Cord Blood Erythropoietin Levels Research Articles

Study of Cord Blood Levels of Erythropoietin, Bilirubin and Reticulocyte Count as Early Predictors of Neonatal Hyperbilirubinemia.

Neonatal hyperbilirubinemia is a serious neonatal problem which has hazardous effects on the neonates when the level of indirect bilirubin is increased to the levels that could cause kernicterus. The aim of this research is to study the cord blood levels of erythropoietin (EPO), bilirubin and reticulocyte count (RC) as early predictors of neonatal hyperbilirubinemia. This is a case-control study, which was conducted at Tanta University Hospital (TUH) from July 2016 to March 2018 on 90 neonates. The studied neonates were divided into 2 groups: Group 1 (45 neonates) who developed pathological hyperbilirubinemia and required treatment and group 2(45 neonates) who did not develop pathological hyperbilirubinemia and did not require treatment. Cord blood levels of EPO, bilirubin and RC were measured in all the studied neonates in both groups. There was a significant difference between both groups with regard to cord blood bilirubin (CBB), hemoglobin, EPO and RC levels where the P. value is 0.001*,0.027, *0.001*&0.001*respectively. There was a significant positive correlation between cord blood EPO levels and both CBB and cord blood RC with r=0.610 and 0.579, respectively and P. value is 0.001* & 0.001* respectively. With regard to ROC curve, there were high cord blood EPO levels where the cut off value was 22.5 mIU/ml while the sensitivity and specificity were 96 and89, respectively. In the cord blood RC, the cut off value was 5.7% while the sensitivity and specificity were 93 and 85, respectively, and lastly, CBB where the cut off value was 1.8 mg/dl while the sensitivity and specificity were 89 and 78 respectively. Cord blood levels of EPO, bilirubin and RC were increased in cases of pathological neonatal hyperbilirubinemia. Cord blood levels of EPO, bilirubin and RC could be used for early prediction of pathological neonatal hyperbilirubinemia.

Hepcidin and erythropoietin measurements in the cord blood of neonates with meconium‐stained amniotic fluid

To compare hepcidin and erythropoietin levels in the cord blood of neonates with meconium-stained amniotic fluid (MSAF) to levels obtained from age-, body mass index- and gravidity-matched neonates with clear amniotic fluid. A cross-sectional controlled study was conducted in secondary and tertiary care centers. Cord blood samples of 40 neonates following term gestations (≥37 weeks' gestation) with MSAF and 40 maternal age-, body mass index- and gravidity-matched controls with clear amniotic fluid were analyzed in this study. Demographic data, delivery outcomes and laboratory evaluations were recorded. Cord blood pH levels were lower in fetuses with MSAF when compared to those with clear amniotic fluid (P=0.0001). Fetuses with MSAF had higher cord blood erythropoietin levels in comparison to those with clear amniotic fluid (P=0.0001). Delivery outcomes and hepcidin measurements were similar in both groups. We demonstrated a significant relationship between erythropoietin levels and meconium passage, but failed to show the existence of a relationship between hepcidin levels and meconium passage.

Polycythaemia in Infants of Diabetic Mothers: β-Hydroxybutyrate Stimulates Erythropoietic Activity

This study tested whether elevated maternal β-hydroxybutyrate (β-OHB) levels contribute to polycythaemia in infants of diabetic mothers. Pregnant diabetic women (n = 27) and non-diabetic controls (n = 20) and their singleton infants were included. Maternal glycosylated haemoglobin and β-OHB levels were studied at 34-36 weeks' gestation; levels were significantly higher in mothers with diabetes than in controls. Birth weights and cord blood levels of insulin and fetal haemoglobin were significantly higher in infants from diabetic mothers compared with control infants, as were haematocrit levels in venous blood samples taken from each infant at 4 h following delivery. Cord blood erythropoietin levels were similar in both groups. There was a positive strong correlation between maternal β-OHB levels and polycythaemia in newborn infants, indicating that β-OHB could activate erythropoiesis independently from intrauterine hyperinsulinaemia and/or erythropoietin levels, and may be important in the pathogenesis of polycythaemia in infants born to diabetic mothers.

