Evidence map›Paper›PMID 24358119›Full record

ArticlePloS one2013

Effects of intra-amniotic lipopolysaccharide and maternal betamethasone on brain inflammation in fetal sheep.

Elke Kuypers, Reint K Jellema, Daan R M G Ophelders, Jeroen Dudink, Maria Nikiforou, Tim G A M Wolfs, Ilias Nitsos, J Jane Pillow, Graeme R Polglase, Matthew W Kemp and 5 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.5field-weighted citation impact, top 7% 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

25 citing papers in PubMed, 42 citations in OpenAlex.

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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

15 authors at 4 institutions in 3 countries.

Elke KuypersDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Reint K JellemaDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Daan R M G OpheldersDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Jeroen DudinkDepartment of Pediatrics, Erasmus Medical Center-Sophia, Rotterdam, The Netherlands.
Maria NikiforouDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Tim G A M WolfsDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
Ilias NitsosSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia ; The Ritchie Centre, Monash Institute of Medical Research, Melbourne, Australia.
J Jane PillowSchool of Anatomy, Physiology and Human Biology, The University of Western Australia, Perth, Australia.
Graeme R PolglaseSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia ; The Ritchie Centre, Monash Institute of Medical Research, Melbourne, Australia.
Matthew W KempSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
Masatoshi SaitoSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
John P NewnhamSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia.
Alan H JobeSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia ; Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Suhas G KallapurSchool of Women's and Infants' Health, The University of Western Australia, Perth, Australia ; Division of Pulmonary Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States of America.
Boris W KramerDepartment of Pediatrics, School of Mental Health and Neuroscience, Maastricht University Medical Center, Maastricht, The Netherlands.
University of Western Australia · AUMaastricht University · NLCincinnati Children's Hospital Medical Center · USErasmus MC · NL

Funding

Mechanisms of Fetal Inflammatory Response Syndrome Induced by ChorioamnionitisR01HD057869 · NICHD · CINCINNATI CHILDRENS HOSP MED CTR · PI KALLAPUR, SUHAS · 2009 to 2013
$1.6M
NICHD NIH HHS HD-57869NICHD NIH HHS R01 HD057869
6 · The paper itself

Abstract

rationaleChorioamnionitis and antenatal glucocorticoids are common exposures for preterm infants and can affect the fetal brain, contributing to cognitive and motor deficits in preterm infants. The effects of antenatal glucocorticoids on the brain in the setting of chorioamnionitis are unknown. We hypothesized that antenatal glucocorticoids would modulate inflammation in the brain and prevent hippocampal and white matter injury after intra-amniotic lipopolysaccharide (LPS) exposure.

methodsTime-mated ewes received saline (control), an intra-amniotic injection of 10 mg LPS at 106d GA or 113d GA, maternal intra-muscular betamethasone (0.5 mg/kg maternal weight) alone at 113d GA, betamethasone at 106d GA before LPS or betamethasone at 113d GA after LPS. Animals were delivered at 120d GA (term=150d). Brain structure volumes were measured on T2-weighted MRI images. The subcortical white matter (SCWM), periventricular white matter (PVWM) and hippocampus were analyzed for microglia, astrocytes, apoptosis, proliferation, myelin and pre-synaptic vesicles.

resultsLPS and/or betamethasone exposure at different time-points during gestation did not alter brain structure volumes on MRI. Betamethasone alone did not alter any of the measurements. Intra-amniotic LPS at 106d or 113d GA induced inflammation as indicated by increased microglial and astrocyte recruitment which was paralleled by increased apoptosis and hypomyelination in the SCWM and decreased synaptophysin density in the hippocampus. Betamethasone before the LPS exposure at 113d GA prevented microglial activation and the decrease in synaptophysin. Betamethasone after LPS exposure increased microglial infiltration and apoptosis.

conclusionIntra-uterine LPS exposure for 7d or 14d before delivery induced inflammation and injury in the fetal white matter and hippocampus. Antenatal glucocorticoids aggravated the inflammatory changes in the brain caused by pre-existing intra-amniotic inflammation. Antenatal glucocorticoids prior to LPS reduced the effects of intra-uterine inflammation on the brain. The timing of glucocorticoid administration in the setting of chorioamnionitis can alter outcomes for the fetal brain.

Indexed as

Amniotic FluidAnimalsBetamethasoneEncephalitisFemaleFetusGlucocorticoidsLipopolysaccharidesPregnancySheepBetamethasoneGlucocorticoidsLipopolysaccharides

Identifiers

PMID24358119
PMCPMC3866104
OpenAlexW2132292508

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.