Sedentary behavior, physical activity, and 24-hour behavior in pregnancy and offspring health: the Pregnancy 24/7 Offspring Study

摘要 在过去的三十年中，儿童肥胖症的发病率出现了惊人的增长。 儿童肥胖导致心血管危险因素过早发生，肥胖和心血管风险两者兼而有之 这些因素会一直延续到成年并导致心血管疾病（CVD）的流行。发展性的 健康与疾病起源理论认为，肥胖和心血管疾病的风险部分是在子宫内设定的。至 为了防止这种早期陷入肥胖和心血管疾病的情况，识别可改变的母体因素 怀孕对幼儿期后代风险的影响至关重要。令人惊讶的是缺乏研究调查 产前久坐行为 (SED)、中等至剧烈强度的体力活动 (MVPA) 和 针对这些不良行为的新型 24 小时行为范式（SED 的组成、体力活动和睡眠） 后代的结果。这是一个关键的研究空白，因为 SED 有强有力的生理学原理， MVPA 和怀孕期间的 24 小时行为可能会影响后代的健康，并且这些行为是可以改变的 妊娠期干预的目标。该提案的总体目标是审查 SED 的协会 （目标 1）和 MVPA（目标 2）贯穿整个妊娠期，影响后代肥胖风险和 CVD 风险直至 24 个月。我们 还将使用新颖的统计方法来确定最佳 24 小时行为组合（目标 3） 怀孕与降低这些不良后代结局的风险有关。我们可以通过以下方式实现这些目标 利用我们正在进行的多中心队列研究 Pregnancy 24/7 (R01 HL153095)，我们前瞻性地 使用最先进的技术测量 500 名女性在怀孕每个三个月的 SED、体力活动和睡眠 监视器（activPAL3 micro 和 Actiwatch Spectrum Plus）。 Pregnancy 24/7 还评估其他相关的产前检查 可能与后代肥胖和心血管疾病风险相关的暴露，即孕前肥胖、妊娠体重 体重、饮食、吸烟和不良妊娠结局。直接回应 NHLBI 的特别通知 兴趣（NOT-HL-19-695），我们建议通过在其中进行一项单独的队列研究来扩大怀孕 24/7 其参与者的后代。在后代研究中，我们建议结合来自 怀孕 24/7，对产后暴露、肥胖和 CVD 风险措施进行新的全面评估 通过病历摘要、问卷调查以及 24 岁时的现场研究访问，对儿童 24 个月内的情况进行调查 几个月。我们假设怀孕期间 SED 较高或 MVPA 较低的女性的后代将患有 BMI Z 分数（主要结果）增加更快，肥胖、血压和脉搏波更严重 24 个月内的速度。此外，我们假设统计上 SED 中的时间重新分配给体力活动， 但睡眠（在充足睡眠时间的人中）不会与更理想的后代结果相关。由 结合产前和产后暴露数据，我们的方法独特地使我们能够隔离 妊娠 SED、MVPA 和 24 小时行为对后代肥胖和幼儿期 CVD 风险测量的影响。这个 该项目将告知迫切需要的原始预防干预措施，以降低肥胖和心血管疾病的风险。

ABSTRACT Over the past three decades, there has been an alarming increase in the incidence of childhood obesity. Childhood obesity leads to early onset of cardiovascular risk factors, and both obesity and cardiovascular risk factors track into adulthood and contribute to the epidemic of cardiovascular disease (CVD). The Developmental Origins of Health and Disease theory posits that risk for obesity and CVD is, in part, programmed in utero. To prevent this early entrenchment into obesity and CVD, identification of modifiable maternal factors during pregnancy that later impact offspring risk in early childhood is essential. A surprising lack of research investigates the role of prenatal sedentary behavior (SED), moderate-to-vigorous-intensity physical activity (MVPA), and the novel 24-hour behavior paradigm (the composition of SED, physical activity, and sleep) on these adverse offspring outcomes. This is a critical research gap because there is strong physiological rationale that SED, MVPA, and 24-hour behavior in pregnancy could influence offspring health, and these behaviors are modifiable targets for intervention during pregnancy. The overall goal of this proposal is to examine the associations of SED (Aim 1) and MVPA (Aim 2) across pregnancy with offspring obesity risk and CVD risk through 24 months. We will also use novel statistical methods to determine the optimal 24-hour behavior compositions (Aim 3) during pregnancy associated with reduced risk of these adverse offspring outcomes. We can achieve these aims by leveraging our ongoing, multi-center cohort study Pregnancy 24/7 (R01 HL153095), where we are prospectively measuring SED, physical activity, and sleep in 500 women in each trimester of pregnancy using state-of-the-art monitors (activPAL3 micro and Actiwatch Spectrum Plus). Pregnancy 24/7 also assesses other relevant prenatal exposures that may associate with offspring obesity and CVD risk, i.e., pre-pregnancy obesity, gestational weight gain, diet, smoking, and adverse pregnancy outcomes. In direct response to the NHLBI’s Notice of Special Interest (NOT-HL-19-695), we propose to expand Pregnancy 24/7 by conducting a separate cohort study among the offspring of its participants. In the Offspring Study, we propose to combine maternal exposure data from Pregnancy 24/7 with new, comprehensive assessments of postnatal exposures, obesity, and CVD risk measures in the child through 24 months via medical record abstraction, questionnaires, and an in-person study visit at 24 months. We hypothesize that offspring of women with higher SED or lower MVPA across pregnancy will have more rapid increases in BMI Z-score (primary outcome), and greater adiposity, blood pressure, and pulse wave velocity through 24 months. Further, we hypothesize that statistically reallocating time in SED to physical activity, but not sleep (among adequate duration sleepers) will be associated with more optimal offspring outcomes. By combining prenatal and postnatal exposure data, our approach uniquely allows us to isolate the effects of pregnancy SED, MVPA, and 24-hr behavior on offspring obesity and CVD risk measures in early childhood. This project will inform critically needed primordial prevention interventions to decrease the risk of obesity and CVD.