Report 9 of the Council on Science and Public Health (A-06) Full text

Standardization of Newborn Screening Programs

Note: This report, written in response to Resolution 530 (A-05), represents information on this subject as of June 2006.

Full text

American Medical Association (AMA) policy on newborn screening endorses efforts to standardize outcomes and guidelines for state programs (Directive D-425.995, AMA PolicyFinder) and supports the continued monitoring and improvement of testing paradigms used in screening (D-480.989).  AMA policy also recognizes that genetic testing of children is an area of particular sensitivity and complexity, where issues of informed consent and clinical benefit must be thoroughly considered (Ethical Opinion E-2.138), along with the potential advantages and disadvantages of multiplex testing formats (E-2.139).    In addition, reports from the Council on Scientific Affairs (CSA) and the Council on Ethical and Judicial Affairs (CEJA) have reviewed various challenges facing newborn screening programs in the United States.  These issues include efforts to create national criteria for newborn screening (CSA Report 4, I-01),¹ the use of DNA-based tests for identifying neonatal metabolic and genetic disorders (CSA Report 3, A-03),² ethical concerns related to genetic testing of children (CEJA Report 4, A-95),³ and use of multiplex formats in genetic testing (CEJA Report 1, I-96).⁴

Recommendations issued by various national advisory committees and national medical specialty and public health organizations have played a vital role in shaping newborn screening programs in this country.  Due to a lack of national consensus and guidance, however, there is a large disparity in screening services offered to newborns by each state.  To address the lack of uniformity among state newborn screening programs, the Health Resources and Services Administration (HRSA) has recently released a draft report outlining a process of standardization of outcomes and guidelines for newborn screening, including a uniform panel of disorders to include in state newborn screening programs.  Accordingly, this report reviews recent efforts to develop and implement nationally recognized newborn screening standards and policies.

Methods

Literature searches were conducted in the MEDLINE database for English-language articles published between 2000 and 2006 using the search terms newborn screening and newborn genetic testing.  In addition, this report reflects a review of two recent studies evaluating newborn screening programs in the 50 states and the District of Columbia.  The report from the first study, conducted by the U.S. General Accounting Office in response to a congressional request for information on variations among the state newborn screening programs, was released in 2003 and is entitled Newborn Screening: Characteristics of State Programs.⁵  A draft report from a more recent study, conducted by an expert panel convened by the American College of Medical Genetics (ACMG) and sponsored by the Maternal and Child Health Bureau (MCHB) of HRSA, was released in March 2005 and is entitled Newborn Screening: Toward a Uniform Screening Panel and System.⁶  A final version of this report is expected to be released in 2006 by the Department of Health and Human Services (HHS) after consideration of public comments; approval by the Secretary of HHS is pending.

Introduction

Newborn screening is recognized as an essential public health tool, intended to ensure the best outcome for the nation’s newborn population.  Because the vast majority of conditions tested are genetic-based, newborn screening is also thought of as a model for public health-based population genetic screening. Newborn screening programs are designed to detect and provide treatment for congenital disorders that if left untreated would lead to early mortality or severe lifelong disability.  It is estimated that one in every 800 infants in this country is born with a potentially severe or lethal condition for which screening and treatment could prevent future medical complications.⁵

The first newborn screening programs in the United States were initiated during the 1960s to detect the congenital disorder phenylketonuria (PKU).⁷  PKU is an autosomal recessive genetic condition resulting from a deficiency in a specific liver enzyme (phenylalanine hydroxylase) that impairs metabolic breakdown of the amino acid phenylalanine.  Although neonates are usually asymptomatic, affected infants begin to exhibit neurological disturbances by 6 months of age due to a build up of toxic levels of phenylalanine.  Without dietary restriction of this amino acid, children with PKU will develop profound and irreversible mental retardation.⁸

