Xiaoxiao Yin ^1,2 Tingting Yu ² Dongmei Jiang ¹ Chunjian Shan ² Jiaai Xia ² Min Su ³ Min Zhang ² Ling Chen ² Hong Zhong ² Xianwei Cui ² Chenbo Ji ^4*

• ¹ School of Nursing, Nanjing Medical University, Nanjing, Jiangsu Province, China
• ² Nanjing Women and Children’s HealthCare Hospital, Nanjing, Liaoning Province, China
• ³ Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
• ⁴ Women’s Hospital of Nanjing Medical University (Nanjing Maternity and Child Health Care Hospital), Nanjing, China

Gestational diabetes mellitus (GDM) significantly affects the fetal metabolic environment, elevating risks of neonatal hypoglycemia and macrosomia. Metabolomics offers promising avenues for early prediction and diagnosis of GDM and associated adverse offspring outcomes. This study analyzed serum samples from pregnant women diagnosed with GDM at 24 to 28 weeks of gestation using untargeted metabolomics. We monitored the health outcomes of their offspring to explore the correlation between initial serum metabolite profiles and subsequent health outcomes, to uncover the predictive markers for hypoglycemia and macrosomia in these offspring. Out of 200 participants, 154 had normal newborns, 33 had offspring with hypoglycemia, and 19 had offspring with macrosomia. From 448 identified metabolites, 66 showed significant differences in cases of hypoglycemia, and 45 in macrosomia. A panel of serum metabolite biomarkers achieved Area Under the Curve (AUC) values of 0.8712 for predicting hypoglycemia and 0.9434 for macrosomia.The study delineated metabolic disruptions in GDM during 24 to 28 weeks of gestation and pinpointed biomarkers capable of forecasting adverse neonatal outcomes. These findings could inform GDM management strategies and minimize the incidence of such outcomes.