Glucose Homeostasis, Metabolomics, and Pregnancy Outcomes After Bariatric Surgery (GLORIA): Protocol for a Multicentre Prospective Cohort Study

Abstract

Background: Metabolic bariatric surgery is a highly effective and long-lasting treatment for obesity and related chronic conditions. Women of reproductive age represent the largest group undergoing these procedures. Observational studies suggest an increased risk of preterm birth and impaired foetal growth in this population, though the underlying mechanisms remain unclear. A key hypothesis is that altered glucose metabolism, characterised by frequent hypoglycaemia and glycaemic fluctuations, may contribute to these adverse outcomes. While glycaemic variability following metabolic bariatric surgery has been documented, its pattern during pregnancy and impact on pregnancy outcomes are still underexplored. Methods: In this Belgian multicentre prospective cohort study, we will investigate glycaemic patterns during pregnancy in women who have undergone metabolic bariatric surgery. Women aged 18-45 years with a confirmed singleton pregnancy up to 11 weeks and 6 days and a history of Roux-en-Y gastric bypass or sleeve gastrectomy will be eligible for inclusion. Women with pregestational diabetes or those taking medication known to interfere with glucose metabolism will be excluded. All participants will receive blinded continuous glucose monitoring (Dexcom^® G6) for a 10-day period at four time points throughout the pregnancy. Foetal body composition and growth will be measured during routine ultrasound; skinfolds will be measured in the neonate. The primary outcome is the association between mean glycemia and glycaemic variability on continuous glucose monitoring and birth weight. The planned sample size is ninety-five women. Linear mixed models for repeated measurements will be used for analysis. Confounders such as smoking, micronutrient deficiency, and surgery-to-conception interval will be added to the model as covariates. In a second exploratory phase, each participant in the surgical group will be matched with a control participant-without a history of metabolic bariatric surgery-based on pre-pregnancy BMI and age. Control participants will undergo the same study procedures, allowing for exploratory comparison of glycaemic patterns and other study outcomes. Discussion: This prospective longitudinal study will be the largest study using continuous glucose monitoring to investigate glucose metabolism during pregnancy after metabolic bariatric surgery and its impact on foetal growth and newborn body composition. Trial registration: ClinicalTrials.gov: NCT05084339. Registration date: 15 October 2021.

Keywords: Roux-en-Y gastric bypass; continuous glucose monitoring; foetal growth restriction; post bariatric hypoglycaemia; pregnancy outcome; premature birth; sleeve gastrectomy; small for gestational age.