Physiological function in children with stunting in rural Zimbabwe

营养不良影响着全球四分之一的儿童。发育迟缓，即儿童长得不像他们的年龄应有的那样高，导致他们成年后因高血压、心脏病和糖尿病等疾病而健康状况不佳。由于这些情况经常同时发生在同一个人身上，我们称之为“多重病”。我们并不完全了解为什么生长不良会增加患这些疾病的风险，但我们想要验证这样一个理论，即身材矮小会伴随着重要器官的生长不良和功能障碍。我们想探索器官损伤的迹象是否在儿童时期就已经很明显了，以及强化营养干预是否也有助于他们的肌肉、骨骼和器官在9岁时生长得更健康。强化营养干预有助于儿童在生命的头2年长高。我们认为，在发育迟缓的儿童中，炎症（身体对伤害或感染的正常反应）过度，会进一步损害关键器官的发育和功能，并导致终身不健康的风险。如果这是真的，仅靠营养干预可能是不够的，我们需要找到新的方法来解决身体的炎症反应，以阻止进一步的器官损伤。我们将跟踪津巴布韦农村的一组儿童，他们参加了之前的一项临床试验，该试验随机分配（就像抛硬币一样）一些儿童在生命的前18个月接受营养补充剂，一些儿童接受常规家庭饮食。接受营养补充的孩子在18个月大时长高了，发育迟缓的可能性也更小。这些孩子现在已经9岁了，这为我们提供了一个机会来调查发育迟缓的长期影响，并探索营养干预是否对健康有持续的好处。我们会对孩子的肌肉质量，骨骼强度，肺大小，心脏功能，肾脏长度，体内脂肪量，以及孩子控制血糖水平的能力进行详细的测试，看看生长不良是否会影响孩子在童年中期的身体功能。这些可能是终生患病风险的“早期预警信号”，因为我们知道，例如，儿童肺部的大小会影响到成年后的生活，而肺功能不佳与过早死亡的风险有关。我们可以比较儿童早期是否服用营养补充剂的测试结果，看看那些因服用营养补充剂而长高的孩子现在是否骨骼和肌肉更强壮，肺和肾脏更大，心脏功能更好，体脂更少。最后，通过使用9岁时采集的血液样本，我们可以验证我们的理论，即儿童时期持续存在高水平的炎症，并与器官功能下降有关。如果发育迟缓的儿童在学龄期就有器官功能低下的迹象，那么这表明发育迟缓对成人疾病（如心脏病发作）的终身影响已经在儿童时期出现。我们认为预防应该从小就开始。如果我们发现营养补充剂对儿童的骨骼、肌肉和器官有长期的好处，这就向政策制定者提供了一个非常有力的信息：我们应该加大力度，在儿童出生后不久补充饮食，因为这种好处可能会延续到儿童中期甚至更久。如果我们发现身体的炎症过程正在导致持续的器官损伤，那么在学龄期可能仍然有机会进行干预，阻止这种损伤的进展，而不是等到高血压和糖尿病等疾病在成人生活中变得明显。这项研究将提供我们设计应对炎症的新方法所需的信息——比如改变饮食、锻炼计划或抗炎药物——以阻止损害，并确保所有儿童都能成为健康和有生产力的成年人。

Undernutrition affects a quarter of children globally. Stunting, when children do not grow as tall as they should for their age, leads to ill-health into adult life due to diseases like high blood pressure, heart attacks and diabetes. Since these conditions often occur together in the same person, we call this "multimorbidity". We do not fully understand why poor growth increases the risk of these diseases, but we want to test the theory that short stature is accompanied by poor growth and function of vital organs. We want to explore whether signs of organ damage are already apparent in childhood, and whether an intensive nutrition intervention - which helped children to grow taller in the first 2 years of life - also helps their muscles, bones, and organs grow more healthily by the time they reach 9 years of age. We believe that inflammation (the body's normal response to wounding or infection) is excessive in children with stunting, further damaging the development and function of key organs, and leading to a lifelong risk of ill-health. If this is true, nutrition interventions alone may not be enough, and we need to find new ways to tackle the body's inflammatory response to stop further organ damage.We will follow up a group of children in rural Zimbabwe who were enrolled into a previous clinical trial, which randomised (like the flip of a coin) some children to receive nutritional supplements in the first 18 months of life, and some children to receive their regular household diet. The children who received the nutritional supplements grew taller and were less likely to be stunted at 18 months of age. These children are now turning 9 years old, and this provides a chance for us to investigate the long-term effects of stunting, and to explore whether the nutrition intervention has sustained health benefits. We will do detailed testing of children's muscle quality, bone strength, lung size, heart function, kidney length, the amount of fat in the body, and how well a child can control their blood sugar levels, to see whether poor growth affects how children's bodies function by mid-childhood. These might be 'early warning signs' of a lifelong risk of disease, because we know that the size of a child's lungs, for example, tracks into adult life, and that poor lung function is linked to a risk of early death. We can compare test results between children who did or did not get the nutritional supplements in early life, to see whether the children who grew taller due to the supplements now have stronger bones and muscles, bigger lungs and kidneys, better heart function, and less body fat. Finally, by using blood samples collected at 9 years of age, we can test our theory that high levels of inflammation persist during childhood and are associated with reduced organ function. If children with stunting have signs of poor organ function at school age, then it suggests the lifelong impact of stunting on adult diseases like heart attacks is already emerging in childhood. We think prevention should start very early in life. If we find that the nutritional supplements have had long-term benefits for children's bones, muscles and organs, this provides a very powerful message to policymakers: we should be scaling up our efforts to supplement children's diets soon after birth, because the benefits may stretch into mid-childhood and beyond. If we find that the body's inflammatory processes are driving ongoing organ damage, there may still be an opportunity to intervene at school age, to stop progression of this damage, rather than waiting for conditions like high blood pressure and diabetes to become apparent in adult life. This study would provide the information we need to design new approaches that can tackle inflammation - such as dietary changes, exercise programmes, or anti-inflammatory drugs - to halt the damage, and ensure that all children can become healthy and productive adults.