Temporal Response of Immunoreactive Erythropoietin to Acute Hypoxemia in Fetal Sheep

Widness, John A.; Teramo, Kari; Clemons, Gisela K.; Garcia, Joseph F.; Cavalieri, Ralph L.; Piasecki, George J.; Jackson, Benjamin T.; Susa, John B.; Schwartz, Robert

doi:10.1203/00006450-198601000-00004

Cited by 116 publications

(79 citation statements)

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“…9 The assumption has been that erythropoietin production, secondary to hypoxia, causes the production of nRBC. It has been shown that in sheep, acute hypoxemia results in erythopoietin increases after at least 3 h, 10 and the resulting reticulocytosis does not peak until 4 days. 11 However, in rats, acute hypoxia resulted in elevated nRBC sometime after 4-12 h. 12 It has also been suggested that acute hypoxia in humans can be associated with elevated nucleated red blood cells.…”

Section: Introductionmentioning

confidence: 99%

Umbilical cord nucleated red blood cell counts: normal values and the effect of labor

et al. 2006

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Objective: To determine the umbilical cord blood nucleated red blood cell (UC-nRBC) count in uncomplicated pregnancies delivered by elective cesarean section or delivered vaginally.Methods: A total of 57-term singleton pregnancies were studied: 33 with elective cesarean sections and 24 with vaginal deliveries. UC-nRBC was analyzed for its nucleated red blood cell counts. A logarithmic transformation of the data was used for statistical analysis.Results: The mean±standard deviation (s.d.) for nucleated red blood cell per 100 white blood cells (nRBC/100WBC) from the elective cesarean section group was 7.8±7.4. The vaginal delivery group had a mean value of 9.3±10.5, which was not significantly different. A value of 22 nRBC/ 100WBC defined the upper 95% confidence limit. The correlation between absolute nRBC and nRBC/100 WBC was 0.97. Conclusion:Although chronic hypoxia is associated with elevated nRBC, the stress of uncomplicated labor does not change the level. This adds credence to its use as a marker for hypoxia preceding labor and delivery.

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Section: Introductionmentioning

confidence: 99%

Umbilical cord nucleated red blood cell counts: normal values and the effect of labor

et al. 2006

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“…HbAlc served as an indicator of chronic maternal glycaemia [7] and plasma erythropoietin (Ep) concentration was utilized to assess fetal oxygenation [8][9][10]. Amniotic fluid levels of glucose, insulin and C-peptide served as intermediary chronic indicators of fetal metabolism [11][12][13].…”

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confidence: 99%

Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

et al. 1990

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Summary. In the present study the antepartum relationship between maternal diabetic glucose control and fetal hypoxaemia was examined in 44 Type i (insulin-dependent) diabetic and 23 non-diabetic control pregnancies. Maternal HbAlc was used to assess maternal integrated blood glucose control while fetal metabolic control was evaluated by antepartum glucose, insulin, and C-peptide determinations in amniotic fluid at elective caesarean delivery. Fetal hypoxaemia was assessed indirectly by fetal umbilical vein plasma erythropoietin level at delivery. A prospectively developed statistical pathway model was used to examine the relationship of these variables. In applying forced stepwise multiple regression with this model, we observed in the diabetic subjects that mean maternal HbA~c during the last month of pregnancy correlated significantly with fetal umbilical venous erythropoietin at delivery (r = 0.57,p < 0.001). Additional significant contributions to umbilical venous erythropoietin were found for amniotic fluid glucose and amniotic fluid insulin when these two independent variables were added in stepwise fashion (p < 0.01). We conclude that in diabetic pregnancy, antepartum control of maternal hyperglycaemia is a significant factor associated with fetal hypoxaemia. We speculate that this effect is mediated through perturbations which accelerate fetal metabolism and which is expressed by amniotic fluid levels of glucose and insulin.Key words: Erythropoietin, HbAlc, fetus, oxygenation, diabetes mellitus.Although in recent years the outcome of diabetic pregnancies has dramatically improved, fetal and neonatal morbidity and mortality remain increased relative to normal pregnancies [1,2]. Some of the pathological features observed in offspring of these pregnancies have been shown to be associated with maternal hyperglycaemia (eg., respiratory distress syndrome, congenital malformations, and neonatal hypoglycaemia); others have not. Among the latter are the increased incidence of late gestation fetal death, antepartum and intrapartum fetal distress, and neonatal polycythaemia. We and others have speculated that these features of diabetic pregnancies have their origins in chronic and/or acute fetal hypoxaemia [3][4][5].The purpose of the present study was to indirectly examine the antepartum relationship between chronic maternal hyperglycaemia and fetal oxygenation in Type 1 (insulin-dependent) diabetic pregnancies delivered by elective caesarean section before the confounding effect of labour [6]. To do so, we prospectively developed a hypothetical pathway model for statistical analyses in which chronic maternal hyperglycaemia was related to chronic fetal hypoxaemia through several intermediate steps. Subjects and methods SubjectsAfter obtaining approval by the Ethical Committee at the University of Helsinki and after obtaining each patient's consent, control and Type i (insulin-dependent) diabetic subjects carrying singleton fetuses were studied at the Women's Hospital of the University Central Hospital of Helsink...

