Epidemiologic studies of maternal and early life metabolic risk

National Institute Of Diabetes And Digestive And Kidney Diseases

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Abstract

The ETCHED study will establish a longitudinal cohort of mother/infant/child dyads among American Indian/Alaska Native (AI/AN) and Hispanic ethnic groups, to study the role of a combination of biological and environmental factors on infant/childhood obesity and cardio metabolic risk. Both Hispanic and AI/AN children have high prevalence of childhood obesity and associated metabolic risk. Prior research conducted at NIDDK, Phoenix, have shown that approximately 50% of children from diabetic pregnancies among Indigenous American populations in the southwestern United States develop type 2 diabetes by 25 years of age (Pettitt DJ, et al. NEJM, 1983). Since intrauterine exposure to diabetes leads to a higher risk of diabetes in the offspring, the risk might be greatly diminished by preventing diabetes during pregnancy or ameliorating its effects. The ETCHED study participants are from both Hispanic and AI/AN urban communities residing in the Phoenix Metropolitan Area in Arizona, and each community shares common cultural beliefs, norms, and experience similar environmental and health exposures, scientific observations from a longitudinal study that follows the health status of the population may be very informative for both these high-risk population groups in framing health policy decisions. The ETCHED study, supported by the NIDDK Division of Intramural Research Program, plans to recruit up to 750 pregnant mothers and and follow them through pregnancy, childbirth, and then the maternal/child dyad until the offspring's 18th birthday. The study is approved by the NIH IRB and registered at https://clinicaltrials.gov/ct2/show/NCT03481829. Patient enrollment in ETCHED is planned for a period of 5-years (April 2022-April 2027), and the total study duration for the ETCHED parent study is 23-years. There are currently ~170 women enrolled in pregnancy who are in active follow up, with ~150 deliveries completed, and ~ 77 mothers have completed their 12-month postpartum follow up research exam. The study has completed ~1,200 research visits. The ETCHED study is highly innovative. Recently with additional support received from the NIH Bench to Bedside grant award (2024-2025), we are examining the gut microbiome structure and function in mothers and their offspring in this high-risk cohort. The ETCHED study is significant because it adds to the scientific knowledge of obesity and metabolic risk from a biological perspective in a high-risk understudied population. One of the strengths of the ETCHED study has been successful development of a collaborative framework within the NIH Intramural Research Program (IRP) and engaging with other investigators and leveraging their expertise in conducting detailed molecular measurements of maternal/fetal-infant bio samples. There is now a potential to integrate the different types of ongoing measurements including, lipidomic, metabolomic analysis from maternal and offspring plasma samples, and gut microbial analysis, into an omics-based multidimensional dataset that provides deep insights into the biological basis of obesity and its related metabolic conditions.