Unveiling Macrosomia Risks of Non-Diabetic Women: Insights from Second Trimester Maternal Lipid Profiles

Background: Macrosomia, characterized by excessive fetal growth, is common in infants born to women with pre-gestational diabetes and gestational diabetes mellitus (GDM). However, macrosomia, which leads to birth-related maternal and fetal complications and metabolic complications in the adolescence of the affected fetuses, also occurs in the pregnancies of non- diabetic women. This study aims to identify the association between second-trimester lipid profiles and macrosomia in non- diabetic pregnant women to aid in early diagnosis. Methods: This retrospective cohort study included 8,956 patients who delivered at a tertiary care center between 2017 and 2019. Exclusion criteria encompassed pre-existing diabetes, GDM, preeclampsia (PE), intrahepatic cholestasis of pregnancy, obesity, fetal chromosomal or genetic abnormalities, tobacco, alcohol, or drug use affecting lipid metabolism. Participants were divided into two groups: 621 with macrosomia and 873 controls. Second trimester maternal lipid profiles and demographic variables such as age, pregnancy week, and gender were assessed. Results: In the study cohort, maternal age (P = 0.002), gestational week (P = 0.003), and cesarean section rate (P< 0.001) were higher in the macrosomic group. High-density lipoprotein-cholesterol (HDL-C) was significantly lower, while total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C) were significantly higher in the macrosomic group (P< 0.001). Univariate analysis revealed positive associations between second-trimester TG (OR 1.023, 95% CI: 1.020-1.033, P < 0.001), TC (OR 1.023, 95% CI: 1.016-1.030, P < 0.001) and LDL-C (OR 1.036, 95% CI: 1.018-1.054, P < 0.001) with macrosomia and a negative association with HDL-C (OR 0.954, 95% CI: 0.923-0.976, P < 0.001). However, after adjusted multivariable logistic analysis, only TG remained statistically significantly associated with macrosomia (OR 1.054, 95% CI: 1.033-1.076, P < 0.001). Conclusion: Our study emphasizes the importance of early recognition and prevention of macrosomia. Structured prospective studies are needed to enhance macrosomia prediction and implement preventive measures, such as dietary modifications. These strategies will be crucial in preventing birth-related complications and long-term health risks, including diabetes, obesity, and cardiovascular diseases, associated with macrosomia.