Evidence map›Paper›PMID 39429154›Full record

ArticleStroke2024

Perinatal Caffeine Administration Improves Outcomes in an Ovine Model of Neonatal Hypoxia-Ischemia.

Jana K Mike, Yasmine White, Janica Ha, Ariana Iranmahboub, Cheryl Hawkins, Rachel S Hutchings, Christian Vento, Hadiya Manzoor, Aijun Wang, Brian D Goudy and 7 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stroke, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing 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.

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

11 citing papers in PubMed.

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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

17 authors.

Jana K MikeDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.ORCID 0000-0002-0938-216X
Yasmine WhiteDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Janica HaDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Ariana IranmahboubDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Cheryl HawkinsORCID 0000-0001-6031-7796
Rachel S HutchingsDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Christian VentoDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.ORCID 0000-0002-3131-7604
Hadiya ManzoorDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Aijun WangDepartment of Biomedical Engineering (A.W.), University of California Davis.ORCID 0000-0002-2985-3627
Brian D GoudyDepartment of Pediatrics (B.D.G., P.V., S.L.), University of California Davis.
Payam ValiDepartment of Pediatrics (B.D.G., P.V., S.L.), University of California Davis.
Satyan LakshminrusimhaDepartment of Pediatrics (B.D.G., P.V., S.L.), University of California Davis.ORCID 0000-0001-6098-2155
Jogarao V S GobburuSchool of Pharmacy, University of Maryland, Baltimore (J.V.S.G.).ORCID 0000-0002-8348-4295
Janel Long-BoyleDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.
Jeffrey R FinemanDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.ORCID 0000-0001-9740-405X
Donna M FerrieroDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.ORCID 0000-0003-0560-9045
Emin MaltepeDepartment of Pediatrics (J.K.M., Y.W., J.H., A.I., C.H., R.S.H., C.V., H.M., J.L.-B., J.R.F., D.M.F., E.M.), University of California San Francisco.

Funding

Precision Therapy for Neonatal Brain InjuryR35NS097299 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI FERRIERO, DONNA M. · 2017 to 2024
$6.3M
Integrating Environmental Cues at the Maternal-Fetal Vascular InterfaceR01HD072455 · NICHD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MALTEPE, EMIN · 2012 to 2023
$4.3M
Arginase-1 signaling after neonatal strokeK08NS125042 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Jana Krystofova Mike · 2023 to 2026
$786k
NICHD NIH HHS R01 HD072455NINDS NIH HHS K08 NS125042NINDS NIH HHS R35 NS097299
6 · The paper itself

Abstract

backgroundNeonatal hypoxic-ischemic encephalopathy disproportionately affects low- and middle-income countries, where ≈96% of affected infants reside. The current standard of care, therapeutic hypothermia, is frequently ineffective in this setting, likely because injury may be occurring earlier during labor. Here, we studied the pharmacokinetics, safety, and efficacy of perinatal caffeine administration in near-term lambs following global ischemic injury to support the development of earlier treatment strategies targeting the fetus in utero as well as the infant postnatally.

methodsEwes were randomly assigned to receive either 1 g IV caffeine citrate or placebo before delivery and placental transport assessed. Near-term lambs (141-143 days) of both sexes were subjected to severe global hypoxia-ischemia utilizing an acute umbilical cord occlusion model. Lambs that received caffeine in utero also received 20 mg/kg IV caffeine citrate following resuscitation and 10 mg/(kg·d) IV for 2 days. An additional cohort received 60 mg/kg followed by 30 mg/(kg·d) (low dose versus high dose) postnatally. Biochemical, histological, and neurological outcome measures in lambs were assessed over a 6-day period.

resultsPerinatal caffeine administration demonstrated excellent placental transport kinetics and was well tolerated with lamb plasma levels comparable to those targeted in neonates with apnea of prematurity. Caffeine administration resulted in a systemic immunomodulatory effect, evidenced by significant reductions in proinflammatory IP-10 levels. Treated lambs demonstrated improved neurodevelopmental outcomes, while histological analysis revealed that caffeine reduced gray matter injury and attenuated inflammation in the cingulate and parasagittal cortex. This neuroprotective effect was greater and via a different mode of action than we previously reported for azithromycin. A higher caffeine dosing regimen demonstrated significant toxicity.

conclusionsPerinatal caffeine administration is well tolerated, attenuates systemic and brain inflammation, and contributes to improvements in histological and neurological outcomes in an ovine model of neonatal hypoxic-ischemic encephalopathy.

Indexed as

Animals, NewbornCaffeineDisease Models, AnimalHypoxia-Ischemia, BrainAnimalsCitratesFemaleMalePregnancySheepCaffeinecaffeine citrateCitratescaffeinedeveloping countriesgray matterhypoxia-ischemia, brainsheep

Identifiers

PMID39429154
PMCPMC11518658

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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.