471: Metabolic Signatures of Fetal Growth Restriction (FGR): 1H NMR Analysis of Human Placenta

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OBJECTIVE: Fetal Growth Restriction (FGR) (estimated fetal weight < 10th percentile) is associated with increased risks of perinatal mortality and morbidity, long term developmental deficits, and adult metabolic syndrome. However, the pathogenesis remains insufficiently understood and half the cases are not prenatally identified. Our goals were to: a) use high resolution 1 H NMR metabolomics to biochemically profile human placental tissue in FGR compared to normal; b) determine the screening efficacy of potential biomarkers for FGR in placental tissue; c) determine if there are metabolic alterations and disruptions to normal pathways in FGR placental tissues.

STUDY DESIGN: 49 human placental tissue samples consisting of n¼30 controls and n¼19 FGR specimens were freeze-dried and homogenized to a fine powder. Metabolomic analysis of the extracted metabolites was performed using a 600 MHz Bruker Avance III Spectrometer. Logistic regression was used to generate predictive algorithms for FGR. Pathway analysis was used to investigate the biochemical pathways that were dysregulated in FGR.

RESULTS: The mean (SD) gestational age (weeks) at delivery for FGR versus controls was 36.4 (3.8) vs 39.8 (0.87) (p-value¼0.005); and birth weight (kgm) was 2126 (752) vs 3505 (381) (p- ¼0.010) for FGR vs control cases, respectively. Multivariate analysis displayed significant differences between FGR and control specimens based on the accurate quantitated concentrations of 59 metabolites (p < 0.0001). Logistic regression analysis of the data revealed that the combination of aspartate, valine, glycine and D-glucose have good accuracy for predicting FGR (AUC ¼ 0.839, CI: 0.709 -0.968). Pathway analysis revealed perturbations to important metabolic pathways including alanine, aspartate and glutamate metabolism (p ¼ 9.41x10-7), and ketone body synthesis and degradation (p¼0 0.02353) (Table 1). These pathways are involved in glucose metabolism in muscle, neurotransmission, the inhibition of antioxidant defenses and fatty acid metabolism.

CONCLUSION: This study demonstrates the potential of high-resolution metabolomics for the study and prediction of FGR. Using this platform, we were able to discriminate between FGR and control placentas. Further, we identified novel disturbances in important pathways involved in energy metabolism and neurotransmission.


37th Annual Society of Maternal Fetal Medicine, Las Vegas, NV, January 23-28, 2017.