line sepsis and thus further prioritisation in those with IFALD at risk of ACLF should be considered.

No abstract