June 14, 2002

Good morning Mr. Chairman, Senator DeWine, and distinguished members of the Subcommittee. I am Dr. Brad Therrell, Research Professor, Department of Pediatrics, University of Texas Health Science Center at San Antonio (UTHSCSA), San Antonio, Texas, and Director, National Newborn Screening and Genetics Resource Center (NNSGRC), Austin, Texas. The NNSGRC was established in 1999 and is funded through a cooperative agreement between the Department of Pediatrics, UTHSCSA and the Maternal and Child Health Bureau (MCHB) of the Health Resources and Services Administration (HRSA). I am pleased to have the opportunity to testify before you today regarding current and past activities in newborn screening, some of the challenges that lie ahead and how you might assist us in making a better screening system.

Previous to directing the NNSGRC, I worked for 28 years at the Texas Department of Health Bureau of Laboratories during which time I served for 20 years directing the newborn screening laboratory. This laboratory routinely analyzed samples from over 2,500 babies daily and, as such, provided newborn screening for more babies than any other laboratory in the world. As part of my newborn screening activities, I was an active participant in activities of the Council of Regional Networks for Genetic Services (CORN), a national umbrella organization coordinating national and regional activities in genetics. In that role, I was the recipient of a small CORN subcontract for collecting, assimilating and publishing annual reports of national newborn screening data voluntarily reported by state and territorial newborn screening programs. This data gathering activity was a cooperative activity with the Association of Public Health Laboratories and has continued as an activity of the NNSGRC. Annual national newborn screening reports since 1996 are now available on the Internet at our website: http://genes-r-us.uthscsa.edu.

The NNSGRC was established to: (1) provide a forum for interactions between MCHB and others regarding policy initiatives and emerging issues in newborn screening and genetics; (2) provide consultation and technical assistance to public health agencies in their newborn screening and genetics activities through expert technical assistance; and (3) develop and implement strategies for providing educational opportunities in newborn screening and genetics, particularly for the public health community. We are now in our third year of operation and have just received funding for another 5 years with a budget of approximately 3.5 million dollars for the agreement period.

Since 1987, HRSA has supported a newborn screening technical review and assistance team comprised of experienced experts in various aspects of the newborn screening system. This team was formed in response to state and territorial health department requests for federal assistance in improving the delivery of newborn screening services. It has been my privilege to serve as a member of this team since its beginning and now it is my role to respond to state requests for assistance through the continuation of this service. During the 15 year period, the team has have reviewed and provided technical evaluations and assistance to over 25 state and territorial newborn screening programs. As a result of the findings of our early reviews, we published (through CORN) a guide for newborn screening programs in which we outlined and commented on the components of a successful newborn screening system, which was reported in the journal Screening in 1992. In debating the various roles and activities of newborn screening, we arrived at its definition as an essential public health program that prevents catastrophic newborn health problems through early detection and treatment of disorders that may be totally or partially asymptomatic at birth. Further, we recognized that efficient and productive outcome from newborn screening occurs only through smooth integration of all parts of the screening system that includes: education, screening, diagnosis, treatment, case management, and system evaluation/improvement. While there is not a national law providing guidance to states on how newborn screening systems should be implemented or how they should function, state legislatures have nonetheless developed laws concerning newborn screening in all states. However, because of the complexities involved in testing, follow-up, and treatment, and the differing political and economic environments across the states, operation of newborn screening varies widely from state to state.

As you may be aware, newborn screening began in the early 1960s with the work of Dr. Bob Guthrie at the State University of New York at Buffalo. He developed a relatively simple and inexpensive test for detecting phenylketonuria (PKU) on blood obtained from a newborn’s heel a few days after birth. These samples could be collected on special filter paper cards, air dried and sent to testing laboratories through the mail making samples easy to collect and transport to centralized facilities. While Guthrie had scientifically validated his technique, because of the relative rarity of PKU, it took consumer advocates to convince public health departments of the cost effectiveness and need for this type of screening. Because early detection and proper dietary treatment of patients with PKU could be demonstrated to essentially eliminate the mental retardation normally resulting from untreated cases and a corresponding decrease in PKU patients residing in state-funded mental institutions conserved tax dollars, most state legislatures accepted the responsibility of funding these screening programs from tax revenues. And even though PKU is a genetic disorder predominantly occurring in Anglo-Europeans with a U.S. frequency of about 1:15,000 (much lower in Hispanics and African Americans), screening was universally mandated on the states’ newborn populations, thus becoming the first such population-wide genetic screening program in the nation.

