Evidence map›Paper›PMID 37944273›Full record

ArticleEBioMedicine2023

Blockade of IL-6R prevents preterm birth and adverse neonatal outcomes.

Marcelo Farias-Jofre, Roberto Romero, Jose Galaz, Yi Xu, Derek Miller, Valeria Garcia-Flores, Marcia Arenas-Hernandez, Andrew D Winters, Bruce A Berkowitz, Robert H Podolsky and 7 more

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

Article in EBioMedicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
5.1field-weighted citation impact, top 4% 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

18 citing papers in PubMed, 24 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

17 authors at 3 institutions in 3 countries.

Marcelo Farias-JofrePregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Roberto RomeroPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI, USA; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI, USA. Electronic address: romeror@mail.nih.gov.
Jose GalazPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Division of Obstetrics and Gynecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile.
Yi XuPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Derek MillerPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
Valeria Garcia-FloresPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA.
Marcia Arenas-HernandezPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Andrew D WintersPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MO, USA.
Bruce A BerkowitzDepartment of Ophthalmology, Visual and Anatomical Sciences, Wayne State University School of Medicine; Detroit, MI, USA.
Robert H PodolskyDivision of Biostatistics and Design Methodology, Center for Translational Research, Children's National Hospital, Silver Spring, MD, USA.
Yimin ShenDepartment of Radiology, School of Medicine, Wayne State University School of Medicine, Detroit, MI, USA.
Tomi KanninenPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Bogdan PanaitescuPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA.
Catherine R GlazierUCD School of Medicine, University College Dublin, Belfield, Dublin 4, Ireland.
Roger Pique-RegiPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
Kevin R TheisPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MO, USA.
Nardhy Gomez-LopezPregnancy Research Branch, Division of Obstetrics and Maternal-Fetal Medicine, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, U.S. Department of Health and Human Services (NICHD/NIH/DHHS), Bethesda, MD, USA; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO, USA; Department of Biochemistry, Microbiology, and Immunology, Wayne State University School of Medicine, Detroit, MO, USA; Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: nardhy@wustl.edu.
United States Department of Health and Human Services · USWayne State University · USUniversity College Dublin · IE

Funding

NICHD NIH HHS HHSN275201300006C
6 · The paper itself

Abstract

backgroundPreterm birth preceded by spontaneous preterm labour often occurs in the clinical setting of sterile intra-amniotic inflammation (SIAI), a condition that currently lacks treatment.

methodsProteomic and scRNA-seq human data were analysed to evaluate the role of IL-6 and IL-1α in SIAI. A C57BL/6 murine model of SIAI-induced preterm birth was developed by the ultrasound-guided intra-amniotic injection of IL-1α. The blockade of IL-6R by using an aIL-6R was tested as prenatal treatment for preterm birth and adverse neonatal outcomes. QUEST-MRI evaluated brain oxidative stress in utero. Targeted transcriptomic profiling assessed maternal, foetal, and neonatal inflammation. Neonatal biometrics and neurodevelopment were tested. The neonatal gut immune-microbiome was evaluated using metagenomic sequencing and immunophenotyping.

findingsIL-6 plays a critical role in the human intra-amniotic inflammatory response, which is associated with elevated concentrations of the alarmin IL-1α. Intra-amniotic injection of IL-1α resembles SIAI, inducing preterm birth (7% vs. 50%, p = 0.03, Fisher's exact test) and neonatal mortality (18% vs. 56%, p = 0.02, Mann-Whitney U-test). QUEST-MRI revealed no foetal brain oxidative stress upon in utero IL-1α exposure (p > 0.05, mixed linear model). Prenatal treatment with aIL-6R abrogated IL-1α-induced preterm birth (50% vs. 7%, p = 0.03, Fisher's exact test) by dampening inflammatory processes associated with the common pathway of labour. Importantly, aIL-6R reduces neonatal mortality (56% vs. 22%, p = 0.03, Mann-Whitney U-test) by crossing from the mother to the amniotic cavity, dampening foetal organ inflammation and improving growth. Beneficial effects of prenatal IL-6R blockade carried over to neonatal life, improving survival, growth, neurodevelopment, and gut immune homeostasis.

interpretationIL-6R blockade can serve as a strategy to treat SIAI, preventing preterm birth and adverse neonatal outcomes.

fundingNICHD/NIH/DHHS, Contract HHSN275201300006C. WSU Perinatal Initiative in Maternal, Perinatal and Child Health.

Indexed as

Premature BirthReceptors, Interleukin-6Amniotic FluidAnimalsAntibodies, MonoclonalChildFemaleHumansInfant, NewbornInflammationInterleukin-6MicePregnancyProteomicsAntibodies, MonoclonalInterleukin-6Receptors, Interleukin-6AlarminIL-1αMicrobiomePregnancyPrematuritySterile intra-amniotic inflammation

Identifiers

PMID37944273
PMCPMC10665693
OpenAlexW4388471471

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.