More than 150 million newborns have been tested since the first screening programs were instituted more than 40 years ago.⁵  Since that time, advances in understanding of genetic diseases coupled with technological improvements in analytical testing have greatly increased the number of conditions considered appropriate for newborn screening panels.  Like PKU, many of these disorders involve enzyme deficiencies that disrupt essential metabolic pathways, allowing metabolites to accumulate to toxic levels that can result in developmental delays, seizures, mental retardation, or death.  For many of these disorders, treatment involves dietary management and monitoring.  Not all disorders included in newborn screening involve inborn errors of metabolism, however.  Many states also screen infants for endocrine disorders (eg, congenital adrenal hyperplasia, congenital hypothyroidism), various hemoglobinopathies (eg, sickle cell anemia, beta thalassemia), cystic fibrosis, hearing deficiencies, and certain infectious diseases (eg, HIV and toxoplasmosis).⁹

Newborn screening is a state public health activity and as such, each state is responsible for designing and implementing its own programs.  While newborn screening is available to all infants born in this country, states vary widely in the number of disorders for which they routinely screen or offer optional screening.  For example, some states mandate screening for as few as eight conditions while others screen for as many as 57. ⁹  Currently, only three disorders (PKU, congenital hypothyroidism, and galactosemia) are universally screened for in all 50 states and the District of Columbia.  Table 1 lists by state the number of disorders for which screening is mandated or made optional (PDF, 30 KB).

State programs differ not only in the disorders for which they screen but also in the testing methodology they use.  Many state programs have expanded their newborn screening panels due to recent advances in an analytical procedure called tandem mass spectrometry (MS/MS).¹⁰  The advent of MS/MS technology now enables the reliable, simultaneous analyses of >20 different metabolites in a short duration run from a single blood-spot specimen.¹¹  Tandem mass spectrometry makes it possible to use a single test to screen for a wide range of rare disorders that in the past had to be assayed individually using different testing formats.¹²  Currently, almost 40 states use this technique to some extent in their screening programs to identify congenital metabolic disorders associated with defects in fatty acid oxidation, organic acid, and amino acid metabolism.  It is anticipated that most, if not all, states will use tandem mass spectrometry in the near future because public health programs are under increasing pressure to adopt this technology in order to expand the repertoire of disorders for which they screen.  An updated list of disorders included in each of the state programs, including their MS/MS panels, is maintained by the National Newborn Screening and Genetics Resource Center (NNSGRC).⁹

The array of newborn screening tests performed by each state is re-evaluated and updated periodically.  In most cases, decisions about screening panels are delegated to state health officials, state boards of health, or advisory committees.⁵  Many of these advisory committees seek input from experts and other state or private newborn screening laboratories in addition to independently reviewing available scientific evidence before making any recommendations.  In some states, decisions about screening are left to the state legislature since it controls the state public health system and its finances.  Common criteria used by states to evaluate whether disorders should be included in their newborn screening panels include evidence of benefit of early intervention, the availability of a sensitive and specific screening test, disease incidence, and costs associated with screening and follow-up.¹³

Differences between state programs extend beyond variations in their individual screening panels and are often related to differences in the public health infrastructure of each state.⁵  For example, while most states offer educational materials for providers (eg, collection and submission of specimens, management of disorders, medical specialists available) and parents (eg, information on how blood specimens are obtained, disorders included in the state’s program, how parents will be notified of testing results), less than 25 percent of the states inform parents of their option to obtain tests for additional disorders not included in their state’s required panel.⁵  In addition, while all state programs notify health care providers of abnormal testing results, less than half routinely notify parents directly of abnormal results, and <25 percent of states have a procedure in place to ensure that testing results are properly communicated to the parent.¹⁴

Other differences between programs include observations that only approximately 75 percent of states indicate that actions taken in response to abnormal results include testing from a second specimen when the initial result is abnormal or unsatisfactory.⁵  Moreover, only about 65 percent of states conduct periodic follow-up on newborns diagnosed with a disorder, which may include monitoring health status and ensuring that the patient continues to receive treatment.  Finally, a lack of uniformity exists among state programs on parental consent for screening and public disclosure of testing results.⁵  Only two states require parental consent for newborn screening.⁵  Thirteen states allow exemptions from screening for any reason, 33 states allow exemptions for religious reasons only, and five states do not allow any exemptions.⁵  More than half of the states have provisions specifying that newborn screening information is confidential, although many will waive this stipulation for certain purposes (eg, statistical analysis or research), often with the requirement that the identity of the subject is not released.⁵

