Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis

Dulay, Antonette T.; Buhimschi, Irina A.; Zhao, Guomao; Luo, Guoyang; Abdel-Razeq, Sonya S.; Cackovic, Michael; Rosenberg, Victor; Pettker, Christian M.; Thung, Stephen; Bahtiyar, Mert O.; Bhandari, Vineet; Buhimschi, Catalin S.

doi:10.1016/j.ajog.2008.01.040

Cited by 55 publications

(43 citation statements)

References 40 publications

(54 reference statements)

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“…This finding is consistent with our previous study in humans, which demonstrated that inflammation represents an important stimulus for nucleated red blood cell production or release in the absence of hypoxia. 86 Thus, from our previously published data, coupled with the results presented here, we conclude that the process of fetal inflammation comprises a variety of acute and chronic pathological processes that collectively induce an imbalance in tissue homeostasis characterized by extracellular release of DAMPs and tissue damage. The current study puts forth the hypothesis that RAGE and HMGB1 are active participants in mediating the process of fetal and neonatal tissue injury that may lead to multiple organ dysfunction.…”

Section: Damps and Fetal Inflammation 971supporting

confidence: 80%

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Buhimschi

Baumbusch

Dulay

et al. 2009

The American Journal of Pathology

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Immune activation represents an adaptive reaction triggered by both noxious exogenous (microbes) and endogenous [high mobility group box-1 protein (HMGB1), S100 calcium binding proteins] inducers of inflammation. Cell stress or necrosis lead the release of HMGB1 and S100 proteins in the extracellular compartment where they act as damage-associated molecular pattern molecules (or alarmins) by engaging the receptor for advanced glycation end-products (RAGE). Although the biology of RAGE is dictated by the accumulation of damage-associated molecular pattern molecules at sites of tissue injury, the role of RAGE in mediating antenatal fetal injury remains unknown. First, we studied the relationships at birth between the intensity of human fetal inflammation and sRAGE (an endogenous RAGE antagonist), HMGB1, and S100␤ protein. We found significantly lower sRAGE in human fetuses that mounted robust inflammatory responses. HMGB1 levels correlated significantly with levels of interleukin-6 and S100␤ in fetal circulation. We then evaluated the levels and areas of tissue expression of RAGE, HMGB1, and S100␤ in specific organs of mouse fetuses on E16. Using an animal model of endotoxin-induced fetal damage and preterm birth, we determined that inflammation induces a significant change in expression of RAGE and HMGB1, but not S100␤, at sites of tissue damage. Our findings indicate that RAGE and Conventional wisdom holds that the primary causes of the high neonatal morbidity and mortality attendant preterm birth are complications of immature organ systems.1-4 However, a growing body of investigation suggests that the poor outcome observed in many preterm children is not entirely dependent on their gestational age at birth. 2,5,6 After correcting for gestational age, several risk factors remain significantly associated with an increased risk of cerebral palsy, such as intra-amniotic infection, histological chorioamnionitis, prolonged rupture of the membranes, and hypoxemic fetal growth re-

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Section: Damps and Fetal Inflammation 971supporting

confidence: 80%

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Buhimschi

Baumbusch

Dulay

et al. 2009

The American Journal of Pathology

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“…For obvious reasons, it would be impossible to control a human study to such an extent. This type of model allows us to eliminate the potential influence of other factors that may affect the NRBC count in the human, such as prematurity or infection/inflammation 33,43…”

Section: Discussionmentioning

confidence: 99%

Nucleated Red Blood Cells as a Marker of Acute and Chronic Fetal Hypoxia in a Rat Model

Minior

Levine

Ferber

et al. 2017

Rambam Maimonides Med J

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ObjectiveTo examine the relationship between duration of fetal hypoxia, nucleated red blood cell (NRBC) count, and fetal growth.MethodsPregnant rats were exposed to a severe hypoxia (9.5%–10% O2) for varying time intervals (2, 6, 12, 24, 48, and 120 hours; n=4 for each time interval) immediately prior to delivery at term. Normoxic controls were exposed to room air (21% O2) and matched for all other study variables (n=4 rats for each time interval). Pups were delivered via hysterotomy while maintaining exposure gas concentrations. Blood gas analysis and NRBC counts were performed, and fetal body and liver weights were recorded. Student’s t test and simple regression were used for statistical analysis.ResultsAs the duration of hypoxia increased, fetal weight, liver weight, blood bicarbonate, and base excess levels decreased significantly; concomitantly, NRBC counts increased. This increase in NRBCs became statistically significant after 24 hours of exposure. After 48 hours of hypoxia there was a 2.5-fold rise in NRBC count, and after 120 hours of hypoxia there was a 4.5-fold rise in NRBC count over control levels. After 12 or more hours of hypoxia, fetal body weights were significantly reduced; 120 hours of hypoxia resulted in a 35% reduction in fetal body weight, a 34% reduction in fetal liver weight, and 356% increase in NRBC count.ConclusionIn a pregnant rat model, chronic maternal hypoxia (≥24 hours) results in a significant increase in fetal NRBC counts as well as reduced fetal body weight and organ growth.

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“…In fetuses, Dulay et al [29] demonstrated the increase in the number of nRBCs in preterm neonates with evidence of choriamnionitis and in the absence of hypoxia. These authors [30] assessed nRBCs counts within 1 h of birth in 68 preterm singletons, establishing a significant correlation between nRBC count and cord blood interleukin-6 level.…”

Section: Discussionmentioning

confidence: 99%

Release of erythroblasts to the peripheral blood suggests higher exposure to hypoxia in cases of SIDS with co-sleeping compared to SIDS non-co-sleeping

Cohen

Yong

Evans

et al. 2010

Forensic Science International

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Nucleated red blood cells are a direct response to mediators of inflammation in newborns with early-onset neonatal sepsis

Cited by 55 publications

References 40 publications

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Characterization of RAGE, HMGB1, and S100β in Inflammation-Induced Preterm Birth and Fetal Tissue Injury

Nucleated Red Blood Cells as a Marker of Acute and Chronic Fetal Hypoxia in a Rat Model

Release of erythroblasts to the peripheral blood suggests higher exposure to hypoxia in cases of SIDS with co-sleeping compared to SIDS non-co-sleeping

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