Metabolomics & Patent Ductus Arteriosus diagnosis: is 1H-NMR (Nuclear Magnetic Resonance) Spectroscopy of urine at birth predictive as ultrasound?

BACKGROUND Patent ductus arteriousus (PDA) is one of the most common problems in the care of premature infants. Its incidence range is between 1/2000 in infants born at term and almost 80% of infants born before 28 weeks of gestational age. It is a type of congenital heart defect in which abnormal flow occurs between two of the major arteries connected to the heart. In fact before birth the aorta and the pulmonary artery are connected by a blood vessel called the ductus arteriosus, an essential part of the fetal blood circulation, this vessel is supposed to close within hours or days after birth. However in some infants, after birth, the ductus arteriosus remains open and can cause an increase of blood pressure in the lung arteries which can raise major cardiological problems in the next future. Recently it has showed that the risk of death in neonates with PDA is eight times greater than in those with closed ductus (Noori et al 2009). Nowadays the gold standard to perform a diagnosis of PDA is based on ultrasound using echocardiography and clinical criteria according to the guidelines and literature (ElHajjar M et al 2005, Evans N 1993, Kluckow M et al. 1995). AIM Aim of this study is to demonstrate the relevance of 1H-NMR metabolomic approaches in anticipation of PDA persistent in infants. METHODS The study was performed on three groups of people admitted to the Pediatrics Division, Cagliari. In the first group there were 4 infants born at term (cross), the second 4 preterm without PDA (circle, mean: 30.8 of gestational age, std: 3.3 week; mean of birth weight 1505 g, std: 983 g; gender rate 1 female 3 male) and the third 6 preterm with PDA (black dots, mean: 30.2 of gestational age, std: 4.5 week; mean of birth weight 1515 g, std: 860 g, gender rate 4 female 2 male). A urine sample was collected from each newborn at birth, and an aliquot of 400 μl was mixed with 200 μl of 0.2 M phosphate buffer solution (pH 7.4) to stabilize the pH of the urine. Then an aliquot of 50 μl of TSP (Trimethylsilyl propanoic acid) in D20 was added to provide an internal reference for the chemical shifts (0 ppm) subsequently urines were analyzed using 1H-NMR Varian 400 MHz. NMR spectra were subjected to multivariate analysis in order to combine metabolic variables using SIMCA-P+ (version 12.0, Umetrics, Sweden) figure 1. RESULTS Using a PLS-DA (Partial least squares discriminant analysis) model we were able to discriminate the term group, preterm group without PDA and the preterm group with PDA. CONCLUSION Based on this finding, metabolomics may become a promising next-generation tool of PDA diagnosis at birth avoiding unnecessary and non ethic nonsteroidal anti-inflammatory drugs (NSAIDS) prophylaxis, predicting and monitoring persistent PDA.