Evidence map›Paper›PMID 34050269›Full record

Trial reportPediatric research2022

Hypothermia is not therapeutic in a neonatal piglet model of inflammation-sensitized hypoxia-ischemia.

Kathryn A Martinello, Christopher Meehan, Adnan Avdic-Belltheus, Ingran Lingam, Tatenda Mutshiya, Qin Yang, Mustafa Ali Akin, David Price, Magdalena Sokolska, Alan Bainbridge and 12 more

Open access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Pediatric research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed, 2 pooled it
6.7field-weighted citation impact, top 3% of its field
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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 30 citations in OpenAlex.

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  13. Stay cool and keep moving forwards.Pediatric research · 2025
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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

22 authors at 10 institutions in 7 countries.

Kathryn A MartinelloInstitute for Women's Health, University College London, London, UK.
Christopher MeehanInstitute for Women's Health, University College London, London, UK.
Adnan Avdic-BelltheusInstitute for Women's Health, University College London, London, UK.
Ingran LingamInstitute for Women's Health, University College London, London, UK.
Tatenda MutshiyaInstitute for Women's Health, University College London, London, UK.
Qin YangInstitute for Women's Health, University College London, London, UK.
Mustafa Ali AkinDepartment of Paediatrics, Ondokuz Mayıs University, Samsun, Turkey.
David PriceMedical Physics and Biomedical Engineering, University College London NHS Foundation Trust, London, UK.
Magdalena SokolskaMedical Physics and Biomedical Engineering, University College London NHS Foundation Trust, London, UK.
Alan BainbridgeMedical Physics and Biomedical Engineering, University College London NHS Foundation Trust, London, UK.
Mariya HristovaInstitute for Women's Health, University College London, London, UK.
Ilias TachtsidisMedical Physics and Biomedical Engineering, University College London, London, UK.
Cally J TannAdolescent, Reproductive and Child Health Centre, London School of Hygiene and Tropical Medicine, London, UK.
Donald PeeblesInstitute for Women's Health, University College London, London, UK.
Henrik HagbergDepartment of Clinical Sciences, Centre of Perinatal Medicine and Health, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden.
Tim G A M WolfsDepartment of Pediatrics, University of Maastricht, Maastricht, The Netherlands.
Nigel KleinPaediatric Infectious Diseases and Immunology, Institute of Child Health, University College London, London, UK.
Boris W KramerDepartment of Pediatrics, University of Maastricht, Maastricht, The Netherlands.
Bobbi FleissSchool of Health and Biomedical Sciences, RMIT University, Melbourne, VIC, Australia.
Pierre GressensUniversité de Paris, NeuroDiderot, Inserm, Paris, France.
Xavier GolayInstitute of Neurology, University College London, London, UK.
Nicola J RobertsonInstitute for Women's Health, University College London, London, UK. n.robertson@ucl.ac.uk.
London Women's Clinic · GBUniversity College London · GBMaastricht University · NLUniversity College London Hospitals NHS Foundation Trust · GBLondon School of Hygiene & Tropical Medicine · GBOndokuz Mayıs University · TRRMIT University · AUUniversité Paris Cité · FRUniversity of Adelaide · AUUniversity of Gothenburg · SE

Funding

Medical Research Council MC_UP_1204/9Medical Research Council MR/M006743/1
6 · The paper itself

Abstract

backgroundPerinatal inflammation combined with hypoxia-ischemia (HI) exacerbates injury in the developing brain. Therapeutic hypothermia (HT) is standard care for neonatal encephalopathy; however, its benefit in inflammation-sensitized HI (IS-HI) is unknown.

methodsTwelve newborn piglets received a 2 µg/kg bolus and 1 µg/kg/h infusion over 52 h of Escherichia coli lipopolysaccharide (LPS). HI was induced 4 h after LPS bolus. After HI, piglets were randomized to HT (33.5 °C 1-25 h after HI, n = 6) or normothermia (NT, n = 6). Amplitude-integrated electroencephalogram (aEEG) was recorded and magnetic resonance spectroscopy (MRS) was acquired at 24 and 48 h. At 48 h, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive brain cell death, microglial activation/proliferation, astrogliosis, and cleaved caspase-3 (CC3) were quantified. Hematology and plasma cytokines were serially measured.

resultsTwo HT piglets died. aEEG recovery, thalamic and white matter MRS lactate/N-acetylaspartate, and TUNEL-positive cell death were similar between groups. HT increased microglial activation in the caudate, but had no other effect on glial activation/proliferation. HT reduced CC3 overall. HT suppressed platelet count and attenuated leukocytosis. Cytokine profile was unchanged by HT.

conclusionsWe did not observe protection with HT in this piglet IS-HI model based on aEEG, MRS, and immunohistochemistry. Immunosuppressive effects of HT and countering neuroinflammation by LPS may contribute to the observed lack of HT efficacy. Other immunomodulatory strategies may be more effective in IS-HI. IMPACT: Acute infection/inflammation is known to exacerbate perinatal brain injury and can worsen the outcomes in neonatal encephalopathy. Therapeutic HT is the current standard of care for all infants with NE, but the benefit in infants with coinfection/inflammation is unknown. In a piglet model of inflammation (LPS)-sensitized HI, we observed no evidence of neuroprotection with cooling for 24 h, based on our primary outcome measures: aEEG, MRS Lac/NAA, and histological brain cell death. Additional neuroprotective agents, with beneficial immunomodulatory effects, require exploration in IS-HI models.

Indexed as

HypothermiaHypothermia, InducedHypoxia-Ischemia, BrainAnimalsAnimals, NewbornBrainDisease Models, AnimalHumansHypoxiaInflammationIschemiaLipopolysaccharidesSwineLipopolysaccharides

Identifiers

PMID34050269
PMCPMC8160560
OpenAlexW3164336448

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.