Cord blood erythropoietin and interleukin-6 for prediction of intraventricular hemorrhage in the preterm neonate

Objective. To evaluate cord blood erythropoietin (EPO) and interleukin-6 (IL-6) levels to predict preterm infants at risk of developing intraventricular hemorrhage (IVH).Methods. Levels of umbilical cord EPO, acid–base status and IL-6 were analyzed in 116 consecutive, preterm newborns (GA at delivery: 29 [23–34 ] weeks) born to mothers who had a clinically indicated amniocentesis to rule out infection. Early-onset neonatal sepsis (EONS) was diagnosed using symptoms, hematological criteria and blood cultures.Results. IVH was diagnosed by cranial ultrasounds. The prevalence of IVH in our population was 25% (29/116). There was a direct relationship between cord blood EPO and cord blood IL-6 concentration (r = 0.225, p = 0.014), independent of GA at birth. Elevated cord blood EPO levels (r = 0.182, p = 0.016) and GA at birth (r = −0.236, p = 0.004) remained significant independent factors associated with the risk of IVH, when evaluated with stepwise logistic regression analyses. Cord blood IL-6, pH, and EONS were not associated with IVH. These relationships remained following correction for GA at birth (p = 0.027).Conclusions. Our results suggest that elevation in cord blood EPO may predict newborns at risk for IVH, independent of fetal inflammatory status. Further studies are warranted to confirm this association.

Role of hypoxia and cAMP in the transdifferentiation of human fetal cardiac fibroblasts: Implications for progression to scarring in autoimmune‐associated congenital heart block

Identification of isolated congenital heart block (CHB) predicts, with near certainty, the presence of maternal anti-SSA/Ro antibodies; however, the 2% incidence of CHB in first offspring of anti-SSA/Ro+ mothers, 20% recurrence in subsequent pregnancies, and discordance in identical twins suggest that an environmental factor amplifies the effect of the antibody. Accordingly, this study was carried out to explore the hypothesis that hypoxia potentiates a profibrosing phenotype of the fetal cardiac fibroblast. Evidence of an effect of hypoxia was sought by immunohistologic evaluation of CHB-affected fetal heart tissue and by determination of erythropoietin levels in cord blood. The in vitro effect of hypoxia on gene expression and phenotype in fibroblasts derived from fetal hearts and lungs was investigated by Affymetrix arrays, quantitative polymerase chain reaction (PCR), immunofluorescence, and immunoblotting. In vivo hypoxic exposure was supported by the prominent intracellular fibroblast expression of hypoxia-inducible factor 1alpha in conduction tissue from 2 fetuses in whom CHB led to death. The possibility that hypoxia was sustained was suggested by significantly elevated erythropoietin levels in cord blood from CHB-affected, as compared with unaffected, anti-SSA/Ro-exposed neonates. In vitro exposure of cardiac fibroblasts to hypoxia resulted in transdifferentiation to myofibroblasts (a scarring phenotype), as demonstrated on immunoblots and immunofluorescence by increased expression of smooth muscle actin (SMA), an effect not seen in lung fibroblasts. Hypoxia-exposed cardiac fibroblasts expressed adrenomedullin at 4-fold increased levels, as determined by Affymetrix array, quantitative PCR, and immunofluorescence, thus focusing attention on cAMP as a modulator of fibrosis. MDL12,330A, an adenylate cyclase inhibitor that lowers the levels of cAMP, increased expression of fibrosis-related proteins (mammalian target of rapamycin, SMA, plasminogen activator inhibitor type 1, and type I collagen), while the cAMP activator forskolin attenuated transforming growth factor beta-elicited fibrosing end points in the cardiac fibroblasts. These findings provide evidence that hypoxia may amplify the injurious effects of anti-SSA/Ro antibodies. Modulation of cAMP may be a key component in the scarring phenotype. Further assessment of the susceptibility of cardiac fibroblasts to cAMP modulation offers a new research direction in CHB.

The effect of nuchal cord on amniotic fluid and cord blood erythropoietin at delivery.

We investigated the effect of a nuchal cord on fetal hypoxia by using amniotic fluid and cord blood erythropoietin as markers of chronic and acute hypoxia, respectively. A total of 167 full-term pregnancies without maternal complications or fetal prelabor complications except fetal growth restriction of unknown cause were studied prospectively. Of these, 47 had a nuchal cord at delivery, and 62 had one or more complications during labor and delivery (nonreassuring fetal heart rate pattern, birth weight less than 2500 g, Apgar score at 1 minute less than 7, presence of meconium-stained amniotic fluid, oligohydramnios), and 26 had both nuchal cord and at least one of the intrapartum complications. Erythropoietin levels (mean +/- standard error of the mean) were not significantly different between the nuchal cord group (n = 47) and the no nuchal cord group (n = 120) in either amniotic fluid (19.3 +/- 4.1 mU/mL versus 13.7 +/- 1.1 mU/mL) or cord blood (57.9 +/- 10.3 mU/mL versus 52.1 +/- 4.9 mU/mL). Similarly, in the 62 fetuses with intrapartum complications, there were no significant differences in amniotic fluid (14.3 +/- 2.0 mU/mL versus 18.8 +/- 2.9 mU/mL) or cord blood erythropoietin (66.9 +/- 16.8 mU/mL versus 72.6 +/- 12.6 mU/mL) levels between those with (n = 26) or without a nuchal cord (n = 36). Among the 107 uncomplicated cases, however, amniotic fluid erythropoietin was significantly elevated in the nuchal cord group (25.5 +/- 8.7 mU/mL, n = 21) compared with that in the no nuchal cord group (11.5 +/- 0.9 mU/mL, n = 84) (P <.05), whereas there was no significant between-group difference in cord blood erythropoietin levels between nuchal cord and no nuchal cord groups (46.8 +/- 10.0 mU/mL versus 43.3 +/- 4.1 mU/mL). Tightness of the nuchal cord did not affect amniotic fluid or cord blood erythropoietin concentrations. Although nuchal cord may not significantly increase the risk of acute or labor-associated fetal hypoxia, it appears to be an independent risk factor of mild, chronic, prelabor fetal hypoxia.

