Association of cord plasma metabolites with birth weight: results from metabolomic and lipidomic studies of discovery and validation cohorts.

Abstract

Birth weight is a good predictor of fetal intrauterine growth and long-term health. Although several studies have evaluated the relationship between metabolites and birth weight, no prior study has comprehensively investigated the metabolomic and lipidomic and further validated and quantified meaningful metabolites. Firstly, a pseudotargeted metabolomics approach was applied to detect 2418 metabolites in 504 cord blood samples in the discovery set enrolled from the Wuhan Healthy Baby Cohort (HBC), China. Metabolome-wide association scan (MWAS) analysis and pathway enrichment were applied to discover metabolites and metabolic pathways that were significantly associated with birth weight for gestational age (BWGA) z-score. Logistic regression models were used to analyze the association of metabolites in the most significantly associated pathways with small for gestational age (SGA) and low birth weight (LBW). Subsequently, 350 cord blood samples in a validation cohort were subjected to targeted analysis to validate the metabolites screened from the discovery cohort. In the discovery set, 513 metabolites were significantly associated with BWGA z-score (PFDR <0.05), of which 298 KEGG-annotated metabolites were included in the pathway analysis. The primary bile acid biosynthesis pathway was the most relevant metabolic pathway associated with BWGA z-score in our study. Elevated cord plasma primary bile acids were associated with lower BWGA z-score and higher odds of SGA or LBW in the discovery and validation cohorts. In the validation set, a 2-fold increase in taurochenodeoxycholic acid (TCDCA) and taurocholic acid (TCA) was associated with 0.10 (95% CI: 0.00, 0.20) and 0.18 (95 %CI: 0.04, 0.31) decrease in BWGA z-score, respectively, after adjusting for covariates. In addition, a 2-fold increase in cord plasma TCDCA and TCA was associated with an adjusted odds ratio of 1.52 (1.00, 2.30) and 1.77 (1.05, 2.98) for SGA, respectively. The adjusted ORs for a 2-fold increase in TCDCA and TCA concentrations were 2.39 (95% CI 1.00, 5.71) and 3.21 (0.96, 10.74) for LBW, respectively. The results indicate a significant association between primary bile acids and lower BWGA z-score, as well as higher risk of SGA and LBW. Abnormalities of primary bile acid metabolism may play an important role in restricted fetal development. This article is protected by copyright. All rights reserved.