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Amniotic Fluid Oxidative and Nitrosative Stress Biomarkers Correlate with Fetal Chronic Hypoxia in Diabetic PregnanciesEscobar J.a · Teramo K.d · Stefanovic V.d · Andersson S.e · Asensi M.A.c · Arduini A.c · Cubells E.a · Sastre J.c · Vento M.a, b
aNeonatal Research Unit, Health Research Centre La Fe, bDivision of Neonatology, University and Polytechnic Hospital La Fe, and cDepartment of Physiology, Faculty of Pharmacy, University of Valencia, Valencia, Spain; dDepartment of Obstetrics and Gynaecology and eDivision of Neonatology, Helsinki University Central Hospital, Helsinki, Finland
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). Objectives: We hypothesized that the degree of fetal hypoxia would correlate with fetal oxidative and nitrosative stress as evidenced by the concentration of specific biomarkers in AF. Material and 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.
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