The non-uniformity across state programs has prompted a call by advocacy groups, medical professionals and specialty societies, and other individuals for more prominent national involvement in newborn screening.¹⁵  With the exception of a 1996 U.S. Preventive Services Task Force recommendation that all newborns be screened for three disorders (PKU, congenital hypothyroidism, and sickle cell disease),¹⁶ there are no specific national guidelines on inclusion of disorders in state newborn screening programs.

Federal involvement in newborn screening

Several federal agencies perform activities related to newborn screening, including collecting and sharing information about state programs, promoting quality assurance, and funding screening services.  The MCHB has the primary responsibility for improving newborn screening in this country, a task consistent with its mission, which is to promote and improve the health of mothers and infants.¹⁷  This agency makes grants available to states (eg, Maternal and Child Health Service Block Grants) that can be used to support newborn screening services.  The MHCB also funds projects to identify strategies and develop materials for examination of the clinical validity and utility of new and emerging technologies.¹⁸  It also supports cooperative agreements with various organizations (eg, medical specialty, public health, and private sector) to educate physicians and families about newborn screening programs.

The MHCB has funded several national initiatives that benefit all state newborn screening programs.  The most prominent of these is the NNSGRC.  The Resource Center, supported by a cooperative agreement between HRSA and the University of Texas Health Science Center at San Antonio, collects information and develops annual reports on state newborn screening activities.⁹  In addition, it provides technical assistance to state programs and educational resources to health professionals, consumers, and the public health community.  The Resource Center also conducts individual and technical reviews of state screening programs on request and provides specific recommendations for improvement.  The states, however, are not obligated to implement these recommendations and the NNSGRC has no authority to require states to make changes.⁵

Recently, the MCHB established a network of Regional Genetics and Newborn Screening Collaboratives,¹⁹ which consists of seven regional centers that focus on the development of service infrastructure to improve newborn screening capacity and to equalize the distribution of genetic screening resources within regions.  The goal of these collaboratives is to develop regional coordinating plans; identify best practice models for optimal diagnosis, follow-up, and management; and design strategies for implementing these practice models.  The network also includes a National Coordinating Center operated by ACMG that focuses on minimizing duplication of efforts and maximizing interregional collaboration.  Other goals of the coordinating center include working with primary care providers to develop a network of genetic service centers, facilitating data information exchange with the appropriate offices at the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), working with various medical specialty organizations such as the American Academy of Pediatrics (AAP) and the American Academy of Family Physicians (AAFP) to design appropriate reimbursement codes, partnering with organizations such as the Joint Commission on Accreditation of Healthcare Organizations to bring uniformity of practice within hospitals for newborn screening programs, and encouraging information-sharing projects (eg, through telemedicine).²⁰

Other agencies within the HHS also offer services or perform activities to help state health departments maintain and improve their newborn screening programs.  In 2003, the HHS established the Secretary’s Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children (SACHDGDNC) to regularly review and report on newborn and childhood screening practices, and recommend improvements in the national newborn and childhood screening programs.^{13, 20}  Also, the CDC provides services that enable states to monitor and evaluate the quality of their screening programs.  All laboratories performing newborn screening voluntarily participate in the CDC’s Newborn Screening Quality Assurance Program (NSQAP) since it enables them to verify the accuracy of the tests they perform, a requirement for reimbursement by the Centers for Medicare and Medicaid Services (CMS).²¹  The NSQAP, operated in cooperation with the Association of Public Health Laboratories, offers proficiency testing for more than 30 newborn disorders, provides quality control specimens, and works with manufacturers to ensure the quality of filter papers used to collect newborn blood specimens.⁵  The CDC also maintains the National Center on Birth Defects and Developmental Disabilities.²²  This center oversees the Early Hearing Detection and Intervention Program, which is designed to identify infants with hearing loss by universal screening, confirm hearing loss by audiologic evaluation, and provide early intervention to improve cognitive development and communication skills.

