Placental metabolomics for assessment of pregnancy complications: a systematic review

Metabolomics is a powerful tool for understanding biological function at the cellular level. While this omics technology has found application in areas ranging from toxicology to cancer, its potential for the study of human pregnancy complications is in its infancy. Proper placental function is critical for a healthy pregnancy and assessing placental metabolism offers a direct window into placental physiology. This review aims to analyse placental metabolomics in pregnancy complications in humans. A systematic search was completed using PubMed and Google Scholar, and the Covidence software was used for the screening process. Following title and abstract screening and full-text review, 32 articles remained and were included in this review. Multiple articles performed metabolomics using mass spectrometry and/or nuclear magnetic resonance to study pre-eclampsia, gestational hypertension, foetal growth restriction, maternal obesity, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and preterm birth. A subset of pregnancy complications was investigated in only a single study each (human immunodeficiency virus in pregnancy, neural tube defects, chromosomal disorders, chronic hypoxia, and recurrent pregnancy loss). Univariate analyses identified potential biomarkers of pregnancy complications. Multivariate analyses demonstrated that the placental global metabolic profiles could separate healthy and complicated pregnancies and identified metabolic pathways (e.g. amino acid metabolism, lipid and phospholipid metabolism) to explain pathogenesis and the mechanisms of disease. We highlight knowledge gaps and future directions, emphasizing the need for data replication and inclusion of variables such as biological sex in the field of placental metabolomics.