UNASSIGNED: Neonatal hyperbilirubinemia is one of the most common conditions for neonate inpatients. Indonesia faces a major challenge in which different guidelines regarding the management of this condition were present. This study aimed to compare the existing guidelines regarding prevention, diagnosis, treatment and monitoring in order to create the best recommendation for a new hyperbilirubinemia guideline in Indonesia.
UNASSIGNED: Through an earlier survey regarding adherence to the neonatal hyperbilirubinemia guideline, we identified that three main guidelines are being used in Indonesia. These were developed by the Indonesian Pediatric Society (IPS), the Ministry of Health (MoH), and World Health Organization (WHO). In this study, we compared factors such as prevention, monitoring, methods for identifying, risk factors in the development of neonatal jaundice, risk factors that increase brain damage, and intervention treatment threshold in the existing guidelines to determine the best recommendations for a new guideline.
UNASSIGNED: The MoH and WHO guidelines allow screening and treatment of hyperbilirubinemia based on visual examination (VE) only. Compared with the MoH and WHO guidelines, risk assessment is comprehensively discussed in the IPS guideline. The MoH guideline recommends further examination of an icteric baby to ensure that the mother has enough milk without measuring the bilirubin level. The MoH guideline recommends referring the baby when it looks yellow on the soles and palms. The WHO and IPS guidelines recommend combining VE with an objective measurement of transcutaneous or serum bilirubin. The threshold to begin phototherapy in the WHO guideline is lower than the IPS guideline while the exchange transfusion threshold in both guidelines are comparably equal.
UNASSIGNED: The MoH guideline is outdated. MoH and IPS guidelines are causing differences in approaches to the management hyperbilirubinemia. A new, uniform guideline is required.

BACKGROUND: In the past decade, there have been substantial advances in our understanding of pediatric AKI. Despite this progress, large gaps remain in our understanding of pharmacology and nutritional therapy in pediatric AKI.
METHODS: During the 26th Acute Disease Quality Initiative (ADQI) Consensus Conference, a multidisciplinary group of experts reviewed the evidence and used a modified Delphi process to achieve consensus on recommendations for gaps and advances in care for pharmacologic and nutritional management of pediatric AKI. The current evidence as well as gaps and opportunities were discussed, and recommendations were summarized.
RESULTS: Two consensus statements were developed. (1) High-value, kidney-eliminated medications should be selected for a detailed characterization of their pharmacokinetics, pharmacodynamics, and pharmaco-\"omics\" in sick children across the developmental continuum. This will allow for the optimization of real-time modeling with the goal of improving patient care. Nephrotoxin stewardship will be identified as an organizational priority and supported with necessary resources and infrastructure. (2) Patient-centered outcomes (functional status, quality of life, and optimal growth and development) must drive targeted nutritional interventions to optimize short- and long-term nutrition. Measures of acute and chronic changes of anthropometrics, body composition, physical function, and metabolic control should be incorporated into nutritional assessments.
CONCLUSIONS: Neonates and children have unique metabolic and growth parameters compared to adult patients. Strategic investments in multidisciplinary translational research efforts are required to fill the knowledge gaps in nutritional requirements and pharmacological best practices for children with or at risk for AKI.

There is no consensus on optimal nutrition for preterm infants, leading to substantial practice variation. We aimed to assess the quality of nutrition guidelines for preterm infants, the consistency of recommendations, and the gaps in recommendations.
We searched databases and websites for nutrition guidelines for preterm infants before first hospital discharge, which were endorsed, prepared, or authorized by a regional, national, or international body, written in English, and published between 2012 and 2023. Two reviewers independently screened articles and extracted the recommendations. Four reviewers appraised the included guidelines using Appraisal of Guidelines, Research, and Evaluation II.
A total of 7051 were identified, with 27 guidelines included, 26% of which were high in quality. Most guidelines lacked stakeholder involvement and rigor of development. We found considerable variation in recommendations, many of which lacked details on certainty of evidence and strength of recommendation. Recommendations for type of feed and breastmilk fortification were consistent among high-quality guidelines, but recommendations varied for intakes of almost all nutrients and monitoring of nutrition adequacy. Different guidelines gave different certainty of evidence for the same recommendations. Most gaps in recommendations were due to very low certainty of evidence.
Future development of nutrition guidelines for preterm infants should follow the standard guideline development method and ensure the rigorous process, including stakeholders\' involvement, to improve the reporting of strength of recommendation, certainty of evidence, and gaps in recommendation. Evidence is needed to support recommendations about macro and micronutrient intakes, breastmilk fortification, and markers on adequacy of intake of different nutrients.

