High-Resolution (1)H NMR Spectroscopy Discriminates Amniotic Fluid of Fetuses with Congenital Diaphragmatic Hernia from Healthy Controls.
Lung hypoplasia in congenital diaphragmatic hernia (CDH) is a life-threatening birth defect. Severe cases can be offered tracheal occlusion to boost prenatal lung development, although defining those to benefit remains challenging. Metabonomics of (1)H NMR spectra collected from amniotic fluid (AF) can identify general changes in diseased versus healthy fetuses. AF embodies lung secretions and hence might contain pulmonary next to general markers of disease in CDH fetuses. AF from 81 healthy and 22 CDH fetuses was collected. NMR spectroscopy was performed at 400 MHz to compare AF from fetuses with CDH against controls. Several advanced feature extraction methods based on statistical tests that explore spectral variability, similarity, and dissimilarity were applied and compared. This resulted in the identification of 30 spectral regions, which accounted for 80% variability between CDH and controls. Combination with automated classification discriminates AF from CDH versus healthy fetuses with up to 92% accuracy. Within the identified spectral regions, isoleucine, leucine, valine, pyruvate, GABA, glutamate, glutamine, citrate, creatine, creatinine, taurine, and glucose were the most concentrated metabolites. As the metabolite pattern of AF changes with fetal development, we have excluded metabolites with a high age-related variability and repeated the analysis with 12 spectral regions, which has resulted in similar classification accuracy. From this analysis, it was possible to distinguish between AF from CDH fetuses versus healthy controls independent of gestational age.
Department of Electrical Engineering (ESAT) - STADIUS, University of Leuven , Kasteelpark Arenberg 10, 3001 Leuven, Belgium.|iMinds, Medical Information Technologies Department, University of Leuven , Kasteelpark Arenberg 10, 3001 Leuven, Belgium.
Anca
A
Croitor-Sava
Department of Development and Regeneration, Faculty of Medicine, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|Department of Obstetrics and Gynecology, University Hospital Gasthuisberg , Herestraat 49, 3000 Leuven, Belgium.
Veronika
V
Beck
Department of Development and Regeneration, Faculty of Medicine, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|Division of Medical Imaging, University Hospital Gasthuisberg , Herestraat 49, 3000 Leuven, Belgium.
Inga
I
Sandaite
Department of Electrical Engineering (ESAT) - STADIUS, University of Leuven , Kasteelpark Arenberg 10, 3001 Leuven, Belgium.|iMinds, Medical Information Technologies Department, University of Leuven , Kasteelpark Arenberg 10, 3001 Leuven, Belgium.
Sabine
S
Van Huffel
Department of Imaging and Pathology, Biomedical MRI Unit, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|MoSAIC, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.
Tom
T
Dresselaers
Department of Development and Regeneration, Faculty of Medicine, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|Division of Medical Imaging, University Hospital Gasthuisberg , Herestraat 49, 3000 Leuven, Belgium.
Filip
F
Claus
Department of Imaging and Pathology, Biomedical MRI Unit, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|MoSAIC, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.
Uwe
U
Himmelreich
Department of Development and Regeneration, Faculty of Medicine, University of Leuven , Herestraat 49, 3000 Leuven, Belgium.|Department of Obstetrics and Gynecology, University Hospital Gasthuisberg , Herestraat 49, 3000 Leuven, Belgium.
Jan
J
Deprest
D000653:Amniotic Fluid / Q000737:chemistry*; D016022:Case-Control Studies; D005260:Female; D005333:Fetus; D005865:Gestational Age; D065630:Hernias, Diaphragmatic, Congenital / Q000175:diagnosis* / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000706:statistics & numerical data; D008297:Male; D055442:Metabolome; D011296:Prenatal Diagnosis; D025341:Principal Component Analysis
NMR spectroscopy; amniotic fluid; classification; congenital diaphragmatic hernia; feature extraction; fetal development; lung