Diet during the first months of life and even before – the impact of the expectant mother’s diet on prenatal nutrition at the foetal stage – triggers a process of metabolic programming that marks the human being for life. Research in this area is very important in the field of preventive medicine. The three European projects that make up the Infant Nutrition Cluster are studying these ‘programmed’ relations in terms of pathologies of foetal growth, infant obesity and insulin-dependent diabetes.
Last July, more than 400 participants from 50 countries and a range of backgrounds – from scientists to representatives from the food industry – gathered in Paris for the conference organised by the Infant Nutrition Cluster. Such a success reflects the growing interest in research based on the new concept of metabolic programming.
The idea originated in the 1990s as a result of an increasingly disturbing convergence between the results of experiments on animals and epidemiological investigations in man. All these studies suggest that what the foetus and newborn infant ingests has a lasting effect on the way in which body cells use, convert and destroy nutrients, this being what is meant by the term metabolism. This modelling can later affect the health of the child, adolescent and adult. Incorrect diet at these early stages is believed to be a root cause of the development of an array of medical problems in later life, including obesity, high blood pressure, diabetes, arteriosclerosis and impaired cardiac function, cognitive capacities and immune defence.
To carry out the necessary further investigations in this field, three distinct lines of enquiry, supported by the EU, were brought together within the framework of the Infant Nutrition Cluster. The three projects are Childhood Obesity, Perilip – which is looking at problems of foetal growth in the latter stages of pregnancy – and Diabetes Prevention, which is the European component of Trigr, a global test on the influence of cow’s milk products on insulin-dependent diabetes.
"Despite the evident difference between our centres of interest in terms of pathologies, we have a common interest in infant nutrition and the concept of metabolic programming,” stresses Peter Dodds, group and Perilip project coordinator. “We therefore felt it essential to come together within this relatively informal framework, free of contractual obligations, to share information and to reflect jointly on possible future action based on our findings.”
Superprotein babies? Two of the projects are interested in examining differences in composition between mother’s milk and manufactured milk preparations for bottle feeding.
"Experiments carried out on animals and epidemiological investigations in man, some on a large scale, suggest that breast feeding reduces the risk of obesity,” explains Doris Oberle, of the Munich Faculty of Medicine, a partner in the Childhood Obesity project. But what is the reason behind this? For a number of years now, scientists have been looking at the relatively high protein content of processed baby milk. To compensate for the fact that the proteins in cow’s milk are less readily digestible, these preparations contain more of them than mother’s milk. Proteins promote growth but also possibly the development of fatty tissue – hence the risk of obesity, which is a possibility that baby milk manufacturers are taking very seriously. Jean-Michel Antoine, a researcher at Danone, the French agri-foodstuffs partner in the Childhood project, believes that “the fields being investigated by the cluster raise a real question regarding a possible review of current standards for protein content”.
To go beyond simply noting statistical links within the population as a whole, Danone and Berthold Koletzko, director of the Nutritional Medicine and Metabolic Diseases Department at Munich’s Von Hauner Hospital, suggested testing this hypothesis clinically. The project was presented in Rome, in October 2003, at the Ninth European Conference on Nutrition. It involves monitoring, over a year, two groups of newborn infants fed on baby milk with different protein contents. Breast-fed babies constitute the control group. The children will be monitored closely until the age of two, at which point it is already possible to draw initial conclusions on the relationship between the proteins ingested, growth, and the risk of obesity. At the same time, an investigation being carried out in the five participating countries – Germany, Belgium, Spain, Italy and Poland – is to look at the practices of various cultures in terms of infant nutrition.
Although recruiting the volunteer mothers proved a long and sensitive process, the current clinical trial concerns 1 151 newborn infants with another 639 breast-fed babies forming the control group. At its plant in Steenvoorde (France), the Danone subsidiary Blédina, which specialises in baby food, has developed and produced two experimental milks with the same protein content but different energy values. The first results are expected at the end of 2005. The children will then continue to be monitored by a subsequent project, until the age of eight.
Future health can be determined in the womb. Researchers are looking at the influence of the mother’s diet – especially lipid intake – on intrauterine and perinatal growth.
Diabetes and breast feeding The issue of cow’s milk proteins present in preparations for newborns is also at the centre of the very different research subject of insulin-dependent diabetes. Again, epidemiological surveys carried out worldwide during the past 20 years suggest that breast-fed babies are less likely to develop diabetes than others. This finding may seem odd as this autoimmune disease, in which the immune system attacks the body itself, has a well-established genetic origin. “Nevertheless, today we are inclined to lend credence to the hypothesis that the immune system of children with a genetic risk of diabetes is unable to cope with intact foreign proteins in their food. These trigger a chain reaction that can lead to the destruction of the pancreatic cells that produce insulin,” explains Michael Dosh who is studying the question at Canada’s Toronto children’s hospital. “Experiments on animals show that hydrolysed cow proteins – proteins that are too small to trigger an immune reaction – do not have this ‘diabetogenic’ effect.”
It took several years of preparation before this hypothesis could be put to the test in humans. Hans Åkerblom, of Helsinki University, first carried out a pilot study in Finland. However, this was done on an insufficient scale and the results could not be regarded as conclusive. Given the scientific interest in the problem it subsequently proved possible, in 2002, to launch the major Trigr(1) trial.
Also coordinated by Hans Åkerblom, this project involves 6 000 diabetic families who will be monitored by some 40 clinical centres in 15 countries, in North America, Europe and Australia. Babies with a genetic risk of diabetes and whose mothers are unable to breast feed them will be fed during six months with either an ‘ordinary’ milk preparation or one with hydrolysed proteins. They will then be monitored until the age of five to detect whether their blood shows early indications of diabetes.