Parenteral nutrition (PN) is prescribed for preterm infants until nutrition needs are met via the enteral route, but unanswered questions remain regarding PN best practices in this population.
An interdisciplinary committee was assembled to answer 12 questions concerning the provision of PN to preterm infants. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was used. Questions addressed parenteral macronutrient doses, lipid injectable emulsion (ILE) composition, and clinically relevant outcomes, including PNALD, early childhood growth, and neurodevelopment. Preterm infants with congenital gastrointestinal disorders or infants already diagnosed with necrotizing enterocolitis or PN-associated liver disease (PNALD) at study entry were excluded.
The committee reviewed 2460 citations published between 2001 and 2023 and evaluated 57 clinical trials. For most questions, quality of evidence was very low. Most analyses yielded no significant differences between comparison groups. A multicomponent oil ILE was associated with a reduction in stage 3 or higher retinopathy of prematurity (ROP) compared to an ILE containing 100% soybean oil. For all other questions, expert opinion was provided.
Most clinical outcomes were not significantly different between comparison groups when evaluating timing of PN initiation, amino acid dose, and ILE composition. Future clinical trials should standardize outcome definitions to permit statistical conflation of data, thereby permitting more evidence based recommendations in future guidelines. This guideline has been approved by the ASPEN 2022-2023 Board of Directors.

BACKGROUND: Vancomycin dosing tailored for newborns is challenging due to the significant influence of maturation and organ function on pharmacokinetics. Population pharmacokinetic (popPK) models can be used to improve target attainment in neonates.
OBJECTIVE: The primary objective was to derive and evaluate a popPK model of intravenous vancomycin for neonates. Second, the predictive performance of this popPK model was compared with published popPK models.
METHODS: This is a retrospective cohort study of neonates admitted to the neonatal intensive care unit receiving intravenous vancomycin. A popPK model was derived with 70% of the dataset using a nonlinear mixed effects modeling method. The predictive performance of the current popPK model was validated and compared with 22 published popPK models using the remaining 30% of the dataset. Monte Carlo simulations (MCS) were performed to derive optimal dosing regimens to treat neonatal sepsis caused by coagulase-negative staphylococci (CoNS).
RESULTS: Among 655 vancomycin courses from 448 neonates, 78% of vancomycin trough concentrations were outside target range (10-15 mg/L) for central nervous system infections and 43% were outside target range (5-12 mg/L) for other infections using the institution\'s vancomycin dosing. A one-compartment model best described the observed data with a mean clearance of 0.11 ± 0.03 L/kg/h and volume of distribution (V) of 1.02 ± 0.08 L/kg. Body weight (WT), postmenstrual age (PMA), and serum creatinine (SCr) were significant covariates associated with clearance (p < 0.001) and body WT was a significant covariate associated with V (p = 0.009). Our study\'s popPK model has similar or better accuracy and precision than other published models. MCS-derived vancomycin doses from the validated model achieved >90% target attainment for a steady state through target range of 10-15 mg/L in the majority of PMA and SCr categories (78%) to treat CoNS sepsis.
CONCLUSIONS: A vancomycin dosing guideline derived from a validated popPK model in neonates with CoNS sepsis is recommended to improve target attainment.

UNASSIGNED: The Japanese Neonatal Pain Guidelines Committee, led by the Japan Academy of Neonatal Nursing, uses the Grading of Recommendations, Assessment, Development, and Evaluation Working Group method to evaluate the quality of evidence and the strength of treatment recommendations. Ratings on the importance of outcomes related to neonatal pain have not been reported. This study aimed to reach a consensus on the importance of outcomes through a guideline panel composed of doctors, nurses, a nurse practitioner, a physical therapist, and families to ensure consistency in systematic reviews of neonatal pain and future revisions to the guidelines.
UNASSIGNED: A total of 26 professionals, including 21 medical personnel from clinical settings and academia and 5 parents from five family associations, participated in 3-stage eDelphi rounds.
UNASSIGNED: The literature review and discussion identified 75 outcomes that were included in round one. The participants proposed three additional outcomes: 78 outcomes were scored in rounds two and three. Round three scores showed different stakeholder groups in terms of priority outcomes. Seventeen outcomes were included in the final core outcome and were considered critical for decision-making.
UNASSIGNED: Core outcomes of the development of neonatal pain guidelines in Japan were identified. The assessment process of importance from this study highlights the difference in the perspectives of medical providers and parents on neonatal pain, thus, involving parents in the assessment and as the spokesperson for the infant admitted to the neonatal intensive care unit is important for a more inclusive evaluation of pain prevention and management.

