Comparing Glycemic Profiles in Pregnancy and Maternal and Child Health Outcomes

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Four million women undergo a 50 gram glucose tolerance test at 24-28 weeks gestation annually in the United States. This universal screen for gestational diabetes mellitus (GDM) is intended to improve health and reduce costs by allowing for treatments that will reduce the known complications associated with GDM. However, as currently screened for, diagnosed, and treated, offspring born to women with GDM are still at much higher risk for childhood obesity compared to the offspring of women without GDM. These female children born to women with GDM are more likely to become obese adults and because GDM risk is dependent on maternal body mass index, these women will be more likely to have GDM themselves when they become pregnant. This cycle of GDM leading to increasingly obese future generations can only be broken with a better understanding of the maternal glycemic profile during gestation so that the timing and types of dysglycemia most associated with pregnancy complications, including childhood obesity, can be identified. The overall objective of this application is to leverage Brown University/Women & Infants Hospital's considerable pregnancy research infrastructure, high rates of early prenatal care, large delivery volume, and track record of successful clinical research in diabetes in pregnancy to ensure this collaborative cohort study investigating maternal glycemia in pregnancy is a success. Brown University/Women & Infants Hospital will enroll at least 400 women (of the 2000 total enrollment) in the first trimester of pregnancy and follow them and their offspring until the children are two years of age. While the final aims will be determined by a steering committee of all participating centers, the following specific aims are proposed: 1) Utilize continuous glucose monitoring (CGM) at 5 time points during gestation (first trimester, early second trimester, 24-28 weeks, third trimester, and post-partum) to better understand critical values and time periods when dysglycemia is associated with pregnancy, and neonatal or early childhood complications, including adiposity and body mass index z-score >85th percentile at 2 years of life; 2) create a biobank of maternal serum at the 5 time points that will be used to compare traditional glucose tests (fasting, glycosylated hemoglobin, and glucose challenge) to CGM results to determine optimal screen-positive cut-offs; 3) use decision modeling to assess the costs and effects to US health care of any changes to the timing or modality of GDM testing in pregnancy. If successful, this project will result in a more complete understanding of glycemic changes over gestation, identify critical measures and gestational age windows most associated with morbidity, and determine the optimal screening test to identify clinically significant dysglycemia. This will allow glucose testing in pregnancy to be re-designed to achieve both a healthier next generation and fiscal savings.