The Effect of Prolonged Rupture of Membranes on Circulating Neonatal Nucleated Red Blood Cells

Mandel, Dror; Oron, Tal; Mimouni, Galit; Littner, Yoav; Dollberg, Shaul; Mimouni, Francis

doi:10.1038/sj.jp.7211389

Cited by 11 publications

(7 citation statements)

References 29 publications

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“…Earlier studies, however, were unable to assess simultaneously amniotic fluid and/or cord blood cytokine levels. [17,18,40]. The results of the current study support the concept that cytokines have an important role in stimulating fetal NRBC production, independent of hypoxia.…”

Section: Discussionsupporting

confidence: 76%

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

Dulay

Buhimschi

Zhao

et al. 2008

American Journal of Obstetrics and Gynecology

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Objective-To test the hypothesis that inflammation modulates fetal erythroblastosis and/or the release of NRBCs independent of hypoxia or fetal stress. We sought to determine if fetal inflammation is associated with an elevation in neonatal NRBC count in the setting of inflammation-associated preterm birth.Study Design-The relationships between peripheral NRBC count, histological chorioamnionitis, umbilical cord interleukin-6 (IL-6), erythropoietin (EPO), cortisol and acid-base status were analyzed in 68 preterm singletons, born to mothers who had an amniocentesis to rule out infection. Proteomic profiling of amniotic fluid identified presence of intra-amniotic inflammation according to established parameters. NRBC counts were assessed within 1-hour of birth. Early-onset neonatal sepsis (EONS) was established based on hematological and microbiological indices. IL-6, EPO and cortisol levels were measured by immunoassays. Fetal acid-base status was determined within 10 minutes of delivery. Parametric or nonparametric statistics was employed.Results-Fetuses with EONS (n=19) were delivered at earlier gestational ages (mean±SD: 27.1±2.8 weeks, P=0.001) and more often by mothers with intra-amniotic inflammation (P=0.022) and histological chorioamnionitis (P<0.001). Neonates with EONS had higher absolute NRBCs Condensation:In inflammation-associated preterm birth and in the absence of hypoxia, elevated neonatal nucleated red blood cell counts may be a direct response to inflammatory mediators. Authors' Contributions:Antonette Dulay is the principal investigator and responsible author. Antonette Dulay, Irina Buhimschi and Catalin Buhimschi designed the study, generated, interpreted the data and wrote the initial draft of the manuscript. Guomao Zhao participated with processing of biological samples, performed immunoassays, revised critically the manuscript and approved the final version. Vineet Bhandari participated with aspects of data analysis and interpretation, revised critically the manuscript and approved the final version. Guoyang Luo; Sonya Abdel-Razeq; Michael Cackovic, Victor Rosenberg, Christian Pettker Stephen Thung and Mert Ozan Bahtiyar participated with patient enrollment, acquisition of demographic and clinical data, critical revision of the manuscript and approved the final version. NIH Public AccessAuthor Manuscript Am J Obstet Gynecol. Author manuscript; available in PMC 2014 May 16. Published in final edited form as: Am J Obstet Gynecol. 2008 April ; 198(4): 426.e1-426.e9. doi:10.1016/j.ajog.2008 NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript counts (P=0.011). NRBC counts were directly correlated with cord blood IL-6 levels (P<0.001) but not with EPO, cortisol or parameters of acid-base status levels regardless of EONS status. These relationships remained following correction for gestational age, diabetes, intrauterine growth restriction (IUGR) and steroid exposure.Conclusion-In the setting of inflammation-associated preterm birth and in the absence of hypoxia,...

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Section: Discussionsupporting

confidence: 76%

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

Dulay

Buhimschi

Zhao

et al. 2008

American Journal of Obstetrics and Gynecology

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“…Elevated neonatal NRBC counts have been reported in patients with prolonged rupture of fetal membranes (>24 hours) [189], histologic chorioamnionitis [190], high acute placental inflammation score [146] and early-onset neonatal sepsis [122]. Since we have reported that FIRS is not associated with changes in the umbilical vein blood gas pH and PaO 2 [191], hypoxia and metabolic acidosis is unlikely to cause the increased erythropoiesis observed herein.…”

Section: Discussionmentioning

confidence: 49%

Hematologic profile of the fetus with systemic inflammatory response syndrome

Romero

Savasan²,

Chaiworapongsa³

et al. 2012

Journal of Perinatal Medicine

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OBJECTIVE-The Fetal Inflammatory Response Syndrome (FIRS) is associated with the impending onset of preterm labor/delivery, microbial invasion of the amniotic cavity and increased perinatal morbidity. FIRS has been defined by an elevated fetal plasma interleukin-6 (IL-6), a cytokine with potent effects on the differentiation and proliferation of hematopoietic precursors. The objective of this study was to characterize the hematologic response of fetuses with FIRS.STUDY DESIGN-Fetal blood sampling was performed in patients with preterm prelabor rupture of membranes and preterm labor with intact membranes (n=152). A fetal plasma IL-6 concentration >=11 pg/ml was used to define FIRS. Hemoglobin concentration, platelet count, total white blood cell (WBC) count, differential count and nucleated red blood cell (NRBC) count were obtained. Since blood cell count varies with gestational age, the observed values were corrected for fetal age by calculating a ratio between the observed and expected mean value for gestational age. RESULTS-1)The prevalence of FIRS was 28.9% (44/152); 2) fetuses with FIRS had a higher median corrected WBC and corrected neutrophil count than those without FIRS (WBC median 1.4; range 0.3-5.6 vs. median 1.1; range 0.4-2.9 p=0.001; neutrophils median 3.6; range 0.1-57.5 vs. median 1.8; range 0.2-13.9 p<0.001); 3) neutrophilia (defined as a neutrophil count >95 th centile of gestational age) was significantly more common in fetuses with FIRS than in those without FIRS [71% (30/42) CONCLUSION-The hematological response of the human fetus with FIRS is characterized by significant changes in the total white blood cell and neutrophil counts. The NRBC count in fetuses with FIRS tends to be higher than fetuses without FIRS.

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“…In a previous study, we showed that infants born after PROM have increased ANRBC counts compared with suitable controls. 1 The earlier mentioned study was the basis for the current one, which aimed to verify the speculation that increased ANRBC counts in PROM is driven by relative fetal hypoxemia (maybe due to cord compression 2 and subsequent EPO driven erythropoiesis). This study, although a pilot one, does not allow in any fashion to confirm this hypothesis.…”

Section: Discussionmentioning

confidence: 83%

Increased Nucleated Red Blood Cells Counts in Prolonged Rupture of Membranes is not Erythropoietin Driven

Barak

Mimouni²,

Stern³

et al. 2014

Amer J Perinatol

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The Effect of Prolonged Rupture of Membranes on Circulating Neonatal Nucleated Red Blood Cells

Abstract: Infants born after PROM have higher ANRBC counts at birth than control infants. We suggest that increased fetal erythropoiesis exists in infants who are delivered after PROM. If correct, our interpretation supports the theory that fetal hypoxia and/or ischemia may result from PROM.

Cited by 11 publications

References 29 publications

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

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

Hematologic profile of the fetus with systemic inflammatory response syndrome

Increased Nucleated Red Blood Cells Counts in Prolonged Rupture of Membranes is not Erythropoietin Driven

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