Born Very Preterm: A Natural Experiment of How Early Adversity and Social Environment affect Life Course Development (Preterm-Lifecourse)

疾病起源的发育理论认为，发育和寿命的个体差异始于子宫。这些发病理论预测，生命早期身体的逆境可能导致疾病和早期死亡。与此相反，生活史理论认为，童年早期的逆境会改变发育的速度，从而导致衰老的提前。但是如何才能改变走向疾病或权衡的发展轨迹呢？我们建议VP出生（妊娠<32周）作为早期逆境如何导致整个生命过程中发育可塑性的自然实验。我将使用全新的方法来研究核心问题：VP的出生如何导致长期的不适应，或者在适当的环境条件下，如何导致适应性发展？第一个关键挑战是确定什么是合适的环境条件，以及它们与早期逆境的关系是什么机制？第二个挑战是研究风险或保护性环境是否会进入大脑并改变大脑结构？第三，保护性环境能否减缓大脑、生理和表观遗传加速老化？第四个挑战是调查早期的逆境如何影响下一代。副副总裁的繁殖成功率是否较低，性别比例是否不同（Trivers-Willard假说），父母对副副总裁后代的投资是否较少？为了解决这些问题，我将在不同的队列中结合对VP和从出生到成年的足月的研究，并在一个队列中对大脑、环境、表观遗传学和功能发育进行深入研究。我测试了不同的发展模型，它们对环境如何与早期逆境相互作用做出了不同的预测。对儿童早期逆境和环境如何影响一生适应的机制的进一步了解，对生命历程理论和干预措施具有重要意义。

Developmental theories of origin of diseases propose that individual differences in development and longevity start in the womb. These pathogenetic theories predict that adversity to the body early in life may lead to disease and early mortality. In contrast, Life History theories propose that early childhood adversity change the speed of development with trade-offs such as earlier ageing. But how can developmental trajectories heading towards disease or trade-offs be altered? We propose VP birth (<32 weeks' gestation) as a natural experiment of how early adversity may nevertheless lead to developmental plasticity across the life course. I will use radically new approaches to study the core question: How does VP birth result in either long term maladaptation or alternatively, under the right environmental conditions, to adaptive development?The first key challenge is to identify what are the right environmental conditions and what are the mechanisms of how they relate to early adversity? The second challenge is the study of whether risk or protective environments get into the brain and alter brain structure? Thirdly, can protective environments reduce accelerated brain, physiological, and epigenetic ageing? The fourth challenge is to investigate how early adversity affects the next generation. Do VP have lower reproductive success, a different sex-ratio (Trivers-Willard hypothesis), and do parents invest less in VP offspring? To address these questions, I will combine study of VP and term born from birth into adulthood across various cohorts with an intensive study of brain, environment, epigenetics and functional development within one cohort. I test alternative developmental models where they make different predictions of how the environment may interact with early adversity. The increased understanding of the mechanisms of how early childhood adversity and environment accounts for lifespan adaptations has implications for life course theory and interventions.