Fetal and Early Postnatal Influences on Child Metabolic Health After Gestational Diabetes

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Gestational diabetes mellitus (GDM), defined as glucose intolerance first recognized during pregnancy, is a heterogeneous condition and the most common obstetric disorder affecting ~240,000 or ~8% of U.S. pregnant women per year. Fetal exposure to GDM is linked with adverse perinatal outcomes, and higher adiposity, obesity, dysglycemia, and type 2 diabetes during childhood and adolescence. Much less is known about the impact of early postnatal factors [breastfeeding, infant diet including sugar-sweetened beverages (SSB), juice, behaviors, sleep habits] on future adiposity and metabolic health of children exposed to GDM in utero, because previous studies have rarely prospectively assessed any early postnatal factors, except current breastfeeding (BF) at birth or age 3 months (Y/N). Thus, it is unknown whether these modifiable early postnatal factors exert persistent effects on future child adiposity and metabolic health independent of fetal exposure to GDM severity and maternal obesity. This represents a major gap for human studies because animal experiments found that manipulation of postnatal nutrition can ameliorate the adverse effects of fetal exposure to maternal diabetes. The Study of Women, Infant Feeding and Type 2 Diabetes after GDM (SWIFT) is a prospective cohort of 1,035 women with GDM [R01HD050625] recruited during pregnancy (within a single integrated healthcare system) and longitudinally assessed at 3 in-person research visits from 6-9 weeks post-delivery (baseline 2008-2011) and annually up to 2 y post-baseline. Each research visit included 2-h 75 g research OGTTs and assessments of maternal anthropometry, lifestyle behaviors, socio-demographics, and health status under standardized protocols. Monthly mailed surveys, phone calls, and 3 in-person study visits prospectively assessed early postnatal factors [breastfeeding duration and intensity, infant diet including sugar-sweetened beverages (SSB), fruit juice, sleep habits and temperament]. The study also obtained GDM severity measures (3-h 100 g OGTT, GDM treatment, gestational age at diagnosis), perinatal outcomes, and additional clinical data (mother/child weight, height, diabetes diagnoses, health outcomes) from electronic health records (EHR). SWIFT research data have been supplemented by EHR data since its inception and updated annually during follow up since baseline with excellent cohort retention through 2 y post-baseline and beyond (78% are KP members in 2019). The proposed SWIFT Child Study efficiently leverages the currently funded [R01DK118409] 4th in-person research visit at 10 y post-baseline in SWIFT women (Fall 2019-2022). This represents a time-sensitive opportunity to conduct concurrent research visits in their children at age ~10 y (prior or proximate to puberty) with continued prospective follow up from fetal life through the early postnatal period and beyond. The SWIFT Child Study will be one of the first to measure GDM severity under treatment in relation to child metabolic health, and the first prospective study to rigorously assess the lasting independent influences of key early postnatal factors on growth, adiposity, and metabolic health in youth exposed to maternal GDM in utero.