The implementation of state screening programs for PKU generated interest in the identification of other disorders that might be detected from the same sample with little or no extra effort and expense. Thus, additional tests were developed for other metabolic disorders [such as maple syrup urine disease (MSUD), homocystinuria (HCY), and galactosemia (GAL)], disorders of the endocrine system [such as congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH)], and hemoglobin disorders [such as sickle cell anemia (S,S Disease)]. During the 1970s, automated sample preparation devices were developed and commercial kit manufacturers began to market test kits for detecting some of these disorders including primary congenital hypothyroidism with an incidence of approximately 1:3,500 (lower in African Americans, higher in Hispanics and Native Americans). Thus, newborn screening became even more cost effective since CH, which also results in mental retardation if untreated, was more frequent, and screening for two or more disorders from the same blood spot increased the probability of detecting a disorder.

Automated sample preparation provided an opportunity to increase the number of disorders included in screening at no additional increase in expense for sample preparation. As a result, some states began adding disorders to their screening programs as funds were available and as local agreement could be reached on which disorders should be added. Usually the decisions to add disorders were based on criteria related to incidence of the condition, cost for the screening test, and outcome from early detection and treatment. Even as newborn screening expanded in some states, others were still developing legislation for screening for PKU and/or CH. It was apparent in some states that tax revenues could not fully support screening and fee-for-service financing began. Today, all but eight states charge a fee for providing newborn screening services and most hospitals also collect a fee to administer the program and collect the sample. These costs are often included in the birthing facilities maternity service package.

During the 1980s, program efficiency increased through the use of micro-computers and scientific research began to focus more on genetics and the human genome. Some newborn screening programs also began pilot testing for cystic fibrosis (CF), although most legislatures did not support this testing because there was no CF cure available, choosing instead to focus on conditions that saved lives or reduced morbidity. In the 1990s, blood spots on filter paper were found useful as sources of DNA and some newborn screening programs began using DNA testing as a second tier test for rapid confirmation of sickle cell diseases and cystic fibrosis. Researchers also developed mechanisms for using dried blood spots as suitable sample sources for analysis with mass spectrometers thus potentially expanding newborn screening capabilities to even more disorders. When it was shown that two mass spectrometers coupled together (tandem mass spectrometry - MS/MS) increased the sensitivity, specificity and speed of mass spectrometry testing even further, its use became viable for pilot testing in newborn screening. Several State programs have now expanded their testing panels to take advantage of this testing methodology. Testing with MS/MS has not been without controversy since it allows detection of disorders that may not yet have a curative treatment and disorders that may be extremely rare. Arguments concerning the rarity of individual disorders are countered by the fact that groups of rare disorders can be simultaneously detected through the screening technique. Thus, in determining cost effectiveness, the cumulative incidence of the groups may be more appropriate as the determining factor rather than the incidence of individual disorders.

Debates about how best to determine newborn screening policy have existed since the beginning of screening. International discussions began shortly after Guthrie developed his screening techniques. The criteria used by most screening programs to decide the disorders for inclusion were developed as a result of World Health Organization (WHO) interest in the late 1960s. The WHO criteria state that screening should not take place unless the disorder screened meet certain screening criteria including:

1. The condition sought should be an important health problem.
2. There should be an accepted treatment for patients with recognized disease.
3. Facilities for diagnosis and treatment should be available.
4. There should be a recognizable latent or early symptomatic state.
5. There should be a suitable test or examination.
6. The test or examination should be acceptable to the population.
7. The natural history of the condition, including development from latent to declared disease, should be adequately understood.
8. There should be an agreed policy on whom to treat as patients.
9. The cost of case finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.
10. Case-finding should be a continuing process and not a “once and for all” project.

