DEPARTMENT OF HEALTH AND HUMAN SERVICES NATIONAL INSTITUTES OF HEALTH
Fiscal Year 2011 Budget Request
Witness appearing before theHouse Subcommittee on Labor-HHS-Education Appropriations
Duane Alexander, M.D.Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentApril 28, 2010
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) 2011 budget request is $1,368,894,000, which includes an increase of $39,897,000 over the FY 2010 appropriated level of $1,329,027,000.
The NICHD conducts and supports research on all stages of human development, from preconception to adulthood, to better understand and ultimately improve the health of children, adults, families, and populations.
With its focus on the developmental sciences, NICHD research seeks to ensure that all individuals have the healthiest beginnings possible. This includes identifying better ways to help children develop optimally, women and families remain healthy, and individuals with disabilities maximize functioning. Without understanding normative development and understanding what goes “right,” it is difficult to determine and fix what goes “wrong.” Thus, NICHD science provides the foundation for research that strives to prevent, treat, or cure specific disease.
Epigenetics is a growing and important area of NICHD research. It involves understanding how a variety of basic cellular or developmental processes may alter an individual’s genes, without actually changing that individual’s DNA. Epigenetic changes, which may be influenced by environmental or behavioral factors and may occur over time, help explain the origin of some diseases and conditions. An NICHD-supported study found that depriving female sheep of vitamin B12 and folate before they were pregnant affected how their DNA information was passed on to the next generation. Without these vitamins, compounds known as methyl groups could not be added to the DNA, influencing how the genetic instructions were carried out. This affected the sheep’s offspring, so when their lambs reached adulthood, they were more likely to be overweight and to develop cardiovascular problems. Given such promising research, the NICHD will support new efforts to examine epigenetic changes that occur throughout development and that may play a critical role in supporting ongoing health.
In other genetic work, NICHD scientists found that specific variations or mutations in a particular gene can raise a man’s risk of familial, or inherited, testicular germ-cell cancer, the most common form of this disease. Men with a family member who had a testicular germ cell cancer are at three-to six-fold greater risk than other men of developing testicular cancer. The researchers analyzed genes from 95 familial testicular cancer patients and found that they all had mutations in a gene known as PDE11A, which regulates how cells respond to hormones. Although not causing cancer directly, the mutation appears to increase an individual’s susceptibility to the disease. In addition, PDE11A is also active in the prostate gland. These findings may lead to new insight into how cancers of the male reproductive system begin.
Traumatic brain injury can change a person’s life, deprive them of social interaction, prevent them from working, deeply affect their family, and increase health care costs. According to the Centers for Disease Control and Prevention (CDC), about 1.4 million people in the United States suffer a traumatic brain injury each year, with 85,000 developing long-term disabilities. Brain-injured persons may need long-term rehabilitation to restore minimal function and enable independence. NICHD-supported research indicates that the brain’s response to an injury may itself impair functioning. Beta-amyloid peptides, found in the brains of Alzheimer’s patients, accumulate in the tissues of humans and animals with traumatic brain injury. Researchers working with rodents have shown that disabling the enzymes that produce beta-amyloid peptides can reduce cell death after traumatic brain injury and some of the corresponding loss of physical and mental function.
Disorders related to prematurity are the second leading cause of infant mortality, according to the CDC, and preterm infants who do survive are at higher risk for serious illness and long-term disability. The Institute’s ambitious program of research in this area has led to significant advances for improving the health of preterm infants and decreasing their chances of disability. A key study showed that preterm infants born to mothers receiving intravenous magnesium sulfate—a common treatment to delay labor—are less likely to develop cerebral palsy than infants whose mothers do not receive it. Another study found that the common practice of treating premature infants in intensive care units with an antacid to prevent esophageal reflux actually increased their risk for necrotizing enterocolitis, a potentially fatal condition of the intestines.
