DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
FY 2002 Hearing on Life Span
Witness appearing before the
House Subcommittee on Labor-HHS-Education Appropriations
Duane Alexander, M.D., Director
National Institute of Child Health and Human Development
April 4, 2001
Mr. Chairman and Members of the Committee:
Thank you for the opportunity to talk about the research of the National Institute of Child Health and Human Development (NICHD), which was the first of the Institutes of the National Institutes of Health (NIH) established to address lifespan issues. In fact, when the Kennedy administration wanted to establish such an Institute, it was such a new concept that they had to seek congressional legislation to do so, because the Secretary and Surgeon General had authority to establish NIH Institutes only related to a disease or an organ. The 1962 legislation for NICHD called for an Institute focusing on the broad problems of human development, especially the health problems of mothers and children and developmental disorders. Its mandate originally encompassed research from preconception through old age, until the National Institute on Aging (NIA) was split off from NICHD in 1974.
Over the ensuing years the research of the Institute has proved the wisdom of the founding concept: that the key to understanding, ameliorating, and preventing mental retardation and many of the developmental disorders and diseases of childhood and adulthood lies in studies of the processes of development. These processes extend from the time of formation of sperm and egg, to their union to form a developing individual, through the experiences of pregnancy and delivery, to the newborn and infancy periods, and on through childhood and adolescence into parenthood when the developmental cycle begins anew. They include both genetic and environmental influences, with environment broadly defined to encompass physical, behavioral, and social aspects. The research addresses the most fundamental question in biology: how a fertilized egg develops into a unique adult human person, and all the factors that influence that process for good or ill.
From this research have come such discoveries as the Nobel-prizewinning identification of releasing factors from the hypothalamus of the brain that mastermind the entire endocrine system of the body; such public health measures as the Hemophilus influenzae type b conjugate vaccine that has nearly eliminated the leading cause of acquired mental retardation in the United States; and medical care improvements that have reduced this Nation's infant mortality rate by 70 percent since the year the Institute was established. Several examples of current areas of research illustrate the importance of this developmental approach to health and wellbeing across the lifespan.
FETAL ORIGINS OF ADULT DISEASE
Part of the mythology of pregnancy dating from antiquity has been that things that happen to the mother during pregnancy influence the developing fetus: a birthmark, for example, would result from the woman being frightened by seeing a rat. Modern medicine has disproved such beliefs and replaced them with such known factors as maternal rubella infection during pregnancy producing congenital rubella syndrome in the infant. We are now in the process of extending that knowledge, not just to immediate effects but to conditions originating during pregnancy that are not manifest until adulthood. Epidemiologic studies extending over 50-60 years show a clear relationship between severe maternal dietary restriction in pregnancy and low birth weight with later development of such conditions as hypertension, elevated cholesterol, atherosclerosis, obesity, and diabetes in adult life. Studies in animal models of dietary or other stress in pregnancy regularly reproduce these findings. For example, stressing a rat during pregnancy yields offspring that have elevated cortisol levels and are hypertensive at birth, remain so throughout life, and have hypertensive offspring themselves, representing intergenerational transmission of an acquired trait. We, along with NIA and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), are currently soliciting research to expand these studies substantially, looking for the mechanisms by which these changes occur. This is a significant area of study suggesting that some, but by no means all, of these and possibly other disorders have their origins in the experiences of the mother and fetus during pregnancy. How we are ushered into life may well be a major factor in how we experience it and leave it. In contrast to the challenge of changing the determinism of our genes, the intrauterine environment is much more potentially modifiable by a woman to promote good future health of her child.
