High amniotic fluid erythropoietin levels are associated with an increased frequency of fetal and neonatal morbidity in type 1 diabetic pregnancies

Diabetologia. 2004 Oct;47(10):1695-703. doi: 10.1007/s00125-004-1515-3. Epub 2004 Oct 22.


Aims/hypothesis: 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/interpretation: Antenatal high amniotic fluid erythropoietin levels can identify type 1 diabetic pregnancies at increased risk of severe perinatal complications.

MeSH terms

  • Adult
  • Amniotic Fluid / chemistry*
  • Biomarkers
  • Birth Weight
  • Blood Glucose / metabolism
  • Cesarean Section
  • Erythropoietin / analysis*
  • Female
  • Fetal Diseases / epidemiology*
  • Gestational Age
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / epidemiology
  • Maternal Age
  • Morbidity
  • Pregnancy
  • Pregnancy in Diabetics / physiopathology*
  • Umbilical Arteries / physiopathology


  • Biomarkers
  • Blood Glucose
  • Erythropoietin