Subsequently, the National Academy of Sciences and others have commented on these criteria, particularly with respect to their preference for a consent process, but have not suggested significant changes in these criteria. The introduction of MS/MS has intensified the argument that these criteria may be outdated because of the technical ability to simultaneously detect any of a number of disorders from one analytical sample.

The federal government has taken a leadership role in assisting public health programs and the medical community in reevaluating the intent, extent, effectiveness and efficiency of newborn screening for the public’s benefit. In 1999, HRSA funded the American Academy of Pediatrics (AAP) to convene a Task Force to reassess newborn screening programs and to develop a national newborn screening agenda. The result was a report, published in the journal Pediatrics in 2000, outlining cooperative public (government) and private efforts that must occur nationally to assure that newborn screening continues to meet its mission as an essential public health prevention program. Perhaps most notably this task force report pointed to discrepant newborn screening systems across the country as an equity issue that should be addressed at a national level. In particular, the Task Force noted that the number of disorders included in state screening systems varied from as few as 3 in some states to as many as 27 in others. Thus, depending upon where a birth occurs, a newborn with a serious debilitating condition may receive screening and early detection and treatment leading in one location, while in another location the condition may go undetected with resultant catastrophic consequences. The Task Force identified newborn screening financing to be complex and significantly variable across the country. The cost to patients for the state mandated portion of screening varies from free in several states to as much as $60 in others. There was little or no comparative relationship between fees and the number of disorders in the screening panels nor to the follow-up services available. The quantity and quality of follow-up services provided as part of the screening systems were also found to vary widely from program to program.

In response to questions about newborn screening fees, the NNSGRC has gathered fee information from each program (see Table 1). This information was obtained through telephone contact with various program personnel in the state newborn screening programs. Without more detailed analysis and information, it is not possible to comment on services provided or program efficiency and effectiveness. The data are useful, however, in illustrating the extent of variability in newborn screening financing schemes across the nation. Other information included in the table includes total births occurring in each state for the year 2000 (latest available from National Center for Health Statistics), the number of different disorders included in the screening panel and the number of routine screening collections required by program rules or state law (some programs require two tests on all newborns - one shortly after birth before leaving the hospital and another at one to two weeks of age - to increase the detection of some disorders that might be missed by very early screening.). An attempt has been made to allocate portions of collected fees to laboratory testing and follow-up activities based on the telephone survey. Any additional information given by the responder regarding outside follow-up services paid from fees is also listed, however, this information is incomplete and systematic data verification has not been made. Medicaid birth data for 1998 (latest available - see notes in table) are also included in Table 1 since newborn screening is allowed as a Medicaid benefit, and a significant number of births nationally qualify for Medicaid. Each state has its own method of determining the amount and method of Medicaid reimbursement for newborn screening services and, therefore, the amount of Medicaid reimbursement across states is also extremely variable. Federal MCH block grant funds may be used in support of newborn screening activities, and the amount used in this way also varies from state to state.

Over the years, some states with limited numbers of births have found it more cost effective to contract with larger states for laboratory and other follow-up services. In some states contracts exist with university medical center facilities or private pathology laboratories to provide testing services and in at least one state, a hospital laboratory and an outside commercial laboratory provide some testing services. The map below (see Figure 1) identifies the location of current newborn screening laboratory activities across the country. Note that in the Northwest, the Oregon public health laboratory serves the states of Oregon, Idaho, Nevada, Hawaii and Alaska. In the Northeast, the University of Massachusetts affiliated newborn screening laboratory serves Massachusetts, Maine, New Hampshire, Vermont and Rhode Island. The public health laboratories in Iowa, Tennessee and Colorado provide services for their own states and for North Dakota, Mississippi and Wyoming respectively. In Nebraska and Indiana, contracts exist with the university medical centers and additionally in Nebraska a second contract exists with a commercial pathology laboratory. In South Dakota, there is a contract with a commercial pathology laboratory and in Pennsylvania and the District of Columbia there are contracts with the same commercial newborn screening laboratory located in Pennsylvania.