The NICHD strives to improve the reproductive health of both women and men. As many as a quarter of all American women are affected by pelvic floor disorders, which may be painful, severely limit physical activity, and reduce overall quality of life. Pelvic floor disorders result when the muscles in the lower part of the pelvis are weakened or injured. Childbirth is a primary contributing factor. The NICHD supports a range of research projects to understand, prevent, and treat this multi-faceted condition. One innovative study seeks to develop a safe mesh that can be implanted surgically to hold pelvic tissues in place; another major study compares treatments for urinary incontinence to determine which may be the most effective in this disorder.
During the past 25 years, obesity in children has tripled from 5 to 15 percent or more. No longer simply a cosmetic problem, childhood obesity often persists through adulthood, with long-term implications for such chronic conditions as atherosclerosis, metabolic syndrome, and type 2 diabetes. Given its mission, the NICHD focuses on prenatal and early childhood causes and predictors of obesity. Recent research demonstrated that maternal dietary restriction during pregnancy predisposes offspring to obesity in adulthood. In a rodent model, researchers showed that offspring who experienced very slow growth during gestation, due to maternal dietary restrictions, were increasingly resistant to hormones that can reduce appetite. This resulted in overeating and obesity as the offspring aged. Other NICHD-funded researchers demonstrated that, after birth, rodents exposed to prenatal stress were at increased risk for diet-induced obesity. This occurred through epigenetic mechanisms and reinforces how early developmental stressors can increase the risk of obesity.
The NICHD has been in the forefront of improving the health of women and children through pharmacological interventions. Often, many promising treatments go untested in pregnant women, because of safety concerns. This may result in pregnant women not receiving the treatment that they and their infants need. The Obstetric Pharmacology Research Units Network recently tested the anti-diabetes drug glyburide in women with gestational diabetes. The study found that plasma glyburide concentrations were 50 percent lower in pregnant women than in non-pregnant women, indicating that a higher dosage may be needed to control diabetes in pregnancy. Historically, the private sector has also been reluctant to test drugs in children; thus, children are often prescribed drugs that have only been tested in adults. Under the Best Pharmaceuticals for Children Act, the NICHD is conducting a series of pediatric drug studies to determine the dosage, safety and efficacy of medications prescribed to children, including those to treat seizures, manic-depressive disease, abdominal infections, and cancers.
The Global Network for Women’s and Children’s Health Research, established in partnership with the Bill and Melinda Gates Foundation, is improving the health of women and children worldwide. A recent network study taught basic newborn care techniques to midwives and traditional birth attendants in six developing countries. This intervention helped to reduce the number of stillbirths by more than 30 percent. In poor countries, where clean water for infant formula is unavailable, breastfeeding is the cornerstone of survival for newborns. In such situations, formula-fed infants are at risk for often fatal diarrheal diseases. Breast milk, however, is also a primary route for HIV transmission. Researchers found that giving an antiretroviral regimen to breastfeeding mothers allowed them to breastfeed for 12 months, helping their infants avoid serious diarrheal disease without increasing their risk for HIV.
Lack of access to high quality tissue samples has hampered clinical research on many developmental conditions. To address this concern, the NICHD has increased funding for an important scientific resource, the Brain and Tissue Bank for Developmental Disorders. Families who have lost a loved one with any of a variety of genetic and developmental disorders, such as Down syndrome and Fragile X, may donate tissue for research studies to this storage bank. The bank allows researchers to conduct detailed studies on brain structure and perform biochemical analyses that could lead to the better understanding of, and improved treatments for, these conditions. Recently, the bank has expanded its efforts to secure samples from individuals with autism, making it the largest such pediatric facility in the nation.
The NICHD has made full use of the funding received under the American Recovery and Reinvestment Act (ARRA). ARRA funds have enabled us to award grants and provide supplements for research on many important projects in the basic developmental sciences, in women’s and pediatric health, and in medical rehabilitation research.
Mr. Chairman and members of the committee, I would like to thank you for your continued support of the NICHD. We will continue to use the new knowledge in the developmental sciences to improve the well-being of men, women, children, and future generations in the United States and around the world.