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

ABSTRACT 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/m 2 ), 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.