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: Correlations and confounding variables

Estimation of cord blood erythropoietin in pre-eclampsia and eclampsia

Objective: The estimation of cord blood erythropoietin in subjects with pre-eclampsia and eclampsia. Method: Erythropoietin was measured, using ELISA, in the cord blood of infants born to 83 mothers with pre-eclampsia, and 7 with eclampsia. Another 90 subjects with no evidence of pre-eclampsia or eclampsia were taken as control subjects. Maternal parity, gestational age, blood pressures, 24-h urine protein and Apgar scores of the infants delivered were also noted. Result: Cord blood erythropoietin levels were statistically significantly higher ( P<0.001) in infants born to mothers with pre-eclampsia and eclampsia. There was a significant positive correlation ( P<0.01) between cord blood erythropoietin levels and maternal blood pressure (systolic and diastolic) and albuminuria. A negative correlation ( P<0.01) was observed with the birth weights of infants. Conclusion: Pre-eclampsia and eclampsia are associated with higher levels of cord blood erythropoietin.

Relationship of amniotic fluid index and cord blood erythropoietin levels in small for and appropriate for gestational age fetuses

Objective: To determine whether low amniotic fluid index (AFI) reflects an increase in cord blood erythropoietin levels and is a marker of antenatal fetal hypoxia in small for gestational age (SGA) and appropriate for gestational age (AGA) fetuses in the third trimester. Methods: Erythropoietin levels in cord blood were measured in 134 high-risk obstetric patients, including 40 with low AFI (7 cm or less) and 94 with normal AFI (greater than 7 cm), which were sampled at elective cesarean delivery of fetuses with a gestational age of 32 to 39 weeks. The infants were divided into the SGA and AGA groups based on birth weight. Partial correlations of AFI with cord blood erythropoietin levels were evaluated by Pearson correlation coefficient after logarithmic transformation of erythropoietin levels in each group. Results: Cord blood erythropoietin levels in SGA fetuses with low AFI ( n = 24) were significantly higher than those in SGA fetuses with normal fluid volume ( n = 16) (171.6 ± 207.4 mIU/dL compared with 36.1 ± 24.1 mIU/dL, P < .001). Conversely, cord blood erythropoietin levels in AGA fetuses with low AFI ( n = 16) were not significantly different than those in AGA fetuses with normal fluid volume ( n = 78) (32.1 ± 18.7 mIU/dL compared with 29.5 ± 15.3 mIU/dL). A significant partial correlation between AFI and erythropoietin levels was demonstrated only within the SGA group ( P < .001, r = −.67). Conclusion: Low AFI could indicate the degree of antenatal fetal hypoxia in SGA fetuses. The impact of a reduced amniotic fluid volume on antenatal fetal condition might be less severe in AGA fetuses than in SGA fetuses.

Elevated Umbilical Erythropoietin Levels During Labor in Newborns of Smoking Mothers

Umbilical cord blood erythropoietin levels and hematocrit are significantly higher in smoking mothers than those nonsmoking ones. In addition, the incidence of newborns with low birthweight is higher in women who smoke. We conclude that in addition to other parameters, cord blood erythropoietin might be used as a valuable indicator of fetal distress in smokers.

Elevated erythropoietin levels in cord blood of newborns with Down's syndrome.

Plasma erythropoietin (Ep) was determined in umbilical cord blood in 18 infants with Down's syndrome. The 16 infants with Down's syndrome who were delivered after labor had significantly elevated plasma Ep levels compared to 36 control infants born after labor (p < 0.001). Six of the ten infants with Down's syndrome who had their packed cell volume (PCV) measured in the first 24 h of life were polycythemic based on a PCV of > or = 0.65. The presence of congenital heart disease in 9 of the 18 infants with Down's syndrome was not associated with a higher plasma Ep or PCV levels. Plasma Ep was correlated with neonatal PCV in the combined group of control and Down's syndrome infants (p = 0.003). Increased plasma Ep levels observed in infants with Down's syndrome suggested chronic fetal hypoxemia as a likely explanation for the high incidence of neonatal polycythemia observed in this group.

