Metabolomic Pathways Predicting Labor Dystocia by Maternal Body Mass Index

Abstract

Objectives The purpose of this study was to evaluate the metabolic pathways activated in the serum of African-American women during late pregnancy that predicted term labor dystocia. Study Design Matched case-control study ( n = 97; 48 cases of term labor dystocia and 49 normal labor progression controls) with selection based on body mass index (BMI) at hospital admission and maternal age. Late pregnancy serum samples were analyzed using ultra-high-resolution metabolomics. Differentially expressed metabolic features and pathways between cases experiencing term labor dystocia and normal labor controls were evaluated in the total sample, among women who were obese at the time of labor (BMI ≥ 30 kg/m2), and among women who were not obese. Results Labor dystocia was predicted by different metabolic pathways in late pregnancy serum among obese (androgen/estrogen biosynthesis) versus nonobese African-American women (fatty acid activation, steroid hormone biosynthesis, bile acid biosynthesis, glycosphingolipid metabolism). After adjusting for maternal BMI and age in the total sample, labor dystocia was predicted by tryptophan metabolic pathways in addition to C21 steroid hormone, glycosphingolipid, and androgen/estrogen metabolism. Conclusion Metabolic pathways consistent with lipotoxicity, steroid hormone production, and tryptophan metabolism in late pregnancy serum were significantly associated with term labor dystocia in African-American women.

Keywords: labor dystocia; mechanisms; metabolomics; obesity; parturition.

Fig. 1

Two-way hierarchical cluster analysis (HCA) (i), principal components analysis (PCA) (ii), and metabolic pathway analysis (iii) showing metabolites and metabolic pathways differentially expressed between women with labor dystocia and normal labor controls among (A) obese and (B) nonobese women caption: Each column in HCA represents a participant and each row represents a metabolite feature. Red hues indicate metabolites with enhanced levels, and blue hues represent metabolites with lower metabolite concentrations. Labor dystocia is represented in green and normal labor in red across x-axis. Red triangles in PCA represent normal labor and green triangles represent labor dystocia. ( A ) Obese women, (i) HCA with top 140/8813 metabolites with a raw p  < 0.05 is shown and (ii) PCA and (iii) Mummichog enriched metabolic pathways differentiating labor dystocia in matched groups ( B ) Nonobese women, (i) HCA with top 109/8704 metabolites with a raw p  < 0.05 is shown and (ii) PCA and (iii) Mummichog enriched metabolic pathways differentiating labor dystocia in matched groups of ( A ) obese and ( B ) nonobese women shown with dotted green line represents pathways significant at p  < 0.05. Metabolic pathway analyses include adjustment within each group for maternal body mass index (continuous, at hospital admission for labor) and maternal age.