Mathematical Modeling of the Biomarker Milieu to Characterize Preterm Birth and Predict Adverse Neonatal Outcomes

Cordeiro, Christina N.; Savva, Yulia; Vaidya, Dhananjay; Argani, Cynthia; Hong, Xiumei; Wang, Xiaobin; Burd, Irina

doi:10.1111/aji.12502

Cited by 19 publications

(12 citation statements)

References 27 publications

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“…In both spontaneous preterm and term labor, this placental lesion is associated with elevated concentrations of pro-inflammatory cytokines such as IL-1α, IL-1β, TNF-α, IL-8, and IL-6 in the amniotic fluid 7–26 and umbilical cord blood 27–33 . Elevated concentrations of these cytokines are linked to adverse neonatal outcomes 20, 21, 27, 34–45 . Therefore, the study herein focused on the mechanisms implicated in acute chorioamnionitis.…”

Section: Introductionmentioning

confidence: 99%

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Neutrophil extracellular traps in acute chorioamnionitis: A mechanism of host defense

Gomez‐Lopez

Romero

Leng

et al. 2017

Am J Reprod Immunol

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Problem Neutrophil extracellular traps (NETs) were recently described as a mechanism for microbial killing in the amniotic cavity of women with intra-amniotic infection. Such a clinical condition can result in acute chorioamnionitis, a placental lesion characterized by the infiltration of maternal neutrophils in the chorioamniotic membranes. Herein, we investigated whether these infiltrating neutrophils form NETs in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. Method of Study Chorioamniotic membrane samples were collected from women who underwent spontaneous term or preterm labor with acute chorioamnionitis (n=10 each). Controls included chorioamniotic membrane samples from women who delivered at term or preterm with or without labor, in the absence of acute chorioamnionitis (n=10 each). NETs were visualized and semi-quantified in the chorioamniotic membranes by using antibodies against neutrophil elastase and histone H3, in combination with DAPI staining. Results NETs were abundant in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. NETs were rarely found, or not visualized at all, in the chorioamniotic membranes from women who delivered at term or preterm with or without labor, in the absence of acute chorioamnionitis. Conclusion NETs are abundant in the chorioamniotic membranes from women who underwent spontaneous term or preterm labor with acute chorioamnionitis. These findings suggest that chorioamniotic neutrophils can form NETs as a mechanism of host defense against infection or danger signals.

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Section: Introductionmentioning

confidence: 99%

“…[27][28][29][30][31][32][33] Elevated concentrations of these cytokines are linked to adverse neonatal outcomes. 20,21,27,[34][35][36][37][38][39][40][41][42][43][44][45] Therefore, the study herein focused on the mechanisms implicated in acute chorioamnionitis.…”

Section: Introductionmentioning

confidence: 99%

Neutrophil extracellular traps in acute chorioamnionitis: A mechanism of host defense

Gomez‐Lopez

Romero

Leng

et al. 2017

Am J Reprod Immunol

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“…Changes in placental function have been associated with many antenatal conditions, which are risk factors for in-utero inflammation, PTB and/or atypical neurodevelopment (Hodyl et al, 2017). Inflammation is present in a significant proportion of PTB and can be associated or not with clinical infections (Nadeau-Vallée et al, 2017;Cordeiro et al, 2016). It is charac3)terized by activation and infiltration of macrophage and neutrophil into each of the uterine tissue compartments and amniotic cavity, in addition to increased levels of pro-inflammatory cytokines and chemokines (Hodyl et al, 2017;Nadeau-Vallée et al, 2017;Cordeiro et al, 2016;Gomez-Lopez et al, 2017a).…”

Section: Introductionmentioning

confidence: 99%

“…Inflammation is present in a significant proportion of PTB and can be associated or not with clinical infections (Nadeau-Vallée et al, 2017;Cordeiro et al, 2016). It is charac3)terized by activation and infiltration of macrophage and neutrophil into each of the uterine tissue compartments and amniotic cavity, in addition to increased levels of pro-inflammatory cytokines and chemokines (Hodyl et al, 2017;Nadeau-Vallée et al, 2017;Cordeiro et al, 2016;Gomez-Lopez et al, 2017a). It generally results in acute chorioamnionitis, which, in turn, contributes to PTB (Gomez-Lopez et al, 2017b) and the subsequent development of fetal inflammatory response syndrome (FIRS) (Nadeau-Vallée et al, 2017;Cordeiro et al, 2016;Lei et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

“…The increase in proinflammatory cytokines represents an independent risk factor for neonatal morbidities (Cordeiro et al, 2016). Some molecules, such as interleukin (IL)-1, IL-6, IL-8, and Tumor Necrosis Factor-α (TNF-α), are described as biomarkers and are associated with fetal inflammatory response and adverse neurologic outcomes (Cordeiro et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates: A Systematic Review

Magalhães

Pimenta

Barbosa

et al. 2017

Intl J of Devlp Neuroscience

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Key roles of glial cells in the encephalopathy of prematurity

Van Steenwinckel,

Bokobza,

Laforge

et al. 2023

Glia

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Across the globe, approximately one in 10 babies are born preterm, that is, before 37 weeks of a typical 40 weeks of gestation. Up to 50% of preterm born infants develop brain injury, encephalopathy of prematurity (EoP), that substantially increases their risk for developing lifelong defects in motor skills and domains of learning, memory, emotional regulation, and cognition. We are still severely limited in our abilities to prevent or predict preterm birth. No longer just the “support cells,” we now clearly understand that during development glia are key for building a healthy brain. Glial dysfunction is a hallmark of EoP, notably, microgliosis, astrogliosis, and oligodendrocyte injury. Our knowledge of glial biology during development is exponentially expanding but hasn't developed sufficiently for development of effective neuroregenerative therapies. This review summarizes the current state of knowledge for the roles of glia in infants with EoP and its animal models, and a description of known glial‐cell interactions in the context of EoP, such as the roles for border‐associated macrophages. The field of perinatal medicine is relatively small but has worked passionately to improve our understanding of the etiology of EoP coupled with detailed mechanistic studies of pre‐clinical and human cohorts. A primary finding from this review is that expanding our collaborations with computational biologists, working together to understand the complexity of glial subtypes, glial maturation, and the impacts of EoP in the short and long term will be key to the design of therapies that improve outcomes.

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Mathematical Modeling of the Biomarker Milieu to Characterize Preterm Birth and Predict Adverse Neonatal Outcomes

Abstract: We developed a novel mathematical model of 27 biomarkers associated with adverse neonatal outcomes in neonates born preterm.

Cited by 19 publications

References 27 publications

Neutrophil extracellular traps in acute chorioamnionitis: A mechanism of host defense

Neutrophil extracellular traps in acute chorioamnionitis: A mechanism of host defense

Inflammatory molecules and neurotrophic factors as biomarkers of neuropsychomotor development in preterm neonates: A Systematic Review

Key roles of glial cells in the encephalopathy of prematurity

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