NDPP-NextGen: A clinical trial to reduce intergenerational obesity and diabetes risks

项目总结 宫内暴露于母亲超重/肥胖和糖尿病会将风险传递给后代，引发 疾病在几代人之间循环。超过一半的美国女性在怀孕时超重或肥胖，约10% 的孕妇受到糖尿病的影响，每年有近200万婴儿接触糖尿病。产前生活方式 干预措施已经得到了很好的研究，但开始得太晚，无法影响怀孕和早孕的关键时期。 在怀孕前开始干预可能是阻止疾病周期的关键。然而，之前的研究是 有限，往往缺乏后代结果(特别是敏感的措施)，包括主要是白人和富人 参与者，并面临着识别可能很快怀孕的女性的挑战。需要对以下问题进行进一步研究 可扩展的战略，以改善未孕和早孕期间的母婴健康，特别是 种族和少数民族或低收入妇女肥胖症和糖尿病患病率高得惊人。这个 国家糖尿病预防计划(NDPP)是一种广泛传播的减肥生活方式干预措施 以及尚未开发的改善母婴健康的潜力的血糖。从实现科学的角度 从角度来看，NDPP的潜在影响比不太可能扩大规模的新干预措施更大， 即使是有效的。自2013年以来，我们已经向1600名成年人提供了NDPP，其中包括350名年轻女性。我们的 初步数据显示，NDPP可能会降低各种低收入女性的围产期风险。而当 年轻妇女在NDPP中的参与有限是一个令人关切的问题，这是增加参与的战略 (激励性的“预备课程”，远程分娩，以及专门为年轻女性开设的课程)前景看好。为 例如，年轻女性在接受会前培训后，参加我们为期12个月的国家发改委的天数增加了2.0% Kg/m2较对照组妊娠早期体重指数降低，A1c降低0.4%。计划一个先入为主的概念 试验中，我们还开发了一种两步筛查方案，以1)使用电子健康记录数据(例如，避孕药 使用)确定更有可能怀孕24个月的女性(36%对所有年轻女性的13%)，以及 2)基于我们的初步数据显示，扩大范围以确认目前的计划生育预期≥60%受孕 73%的人在24个月前受孕，如果他们支持怀孕或性行为活跃，而不是高度 有效的避孕措施。我们提出了一项增强型NDPP(NDPP-NextGen)的随机对照试验 在怀孕前启动，以评估对母婴健康的影响。我们将招募360名年龄在18-39岁的女性 超重/肥胖的年份，他们可能在24个月内怀孕。女性将被随机分配到NDPP- NextGen或常规护理对照组。我们的具体目标是1)评估NDPP-NextGen对周边地区的影响 2)评估NDPP-NextGen对妊娠增重的影响； 3)探讨NDPP-NextGen对新生儿肥胖及妊娠结局的影响。 解释机制。

PROJECT SUMMARY Intrauterine exposure to maternal overweight/obesity and diabetes transmits risks to offspring, triggering a disease cycle across generations. Over half of US women have overweight or obesity at conception and ~10% of pregnancies are affected by diabetes, exposing nearly 2 million infants each year. Prenatal lifestyle interventions are well-studied, yet begin too late to impact the critical period of conception and early pregnancy. Starting interventions before conception may be key to halting the disease cycle. However, prior research is limited, often lacks offspring outcomes (especially sensitive measures), includes mostly white and affluent participants, and has been challenged to identify women likely to conceive soon. Further research is needed on scalable strategies to improve maternal-child health during preconception and early pregnancy, especially for racial and ethnic minority or low-income women with disparately high prevalence of obesity and diabetes. The National Diabetes Prevention Program (NDPP) is a widely-disseminated lifestyle intervention to reduce weight and glycemia that has untapped potential to improve maternal-child health. From an implementation science perspective, the NDPP has greater potential impact than new interventions that are unlikely to be scaled up, even if efficacious. We have delivered the NDPP to >1600 adults since 2013, including >350 young women. Our preliminary data shows that the NDPP may reduce peri-conceptional risks in diverse, low-income women. While limited engagement by younger women in the NDPP is a concern, strategies to increase engagement (motivational “pre-sessions”, remote delivery, and classes specially for young women) are promising. For example, young women attended our 12-month NDPP for 64 days longer after receiving a pre-session, with 2.0 kg/m2 lower preconception BMI and 0.4% lower A1c in early pregnancy, than controls. To plan a preconception trial, we also developed a 2-step screening protocol to 1) use electronic health record data (e.g., contraceptive use) to identify women who are more likely to conceive by 24 months (36% vs. 13% for all young women), and 2) outreach to confirm current family planning to expect ≥60% conception, based on our preliminary data showing that 73% conceived by 24 months if they endorsed intention to conceive or being sexual active without highly effective contraception. We propose a randomized controlled trial of an enhanced NDPP (NDPP-NextGen) initiated before pregnancy to evaluate effects on maternal-child health. We will recruit 360 women aged 18-39 years with overweight/obesity who are likely to conceive within 24 months. Women will be randomized to NDPP- NextGen or a usual care control group. Our specific aims are 1) to assess effects of NDPP-NextGen on peri- conceptional BMI and prenatal glycemia; 2) to assess effects of NDPP-NextGen on gestational weight gain and behavioral outcomes in pregnancy; and 3) to explore effects of NDPP-NextGen on neonatal adiposity and explanatory mechanisms.