Glycerophospholipid and detoxification pathways associated with small for gestation age pathophysiology: discovery metabolomics analysis in the SCOPE cohort

Introduction: Small for gestational age (SGA) may be associated with neonatal morbidity and mortality. Our understanding of the molecular pathways implicated is poor. Objectives: Our aim was to determine the metabolic pathways involved in the pathophysiology of SGA and examine their variation between maternal biofluid samples. Methods: Plasma (Cork) and urine (Cork, Auckland) samples were collected at 20 weeks’ gestation from nulliparous low-risk pregnant women participating in the SCOPE study. Women who delivered an SGA infant (birthweight < 10th percentile) were matched to controls (uncomplicated pregnancies). Metabolomics (urine) and lipidomics (plasma) analyses were performed using ultra performance liquid chromatography-mass spectrometry. Features were ranked based on FDR adjusted p-values from empirical Bayes analysis, and significant features putatively identified. Results: Lipidomics plasma analysis revealed that 22 out of the 33 significantly altered lipids annotated were glycerophospholipids; all were detected in higher levels in SGA. Metabolomic analysis identified reduced expression of metabolites associated with detoxification (D-Glucuronic acid, Estriol-16-glucuronide), nutrient absorption and transport (Sulfolithocholic acid) pathways. Conclusions: This study suggests higher levels of glycerophospholipids, and lower levels of specific urine metabolites are implicated in the pathophysiology of SGA. Further research is needed to confirm these findings in independent samples.