Improving the survival, growth and developmental of low birth weight newborns through better nutrition

在世界范围内，出生后第一个月内的死亡人数已经占所有儿童死亡人数的近一半。随着年龄较大儿童的存活率比新生儿的存活率提高得更快，这一比例将上升。非洲和亚洲每10名新生儿中就有9名以上死亡，其中每10名新生儿中就有8名以上出生体重不足。风险最大的是非常小的婴儿（出生体重小于1500克），每1000个婴儿中有700个死亡。存活下来的小婴儿往往长期生长发育不良，对家庭和社会造成非常严重的后果。出生时身材矮小主要是由于出生过早（早产），在子宫内发育不良或两者兼而有之。不幸的是，我们没有有效的干预措施来防止这两个问题。因此，这些小婴儿是一个越来越大的挑战，特别是在较贫穷的国家。我们知道，生命早期的营养和生长对于身体器官的发育至关重要，包括大脑，并能够抵御导致许多新生儿死亡的感染。改善营养和最佳生长也可以预防在较贫穷国家的晚年生活中重要的疾病，如肺病。然而，实现小婴儿的最佳营养仍然是一个巨大的挑战，特别是通过静脉进行高质量、安全的喂养，弥补出生和完全口服喂养之间的差距，在资源匮乏的国家很难获得。此外，早产儿肠道的结构和功能还不成熟，过快地进行口服喂养可能会导致危及生命的肠道损伤。不成熟的肠道不仅难以科普牛奶饲料，而且还允许肠道细菌进入体内并引起感染。小婴儿通常需要在新生儿病房（NNUs）护理4-6周或更长时间，这正是他们的肠道可以定植对可用抗生素具有耐药性的危险细菌的地方。很少有研究告诉我们如何最好地喂养贫穷国家的NNUs的小婴儿。即使是基本的原则，如何时引入饲料和如何快速饲料可以安全地增加仍然不清楚。此外，较富裕的国家正在制定一些有希望的干预措施，这些措施在资源匮乏的环境中很可能是相关的、可行的和负担得起的。这些措施包括使用益生菌（安全、“健康”的细菌）和母乳中的成分（“乳铁蛋白”）的营养补充剂，以预防肠道感染和提高婴儿的免疫力。我们将建立一个由6个NNU（4个尼日利亚/2个肯尼亚）组成的核心网络，将非洲临床医生和研究人员以及新生儿营养、肠道健康和长期肺和大脑发育方面的国际专家联系起来。该网络将在那些先前研究经验有限的非核国大学进行能力建设，并吸引新到较贫穷国家工作的研究人员参与。在尼日利亚和肯尼亚举办的讲习班将使该小组能够记录目前的做法，分享实际喂养问题的经验，并审查可能的干预措施以进行测试。诊断常见问题（如感染）的标准国际标准将适用于整个网络，我们将建立一个数据库，以共享重要的临床信息。我们将测试新的方法来检测使细菌对抗生素产生耐药性的基因，并测量小体积血液样本中的关键营养素。我们还将保存样本以供日后研究。我们将确保我们开发的流程即使在资源较少的情况下也可以实现，以便它们可以推广到其他NNU以扩展网络。我们的目标是通过更好的营养改善低出生体重婴儿的生存、生长和发育。我们将建立的网络和流程将使我们能够设计和实施大规模的临床试验，以促进这些最脆弱婴儿的护理。

Worldwide, deaths in the first month of life already account for nearly half of all child deaths. This proportion is set to rise as survival in older children is improving faster than in newborns. More than 9 in 10 newborn deaths occur in Africa and Asia and more than 8 in 10 of these deaths are in babies with low birthweight. The greatest risk is in very small babies (birthweight less than 1500g) where as many as 700 of every 1000 die. Small babies who survive often have poor longer-term growth and development posing highly significant consequences for families and societies.Being small at birth is due mainly to being born too early (preterm), not growing well in the womb or a combination of both. Unfortunately, we do not have effective interventions to prevent either of these problems. Therefore, these small babies are a growing challenge especially in poorer countries.We know that nutrition and growth in early life are critically important for the development of the body organs, including the brain, and being able to fight-off the infections that cause many newborn deaths. Improved nutrition and optimal growth may also prevent diseases that are important in later life in poorer countries such as lung disease. However, achieving optimal nutrition in small babies remains a huge challenge especially as high quality, safe feeding through the veins, that bridges the gap between birth and full oral feeding, is rarely available in low-resource countries. In addition, the structure and function of the gut in preterm babies is immature and advancing oral feeds too quickly may cause life-threatening gut damage. The immature gut not only struggles to cope with milk feeds but also allows gut bacteria to cross into the body and cause infection. Small babies often need nursing in neonatal units (NNUs) for 4-6 weeks or more and this is exactly where their gut can be colonized with dangerous bacteria that are resistant to the available antibiotics. There has been little research to tell us how best to feed small babies in NNUs in poorer countries. Even basic principles such as when to introduce feeds and how quickly feeds can be increased safely remain unclear. In addition, there are several promising interventions being developed in richer countries that may well be relevant, feasible and affordable in low-resource settings. These include using nutritional supplements of probiotics (safe, "healthy" bacteria) and components in breast milk ("lactoferrin") to prevent gut infections and boost the baby's immunity.We will establish a core network of 6 NNUs (4 Nigeria/2 Kenya) linking African clinicians and researchers together and with international experts in newborn nutrition, gut health and longer-term lung and brain development. The network will build capacity in those NNUs with limited previous research experience and also engage researchers who are new to working in poorer countries. Workshops in Nigeria and Kenya will allow the team to document current practices, share experience of practical feeding problems and review possible interventions for testing. Standard international criteria for the diagnosis of common problems (such as infection) will be adapted for use across the network and we will set-up a database to share essential clinical information. We will test novel methods to detect genes that make bacteria resistant to antibiotics and to measure key nutrients in small volume blood samples. We will also store samples for later research. We will ensure that we develop processes that are achievable even with low-resources so that they can be rolled-out to other NNUs to expand the network. Our goal is to improve survival, growth and development in low birthweight babies through better nutrition. The network and processes that we will establish will enable us to design and implement the large-scale clinical trials that will be needed to advance care in these most vulnerable infants.