title: Amniotic fluid oxidative and nitrosative stress biomarkers correlate with fetal chronic hypoxia in diabetic pregnancies.
abstract: BACKGROUND
  In spite of improvement in obstetrical care, pregnancy in women with type 1 diabetes mellitus is associated with increased perinatal morbidity and mortality. Hyperglycemia during pregnancy causes excessive fetal growth and chronic fetal hypoxia as reflected in increased erythropoietin (EPO) levels in amniotic fluid (AF).
  
  
  OBJECTIVE
  We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced ty the concentration of specific biomarkers in AF.
  
  
  METHODS
  19 pregnant women with type 1 or insulin-treated gestational diabetes mellitus were studied. AF samples were collected and processed for EPO, meta-tyrosine, nitro-tyrosine and 8-hydroxy-2-deoxiguanosine by chemiluminescent immunoassay and high-performance liquid chromatography coupled to tandem mass spectrometry methods, respectively.
  
  
  RESULTS
  The mean (SD) of the last HbA1c concentration before delivery was 7.7% (1.1). Median gestational age was 258 days (range 231-268). Birth weight was 3,868 ± 695 g with a z-score >2 SD in 47% of the cases. A significant correlation was found between the concentrations of AF EPO and meta-tyrosine/phenylalanine ratio (p < 0.001), nitro-tyrosine (p < 0.01) and 8-oxo-dG/2dG ratio (p < 0.001).
  
  
  CONCLUSIONS
  We confirmed that fetuses of type 1 diabetes or insulin-treated gestational diabetes pregnancies experience chronic hypoxia as reflected by increased EPO concentrations in AF near term. Moreover, EPO levels significantly correlated with the concentration of oxidative and nitrosative stress biomarkers in AF. This pro-oxidant status may predispose newborn infants to poor postnatal adaptation and early neonatal complications.
authors.affiliation: Neonatal Research Unit, Health Research Centre La Fe, University and Polytechnic Hospital La Fe, Valencia, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Escobar
authors.forename: Kari
authors.initials: K
authors.lastname: Teramo
authors.forename: Vedran
authors.initials: V
authors.lastname: Stefanovic
authors.forename: Sture
authors.initials: S
authors.lastname: Andersson
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Asensi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Arduini
authors.forename: Elena
authors.initials: E
authors.lastname: Cubells
authors.forename: Juan
authors.initials: J
authors.lastname: Sastre
authors.forename: Máximo
authors.initials: M
authors.lastname: Vento
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000649:Amniocentesis; D000653:Amniotic Fluid / Q000737:chemistry*; D015415:Biomarkers / Q000032:analysis; D001724:Birth Weight; D002851:Chromatography, High Pressure Liquid; D002908:Chronic Disease; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000188:drug therapy / Q000378:metabolism; D016640:Diabetes, Gestational / Q000188:drug therapy / Q000378:metabolism*; D004921:Erythropoietin / Q000032:analysis; D005260:Female; D005311:Fetal Hypoxia / Q000209:etiology* / Q000378:metabolism; D005865:Gestational Age; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007118:Immunoassay; D007231:Infant, Newborn; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D015538:Nitrosation; D018384:Oxidative Stress; D010865:Pilot Projects; D011247:Pregnancy; D011254:Pregnancy in Diabetics; D053719:Tandem Mass Spectrometry; D014443:Tyrosine / Q000031:analogs & derivatives / Q000032:analysis; D055815:Young Adult
chemical_list: D000080242:8-Hydroxy-2'-Deoxyguanosine; D015415:Biomarkers; D003849:Deoxyguanosine; D004921:Erythropoietin; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D014443:Tyrosine; C554270:EPO protein, human; C517652:hemoglobin A1c protein, human; C002744:3-nitrotyrosine