EMERGE Mothers and Kids: a longitudinal cohort study of mothers and children enrolled in the randomized placebo-controlled trial of metformin in women with GDM (EMERGE): study protocol

BACKGROUND: Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with increased risks of adverse perinatal outcomes and with long-term metabolic and cardiovascular consequences for both mother and child. The original EMERGE randomized controlled trial (RCT) evaluated the effectiveness of early metformin in addition to usual care in women with GDM on glycemic control and perinatal outcomes. The primary objective of the EMERGE Mothers and Kids study is to evaluate long-term maternal cardiometabolic health and child anthropometric and neurodevelopmental outcomes following participation in the EMERGE trial. METHODS: This is a prospective, observational longitudinal cohort follow-up study of women and their children previously enrolled in the EMERGE trial (NCT06327191). Participants are invited to attend a follow-up visit in a single-site hospital-based clinical research setting at the Clinical Research Facility Galway, Ireland. Key inclusion criteria are women and their children who participated in the EMERGE trial and consent to follow-up. Key exclusion criteria include participants who did not provide consent for future follow-up studies. The planned follow-up sample is a pragmatic convenience sample of up to 321 mother-child pairs. A single follow-up visit will be conducted up to 6 years after the index pregnancy. Maternal assessments include anthropometric data, glucose tolerance, and metabolic parameters. Child assessments include growth metrics, adiposity measured via skinfold thickness, and neurodevelopmental status assessed through validated questionnaires. Additional data on quality of life, mental health, breastfeeding, and health economics will also be collected. DISCUSSION: This study aims to provide insights into the long-term safety and efficacy of metformin use during pregnancy, addressing the evidence gap in maternal cardiometabolic outcomes after metformin-treated GDM while also assessing child anthropometric and neurodevelopmental outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT06327191. Registered on November 21, 2023. First planned enrollment in this follow-up study: July 2024. Trial record available at https://clinicaltrials.gov/study/NCT06327191.