Professor José Villar und Professor Stephen Kennedy

Professor José Villar und Professor Stephen Kennedy
University of Oxford, Studienleiter, INTERPRACTICE-21st

Bis heute wurden die INTERGROWTH-21st-Wachstumsstandards und Ernährungsprotokolle für Frühgeborene in Tausenden von medizinischen Einrichtungen in 195 Ländern und Regionen eingeführt. Was ist INTERPRACTICE-21st und wozu dient es?

Professor Villar: Es braucht einen Paradigmenwechsel, um sicherzustellen, dass Frühgeborene gesund aufwachsen und nicht überernährt werden, was später das Risiko für Übergewicht begünstigt. Der Paradigmenwechsel bedeutet, wegzukommen vom Denken, Frühgeborene müssten wie Föten oder Termingeborene wachsen. Stattdessen sollte ihr Wachstum anhand spezieller Tabellen für Frühgeborene gemessen und sie sollten mit Muttermilch ernährt werden. Dies sind wichtige Befunde aus unserem INTERGROWTH-21st-Projekt. Sie belegen, dass Frühgeborene, wenn sie mit Muttermilch ernährt werden, in ihrem eigenen Tempo gesund wachsen und bis zum Alter von sechs Monaten eine ähnliche Grösse erreichen wie Termingeborene.

INTERPRACTICE-21st konzentriert sich auf die Umsetzung der Muttermilchernährung für Frühgeborene und der Wachstumsüberwachung anhand der INTERGROWTH-21st-Standards und trägt dazu bei, den Paradigmenwechsel bei Kinderärzten und Eltern durchzusetzen. Das Projekt zeigt bereits weltweit Wirkung.

Berücksichtigen die INTERGROWTH-21st-Standards auch regionale Besonderheiten?

Professor Villar: Die INTERGROWTH-21st-Standards beschreiben, wie sich alle Frühgeborenen in den ersten sechs Lebensmonaten entwickeln sollten. Sie gelten unabhängig von der Ursache der Frühgeburt, weil sie auf einem generellen Prinzip basieren: Sind die Bedingungen angemessen und werden die Frühgeborenen mit Muttermilch ernährt, werden ihr Wachstum und ihre Entwicklung optimal sein. 

Inwiefern fördert die Partnerschaft mit der Stiftung die Übersetzung von Forschungsbefunden in weltweit  nutzbare Instrumente?

Professor Kennedy: Die Stiftung ist unter den globalen Geldgebern einzigartig, weil sie sich auf Muttermilchforschung konzentriert, erfahren ist bei der Operationalisierung neuartiger Konzepte und eine langfristige Perspektive einnimmt. Die Stiftung ist daher die perfekte Partnerin bei der Unterstützung des universitären Ziels sicherzustellen, dass jedes kleine, gefährdete Neugeborene weltweit mit Hilfe der INTERGROWTH-21st Tools untersucht wird, weil diese Babys enorm von den Vorteilen der Muttermilch profitieren. Unsere gemeinsame Arbeit leitet hier einen tiefgreifenden Wandel ein. 

Extended interview, in English

To date, the INTERGROWTH-21st Preterm Postnatal Growth Standards and Feeding Protocols have been implemented in thousands of medical facilities, in 195 countries and regions. What is INTERPRACTICE-21st and what needs does it serve?

Professor Villar: The INTERPRACTICE-21st Project, generously funded by the Family Larsson-Rosenquist Foundation, emerged from the clear, clinical demand for a paradigm shift in the way we think about feeding preterm babies and monitoring their growth, focused on accepting that they should not be evaluated as if they are fetuses or term babies.

In fact, the problem of how best to feed preterm babies has been a source of concern and frustration for decades. On the one hand, neonatologists and pediatricians may have been underfeeding these babies, resulting in them not getting enough protein, calories or nutrients; however, it is probably more likely now that they are being overfed. This is a major public health issue worldwide because overfeeding can lead to obesity and increased risk of cardiometabolic disease in later life.

Naturally, mothers have been demanding action because when preterm infants are evaluated by the family doctor or a pediatrician, it can often look as if they are not growing properly. Mothers of preterm infants are understandably concerned: "What should I do, should I start feeding my child more?" 

The INTERPRACTICE-21st Project was specifically designed to address these important issues by implementing globally: a) the INTERGROWTH-21st Preterm Postnatal Growth Standards to monitor the postnatal growth of preterm babies and b) the use of human milk for these babies so as to achieve optimal growth and development. 

The scientific rationale for INTERPRACTICE-21st is based on our international research program (The INTERGROWTH-21st Project). We followed a large group of mothers and their babies from early pregnancy to two years of age. The great majority of the babies that were born preterm, when given human milk as basic intake, grew healthily at their own pace (provided they did not develop any complications or illnesses) and, by six months of age, they reached the size of infants that were born at term. Crucially, at two years of age, they also had adequate neurodevelopment.

Our work should reassure both mothers and healthcare professionals. Preterm babies will grow and develop healthily if they are given human milk and their postnatal growth is monitored using the appropriate charts, namely the INTERGROWTH-21st Preterm Postnatal Growth Standards. None of the other charts available were produced by following babies prospectively from early pregnancy to two years of age. They were mostly assembled using multiple single measurements of fetuses or newborns and their continued use, therefore, is not in the best interests of babies born preterm.

