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

摘要 在过去的三十年里，儿童肥胖症的发病率出现了惊人的增长。 儿童肥胖会导致心血管危险因素的早期发作，肥胖和心血管风险都会出现。 这些因素可追溯到成年，并导致心血管疾病(CVD)的流行。发展中的 《健康与疾病的起源》理论认为，肥胖和心血管疾病的风险在一定程度上是在子宫内编程的。至 预防肥胖和心血管疾病的早期根深蒂固，在 在儿童早期怀孕对后代风险的影响是至关重要的。令人惊讶的是缺乏研究调查 产前久坐行为(SED)、中等强度到剧烈的体力活动(MVPA)以及 针对这些不利因素的新的24小时行为模式(SED、体力活动和睡眠的组成) 后代的结果。这是一个关键的研究缺口，因为有很强的生理学基础， MVPA和怀孕24小时的行为会影响后代的健康，这些行为是可以改变的 孕期干预目标。这项提案的总体目标是研究SED的关联 (AIM 1)和MVPA(AIM 2)在怀孕期间有子代肥胖风险和24个月的心血管疾病风险。我们 还将使用新的统计方法来确定最佳的24小时行为成分(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24/7全天候怀孕的多中心队列研究(R01 HL153095)，我们预期 使用最先进的技术测量500名怀孕三个月的妇女的SED、体力活动和睡眠 显示器(Actiwatch PAL3Micro和Actiwatch Spectrum Plus)。24/7全天候怀孕还评估其他相关的产前 可能与子女肥胖和心血管疾病风险相关的暴露，即孕前肥胖、妊娠体重 体重增加、饮食、吸烟和不良妊娠结局。直接回应NHLBI的特别通知 感兴趣(非HL-19-695)，我们建议通过在以下人群中进行单独的队列研究来延长妊娠时间 其参与者的后代。在后代研究中，我们建议将母亲接触到的数据与 全天候妊娠，对出生后暴露、肥胖和心血管风险测量进行新的、全面的评估 通过病历摘要、问卷调查和24岁时的亲身研究访问，在孩子的24个月内 月份。我们假设，SED较高或MVPA较低的女性的后代在怀孕期间将会有 BMI Z评分(主要结果)增加更快，肥胖、血压和脉搏波增加更多 24个月的速度。此外，我们假设在统计上将SED中的时间重新分配给体力活动， 但没有睡眠(在睡眠时间足够长的人中)将与更理想的后代结局相关。通过 结合出生前和出生后的暴露数据，我们的方法独特地使我们能够分离出 在儿童早期，妊娠SED、MVPA和24小时行为对子女肥胖和心血管疾病风险的测量。这 该项目将向迫切需要的原始预防干预措施提供信息，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.