Parenteral nutrition (PN) is a standard of care for preterm infants in the first postnatal days. The European Society of Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) has updated their guideline recommendations on PN in 2018. However, data on actual 2018 guideline adherence in clinical practice are sparse. In this retrospective study, conducted at the neonatal intensive care unit (NICU) of Ghent University Hospital, we analyzed the ESPGHAN 2018 PN guideline adherence and growth for 86 neonates admitted to the NICU. Analyses were stratified by birth weight (<1000 g, 1000 to <1500 g, ≥1500 g). We documented the provisions for enteral nutrition (EN) and PN, and we tested the combined EN and PN provisions for ESPGHAN 2018 adherence. The nutrition protocols showed a high adherence to PN guidelines in terms of carbohydrate provisions, yet lipid provisions for EN and PN often exceeded the recommended maximum of 4 g/kg/d; although, PN lipid intakes maxed out at 3.6 g/kg/d. Protein provisions tended to fall below the recommended minimum of 2.5 g/kg/d for preterm infants and 1.5 g/kg/d for term neonates. The energy provisions also tended to fall below the minimum recommendations, especially for neonates with a birth weight (BW) < 1000 g. Over a mean PN duration of 17.1 ± 11.4 d, the median weekly Fenton Z-scores changes for length, weight, and head circumference were positive for all BW groups. Future studies have to assess how protocols adapt to current guidelines, and how this affects short- and long-term growth across different BW groups. In conclusion, the reported findings provide real-world evidence regarding the effect of ESPGHAN 2018 PN guideline adherence, and they demonstrate how standardized neonatal PN solutions can safeguard stable growth during NICU stays.

Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children\'s Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8-12 mg/L for neonates and 15-20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment.

In pediatrics, accurate measurement of total serum bilirubin (TSB) is of major importance for reliable diagnosis and appropriate management of neonatal jaundice. However, several studies evidenced poor comparability of results obtained with the different available methods either in central lab or in POCT, on serum, capillary blood or transcutaneous. This situation is partly due to the lack of Reference Materials, especially for high bilirubin concentrations but also on poor communication between central lab and neonatology unit. To progress on these issues, we have compiled some data from CNRHP to propose guidelines for choice, use and management of POCT devices and to help clinical laboratories to achieve a better answer to clinical needs with specific local constraints. The results from several CNRHP studies are presented: traceability to International System of Units, inter-laboratories comparability, POCT vs central labs comparisons with POCT CO-oximeter or photometer, integration of transcutaneous bilirubinometer. We propose, based on an analysis of devices advantages and issues, guidelines to help labs either to improve neonates monitoring in their local context; we distinguished the choices inside laboratory for a better harmonization of results compared to published thresholds and outside lab contexts, to organize a coordinated chain with POCT devices, with capillary and/or transcutaneous approaches.
En néonatalogie, la mesure précise de la bilirubinémie est essentielle pour le diagnostic et le suivi de l’ictère, en regard de seuils consensuels internationaux. Toutefois, une faible comparabilité des résultats est observée entre les laboratoires de biologie médicale (LBM) et avec les dispositifs délocalisés ou transcutanés. Cette situation est en partie due à des défauts de standardisation des méthodes, mais aussi à une coordination insuffisante entre les laboratoires et les unités de soins. L’objectif de ce travail est de progresser dans l’optimisation de la prise en charge des nouveau-nés en proposant des critères de choix et d’articulation des différentes réponses biologiques, EBM, EBMD et TROD, en fonction des besoins cliniques locaux et des moyens disponibles. Les résultats de plusieurs études ciblées sur la bilirubinémie néonatale sont présentés : raccordement au système international, harmonisation interlaboratoires, comparabilité EBMD-CNRHP d’un CO-oxymètre délocalisé en maternité, comparabilité EBMD-CNRHP d’un photomètre délocalisé en maternité, intégration d’un bilirubinomètre transcutané. Nous proposons ensuite, sur la base d’une analyse critique des différents types de dispositifs, des recommandations pour aider les LBM à améliorer la prise en charge des nouveau-nés dans leur contexte local, d’une part sur la mesure de la bilirubinémie néonatale au sein du LBM et d’autre part sur l’organisation d’une chaîne coordonnée EBM – EBMD – TROD en concertation avec les unités de soins.

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