Fetal Erythropoietin Levels in Growth-Restricted and Appropriately Grown Neonates With and Without Abnormal Fetal Heart Rate Tracings: A Comparison With Cord Blood Gases and Apgar Scores

Abstract

OBJECTIVE:To determine if umbilical cord plasma erythropoietin (EPO) levels in combination with cord blood gases and Apgar scores can distinguish between subacute and chronic uteroplacental insufficiency. METHODS:A total of 184 neonates delivered between 1993 and 1997 at Tampa General Hospital were studied. Cord plasma EPO levels, cord blood gases, and Apgar scores were determined prospectively and compared in four subgroups that were defined based on the presence or absence of fetal growth restriction (FGR; chronic fetal hypoxia), abnormal fetal heart rate tracings during labor (FHR; subacute/acute fetal hypoxia), or both. RESULTS:Both growth-restricted and appropriately grown newborns with abnormal intrapartum FHR tracing had elevated umbilical cord plasma EPO (183.5 and 135.2 mIU/ml, respectively; normal ϭ 20.7 mIU/ml) and base deficit, whereas pH, PO 2 , and 1-minute and 5-minute Apgar scores were significantly lower, compared with appropriately grown newborns with a normal intrapartum course. Among newborns with normal heart rate tracings and FGR, the mean plasma EPO levels were elevated (89.5 mIU/ml), whereas the other parameters were not different from normal. CONCLUSION:Our findings suggest that, although cord blood gases and Apgar scores may reflect subacute and acute events, they are not good predictors of chronic uteroplacental insufficiency. The supplemental use of umbilical cord plasma EPO levels may improve our ability to identify chronic uteroplacental insufficiency.Intrauterine fetal well being has been traditionally assessed by ultrasound studies and fetal heart rate monitoring.1-3 These surveillance methods, however, have not helped decrease the incidence of cerebral palsy.4,5 It has been suggested that chronic, rather than subacute or acute, fetal hypoxia is a better predictor of neurologic deficits in the newborn.6 -11 To improve pregnancy outcomes, investigators have searched for better markers of chronic fetal hypoxia.Erythropoietin (EPO) is a glycoprotein produced by the fetal kidney and liver, and its production increases only in response to fetal hypoxia. 12 The presence of EPO in fetal blood has been documented as early as the 16th week of gestation. 13 Elevated EPO has been associated with uteroplacental insufficiency, like fetal growth restriction (FGR) 14 and intrauterine fetal hypoxia. 15,16 A strong correlation between EPO and cord blood gases has also been reported. [17][18][19] As an indicator of chronic hypoxia, EPO may prove useful in identifying fetuses at risk for long-term irreversible end organ damage such as cerebral palsy. The purpose of this study was to determine if fetal EPO could provide a better method for identifying infants with chronic uteroplacental insufficiency than cord blood gases and Apgar scores alone. METHODSThe study protocol was approved by the Institutional Review Board of the University of South Florida College of Medicine. The estimated gestational age of the infants at delivery was 24 to 40 completed weeks, based on menstrual history, early ultraso...

Increased cord serum inflammatory markers in small-for-gestational-age neonates

“…17 IUGR creates an adverse intrauterine environment to the fetus, to the inclusion of relative oxygen deprivation. In support of this are several facts: (1) fetal hypoxia has been documented in IUGR fetuses by cordocentesis 18 ; (2) erythropoietin is elevated in newborn SGA infants (presumably in response to fetal hypoxia) 19 ; and (3) IUGR is a known risk factor for increased erythropoiesis, as evidenced by increased numbers of circulating nucleated red blood cells at birth 20 and increased rates of polycythemia. 21 Therefore, as hypoxia-ischemia is known to be capable of stimulating an inflammatory response, we speculate that relative ischemia in IUGR is responsible for the inflammatory picture that we here describe.…”

Eritropoyetina en cordón umbilical y estado metabólico en recién nacidos con sufrimiento fetal intraparto

“…Varios estudios han documentado la asociación entre hipoxia fetal y concentraciones elevadas de EPO en el plasma de cordón umbilical 13,14 . Richey et al 12 reportaron altas concentraciones en partos complicados con sufrimiento fetal; sin embargo, también se observó una edad gestacional significativamente mayor en los partos complicados con sufrimiento fetal.…”

“…Las concentraciones elevadas han sido asociadas con insuficiencia útero-placentaria, restricción del crecimiento intrauterino del feto e hipoxia fetal intrauterina 12,13 . También se ha descrito una fuerte correlación entre las concentraciones y los gases del cordón umbilical 14 . Estudios en animales y humanos han demostrado un aumento varias horas después de la hipoxia 7,15 .…”

Prohepcidin concentrations and erythroid progenitors in cord blood of appropriate versus small for gestational age neonates

“…4,5 Intrauterine growth restriction (IUGR) creates an adverse intrauterine environment to the fetus, to the inclusion of relative oxygen deprivation. In support of this are the facts that fetal hypoxia has been documented in IUGR fetuses by cordocentesis; 6 that EPO is elevated in newborn small for gestational age (SGA) infants (presumably in response to fetal hypoxia), 7 and IUGR is a known risk factor for increased erythropoiesis, as evidenced by increased numbers of circulating nucleated red blood cells at birth 8 and increased rates of polycythemia. 9 We therefore conducted this prospective study to test the hypothesis that cord blood of SGA neonates has higher circulating EPO, lower circulating Pro-Hep and higher circulating erythroid progenitors than cord blood of appropriate for gestational age (AGA) neonates.…”