Maximising the public health impact of a human milk bank

母乳非常复杂，包含数千种因素，这些因素指导发育，保护婴儿免受感染，并训练他们的免疫系统识别危害。母乳喂养也给母亲带来了重大的健康益处，但这些好处在很大程度上是未知的，也无法解释。此外，近几十年来，在母亲母乳供应不足的情况下，向患病婴儿提供经过筛选的捐赠母乳的母乳银行一直受到限制，这意味着捐赠的母乳现在只分配给最早产的婴儿。英国没有专门的母乳研究中心，世界上也没有几个中心专注于母乳喂养对母亲健康的影响。两年前，我创建了英国第一家独立的非营利性母乳公司，为启动一个由三个研究项目组成的创新项目奠定了基础，每个项目都将为更大规模的有影响力的研究和临床进步奠定基础。这三个项目总结如下：1：已知基因突变会导致乳腺癌(例如BRCA1突变)，但对表观遗传风险知之甚少。表观遗传学描述了对DNA的修饰，以调节有多少DNA转化为蛋白质。表观遗传模式是组织特有的，因此在乳腺细胞中检测到的模式不同于其他组织，如血液。之前的研究，包括我们自己的工作，已经在血液DNA的DNA中确定了乳腺癌风险的表观遗传模式。我们已经发现了不同的癌症风险因素，如吸烟、酒精和BMI，影响这些模式的证据。然而，很难将这些发现推论到乳房组织。母乳含有大量来自乳腺导管内层的细胞，这些细胞与可能患乳腺癌的细胞类型相同。许多导致乳腺癌的分子变化可能在癌症发展之前很久就发生了，并可能在这些细胞中被检测到。首先，我将招募更多的受试者加入我们的研究队列，使其至少达到300名受试者。我们将评估已知的表观遗传风险标记物，包括衰老、吸烟、酒精和BMI。该项目将提供正常乳腺细胞早期变化的证据，并为这些变化如何增加风险提供重要的生物学见解。最后，这项工作将提供所需的证据，以创建一项针对2万名女性的大型母乳研究，以开发新的癌症筛查测试。2：世界卫生组织建议儿童母乳喂养至少2年，但关于6个月以上母乳成分的数据很少。我们将招募45名母亲，在至少两年的时间里，每3个月提供一次牛奶样本，并分析每个样本中的1000种脂肪酸，以了解牛奶成分的变化。这些信息将指导母乳捐赠者的招募，解决6个月以上母乳喂养的价值，并为未来针对有特殊营养需求的婴儿提供母乳的研究提供信息。3：早产仅几周的婴儿，即所谓的晚期早产儿，比足月婴儿死亡和健康不佳的风险更高。他们的体重通常很好，而且大多数情况下不需要呼吸方面的帮助，但仍然有微妙的问题。其中一个问题是建立母乳喂养的机会较低。与接受配方奶的婴儿相比，只接受母乳或捐赠者母乳的极早产儿在短期和长期内都表现得更好。婴儿接受捐赠母乳的母亲将其视为表达或哺乳的“桥梁”。我们将招募120名早产较晚的婴儿和母亲，随机让他们接受捐献的母乳，并与支持哺乳的配方奶粉进行比较，以评估这是否有助于母亲建立母乳喂养。本次奖学金解决的三个问题旨在帮助提高英国的母乳喂养率，英国20多年来一直是世界上母乳喂养率最差的国家之一。这一奖学金为推动变革提供了一个独特的机会。

Human milk is hugely complex, containing thousands of factors that guide development, protect babies from infections, and train their immune system to recognise harms. Breastfeeding also gives major health benefits to mothers, but these are largely unknown and unexplained. Furthermore, human milk banks, which provide screened donated breast milk to sick infants when a mother's milk supply is insufficient, have been restricted in recent decades, meaning donor milk is now rationed to only the most preterm babies.The UK has no dedicated centre of research into human milk, and few centres in the world focus on the maternal health impact of breastfeeding. Having founded the first independent non-profit human milk in the UK 2 years ago, I have laid the groundwork to launch an innovative programme of three research projects, each of which will lay the foundations for a larger body of impactful research and clinical advances. The three projects are summarised:1: Genetic mutations are known to cause breast cancer (e.g. BRCA1 mutations), but much less is known about the epigenetic risk. Epigenetics describes the modifications to DNA that regulate how much of the DNA is turned into proteins. Epigenetic patterns are tissue-specific, so patterns detected in breast cells are different to other tissues such as blood. Previous research, including our own work, has identified epigenetic patterns of breast cancer risk in the DNA of blood DNA. We have found evidence that different cancer risk factors, such as smoking, alcohol and BMI, influence these patterns. However, it is difficult to extrapolate these findings to breast tissue. Breast milk contains a large number of cells from the lining of the breast ducts that are the same cell type that may develop breast cancer. Many of the molecular changes that cause breast cancer may occur long before the cancer has developed and may be detectable in these cells. First, I will recruit more subjects into our research cohort to reach a minimum of 300 subjects. We will assess known epigenetic markers of risk including aging, smoking, alcohol and BMI. This project will provide evidence of early changes in normal breast cells and provide important biological insights into how these increase risk. Finally, this work will provide the evidence needed to create a large study of milk from 20,000 women to develop new cancer screening tests.2: The World Health Organisation recommends children are breastfed for at least 2 years, but only tiny amounts of data exists on the composition of human milk beyond 6 months. We will recruit 45 mothers to give samples of milk every 3 months over at least 2 years, and profile each sample for the 1000s of fatty acids to understand how milk composition changes, if at all. This information will guide milk donor recruitment, address the value of breastfeeding beyond 6 months, and inform future studies of targeting donor milk for babies with specific nutritional needs.3: Babies born just a few weeks prematurely, so-called late preterm babies, have a higher risk of death and ill health than full-term babies. They are often a good weight and mostly do not need help with breathing, but still have subtle problems. One of these problems is a lower chance of establishing breastfeeding. Extremely premature babies who receive only mother's milk or donor milk do better in both the short- and long term compared to those who receive formula. Mothers whose babies receive donor milk see it as a 'bridge' to expressing or breastfeeding. We will recruit 120 babies and mothers born late preterm and randomise them to receive donor milk compared to formula with lactation support to assess whether this helps mothers to establish breastfeeding.The three questions addressed in this Fellowship aim to help improve the UK's breastfeeding rates, which have been among the worst in the world for more than two decades. This Fellowship presents a unique opportunity to drive change.