The net effect of using the INTERGROWTH-21st Preterm Postnatal Growth Standards instead of the other charts is to reduce the number of preterm infants diagnosed with extrauterine growth restriction, (i.e., poor postnatal growth). In my opinion, that represents our major contribution to the paradigm shift that was needed. When a preterm infant is diagnosed with extrauterine growth restriction, everyone (healthcare professionals, mothers, grandmothers etc.) feels they have to do something – and doing something means overfeeding. It’s not that they say, “Im going to overfeed these babies.” They introduce more nutrients, and when you introduce more nutrients, you inevitably overfeed, which is a treatment for a disease that did not exist in the first place.

It follows that the growth standards and feeding protocols based on the use of human milk are a form of preventive medicine. That explains why we are so excited and also so grateful to the Foundation for supporting us through the INTERPRACTICE-21st implementation period.

Are the INTERGROWTH-21st tools aimed at addressing challenges that are specific to different regions? 

Professor Villar: The INTERGROWTH-21st international standards describe how all preterm babies should grow in the first six months of life. They are applicable whatever the reasons for the preterm birth (which are region-specific based on local conditions) because they promote a universal principle: without complications, most preterm babies fed human milk grow and develop adequately.

Thus, these tools are definitely not for specific groups, such as people living in privileged conditions. They can be used anywhere as they apply to all preterm babies without exception, which explains why some of the leading obstetricians, neonatologists and pediatricians in the world have adopted them so as to promote healthy growth and development in the most appropriate manner, which is with the use of human milk.

Importantly, the tools were designed to prevent both under- and overnutrition. For example, in sub-Saharan Africa, many preterm babies will be born growth restricted and will remain poorly grown because of infection and/or malnutrition. They need to be adequately nourished. In other settings, e.g., Latin America, Asia, China, India, Pakistan, the problem may be overnutrition, itself generated by malnutrition; thus, in those settings, the tools are useful because they prevent overfeeding. However, the basic recommendations are the same irrespective of the setting: achieve better maternal nutrition, use human milk, and monitor the effects of feeding with the INTERGROWTH-21st international standards.

How did the partnership with the Foundation develop, and how does it enable extending your research into tools for global scale up?

Professor Kennedy: Nick Rawlins, Professor of Behavioural Neuroscience at the University of Oxford, who was then Head of Development for the University, happened to be sitting on a train opposite Janet Prince, an original member of the Foundation. She started telling him about the Foundation’s commitment to funding research in human lactation. Her enthusiasm was rather infectious. Later that day, he emailed a few research groups across the University, asking: Is anyone interested in talking to the Foundation, which of course we were.

And that’s exactly how the relationship started – pure serendipity. From that initial contact, the INTERPRACTICE-21st Project arose with the Foundation’s very generous support. Later José and I met the Larssons, who made the decision to fund the Larsson-Rosenquist Foundation Oxford Centre for the study of the Endocrinology of Human Lactation (LRF OCEHL) – the first research center in the world to focus on this important subject.

The relationship has proved incredibly beneficial because there are very few funders with an interest in human milk science. We saw the INTERPRACTICE-21st Project as a wonderful opportunity to build on the massive investment from the Gates Foundation that was already funding our studies into the effects of breastfeeding on human growth and neurodevelopment in general, which were beginning to produce some interesting findings about the benefits of breastfeeding. The Foundation’s support has enabled us to focus specifically on preterm babies across the world; in other words, the babies who are most likely to benefit from being given human milk.

How is collaborating with the Foundation different from working with other philanthropic funders? 

Professor Kennedy: Our ultimate goal is to convince healthcare professionals and mothers of the absolute need to implement the INTERGROWTH-21st growth standards and feeding protocols based on the use of human milk. However, not all funders are interested in implementation of research findings and virtually none have any experience of the kind of operationalization needed to achieve our aims. 

That is why having Katharina (Lichtner) at the helm is so important. As researchers we have little experience of implementation, especially of the processes required to persuade clinicians to change their practice. What she brings to the table is an appreciation of the value chain – the journey from science to impact, focused on three interconnected areas: knowledge discovery, knowledge translation and knowledge deployment – and the wide gap between public policy and actual implementation.

And, of course, the Foundation is unique because, unlike every other funder I have ever worked with, it takes a long-term view and is really motivated by the need for impact. It is so refreshing and helpful because the barriers we face cannot be overcome overnight.

Despite its importance for global health, breastfeeding does not receive sufficient attention amongst clinicians and scientists, which mainly explains why research funding in the field of human lactation is so limited. That’s why the Foundation’s commitment is so important. With their support, we anticipate our work – not just the specific project that aims to assess the effects of human milk on the growth and development of preterm babies, but also the much broader aim of implementing the INTERGROWTH-21st standards at regional, national and international level – will be transformational.

Working with the Foundation is very collaborative. And that’s different to what usually happens in science. Most funders remain independent and do not involve themselves directly in one’s research, which makes no sense when they possess valuable expertise that you don’t. The interactions with the Foundation are genuinely interactive, which I’m sure is largely due to Katharina’s influence. Ultimately, our work together will benefit hundreds of thousands of the most vulnerable newborns across the world.