Twelve centres are participating in the European branch of the project, known as Diabetes Prevention, which will end in 2006. Trigr itself will continue until 2012, when the global results are expected.
Before birth The ‘destiny’ of an individual’s health also seems to be partly decided before birth. In Europe, between 3% and 7% of babies have achieved insufficient growth at the end of pregnancy. They may be born too small, sometimes deformed, and later risk suffering from physiological and metabolic problems, even learning difficulties. Most very premature infants, who are placed in an incubator and fed through a drip, show the same symptoms.
Scientists suspect the cause lies in a deficiency in certain fatty acids, the essential components of lipids. “We know that the perinatal supply of these acids, carried in the mother’s blood, has a considerable long-term impact on neurological development or the immune system,” states Hans Demmelmair of Munich University (DE), one of the partner centres working on the Perilip project.
Researchers therefore want to understand the influence of maternal lipid intake on intrauterine and perinatal growth. This complex subject covers the metabolism of various fatty acids by the mother, their passage through the placenta and into the milk and, finally, their effect on the foetus. To study this, seven partners with very diverse specialities are carrying out a set of experiments on animal models (rats and piglets) or cell and organ cultures. “Although some non-invasive measurements can be envisaged in pregnant women, newborns or premature babies, given the present state of knowledge, the project’s fundamental approach is to explore the molecular and cellular mechanisms before attempting any direct testing on the human being,” stresses Hans Demmelmair.
Perilip should provide dietetic recommendations for nutrition during pregnancy and, in the longer term, an improved diet for premature babies.
Paradoxically, as the animals used as models by some partners are mainly piglets, an unexpected and much more immediate benefit will concern the diet of reproducing sows. Insufficient growth at the time of birth and consequent mortality are serious problems for pig farmers, which is no doubt the reason why Cotswolt, a British pig feed producer, is participating in the Infantile Nutrition Cluster.
(1) Trial to Reduce Insulin-Dependent Diabetes in the Genetically at Risk
Baby milk: European regulations
The European legislative framework for preparations for newborns – which are only awarded the ‘milk’ label if their proteins come exclusively from cow’s milk – dates from 14 May 1991. Directive 91/321/EEC “on infant formulae and follow-on formulae” defines the ...
The obesity epidemic
Urgency – that is the word that on everyone’s lips as soon as there is talk of obesity. In 1996, the World Health Organisation (WHO) sounded a warning, speaking of a global epidemic and even formulating the term “globesity” to describe it. Since then, things have beciome ...
A successor to the Infantile Nutrition Cluster under the Sixth Framework Programme, this project is dedicated to the early metabolic programming of adult health through early nutrition. The many activities include the follow-up of present studies, fundamental experiments, and sociological surveys of ...
The European legislative framework for preparations for newborns – which are only awarded the ‘milk’ label if their proteins come exclusively from cow’s milk – dates from 14 May 1991. Directive 91/321/EEC “on infant formulae and follow-on formulae” defines the labelling requirements for these foods, their composition and the origin of their ingredients. It strictly limits advertising for these products and requires Member States to circulate among the general public and institutions concerned information on the nutritional needs of young children. The most recent updating of this regularly amended text was in February 2003. The Scientific Committee on Food, under the Health and Consumer Protection Directorate-General, is responsible for monitoring observance of these recommendations.
The obesity epidemic
Urgency – that is the word that on everyone’s lips as soon as there is talk of obesity. In 1996, the World Health Organisation (WHO) sounded a warning, speaking of a global epidemic and even formulating the term “globesity” to describe it. Since then, things have beciome even worse.
In May 2004, on the occasion of the 13th European Congress on Obesity, in Prague, the International Obesity Task Force (IOTF) presented the European chapter of its report. A quarter of all children in Europe are overweight and 3 million of them display characteristics of obesity. The situation is most serious in southern Europe, with more than a third of Italian children affected compared with 10% of young Slovaks. Philip James, IOTF president, was hardly reassuring: “the epidemic is accelerating and seems to be running out of control. It is exceeding our worst expectations.”
Although physiological factors, such as hormone disorders, pose specific scientific questions of importance, the sociological causes of this explosion, in any event, are well known and in developed countries are linked to behaviour, especially among children and adolescents: an unsuitable diet (meals that are too rich, snacks between meals, sweets, soft drinks) and reduced physical activity (motorised transport, television, video games). As Berthold Koletzko, coordinator of the Childhood Obesity project, points out, “infant obesity has serious short- and medium-term effects during childhood and adolescence as well as long-term effects throughout adult life”. In addition to psychological and social integration problems beginning at a very young age, obesity significantly increases the risk of non-insulin dependent (type 2) diabetes, cardiovascular disease, high blood pressure, gallstones, arthritis, respiratory ailments and even certain cancers in later life.
In the face of this worrying public health problem, the European Commission decided to act. The Fifth Framework Programme for research includes more than 20 projects devoted to various aspects of obesity, with subjects ranging from the lifestyle of adolescents to obesity in elderly people, molecular or fundamental metabolic studies, and socio-psychological aspects of the problem.
A successor to the Infantile Nutrition Cluster under the Sixth Framework Programme, this project is dedicated to the early metabolic programming of adult health through early nutrition. The many activities include the follow-up of present studies, fundamental experiments, and sociological surveys of Europeans’ nutritional habits. The project is being coordinated by Berthold Koletzko of Munich University and includes partners from 12 countries.