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Report of the Meeting of the Working Group on Life Cycle Consequences of Fetal and Infant Malnutrition (Policy and Programmes)Saturday, 10 April 1999, UNHCHR, Geneva 1. Overview of Evidence for Life Cycle Consequences of Fetal and Infant MalnutritionThe Chair, Nevin Scrimshaw opened the meeting by explaining that it has become increasingly apparent in the last decade that the adverse effects of intrauterine growth retardation (IUGR) can influence the performance and health of offspring throughout life. For infants born with low birth weight (LBW) at the end of a term pregnancy, intrauterine growth retardation has occurred. Most low birth weight can be prevented by better food intake resulting in greater weight gain during pregnancy. In many developing countries over 20% of infants have intrauterine growth retardation as judged by LBW for term gestation. There is growing evidence that adverse effects of IUGR can extend throughout the life span. As early as the 1950s Cravioto in Mexico showed that among preschool children from families of low socioeconomic status those in the lowest quartile of weight for height had impaired performance in multiple tests of intersensory integration compared with higher quartiles. In a Guatemalan study described by Reynaldo Martorell and coworkers, nutritional supplementation (of the mother during pregnancy and of child up to two years of age) was reflected, some 14+ years later, in significantly better scholastic achievement and cognitive performance compared with children in two control villages. There is now evidence that IUGR may be manifested adversely in older adults. Barker's group in the U.K. has initiated this major expansion of our understanding of the factors contributing to chronic diseases in later life. These observations were described initially in a series of more than 50 papers, beginning in 1986, most of them first published in the British Medical Journal. Many of them were reprinted in the 1993 book the Fetal Origins of Adult Disease. These papers presented evidence from several populations in England and Wales that low birthweight at term and, in some cases, low weight at one year of age of individuals from the 1920s and 1930s were associated with an increased adult risk of hypertension, coronary heart disease, non-insulin dependent diabetes, and autoimmune thyroid disease. More of the work is summarized and discussed in Mothers, Babies and Disease in Later Life published in 1994. The case for a causative relationship between LBW and these outcomes is strengthened by evidence of possible mechanisms including increased serum fibrinogen and lower insulin tolerance in adults. Confounding socioeconomic factors per se do not provide an adequate explanation for the associations of LBW with chronic diseases in later life. Moreover, no matter what combination of poor nutrition and other environmental factors is involved in fetal growth retardation, the concept of fetal origins of adult disease in this population still emerges as valid. To generalize from the populations of England earlier in this century requires confirmation in other populations and by other investigators. However, relationships similar to those hypothesized by the Barker group have been found wherever they have been properly looked for in other populations. More than 30 studies show a relationship between short stature and increased hypertension. For coronary heart disease, the initial findings in populations in Sheffield, England have now been corroborated in Caerphilly, Wales, Uppsala, Sweden, in the Nurses health study in the United States and in Helsinki, Finland. A study in Mysore, India provides the first confirmatory evidence from a contemporary developing country. In the Gambia the blood pressure of children at eight years of age has been found inversely proportional to their mother's weight gain in the last trimester of pregnancy. It is postulated that individuals who were born with low birthweight and who as adults become more affluent and adopt a Western diet and lifestyle are at the highest risk of developing heart disease. Without in any way detracting from the seminal contributions of the Barker group, and stimulated by these and related studies, a broader and more comprehensive paradigm is emerging that extends the concept of the fetal origins of adult disease. Most human embryos have the potential for developing into individuals with long and healthy lives. However, from the moment of conception adverse environmental forces begin to limit this potential. Intrauterine growth retardation due to poor maternal malnutrition is an important limiting factor; so are the diets at all ages, cigarette smoking, a sedentary lifestyle, the use of drugs and others. It is clear that preventive measures should begin with improving nutrition and health status of women of childbearing age in order to prevent damage to the fetus from malnutrition and related factors in early pregnancy. There is little doubt that fetal and early childhood malnutrition affects the distribution of chronic disease in adults. Moreover, its relationship with cognitive performance and physical capacity in children and adults is an additional reason for attention to the nutrition of the mother during pregnancy and of the young child in the first 18 - 24 months postpartum. 2. Causes and Consequences of Intra Uterine Growth Retardation: Results of the International Dietary Energy Consultative Group (IDECG) workshop, held in Baton Rouge, 1996Beat Schürch spoke about the causes and consequences of IUGR as described in the recommendations of the IDECG workshop, published as a supplement to the European Journal of Clinical Nutrition (1996). Current estimates by the World Health Organization (WHO) suggest that IUGR is a major public health problem in many developing countries. Highest incidences are reported in South Asia and Central Africa. It is estimated that LBW babies have a ten-fold peri-natal mortality risk and a four-fold post-natal mortality risk. He further reported that stunting at birth carries a higher risk than wasting. Dr. Schürch highlighted several interventions known to influence birth weight such as supplementation of pregnant women who have low BMI prior to gestation, prevention of malaria during pregnancy in endemic areas, and cessation of smoking in pregnancy. 