COMPLICATIONS OF PREGNANCY/LABOR/DELIVERY FOR MOTHER AND INFANT
It is often said that the most hazardous journey of life is the travel from the uterus to the outside world. Complications of this journey (breech delivery, placenta blockage or early separation, hemorrhage, umbilical cord around the neck, or too small a pelvis to permit delivery) can portend a lifetime of problems for both mother and child. Pregnancy and delivery difficulties lead to future pelvic floor disorders for the mother with incontinence, prolapse, and the associated discomfort and disability. For the child, partial paralysis, brain injury, and mental retardation or learning disabilities are too often the lifelong consequences, and are all the more likely if labor began too soon. Our research is attempting to identify ways to manage labor and delivery to reduce the likelihood of maternal pelvic floor injury, and of damage to the infant from the birth process. Major efforts are being directed by NICHD and NINR toward ascertaining the causes of preterm labor and ways to prevent or stop it. Success in these efforts will lead to further reductions in infant mortality, one of this country's major health disparities, as well as the associated maternal and child morbidity across the lifespan.
Birth defects may be so severe that they are incompatible with life (making them our leading cause of infant mortality), but more often allow survival with varying degrees of limitations of function that are often lifelong. Their duration and severity make them one of the costliest medical conditions. Our research is attacking this problem on a number of fronts. A joint effort with the NIEHS and the NIDCR is applying the discoveries of the Human Genome Project to assessing genetic factors contributing to birth defects, with a focus on gene-environment interactions that may be causative. We are developing and evaluating fetal surgery approaches to correcting such abnormalities as urethral valves and neural tube defects during pregnancy with the hope of improving outcome. We are developing improved medical rehabilitation techniques to help children and adults function effectively in society. The NICHD, in cooperation with the NIEHS, is leading a multiagency effort to design and conduct a large longitudinal birth cohort study of the effects of the environment on children's health and development. A major component of this study will examine birth defects, in addition to longer term outcomes such as fetal origins of adult diseases.
One of the most important parts of the development process, with lifespan ramifications, is learning. Consequently we devote significant resources to studying learning, both with or without formal instruction, in normal children as well as children for whom learning is a major challenge. Much of this work has focused on how children learn to read. From this research we know the basic concepts that must be mastered in order to read, how to teach those concepts most effectively, how to identify well before school age those children likely to have difficulty learning those concepts, and how to intervene effectively with those children so that below grade level achievement at the end of third grade is reduced from 35% to less than 5%. Translating this research into practice is a current focus of our efforts. Learning to read is one of the most significant lifespan predictors not only of academic and economic success, but of health and social behavior as well.
With the advances of the last century in medicine and public health, achieved by translating research discoveries into practice, we have reached a point where eight of the ten leading causes of death in the United States and most developed countries are strongly related to behavior. Cigarette smoking, obesity, physical inactivity, substance abuse, risky sexual behavior, deficient calcium intake, and other behaviors are linked to cardiovascular disease, cancer, diabetes, liver disease, AIDS, osteoporosis, and other conditions that cause not just death but enormous disability and morbidity that take a huge physical, mental, and economic toll. Virtually all of these behaviors have their origins in childhood. If we could help children choose and maintain healthy behaviors, we would have an enormous impact on the age of onset and prevalence of these diseases in adulthood. In one of these cases, osteoporosis, childhood is our only chance for effective behavioral change, because research has shown that nearly all the calcium we ever get in our bones is there by around age 20. The more calcium that is in the bones, the longer it will be before osteoporosis develops, if ever. But calcium is the major deficiency in the diet of America's children. If this is not corrected by behavioral change, we face a mounting problem with vertebral and hip fractures not just in the elderly, but in people in their 50's and even 40's. Through a combination of research and a public information campaign, we are trying to change this health behavior in childhood that will have its consequences years in the future. There is no clearer example of the importance of lifespan research.
The topics I have discussed are but a few of the many examples that could be cited of the importance of research on development for health across the lifespan, and of the enormous potential payoff for health and wellbeing of focussing efforts on children, before and after birth. To the extent that this research succeeds, this Institute will achieve its mission of helping women have the children they want at the time they want them, suffer no adverse consequences from the process of childbearing, and have those children reach adulthood free of disease or disability or adverse health behaviors so that they may achieve their full potential.