The availability of MS/MS as a viable laboratory technology for newborn screening has created a complex question for newborn screening programs. The initial expense of the instrumentation is high and the skillful interpretation of results is demanding. Additionally, the availability of appropriate medical expertise for follow-up of the screening results is sparse and the true incidence of the conditions available for screening is not well studied. Since early detection of rare disorders by MS/MS through newborn screening is relatively new, the resultant clinical outcomes from the screening process are not yet established. Treatment for some of the detectable disorders may not result in a cure for the disorder. The net result has been conservative implementation of MS/MS screening in many states. In some states where MS/MS expertise and equipment are not available in the screening program or where MS/MS testing is not yet thought to be cost effective, new laboratory contracts between states have developed so that patients desiring this testing option may obtain it. Because of the way the technology operates, however, variable numbers of disorders may be available in different laboratories. Some programs have taken the point of view that this type of testing is still in the research phase until more information is available on incidence and outcome, and have therefore introduced the obligation of informed consent (opt in) for certain MS/MS tests as opposed to the normal procedure in their mandatory program of informed dissent (opt out). All of this is compounded by the fact that many state newborn screening programs still do not screen for all of the disorders readily detectable by well established technology for which outcomes and incidence are better known (see Figure 2). The map below (Figure 3) illustrates the currently availability of expanded newborn screening for disorders detectable with MS/MS. The current situation since the technology allows for detection of some of the traditional amino acid screening disorders and because some states have mandated one or more disorders while providing others as options that may be selected by the parent. Note, for example, that the programs in South Dakota and Nebraska provide expanded screening as an option and the follow-up, and therefore the incidence and outcome data, are coordinated through the state newborn screening program through contract with the testing laboratory at the Institute for Metabolic Disease in Dallas, TX. Similar, although not identical, testing arrangements are offered as options in Montana (through the Wisconsin newborn screening laboratory, Hawaii (pilot testing in cooperation with the California newborn screening reference laboratory, and North Dakota (pilot testing in cooperation with the Iowa newborn screening program. The Massachusetts newborn screening program requires one test that must be performed with MS/MS and offers optional testing to its residents for expanded MS/MS testing and cystic fibrosis testing. Because the Massachusetts laboratory serves most New England States, the same testing is available to other states in the region (ME, VT, NH, RI); however, its utilization is realized differently in each state. Each of the programs indicated as having a screening mandate to utilize MS/MS testing has implemented it to a different degree (that is, each state screens for a different panel of disorders depending on the advice of its advisory committees). Screening is offered to hospitals and physicians desiring to submit samples by commercial or non-profit laboratories in several locations with predominance in this market realized by two laboratories (one in Pennsylvania and one in Texas, as indicated on the map). At least one state law (Mississippi) has been changed to require physicians to notify parents of the availability of expanded newborn testing outside of the state mandated screening.

In cases where testing is obtained outside of the routine screening system, it is often unclear as to the mechanisms by which samples are collected (including liability and financing) and the extent to which follow-up of abnormal or questionable results is available. Thus, in many cases these components of the newborn screening process are “absorbed” by hospitals and state follow-up systems. Similarly, the education of consumers and professionals concerning the meaning of expanded newborn screening and interpretation of its results is often overlooked. Such education is an essential component of the system and also recognized as a difficulty in state newborn screening programs where monies are often available only for testing and related follow-up. Education has become an increasing problem as the science of newborn screening has increased in complexity. Quality assurance of the system, particularly the laboratory, is always problematic, however, steps have already been taken by the Centers for Disease Control and Prevention (CDC) to assist the testing laboratories in testing implementation, and these services are available to both public and private laboratories.

Figure 4 illustrates the extent to which expanded screening with MS/MS is advancing. By the end of the year, over half of the states will have either MS/MS testing capabilities or the availability of such capabilities. The largest problem facing these programs is the lack of sufficient human resources trained in testing, result interpretation and follow-up (including trained biochemical geneticists). The second largest problem is sufficient education of health care professionals and consumers who will interact with the screening system.