The National Institute of Child Health and Human Development also sponsors research on newborn screening disorders, issues pertaining to the effectiveness of screening and treatments, and the application of new technologies for identifying congenital disorders.²³  In addition, the Children's Health Act 2000 authorized the HHS to award grants to improve and expand the ability of states to provide screening, counseling, and health care services for newborns and children who have or are at risk for heritable disorders and to evaluate the effectiveness of these services.⁵  The act also authorized the establishment of a committee to advise the HHS Secretary on reducing mortality and morbidity of newborns with congenital disorders.

Standardizing newborn screening programs

Historically, various expert panels, task forces, and federal agencies provided the foundation for advancing newborn screening.  One of the first national bodies to play a prominent role in developing guidelines to increase consistency among state newborn screening programs was the newborn screening committee of the Council of Regional Networks for Genetic Services (CORN).²⁴  The Council was established in 1985 and replaced by the NNSGRC in 1999.  That same year, the AAP and HRSA convened a Newborn Screening Task Force to address the lack of uniformity in newborn screening programs and seek a more definitive national agenda.¹⁵  The task force specifically recommended that HRSA “engage in a national process involving government, professionals, and consumers to advance the recommendations of this task force and assist in development and implementation of nationally recognized newborn screening system standards and policies.”  Recognizing that few existing systems were available for assessing conditions to determine their appropriateness for newborn screening, the task force recommended that federal and state public health agencies, in partnership with health professionals and consumers, develop and disseminate model state regulations to guide implementation of state newborn screening systems, including criteria for inclusion of disorders.

In 2001, HRSA contracted with the ACMG to convene an expert committee to analyze the scientific literature and use the best scientific evidence to develop a panel of disorders recommended for inclusion in all state newborn screening programs.⁶  Other specific objectives of this committee included formulation of model policies and procedures as well as minimum standards for state programs, development of a decision matrix that could be used by states considering program expansion, and consideration of the value of a national process for quality assurance and oversight.  The committee, referred to as the Newborn Screening Expert Group, initially defined the following set of guiding principles as a framework to identify criteria by which conditions were to be evaluated for inclusion in a standardized newborn screening panel: (1) newborn screening programs are an essential public health responsibility designed to improve the health outcome of affected children; (2) policy in this area should be driven by what is in the best interest of affected newborns with secondary consideration given to interests of unaffected newborns, families, health professionals, and the public; (3) newborn screening includes not only testing but is also a coordinated and comprehensive system consisting of education, screening, follow-up, diagnosis, treatment and management, and program evaluation; (4) programs should include centralized health information data collection for longitudinal assessment of disease-specific screening programs; (5) specimens are a valuable resource and policies should be in place to ensure confidential storage and appropriate usage; and (6) programs should include public awareness activities along with professional training and family education.⁶

Based on these principles, the Newborn Screening Expert Group developed criteria to evaluate disorders for consideration in a standardized newborn screening panel.⁶  The criteria focused on three main areas: clinical characteristics (eg, incidence, burden of disease if not treated, newborn phenotype), analytical characteristics of the screening test (eg, availability, platform feature, sensitivity, specificity), and characteristics of the condition itself, such as knowledge of its natural history, diagnosis, treatment, and management.  Certain other criteria (eg, cost) were also considered but had less influence compared to the objective criteria.  Eighty-four disorders were selected for evaluation using several parameters such as whether they were currently included in any private, state, or national screening programs; were coincidentally revealed by multiplex technologies used in newborn screening; or were recommended by members of public or expert groups as worthy of consideration.  Congenital disorders resulting from infectious diseases (eg, HIV, cytomegalovirus, and toxoplasmosis) were not considered since it was felt that the working group had insufficient expertise to adequately assess the appropriateness of these conditions in newborn screening.

