title: High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies.
abstract: OBJECTIVE
  In this study we investigated whether chronic fetal hypoxia, as indicated by amniotic fluid erythropoietin levels, is associated with perinatal morbidity in type 1 diabetic pregnancies.
  
  
  METHODS
  A total of 331 women with type 1 diabetes had at least one childbirth between 1995 and 2000. The amniotic fluid erythropoietin concentration was measured in 156 diabetic singleton pregnancies at a median time of 1 day before Caesarean section without labour contractions and in 19 healthy control subjects at Caesarean section.
  
  
  RESULTS
  The median amniotic fluid erythropoietin level was 14.0 mU/ml (range 2.0-1975.0) in diabetic pregnancies and 6.3 mU/ml (range 1.7-13.7) in controls (p<0.0001). Of the 156 diabetic patients, 21 (13.5%) had amniotic fluid erythropoietin levels higher than 63.0 mU/ml. Amniotic fluid erythropoietin levels correlated negatively with umbilical artery pH (r=-0.49, p<0.0001) and pO2 (r=-0.62, p<0.0001) at birth and neonatal lowest blood glucose level (r=-0.47, p<0.0001). Positive correlations were found between amniotic fluid erythropoietin levels and umbilical artery pCO2 (r=0.49, p<0.0001) and last maternal HbA1c (r=0.43, p<0.0001). Furthermore, a U-shaped correlation was demonstrated between amniotic fluid erythropoietin levels and birthweight z score (z score below -0.6 SD units: r=-0.63, p=0.0007; z score above +1.0 SD units: r=0.32, p=0.0014). Neonatal hypoglycaemia, hypertrophic cardiomyopathy and admission to the neonatal intensive care unit occurred significantly more often in cases with high amniotic fluid erythropoietin levels (>63.0 mU/ml) than in those with normal levels. Multivariate logistic regression analysis revealed that amniotic fluid erythropoietin was the only variable independently related to low umbilical artery pH (<7.21; p<0.0001) and neonatal hypoglycaemia (p=0.002). Low umbilical artery pO2 (<15.0 mm Hg) was explained by amniotic fluid erythropoietin (p<0.0001) and birthweight z score (p=0.004).
  
  
  CONCLUSIONS
  Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.
authors.affiliation: Department of Obstetrics and Gynaecology, University Central Hospital, Helsinki, Finland. kari.teramo@huch.fi
authors.forename: K
authors.initials: K
authors.lastname: Teramo
authors.forename: M A
authors.initials: MA
authors.lastname: Kari
authors.forename: M
authors.initials: M
authors.lastname: Eronen
authors.forename: H
authors.initials: H
authors.lastname: Markkanen
authors.forename: V
authors.initials: V
authors.lastname: Hiilesmaa
mesh_terms: D000328:Adult; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers; D001724:Birth Weight; D001786:Blood Glucose / Q000378:metabolism; D002585:Cesarean Section; D004921:Erythropoietin / Q000032:analysis*; D005260:Female; D005315:Fetal Diseases / Q000453:epidemiology*; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000453:epidemiology; D008423:Maternal Age; D009017:Morbidity; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000503:physiopathology*; D014469:Umbilical Arteries / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D004921:Erythropoietin