3. Life Cycle Consequence of Fetal and Infant Malnutrition: Research NeedsEileen Kennedy of the US Department of Agriculture (USDA) identified areas that limit the interpretation of the Barker findings and emphasized the need for further research. These areas include the lack of information on possible confounding lifestyle and environmental factors, limitation of the initial Barker studies to two populations in the U.K., the retrospective nature of the observations, and differences in study methodologies among studies making comparisons. Dr. Kennedy pointed to the need to establish a core research protocol to investigate a longitudinal relationship between IUGR and disease in later life. If the Barker hypothesis is valid, this will provide additional justification to develop nutritional programmes to prevent IUGR and to minimize consequences in later life. 4. Life Cycle Consequences of Fetal and Infant Nutrition: The need to develop, test and evaluate LBW reduction programmes in developing countriesRoger Shrimpton, UNICEF, pointed out that despite a goal set out at the World Summit for Children to reduce the prevalence of LBW (to 10 per cent or less), globally 20.5 million LBW babies are born each year with little evidence that this situation is improving. This figure represents 16.4% of newborns each year in developing countries. Furthermore, there are limited data supporting the effectiveness of nutritional interventions during pregnancy. Roger Shrimpton suggested that in societies with high rates of IUGR, beneficial results could only be achieved by multiple interventions. Dr. Shrimpton also suggested that the IDECG report had generated skepticism about the efficacy of nutrition interventions for improving birth weight. He indicated that there is a lot of evidence and pointed out that most of this evidence was not considered by IDECG because it was not based on randomized controlled trials. He reviewed some of the evidence from the non-randomized studies and evaluations including data from the Gambia, INCAP in Guatemala, and Narangwal, India which show clear evidence of nutritional effects on birth weight and neo-natal mortality. According to report of the Institute of Medicine the Women, Infants and Children (WIC) programme in the US decreases LBW. The report recommended including nutritional supplementation as part of any comprehensive strategy to reduce the incidence of LBW. Dr. Shrimpton proposed that programmes to address IUGR could be based on the Care for Women component of the UNICEF Care Initiative. He suggested that an inter-agency meeting could usefully explore these issues in greater depth and would help to move programmes forward in this area. UNICEF and the World Bank in collaboration with ICDDR,B will hold a meeting in Bangladesh in June 1999. A recommendation was made to identify and document best practices which could be integrated into new comprehensive programs, including monitoring and evaluation. 5. Comments from WHO and PAHOThe reduction of LBW prevalence is a priority for WHO. Lately, the agency’s emphasis has been on improving essential obstetric practices. WHO has conducted epidemiological studies on the prevalence of LBW and has also provided recommendations for the reduction of maternal and peri-natal mortality. In 1998, PAHO organized a workshop to review the appropriateness of anthropometric indicators during pregnancy where it was recommended that monitoring weight is useful for monitoring pregnancy outcomes. It was further agreed that the successful approaches of Chile, Cuba, and Costa Rica to minimize LBW should be reviewed for lessons learned. 6. Agency reportsElly Leemhuis-de Regt of the Government of the Netherlands and Ted Greiner representing the Swedish Government stressed the need to present LBW prevention programmes as part of reproductive health care programmes and welcomed the holistic approach outlined by UNICEF. Frances Davidson of USAID indicated the importance of the Barker hypothesis for policy making and suggested that the impact of programme investments to reduce LBW should be highlighted for policy makers. Marion Kelly of DFID (UK) mentioned the agency’s support to elucidate remaining unclear issues of the Barker hypothesis. Kraisid Tontisirin (Mahidol University, Thailand) said that a major determinant of high incidence of LBW in many South East Asian countries is poor antenatal care coverage and suggested that community mobilization is essential to improve the effectiveness of LBW reduction programs. Vinodini Reddy representing the International Union of Nutritional Sciences (IUNS) mentioned that they had established a working group to review the relationship between fetal and adult nutritional status. Ricardo Uauy of the AGN emphasized the importance of conducting research into the relative contribution of malnutrition to LBW in countries with high LBW incidence, because the impact of nutritional factors will most likely be greater under these conditions. Dr. Uauy added that most recent well-designed controlled trials have been conducted in developed countries, or in countries where LBW is less than 10% of births, thus minimizing the effects of the intervention. 7. Conclusions and priorities for actionThe Chair of the Working Group, Nevin Scrimshaw, concluded by commenting that despite some weaknesses and criticisms of the early Barker studies, these studies have since been greatly expanded and standardized, and the results supported by similar findings in a considerable number of other countries, both industrialized and developing. Overall, the evidence of adverse long-term effects of maternal, fetal and infant malnutrition is very strong. He recommended that this new Working Group be continued in order to provide the ACC/SCN with an annual critical assessment of developing scientific evidence, to give ACC/ SCN members a chance to contribute to the dialogue and to stimulate research, policy formulation and programme guidelines on this important topic.
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