A two-tiered analysis was completed to categorize each selected disorder.⁶  First-tier analysis of the 84 conditions consisted of gathering expert opinion from a wide range of individuals and organizations with interest in newborn screening.  The data collection instrument used was a survey that was made widely available to an indeterminate number of stakeholders.  The survey was constructed to collect expert information and to quantify expert opinion on the various features of the conditions.  Each of the conditions was then subjected to a second tier of analysis consisting of a systematic literature review concerning details on the screening tests, efficacy of treatments, and knowledge base about the condition.  On completion of this analysis, each of the 84 conditions was placed into one of three categories: core panel, secondary panel, or those not appropriate for newborn screening at this time.

Twenty-nine of the 84 disorders were identified as primary targets and recommended for inclusion in a standardized newborn screening core panel (Table 2 [PDF, 30 KB]).  These conditions were deemed most appropriate since each had a reliable screening test available, had an established treatment, and an adequate knowledge of its natural history existed.  Thirty-four states currently mandate screening, and five more offer optional screening, for at least 22 of the 29 core conditions.⁹  Twenty-three of the 29 core conditions are screened using a multiplex platform (eg, tandem mass spectrometry, high pressure liquid chromatography).^{6, 9} 

The expert group also identified a secondary target panel of 25 disorders that are often revealed as part of the differential diagnosis of a condition in the core panel, and could be screened for at minimal additional cost (Table 3 [PDF, 30 KB]).  These conditions were not included in the primary panel since they either lacked evidence of available efficacious treatment or there was inadequate understanding of the natural history of the condition, usually because of the rarity of the disorder.  The expert group suggested that the secondary target disorders be treated as “report only” since many do not have validated treatments available.  The expert group’s rationale for endorsing a secondary panel was to provide a mechanism to collect information on each of these disorders on a national level in order to better understand the disease process and facilitate the development of clinical treatments.  Thirty states currently either mandate screening or offer optional screening for at least 16 of the 25 secondary disorders.⁹ 

Finally, to assist states in the ongoing review of their newborn screening panels, the expert group consolidated its analytical framework into a decision-making algorithm that could be used to periodically reevaluate conditions that might not be appropriate for the core panel at this time, but whose status might change as new tests and treatments evolve.

In addition to developing the standardized testing panels and assessment tool, the expert group also suggested that state screening programs report to child health professionals any abnormal results associated with clinically significant conditions, including definitive identification of carrier status.  It also urged states to maximize the use of multiplex technologies and consider the range of benefits realized by newborn screening, including treatments that go beyond infant mortality and morbidity.  To facilitate implementation of these guidelines, it further proposed a number of changes in the current screening system, including conducting scientific evaluation of conditions and screening technologies at a national level, standardizing case definitions and reporting procedures, increasing uniformity in language and definition of performance standards (eg, repeat tests, second tests), improving communication of results and ensuring short-term follow-up of affected newborns, enhancing the oversight of hospital-based screening activities, promoting long-term data collection and surveillance, and giving more consideration to the financial needs of state programs.⁶

Public comments submitted by medical professional societies, non-profit advocacy groups, physicians, researchers, and private individuals during the report review period reflected overwhelming support for the ACMG recommendations, although some concerns were noted.²⁵  The Newborn Screening Expert Group was widely commended for its efforts to systematically and impartially evaluate a large number of congenital disorders for inclusion in a uniform newborn screening panel, but several deficiencies were noted in both the methodology employed and the data used to support recommendations in the report.  For example, there was no mention of how critically the data collection tool (survey) was evaluated in regard to both design format and the questions asked to ensure it conformed to standard professional practices.  The committee did not exercise control over how surveys were distributed and to whom, meaning it could not calculate a response rate or identify potential bias towards specific groups or advocates actively involved in newborn screening.  There was also little justification given for how the expert group decided on the scoring system applied to survey responses; consequently, it remains unclear whether the conditions on the primary panel are qualitatively different from conditions that were excluded.  In addition, the report stated that a basic cost-effectiveness study of newborn screening was performed; however, details of the study have only recently been published.²⁶ Finally, the report gave little insight or guidance on how state programs, primary care providers, and families will manage information generated on a large number of rare and complex disorders without readily available expertise to guide them.