CONCLUSION

So, Mr. Chairman and members of the Subcommittee, I think you can see that newborn screening is much more than just a laboratory test and its implementation for the benefit of the public’s health is complex. As I mentioned, newborn screening education of both health professionals and the public is a pressing need, particularly with the continuing advances in technology and the ability to detect more disorders. The emerging and evolving technologies are creating increased challenges for an already overburdened system. Each new disorder added to a newborn screening system brings with it complex issues of testing and follow-up, but it also creates new information about the history of the disorder. Often there is reluctance to offer new testing without reliable information about incidence and treatment outcome resulting from early diagnosis, but this information cannot be obtained without the testing.

To assist in the education needed with implementation of MS/MS testing in state newborn screening programs, the NNSGRC has co-sponsored (with HRSA, CDC, and APHL) two national working meetings on integrating MS/MS into newborn screening programs and plans for a third meeting are underway. Additionally we have co-sponsored two workshops for laboratory technologists in order to assist state programs in meeting their needs regarding trained personnel to operate the laboratory portion of this expanded testing. As you might imagine, such training is difficult to accomplish since the facilities and trainers available for such training are limited and the training must be done in small groups to provide the necessary level of customized instruction needed. Additional workshops are planned along with new workshops for non-laboratory personnel who serve in the role of transmitting the laboratory information to the physician community for confirmation and diagnosis.

To meet the needs of the public health screening community seeking to know the results being obtained from MS/MS screening projects, the NNSGRC has organized a data-sharing consortium of programs with information to share. By sharing analytical information as cases are detected, screening laboratories are more likely to improve the analytical sensitivity and specificity of their testing techniques faster. Otherwise, because of the rarity of the cases detected, individual screening laboratories may accumulate this program evaluation data only at a very slow rate thus hindering the rapid implementation of the screening technology.

More education, data sharing, and program improvement is needed and this requires financial resources. I hope that this committee will agree with this needs assessment and will consider how it might assist in this effort. Congress has authorized Title XXVI of the “Children’s Health Act of 2000” (P.L. 106-310) which provides an opportunity to improve and assist state newborn screening programs, but funding has yet to be established. While, several federal initiatives have occurred in response to the AAP Task Force report, and these are commendable, more is needed if we are to have widespread efficient and effective newborn screening. There must be a larger pool of trained technologists, trained physicians, trained nurses, trained counselors, and trained public health professionals in order to meet these pressing needs. It is essential that more and better information about newborn screening be given to the general public. State newborn screening systems cannot adequately meet these demands and it will take more support from the federal government if we are to overcome the national issues of newborn screening equity and availability.

I support strongly the actions of Dr. Van Dyke and HRSA in their plans to organize the Advisory Committee on Heritable Diseases in Newborns and Children created by Title XXVI. Ongoing efforts to address issues of consent and privacy in newborn screening and the development of a national panel of tests will provide badly needed guidance for consideration by this Committee, but implementation of any of the suggestions in these deliberations will require financial support and more education.

The concept of regional centers for treatment referral for the rare disorders identified through screening provides a sensible and cost effective approach to assisting in geographic areas where needed medical expertise is not available and this, too, will require financial support. Likewise, efforts by HRSA and CDC to expand education, research, and quality assurance related to implementing new screening technologies, and improving and enhancing newborn screening programs that already exist, will provide some of the needed support for state programs. Continued emphasis on the provision of a satisfactory medical home for all newborns is also needed along with better education of the public and the healthcare community as to how this can best be accomplished for families impacted by a disorder detected through newborn screening.

The NNSGRC has taken an active role in seeing that there is an information resource available and in supporting, to the extent possible through our funding, education and technical assistance to state and territorial health departments in the area of newborn screening. We are committed to continuing these efforts and to assisting federal and state agencies in whatever way we can to improve newborn screening programs across the country. We know that newborn screening saves lives and hope that we can help in assuring the highest quality, efficient, effective and equitable newborn screening possible for all newborns.

Thank you Mr. Chairman and members of the Subcommittee, for the opportunity to testify today, and I will be happy to answer any questions that you may have.

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