Investigation of a new sequential multiple hit model to examine risk and resilience in a prospective longitudinal cohort of children in Ghana

项目摘要 据估计，中低收入国家(LMIC)有2.5亿名5岁以下儿童 由于贫困，他们面临着无法在认知和社会情感发展方面发挥潜力的风险- 相关风险因素。这项提案的长期目标是为循证方案和政策提供信息，以 支持低收入社区的儿童充分成长和发展。虽然许多关于 发展科学中的风险和复原力侧重于单一或少数风险和保护性 因素和时间点，发展是一个动态系统，儿童经常与 风险可能会随着时间的推移而变化并相互影响，而不是个别的不利情况 情况。研究这些关于风险和保护的时机和相互作用的问题面临的挑战 预测发育结果的因素是所需的大样本量、高成本和高人力 收集纵向数据所需的资源投入。这项建议是进行二次分析 在孕期、婴儿期和儿童期收集的现有数据来自国际注册的样本 加纳2009-2012年≤孕期20周的脂质营养补充剂项目(n=1320)。这个 数据集包含30多个生物风险指标(如低出生体重、早产、 生长发育迟缓和贫血)和心理社会风险(如产妇抑郁和缺乏学习 家庭环境中的机会)和多层次的保护因素(包括儿童、家庭和学校) 孕期、出生时、婴儿期(18个月；n=1173)和幼儿园年龄(4-6岁；n=966)。一个 目前正在2020-2021年对8-10岁儿童进行额外的后续评估。这个富有的， 将利用纵向数据集来研究一种新的风险和弹性的连续多次命中模型， 它扩展了临床研究中用来解释癌症等疾病的病因的多重命中模型。 和阿尔茨海默氏症。根据一种多点击打模式，早期的无击打体验可以保护儿童免受 与较晚的击中相关的不良后果，而相反，较早的击中会导致儿童更多 容易受到后来的热门歌曲的影响。将该模型应用于风险和弹性，我们将Hit概念化为高风险敞口 在特定时间点的生物或心理社会风险。这导致了一种假设，即早期的低风险经历 将保护儿童免受与以后的风险暴露相关的不良后果。也就是说，在患有 早期暴露于更大程度的风险，与早期风险暴露较低的人相比，更强的相关性 将在以后的风险暴露和结果之间发现。对计时动态的进一步理解 这种接触的相互作用是设计以风险预防为目标的干预措施的关键第一步，因为 以及促进保护因素，在这些因素最有可能对 孩子们的结局。

Project Summary An estimated 250 million children under five years of age in low- and middle-income countries (LMICs) are at risk of failing to reach their potential in cognitive and social-emotional development because of poverty- related risk factors. The long-term goal of this proposal is to inform evidence-based programs and policies to support children in low-income communities to grow and develop to their full potential. While many studies of risk and resilience in developmental science have focused on singular or a small number of risk and protective factors and time points, development is a dynamic system, and children often contend with constellations of risks that can change over time and interact with each other, rather than isolated instances of adverse circumstances. Challenges for studying these questions about the timing and interactions of risk and protective factors predicting developmental outcomes are the large sample size required and the high cost and human resource investment necessary to collect longitudinal data. This proposal is to conduct secondary analysis of existing data collected during pregnancy, infancy, and childhood from the sample enrolled in the International Lipid-Based Nutrient Supplements Project in Ghana 2009-2012 at ≤ 20 weeks of gestation (n=1320). The dataset contains more than 30 indicators of biological risks (such as low birth weight, premature delivery, growth stunting, and anemia) and psychosocial risks (such as maternal depression and lack of learning opportunities in the home environment), and multilevel protective factors (including child, home and school) during pregnancy, at birth, in infancy (18 months; n=1173), and at kindergarten age (4-6 years; n=966). An additional follow-up assessment is currently being conducted in 2020-2021 at age 8-10 years. This rich, longitudinal dataset will be leveraged to investigate a new sequential multiple hit model of risk and resilience, which expands on multi-hit models used in clinical research to explain the etiology of diseases such as cancer and Alzheimer’s disease. According to a multi-hit model, an early hit-free experience protects children from adverse outcomes associated with later hits, while conversely an early hit causes children to be more susceptible to later hits. Applying this model to risk and resilience, we conceptualize a hit as high exposure to biological or psychosocial risks at a given time point. This leads to the hypothesis that early low risk experience will protect children from adverse outcomes associated with later risk exposures. That is, among children with early exposure to a greater magnitude of risks, versus those with low early risk exposure, stronger associations will be found between later risk exposure and outcomes. Further understanding of the dynamics of the timing and interaction of such exposures is an essential first step to design interventions targeting risk prevention, as well as promotion of protective factors, at the time points when they will most likely show positive impacts on child outcomes.