Evidence map›Paper›PMID 30596885›Full record

ArticleBiology of reproduction2019

Inhibition of the NLRP3 inflammasome can prevent sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes†.

Nardhy Gomez-Lopez, Roberto Romero, Valeria Garcia-Flores, Yaozhu Leng, Derek Miller, Sonia S Hassan, Chaur-Dong Hsu, Bogdan Panaitescu

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

Article in Biology of reproduction, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.

0numbers the graph read from it
0cells of the map it votes in
74citing papers in PubMed
8.3field-weighted citation impact, top 2% 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

74 citing papers in PubMed, 98 citations in OpenAlex.

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  11. Understanding a Potential Role for the NLRP3 Inflammasome in Placenta-Mediated Pregnancy Complications.American journal of reproductive immunology (New York, N.Y. : 1989) · 2025
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14 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

Nardhy Gomez-LopezPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Roberto RomeroPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Valeria Garcia-FloresPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Yaozhu LengPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Derek MillerPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Sonia S HassanPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
Chaur-Dong HsuDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan, USA.
Bogdan PanaitescuPerinatology 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, Bethesda, Maryland, and Detroit, Michigan, USA.
National Institutes of Health · USWayne State University · US

Funding

The Role Of Subclinical Infection And Cytokines In Preterm ParturitionZIAHD002400 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI ROMERO, ROBERTO · 2009 to 2025
$254.4M
NICHD NIH HHS HHSN275201300006C
6 · The paper itself

Abstract

Sterile intra-amniotic inflammation is commonly observed in patients with spontaneous preterm labor, a syndrome that commonly precedes preterm birth, the leading cause of perinatal morbidity and mortality worldwide. However, the mechanisms leading to sterile intra-amniotic inflammation are poorly understood and no treatment exists for this clinical condition. Herein, we investigated whether the alarmin S100B could induce sterile intra-amniotic inflammation by activating the NLRP3 inflammasome, and whether the inhibition of this pathway could prevent preterm labor/birth and adverse neonatal outcomes. We found that the ultrasound-guided intra-amniotic administration of S100B induced a 50% rate of preterm labor/birth and a high rate of neonatal mortality (59.7%) without altering the fetal and placental weights. Using a multiplex cytokine array and immunoblotting, we reported that S100B caused a proinflammatory response in the amniotic cavity and induced the activation of the NLRP3 inflammasome in the fetal membranes, indicated by the upregulation of the NLRP3 protein and increased release of active caspase-1 and mature IL-1β. Inhibition of the NLRP3 inflammasome via the specific inhibitor MCC950 prevented preterm labor/birth by 35.7% and reduced neonatal mortality by 26.7%. Yet, inhibition of the NLRP3 inflammasome at term did not drastically obstruct the physiological process of parturition. In conclusion, the data presented herein indicate that the alarmin S100B can induce sterile intra-amniotic inflammation, preterm labor/birth, and adverse neonatal outcomes by activating the NLRP3 inflammasome, which can be prevented by inhibiting such a pathway. These findings provide evidence that sterile intra-amniotic inflammation could be treated by targeting the NLRP3 inflammasome.

Indexed as

AnimalsAnimals, NewbornCytokinesFemaleFetusFuransGene Expression RegulationHeterocyclic Compounds, 4 or More RingsIndenesInflammationMiceNLR Family, Pyrin Domain-Containing 3 ProteinObstetric Labor, PrematurePlacentaPregnancyPremature BirthCytokinesFuransHeterocyclic Compounds, 4 or More RingsIndenesN-(1,2,3,5,6,7-hexahydro-S-indacen-4-ylcarbamoyl)-4-(2-hydroxy-2-propanyl)-2-furansulfonamideNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseS100b protein, mouseS100 Calcium Binding Protein beta SubunitSulfonamidesSulfonesacute chorioamnionitisalarminsamniotic fluidcaspase-1cytokinesdamage-associated molecular patternsdanger signalsfunisitisinhibitorinterleukin-1βmiceS100B

Identifiers

PMID30596885
PMCPMC6497524
OpenAlexW2907609811

What OpenQuestion holds

Textmetadata
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.