DEPARTMENT OF HEALTH AND HUMAN SERVICES
NATIONAL INSTITUTES OF HEALTH
Fiscal Year 2009 Budget Request
Witness appearing before the
House Subcommittee on Labor-HHS-Education Appropriations
Duane Alexander, M.D.
Eunice Kennedy Shriver National Institute of Child Health and Human Development
March 5, 2008
Richard J. Turman, Deputy Assistant Secretary, Budget
Mr. Chairman and Members of the Committee:
I am pleased to present the President's budget request for the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). The Fiscal Year (FY) 2009 budget request is $1,255,920,000 includes an increase of $1,212,000 over the FY 2008 appropriated level of $1,254,708,000.
Forty-five years ago, Eunice Kennedy Shriver sought to create a research endeavor that would support the world’s best minds in investigating human development throughout the life process, focusing on understanding developmental disorders, including intellectual disabilities, and illuminating important events that occur during pregnancy and childhood. Together with her friend and scientific advisor to President Kennedy, Dr. Robert E. Cooke, they paved the way for establishing the NICHD. This year, on the Institute’s forty-fifth anniversary, we are honored to have the name expanded by Congress to the Eunice Kennedy Shriver National Institute of Child Health and Human Development.
Ending Pediatric Aids
This year the NICHD reached another milestone in its long effort to end pediatric AIDS. Beginning with demonstration of the first effective treatments for children with AIDS in the early 1990s, we moved on, in collaboration with the NIAID, to achieve reduction of the transmission rate of HIV from mother to fetus in the U.S. from 28 to 7 percent with AZT alone, and then in recent years to less than 2 percent with multi-drug therapy to mother and newborn. In developing countries we devised regimens that reduce transmission rates to newborns from over 30 percent to 4 to 6 percent. Our newest success this year is the reduction of transmission of HIV during breastfeeding, when half the infections occur, by nearly 60 percent at 9 months by use of the drug Nevirapine for the first 14 weeks, sparing infants from infection and death. Applying this regimen in this last frontier of pediatric AIDS will save 100,000 infant lives a year. Our efforts will continue to improve these preventive interventions and end AIDS in children completely.
The NICHD is continuing its ambitious research effort to develop technologies that can screen for hundreds of genetic or metabolic disorders from a single drop of a newborn infant’s blood. This key effort in preventive medicine builds on the success of current screening programs, such as those that enable physicians to identify and treat infants with congenital hypothyroidism, preventing irreparable brain damage. Paramount among NICHD’s newborn screening efforts is developing an affordable test to detect the presence of the gene that causes Fragile X Syndrome. This condition can result in intellectual disability, attention deficit disorder, and autistic behaviors. Fragile X results from a change in the gene known as FMR1 located on the X chromosome. The change increases the length and alters the function of the gene. As this changed gene is passed from generation to generation, it continues to worsen, eventually reaching a level that causes significant intellectual disabilities. Fortunately, until it reaches a critical point, the change is not severe enough to result in full Fragile X Syndrome. However, male carriers over age 50 may develop a Parkinson’s-like condition known as Fragile X ataxia, and about one in five female carriers develop premature ovarian failure - a menopause-like condition that can affect women as early as their teens. Developing a successful screening test would provide families with information to obtain early interventions and experimental therapy.
Reproductive Health and Obesity
Over the last four decades, the prevalence of obesity in the general population has been increasing. In addition to other adverse consequences, increasing rates of obesity are having a negative impact on reproductive health. For many years, the function of adipose tissue or fat was thought to be as an energy storage reservoir, an innocent bystander in the body's efforts to maintain physiological homeostasis. However, we now know that a high body mass index (BMI), a measure of obesity, is associated with higher risk for pregnancy complications and lower success rates for live births following assisted reproduction. Men with increased BMI are significantly more likely to be infertile than their normal weight counterparts. Understanding the role of adipose tissue in regulating metabolic and inflammatory processes has enormous implications for reproductive physiology. Recently adipose tissue was shown to synthesize a variety of substances collectively called "adipokines", molecules that regulate energy and others that regulate innate immune responses. There is evidence that these abnormalities in the immune response can have a significant impact on incidence and progression not only of diseases such as cancer, diabetes and heart disease, but also on reproductive disorders such as polycystic ovary syndrome (PCOS) and endometriosis. The NICHD has initiated a series of studies that will help explain how surplus of fat adversely influences reproduction. Another NICHD approach linking obesity and reproduction addresses epigenetics, that works not by changing DNA, but by altering how DNA’s instructions are carried out. To assess whether diet before pregnancy influences development of obesity-associated diseases in adulthood in the offspring, researchers deprived female sheep of dietary vitamins B12 and folate for 8 weeks before the sheep became pregnant. Six days after the sheep became pregnant, their embryos were transferred to female sheep who had been fed a normal diet. The ewes carried their pregnancies to term and gave birth normally, and the newborn lambs appeared normal. But by one year of age, the lambs were fatter and heavier than lambs whose mothers had been fed a normal diet, and also had insulin resistance and high blood pressure - conditions common among overweight people. The conclusion is that the lambs’ early diet deficiency had altered the instructions contained in their DNA, predisposing them to obesity and the diseases accompanying it. While these basic mechanistic studies continue, we are also engaged in designing multilevel studies of medical and behavioral interventions to prevent or reverse childhood obesity.
