Supervisors info:
Βραχνής Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Χρέλιας Χαράλαμπος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Σαλάκος Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Pregnancy is considered to be a condition of vast biochemical alterations dictated by a multitude of adaptational processes. Metabolomic analysis is a widely documented method, used to study complex samples such as urine, amniotic fluid and plasma. This technique allows simultaneous analysis of many biochemical markers as long as their concentration in the amniotic fluid is adequate, making it therefore possible to outline the fetus’ metabolic profile and diagnose disorders such as metabolic abnormalities, intrauterine infections, genetic disorders, neural tube defects and hematopoiesis disorders prenatally. It is also possible to evaluate fetal lung maturity and fetal distress. Many bibliographic references analyze the use of metabolomics in amniotic fluid both in uncomplicated and in complicated gestations. Metabolomic analysis of amniotic fluid in uncomplicated gestation shows a small decline in glucose levels, albumin and total protein count and elevation of choline and alkaline phosphatase during the third trimester mainly due to the rapid growth of the fetus. Additionally, a concurrent increase in creatinine and uric acid is an indicator of renal maturation. Measuring bilirubin after the 36th week of gestation is useful in cases of hemolysis or Rhesus immunization. Another useful marker is the lecithin/sphingomyelin ratio (L/S) which assesses fetal lung maturity. Furthermore, metabolomics can be used to predict many pathological conditions. Elevated cholic acid is associated with fetal distress, triglyceride and total cholesterol elevation with increased odds of preterm labour, low inositol levels with respiratory distress syndrome in preterm infants, increased cathepsin G and pentraxin 3 suggest intrauterine infection in premature rupture of membranes and increased lactic acid is associated with increased probability of abortion. Many studies using metabolomics are now focusing on evaluating a series of biomarkers in amniotic fluid, aiming to better understand embryonic maturation, while allowing the documentation of every dynamic process regarding the phenotype as well as the homeostasis of all fetal organ systems. One particular study based on metabolomic analysis showed that impaired fetal growth means increased production of brain derived neurotrophic factor which speeds up brain development and maturation as an adaptational process in the unwelcoming uterine environment. Impaired metabolic biomarkers in the amniotic fluid have also been correlated to Down syndrome where metabolic changes mean altered gene expression of Chromosome 21, especially in genes linked to intellectual disability and hematopoiesis. That being said, changes in amniotic fluid metabolites provide important information in understanding the pathophysiology of fetal disease beyond the scope of genomics, epigenetics and proteomic analysis. In a recent study, the presence of oxidative stress in the amniotic fluid of fetuses with neural congenital disorders was confirmed, which is reflected by the decline in the antioxidant mechanisms of catalase and glutathione in pregnant women carrying these fetuses. Metabolomic analysis of amniotic fluid showed that amniotic fluid corticoeclytin seems to be involved in fetal developmental processes; stress, however, may affect its secretion from the placenta. Accordingly, prolonged fasting during the third trimester alters amniotic fluid metabolic biomarkers and increased levels of glycerol, non esterified fatty acids and b-hydroxybutyrate acid can be detected. Last but not least, a substantially useful result in metabolic markers research is that in fetuses with increased nuchal translucency, metabolic pathways are altered and tend to turn towards glycolytic pathways (alanin, aspartic acid, glutamate, nitrate, arginine, proline, glycolysis, gluconeogenesis and pyruvate metabolism) with a concurrent decrease in antioxidant molecules such as ascorbic acid and glutathione as well as a decrease in glucose and increase in lactic acid. Future studies are needed in order to properly identify the diagnostic and therapeutic contribution of metabolomic analysis of amniotic fluid in prenatal and perinatal aspects of Perinatal Medicine.
Keywords:
Amniotic fluid, Metabolomic, Metabolic markers,Down syndrome,Lecithin/sphingomyelin
