PRenatal and Obstetric Maternal Exposures and ISlet Autoantibodies in Early Life

We will assemble a prenatal cohort where the offspring has a first degree relative (FDR) with T1D (mother, father or full sibling). In order to enroll sufficient participants, we are conducting a multi-center study at the Barbara Davis Center for Diabetes (BDC) in Aurora, CO [coordinating center], Mt Sinai Hospital in New York, NY, the Joslin Diabetes Center (JDC) in Boston, MA, and Ohio State University (OSU) in Columbus, OH. These sites were chosen based on a history of successful prior collaborations, access to large established populations of people with T1D (these centers are some of the largest in the United States with respect to pregnancy care for women with T1D, and also have adult and pediatric clinics), site-specific connections to obstetric practices, and a history of successful recruitment into study cohorts. In addition to the four study sites named, we have approached additional potential sites in order to ensure success with recruitment. We have identified an additional potential site at the Mayo Clinic College of Medicine under the direction of Yogish Kudva, and this site is prepared to activate should recruitment in the first year of the grant at the four sites fall short of expectations. Our goal is to assemble a pregnancy cohort of 800 during this initial funding period, and to enroll up to an additional 1,200 in phases 2 and 3 (total N=2,000).

D. Description, Risks and Justification of Procedures and Data Collection Tools:

Screening and Consent Procedures: Participants will be screened, consented (available through paper and electronic consent process) and will complete questionnaires through an online database with electronic survey capabilities (REDCap) that is HIPAA compliant and can be accessed anywhere with internet access. If needed, REDCap access can be provided in the clinic using a tablet. We have successfully used the REDCap database system for numerous studies involving survey collection and have used online screening and consenting procedures extensively in studies of adults with T1D (including pregnant women) during the Covid-19 pandemic. Study staff will be available to review the consent form with potential participants over the phone, using a HIPAA-compliant video platform such as Zoom, or in person, depending on the circumstances. Screening questions will include the history of T1D in the pregnant woman or father/sibling of the fetus, maternal age, and obstetric history for the pregnant woman, including current pregnancy dates (last menstrual period date, expected date of delivery).

Visit and Specimen Collection Schedule: Study visits and specimen collection (Table 2) will be scheduled at one of the study sites, at one time point for fathers and at four time points for mothers: first trimester (8-<14 weeks), second trimester (14-<28 weeks), third trimester (28+ weeks), and up to 12 weeks postpartum. Medical records will be obtained using medical record release forms for the pregnancy, delivery and post-partum visits, and for the infants' birth records. All study sites have access to electronic health records (EHR) that will allow investigators to obtain medical records for prenatal care and delivery for study participants who deliver within their hospital network, and all sites have protocols in place and experience obtaining records from outside facilities using medical record release forms. At the BDC coordinating center, we have previously collected medical records for pregnancy, delivery and infant birth records and have abstracted these data into REDCap databases. We will follow our established procedures for abstraction of obstetric and newborn records for this study. Maternal and fetal outcomes of women included in this study that are reported to BDC providers will be obtained by manual chart review of EHR charts. Maternal and fetal hospitalizations at any hospital system utilizing EPIC and for whom patients authorize sharing of records can be viewed through EPICS's interoperable sharing tool called Care Everywhere. Manual review of records will be used to obtain specific outcome measures.

All records will be collected and abstracted at the Barbara Davis Center, to maintain quality control standards and to streamline training and oversight of staff.