Study Protocol for the Health Outcomes in Pregnancy and Early Childhood (HOPE) Study: A Mother-Infant Study in American Samoa

Introduction Pacific Islanders, including those in American Samoa, face a disproportionately high burden of gestational diabetes mellitus (GDM) and related sequalae of metabolic conditions. The CREBRF rs373863828 genetic variant, which is uniquely common among Pacific Islanders, has been paradoxically associated with higher body mass index (BMI) but lower risk of type 2 diabetes. While emerging evidence suggests this variant may influence both maternal metabolic outcomes and infant growth, studies in pregnancy and early life remain limited. The purpose of this paper is to describe the protocol for a study designed to address these gaps.

and analysis The Health Outcomes in Pregnancy and Early Childhood (HOPE) Study is an observational, longitudinal cohort study that will enroll up to 180 Samoan pregnant women and their infants (target n=150 dyads completing study protocols) in American Samoa, with follow-up through six months postpartum/postnatal. The study includes questionnaires, anthropometric measurements, and biospecimen collection. Genetic and epigenetic analyses will examine associations between maternal and infant CREBRF rs373863828 genotype, gestational diabetes status, infant body size, and cord blood DNA methylation. Ethics and dissemination The study is approved by the Institutional Review Boards at the University of Pittsburgh, Yale University, and the American Samoa Department of Health, as well as the Lyndon B. Johnson Tropical Medical Center (American Samoa) Research Oversight Committee. Findings will be disseminated through peer-reviewed publications, conference presentations, and community reports. Competing Interest Statement The authors have declared no competing interest. Funding Statement Yes Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study has received Institutional Review Board (IRB) approval from both the University of Pittsburgh and Yale University, with the University of Pittsburgh serving as the IRB of record through a multi-site IRB agreement (STUDY24020055). Local and territorial approval has been granted by the American Samoa IRB. In addition, the study has been approved by the Lyndon B Johnson Tropical Medical Center (LBJ) Research Oversight Committee for all hospital-related activities. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability This is a study protocol paper--data collection for this study has just begun. However, participants in this study will be optionally consented for broad data sharing in federal registries. For those who consent, data will be available in dbGaP under accession number phs003874.v1.p1.