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

妊娠期糖尿病（GDM），定义为妊娠期间首次发现的葡萄糖耐受不良，是一种异质性疾病，也是最常见的产科疾病，每年影响约24万或约8%的美国孕妇。胎儿暴露于GDM与不良的围产期结局、儿童期和青春期较高的肥胖、肥胖、血糖异常和2型糖尿病有关。关于早期产后因素[母乳喂养，婴儿饮食包括含糖饮料（SSB），果汁，行为，睡眠习惯]对子宫内暴露于GDM的儿童未来肥胖和代谢健康的影响知之甚少，因为以前的研究很少前瞻性地评估任何早期产后因素，除了出生时或3个月时的母乳喂养（BF） （Y/N）。因此，尚不清楚这些可改变的早期产后因素是否会对未来儿童肥胖和代谢健康产生持续影响，而不受胎儿暴露于GDM严重程度和母亲肥胖的影响。这代表了人类研究的一个主要空白，因为动物实验发现，操纵产后营养可以改善胎儿暴露于母体糖尿病的不利影响。GDM后妇女、婴儿喂养和2型糖尿病研究（SWIFT）是一项前瞻性队列研究，纳入1035名妊娠期（在单一综合医疗系统内）GDM妇女[R01HD050625]，并在分娩后6-9周（2008-2011年基线）和每年基线后2年进行3次亲自研究访问，纵向评估。每次研究访问包括2小时75克研究ogtt，并根据标准化方案评估产妇的人体测量、生活方式行为、社会人口统计学和健康状况。每月的邮寄调查、电话调查和3次面对面的研究访问前瞻性地评估了早期产后因素[母乳喂养的持续时间和强度，婴儿饮食包括含糖饮料（SSB）、果汁、睡眠习惯和气质]。该研究还从电子健康记录（EHR）中获得了GDM严重程度测量（3小时100克OGTT、GDM治疗、诊断时的胎龄）、围产期结局和其他临床数据（母亲/儿童体重、身高、糖尿病诊断、健康结局）。SWIFT的研究数据自成立以来一直得到电子病历数据的补充，并在基线后的随访期间每年更新一次，基线后两年及以后的队列保留率都很好（2019年78%是KP成员）。拟议的SWIFT儿童研究有效地利用了目前资助的[R01DK118409]在基线后10年对SWIFT女性进行的第四次亲自研究访问（2019-2022年秋季）。这是一个时间敏感的机会，可以对10岁（青春期之前或接近青春期）的孩子进行同步研究访问，并从胎儿期到产后早期及以后进行持续的前瞻性随访。SWIFT儿童研究将是第一个测量治疗中GDM严重程度与儿童代谢健康之间关系的研究之一，也是第一个严格评估关键产后早期因素对子宫内暴露于母体GDM的青少年生长、肥胖和代谢健康的持久独立影响的前瞻性研究。

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.