Erythropoiesis in infants of diabetic mothers.

Neonatal polycythemia is a well-established perinatal complication in infants of diabetic mothers (IDM). To investigate the regulation of erythropoiesis in these infants, we measured cord blood erythropoietin (EP) levels by a sensitive radioimmune assay and examined the growth of erythroid progenitor colonies in a series of IDM and control infants. Fifteen of 18 diabetic mothers were managed on a protocol emphasizing careful glycemic control throughout pregnancy; 10 had glycosolated hemoglobin values within the normal, nondiabetic range during the third trimester. Cord blood EP was elevated in one of 18 IDM and in two of 13 controls (p = NS). In IDM, cord blood EP values were higher in infants delivered following maternal labor and were inversely correlated with umbilical artery pH (r = -0.72; p = 0.006). Growth of burst forming units-erythroid was similar in IDM and controls in the presence of 0.1 to 2.0 U of exogenous EP per ml of methylcellulose medium. Individual infants tended to respond consistently over the entire range of EP doses tested. The number of burst forming units-erythroid observed did not correlate with cord blood EP, birth weight, or neonatal hematocrits. We conclude that: umbilical cord blood EP levels are generally normal in IDM delivered by mothers in whom good glycemic control is maintained throughout gestation, cord blood EP values are strongly influenced by perinatal events, and the response of erythroid progenitors to EP is intrinsically normal in IDM. These data suggest that polycythemia is an adaptive response in IDM and is not associated with a primary abnormality in erythropoiesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased immunoreactive erythropoietin in cord serum after labor

Since several hours of hypoxemia in fetal animals is sufficient to cause an increase in the plasma erythropoietin level and since labor may be associated with fetal hypoxemia, this study was undertaken to determine if erythropoietin levels in cord blood were higher in fetuses subjected to labor. Two groups of term (37 to 41 weeks) singleton pregnancies were compared: (1) those delivered by elective repeat cesarean section without prior labor (n = 18) and (2) those delivered vaginally (n = 23). Erythropoietin was measured by a radioimmunoassay in which a highly purified human erythropoietin (70,000 U/mg of protein) was used and which has a sensitivity limit of 4 to 5 mU/ml. The mean cord serum erythropoietin level was higher in pregnancies with labor (46 +/- 34 mU/ml, mean +/- SD) compared to those without (26 +/- 10, p less than 0.02). There were no differences between the two groups for maternal age, gestational age, birth weight, infant sex, or Apgar scores. No association of erythropoietin with either gestational age or sex was found. In 11 pregnancies without labor, comparisons were made among simultaneously obtained samples of umbilical arterial plasma, umbilical venous plasma, and mixed cord serum. Although there were no differences between umbilical arterial and umbilical venous plasma erythropoietin levels (21.3 +/- 9.3 versus 19.0 +/- 7.8 mU/ml), mixed cord serum was inexplicably higher (24.4 +/- 9.5 mU/ml, p less than 0.01). We concluded that in uncomplicated pregnancies the duration and intensity of labor are sufficient to cause an increase in the fetal erythropoietin level at delivery.

Erythropoietin Levels in Cord Blood as an Indicator of Intrauterine Hypoxia

SummaryThe erythropoietin content in cord blood was determined from normal full term infants, fants, from infants born more than 2 weeks after term, from infants of preeclamptic, diabetic and Rh‐immunized mothers. The group of normal infants showed higher ergthropoietin levels than the premature group. Highly elevated erythropoietin levels were found in some infants in the preeclamptic, the postmature group and in the infants of diabetic mothers. The greatest frequency of increased erythropoietin levels were found in the preeclamptic group. The infants with the greatest rise in erythropoietin content often showed clinical signs of dysmaturity. Erythroblastotic infants seemed to show a rise in erythropoietin levels when capillary hemoglobin fell below 13‐11 g. The results indicate that both anemic and hypoxic hypoxia may give an increase in erythro‐poietin content, and that erythropoietin is a stimulating factor for red cell production in fetal life, at least in the last months.

PLASMA ERYTHROPOIETIN LEVELS IN CORD BLOOD AND IN BLOOD DURING THE FIRST WEEKS OF LIFE.

SUMMARYPlasma erythropoietin levels have been studied in cord blood from normal and erythroblastotic infants, and in blood from normal and hypoxic infants during the first weeks of life. The erythropoietins are slightly elevated in cord plasma from normal infants, and markedly elevated in plasma from severely anemic infants. No erythropoietin is detectable in plasma from normal infants during the first weeks of life while hypoxic infants have elevated plasma erythropoietin levels. It is concluded that the vital regulatory mechanism of erythropoiesis through erythropoietins is intact in the last part of intrauterine life and in the neonatal period. The present findings are another confirmation of the concept that the postnatal fall in erythropoiesis is due to an improvement of oxygenation following birth.