Oligosaccharides – A New Way to Overcome Infections
According to the World Health Organization, one out of every five of the world's 10 million children younger than age 5 who die in a given year succumb to enteric microbial infections. Developing a new class of inexpensive antimicrobial agents that will not induce resistant bacterial or viral strains would be of great public health importance. Oligosaccharides are composed of sugar molecules linked together to form short chains. After lipids and galactose, oligosaccharides are the third most prevalent component of human milk. However, oligosaccharides have no nutritional value to infants. Why are they present? Evidence is accumulating that oligosaccharides in human milk have direct antimicrobial properties and also provide nutrients that encourage the growth of beneficial intestinal bacteria. In a new initiative, NICHD scientists will investigate ways to use oligosaccharides to prevent and pre-empt gastrointestinal bacterial and viral infections. An advantage of oligosaccharides is that they do not interfere with protein synthesis and bacterial/viral replication and should not induce resistance. We might then predict which individuals are susceptible to specific infections. An important goal of the research is to develop personalized therapy with specifically tailored oligosaccharides to treat or prevent infection.
According to the National Center for Health Statistics, more than 12 percent of infants born in the U.S. are premature. Over the last 25 years, the rate of preterm birth has increased from 9.1 to 12.7 percent, and the rate of late preterm deliveries (deliveries between 34 and 36 weeks) has also increased significantly since 2002. In some cases, doctors understand the reasons for premature delivery, but in other cases, there is no apparent reason for the early delivery. Compared to term babies, these infants have significantly higher neonatal and infant mortality rates, far more neonatal complications, and higher neurological and developmental morbidity rates during childhood. To help reduce the rate of late pre-term deliveries, NICHD scientists will obtain biologic samples and behavioral data from pregnant women to identify predictive markers for late preterm births. This information will allow the scientists to use combinations of markers to develop personalized risk assessments identifying women at highest risk for late-preterm birth and be pre-emptive to intercede before late preterm birth takes its personal and economic toll.
Achieving the NICHD’s mission requires translation of our research discoveries through innovative outreach to multiple publics. The NICHD is building on its successful Back-to-Sleep campaign to reduce the risks of SIDS through innovative outreach approaches to the highest risk populations in Mississippi, Arkansas, and the District of Columbia, enlisting nurses and pharmacists to spread the message. We are also pleased to be collaborating with the National Council of Negro Women (NCNW) to help parents help their children maintain a healthy weight. Members of the NCNW throughout the country will be implementing the NIH-developed family oriented program known as WE CAN which focuses on increasing physical activity, selecting healthy foods, and reducing time in front of television, computer and video screens.
Biographical Sketch - Duane Alexander, M.D.
Duane Alexander, M.D., was named NICHD Director on February 5, 1986, after serving as Acting Director. Dr. Alexander also served a four-year term as the Institute's Deputy Director and was the Assistant to the Director, beginning in 1978.
Much of his career has been with the NICHD. After receiving his undergraduate degree from Pennsylvania State University in 1962, Dr. Alexander earned his medical degree from Johns Hopkins University School of Medicine in 1966. Following his internship and residency at the Department of Pediatrics at Johns Hopkins Hospital, Dr. Alexander joined the NICHD in 1968, as a clinical associate in the Children's Diagnostic and Study Branch. Following his tenure with the Branch, Dr. Alexander returned to Johns Hopkins as a fellow in pediatrics (developmental disabilities) at the John F. Kennedy Institute for Habilitation of the Mentally and Physically Handicapped Child.
Dr. Alexander returned to the NICHD in 1971, when he became Assistant to the Scientific Director and directed the NICHD National Amniocentesis Study. The study established the safety and accuracy of prenatal diagnosis using amniocentesis, now widely used to detect numerous genetic disorders and inborn errors of metabolism.
From 1974 to 1978, Dr. Alexander served as medical officer in the Office of the Assistant Secretary for Health, in what is now the Department of Health and Human Services (DHHS). During that time, he was also the physician on the staff of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, whose recommendations form the basis of current DHHS regulations that protect human subjects in research.
Dr. Alexander is a diplomat of the American Board of Pediatrics, a member of the American Academy of Pediatrics (AAP), and the American Pediatric Society. For many years, he served as the United States' Observer on the Steering Committee on Bioethics for the Council of Europe. As an officer in the Public Health Service (PHS), Dr. Alexander received numerous PHS awards, including the Commendation Medal in 1970, the Meritorious Service Medal in 1985, the Surgeon General's Exemplary Service Medal in 1990 and the Surgeon General’s Medallion in 1993 and 2002.
In 2002, Dr. Alexander received the Arnold J. Capute Award from the AAP for his contributions to the health and well-being of children with disabilities. In 2004, the American Medical Association (AMA) awarded him the Dr. Nathan Davis Award for Outstanding Government Service. He has also received outstanding public service awards from numerous organizations, including the American College of Obstetricians and Gynecologists, American Psychological Association, American Academy of Physical Medicine and Rehabilitation, American Academy of Pediatrics, Society for Research in Child Development, Association of Academic Physiatrists, and the American Society for Reproductive Medicine.
Dr. Alexander is the author of numerous articles and book chapters, most of which relate to his research in developmental disabilities.
Department of Health and Human Services, Office of Budget - Richard J. Turman
Mr. Turman is the Deputy Assistant Secretary for Budget, HHS. He joined federal service as a Presidential Management Intern in 1987 at the Office of Management and Budget, where he worked as a Budget Examiner and later as a Branch Chief. He has worked as a Legislative Assistant in the Senate, as the Director of Federal Relations for an association of research universities, and as the Associate Director for Budget of the National Institutes of Health. He received a Bachelor’s Degree from the University of California, Santa Cruz, and a Masters in Public Policy from the University of California, Berkeley