Altered placental morphology and metabolomic profile in association with uncomplicated metabolically healthy obese pregnancy

Metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUO) in pregnancy represent two distinct cardiometabolic populations, each potentially necessitating alternative clinical management. However, the understanding of the unique physiological effects of uncomplicated MHO or MUO on fetoplacental growth and metabolism remains limited. This study aimed to identify changes in placental morphology and metabolites concerning maternal obesity, independent of pregnancy-related cardiometabolic complications. Placentae from women with a pre-pregnancy body mass index (BMI) <25 kg/m ² (control; n = 15) and women with MHO (pre-pregnancy BMI >30 kg/m ² with no cardiometabolic diseases; n = 15) were analysed for indices of placental growth and untargeted metabolomics. Complementary measures of pro-inflammatory and antioxidant genes, as well as antioxidant proteins, enzymes, and lipid peroxidation markers were conducted. A clear placentomegaly without histopathological changes was observed in uncomplicated MHO pregnancies. The metabolite 3-aminoisobutanoic acid emerged as the top-ranked feature distinguishing MHO from control placentae, and cysteine, methionine, and vitamin B6 metabolism pathways were among the most distinct signatures identified. These findings illustrate an altered placental morphology and metabolomic profile specific to uncomplicated MHO, offering new insights into how obesity without cardiometabolic complications influences fetoplacental growth and metabolism. They also represent a crucial first step towards marker identification for MHO pregnancies and underscore the importance of alternative care pathways when obesity is present but metabolic comorbidities are absent.