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“…That study found that in vitro a rise in leptin production in placental cells did not take place until after 72 h of hypoxia [14]. Because during hypoxic conditions a significant increase in fetal EPO concentrations can be observed within 2 to 4 h [16], the increased cord plasma leptin, together with the increased EPO concentrations in both amniotic fluid and cord plasma, probably reflect chronic or subchronic rather than acute fetoplacental hypoxia.…”

Section: Discussionmentioning

confidence: 92%

“…Erythropoietin (EPO), which regulates the synthesis of bone marrow progenitor cells and erythrocytes [15], is produced in the fetal liver and near term also in the kidney [15]. The main stimulator of EPO production is tissue hypoxia [15,16]. Erythropoietin has also been shown to be produced by placental trophoblast cells.…”

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confidence: 99%

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Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

et al. 2000

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Leptin is an adipocyte-derived hormone involved in energy metabolism and fuel homeostasis [1±3]. It could also be important in fetal development because both the leptin gene and leptin receptors are expressed in numerous fetal tissues [4,5]. In addition, leptin has been shown to stimulate fetal erythroid development and to have angiogenic activity [6,7].In term infants, cord blood leptin concentrations correlate directly with birth weight [8±11]. Maternal diabetes mellitus and pre-eclampsia are also associated with increased cord blood leptin concentrations [12±14]. It has been postulated that hypoxic conditions during pre-eclampsia augment placental production of leptin [14]. Erythropoietin (EPO), which regulates the synthesis of bone marrow progenitor cells and erythrocytes [15], is produced in the fetal liver and near term also in the kidney [15]. The main stimulator of EPO production is tissue hypoxia [15,16]. Erythropoietin has also been shown to be produced by placental trophoblast cells. Whether EPO expression in placenta is regulated by hypoxia and the proportion of placental EPO of all EPO in feto-placental circulation is not known [17]. Because EPO is not stored, plasma EPO concentrations are an indicator of the rate of EPO synthesis. Fetal plasma EPO concentrations correlate well with those of amniotic fluid EPO before labour both in normal and in abnormal pregnancies [18]. In response to moderate to severe tissue hypoxia, a sta- Diabetologia (2000) AbstractAims/hypothesis. The purpose of this study was to examine whether fetal leptin concentration correlates with severity of chronic or subchronic fetal hypoxia as indicated by increased fetal concentrations of erythropoietin in fetuses of mothers with Type I (insulin dependent) diabetes mellitus. Methods. We measured leptin and erythropoietin concentrations in cord plasma and amniotic fluid with radioimmunoassay in 25 pregnancies (gestational age 37.2 ± 1.0 weeks). Fetuses with amniotic fluid erythropoietin over 22.5 mU/ml were classified as hypoxic (n = 9) and those with amniotic fluid erythropoietin below 22.5 mU/ml (n = 16) as non-hypoxic. Results. The hypoxic fetuses had significantly higher cord leptin concentrations than non-hypoxic fetuses

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Temporal Response of Immunoreactive Erythropoietin to Acute Hypoxemia in Fetal Sheep

Cited by 116 publications

References 2 publications

Umbilical cord nucleated red blood cell counts: normal values and the effect of labor

Umbilical cord nucleated red blood cell counts: normal values and the effect of labor

Direct relationship of antepartum glucose control and fetal erythropoietin in human Type 1 (insulin-dependent) diabetic pregnancy

Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

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