Evidence map›Paper›PMID 41680910›Full record

Trial reportCritical care (London, England)2026

Hypophosphatemia as a biomarker of metabolic intolerance to enhanced nutrition in the PICU: a secondary analysis of the PEPaNIC RCT.

Ilse Vanhorebeek, Nazlı Umman Serin, Fabian Güiza, Liese Mebis, Sascha C A T Verbruggen, Koen F M Joosten, Greet Van den Berghe, Jan Gunst

Registry-linked trialAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Critical care (London, England), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01536275 (Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Paediatric Critically Ill Patients), which is not on this map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT01536275 naactive not recruitingnot on this map

Impact of Early Parenteral Nutrition Completing Enteral Nutrition in Paediatric Critically Ill Patients

TypeinterventionalSponsorKU LeuvenRan2012 to 2026Enrolled1,440ConditionsCritical Illness, ChildrenArmsLate parenteral nutrition
3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Trial
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Ilse VanhorebeekDepartment of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium. ilse.vanhorebeek@med.kuleuven.be.ORCID http://orcid.org/0000-0002-5261-5192
Nazlı Umman SerinDepartment of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium.ORCID http://orcid.org/0000-0001-8215-8909
Fabian GüizaDepartment of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium.ORCID http://orcid.org/0000-0001-7026-0957
Liese MebisDepartment of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium.ORCID http://orcid.org/0000-0002-6941-3044
Sascha C A T VerbruggenDepartment of Neonatal and Pediatric ICU Division of Pediatric Intensive Care Unit , Erasmus Medical Center Sophia Children's Hospital , Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0003-4866-9865
Koen F M JoostenDepartment of Neonatal and Pediatric ICU Division of Pediatric Intensive Care Unit , Erasmus Medical Center Sophia Children's Hospital , Rotterdam, The Netherlands.ORCID http://orcid.org/0000-0002-0504-2475
Greet Van den Berghe *Department of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium.ORCID http://orcid.org/0000-0002-5320-1362
Jan Gunst *Department of Cellular and Molecular Medicine Clinical Division and Laboratory of Intensive Care Medicine, KU Leuven, Herestraat 49 , Leuven, B-3000 , Belgium.ORCID http://orcid.org/0000-0003-2470-6393

Funding

European Society for Clinical Nutrition and Metabolism (ESPEN) Research GrantFP7 Ideas: European Research Council AdG-2012-321670H2020 European Research Council AdG-2017-785809HORIZON EUROPE European Research Council AdG-2023-101133276Institute for Science and Technology, Flanders, Belgium IWT-TBM150181 and IWT-TBM110685KU Leuven STG/23/032Methusalem Program of the Flemish government METH14/06Research Foundation-Flanders 1842724N and G029525NSophia Research Foundation SSWO grant
6 · The paper itself

Abstract

backgroundThe PEPaNIC RCT showed that early supplementation of insufficient enteral nutrition by parenteral nutrition (early-PN) worsened outcome of critically ill children as compared with withholding PN for 1 week (late-PN). The best timing to initiate nutritional support in the pediatric intensive care unit (PICU) remains unclear. In adults, declining phosphate levels may identify patients who are particularly harmed by early-PN. We therefore assessed whether early hypophosphatemia in critically ill children may indicate metabolic intolerance to nutrition.

methodsIn this secondary analysis of the PEPaNIC RCT (n = 1440), we investigated whether development of hypophosphatemia statistically interacts with the randomized intervention for its impact on clinical outcome, adjusting for baseline risk factors. Outcomes of interest included the incidence of new infections and the duration of PICU dependency as primary endpoints, 90-day mortality as safety endpoint, and duration of mechanical ventilation and of hospital stay as secondary endpoints. Subsequently, the impact of early-PN vs. late-PN in patients with and without early hypophosphatemia was assessed. Analyses were performed for phosphate abnormalities on PICU day 1 and 2, with and without imputing 20.3% (day 1) or 22.0% (day 2) missing phosphate data.

resultsOf patients with available phosphate measurements, 19.9% (211/1060) and 27.5% (243/883) developed hypophosphatemia on day 1 and day 2, respectively. Day 1 hypophosphatemia did not interact with the randomized intervention for any studied outcome. On day 2, hypophosphatemia interacted with randomization for risk of new infection (P = 0.031), likelihood of earlier live PICU discharge (P = 0.030), and time to live weaning from mechanical ventilation (P = 0.025). Harm by early-PN was more pronounced in patients with hypophosphatemia than in those without. Results after imputing missing phosphate data were similar, with an additional interaction for 90-day mortality (P = 0.038) revealing higher mortality with early-PN in patients with hypophosphatemia.

conclusionsDevelopment of hypophosphatemia may identify critically ill children who are particularly harmed by early-PN. This opens perspectives for its use as a biomarker of metabolic intolerance to enhanced nutrition, which requires further investigation.

trial registrationClinicalTrials.gov NCT01536275, registered February 2012.

Indexed as

HypophosphatemiaBiomarkersChildChild, PreschoolCritical IllnessFemaleHumansInfantIntensive Care Units, PediatricMaleParenteral NutritionSecondary Data AnalysisBiomarkersChildrenClinical outcomeCritical illnessHypophosphatemiaInfectionMechanical ventilationMortalityParenteral nutritionPICU

Identifiers

PMID41680910
PMCPMC12896274

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.