Lifestyle Intervention During Pregnancy Is Associated With Favourable Changes of Vitronectin in Women With Obesity: Results From the Randomised LiP Trial.

Obesity in pregnancy is a well-established risk factor for adverse maternal and neonatal outcomes, including gestational diabetes mellitus (GDM). This study aimed to examine the effects of lifestyle intervention during pregnancy on the cardio-metabolic protein profile and its association with maternal and neonatal health. The Lifestyle in Pregnancy (LiP) study was a randomised controlled trial conducted between 2007 and 2010 in Denmark. It included 360 pregnant women with obesity (BMI 30-45 kg/m2), aged 18-40 years, who were allocated to either a lifestyle intervention (dietary counselling, physical activity program, free fitness club membership) or standard care. Fasting serum samples from 303 women were collected at 12-15 and 28-30 weeks' gestation and analysed using a 26-plex cardio-metabolic proteomics assay. When comparing the cardio-metabolic protein profiles between the intervention and control groups before and after the intervention in pregnancy, we found that in late pregnancy the levels of two proteins, vitronectin and vitamin D-binding protein, were significantly lower in the intervention group. In the total cohort, elevated vitronectin was associated with a higher risk of GDM (adjusted odds ratio = 1.45 (95% CI: 1.06-1.98), p = 0.02) and neonatal intensive care unit (NICU) admissions (adjusted odds ratio = 1.68 (95% CI: 1.03-2.73), p = 0.037). Vitronectin may represent a modifiable biomarker linked to metabolic dysfunction in pregnant women with obesity, suggesting a potential underlying pathway by which lifestyle interventions could improve pregnancy outcomes.