Although the ACMG was not charged by HRSA to address ethical, legal, and social issues in its report, a small number of groups submitting public comment were nonetheless concerned that there was little discussion of the ethical questions that are fundamental to any debate about expanding newborn screening programs.^27-29  Among concerns are the anticipated impact of false-positive results and the ramifications of identifying disorders that it is unclear will ever cause disease.³⁰  There is a possibility that children may actually be harmed when unnecessarily placed on medications or restricted diets, and that false-positive results may have a psychological impact on parents who experience guilt and distress over the long-term health of their child.^30-32  There was also no significant discussion of the implications of mandating testing for disorders for which there is no recommended treatment, or for which the treatment lacks formal evidence of clinical benefit.^{29, 33} 

Despite concerns, the need for standardized newborn screening was almost universally acknowledged by those commenting, and the report was supported by several organizations including the AAP, the Society for Inherited Metabolic Diseases, the March of Dimes, Genetic Alliance, the National Society of Genetic Counselors, the Association of Maternal and Child Health Programs, the Association of Public Health Laboratories, and the American Association for Clinical Chemistry.²⁵  The American Academy of Family Physicians chose not to support the ACMG report, citing concerns that it failed to recognize the role of primary care physicians in managing patients and families of patients who test positive, and that it had methodological flaws and biases, including a lack of rigor in the evidence base for disorders recommended for standard screening.²⁵

Barriers to implementing national standards

Significant barriers to adopting nationalized standards for newborn screening, especially if they require expanding existing testing panels and associated services, have been identified in various reports and include issues relating to cost, scarcity of resources, and a lack of evidence confirming the clinical benefits and cost-effectiveness of current screening programs.^5,6,15  It is difficult, however, to address all these factors given the diverse political and economic environments of state public health systems.

While stakeholders agree that clinical evidence should be the primary factor in determining which disorders are included in state screening panels, they acknowledge that financial considerations are often the basis on which these decisions are ultimately made.  In 2001, the majority of states spent between $20 and $40 for each infant screened.⁵  State programs are funded primarily through newborn screening fees, which cover approximately 64 percent of yearly screening expenditures.⁵  In 2004, 44 states charged between $10 and $70 for screening, one state charged more than $100, and five states and the District of Columbia did not charge.³⁴  Most fees are paid by the birthing facility or health care provider, and in some cases, paid by Medicaid or private insurance.³⁴  State funding and federal grants are used to pay the balance of screening costs.  Newborn screening expenditures totaled approximately $120 million in 2001, with yearly state costs ranging from $87,000 to $27 million.⁵  Approximately 74 percent of screening costs are associated with laboratory expenditures (eg, analyzing samples, notifying health care providers and parents of test results, evaluating the quality of laboratory activities), while the remainder are related to program administration and follow-up expenses (eg, confirming infants received additional laboratory testing, confirming that infants diagnosed with disorders receive treatment, providing education to health care providers and parents). 

Newborn screening competes with other public health programs for limited resources, and adopting national standards, especially those mandating expanded screening panels, will require states to identify new funding sources.  Many states will undoubtedly be forced to increase their screening fees and look for additional funding from the federal government.^5,15  With respect to the proposed HRSA/ACMG standardized core panel of 29 disorders, financial shortfalls would probably be especially severe for the 16 states that currently mandate screening for 17 or fewer disorders, and most severe for those states that do not use tandem mass spectrometry in their mandated or optional screening programs.^{9, 34}

Pressures to expand newborn screening have brought public health officials under increased scrutiny to justify the cost of newborn screening compared to the value it provides to the public.¹⁵  Newborn screening has long been accepted as cost-effective based primarily on evidence for a small subset of disorders.^{35, 36}  The CDC recently reported that lifetime costs of developmental disabilities that can be prevented by newborn screening range from $500,000 to $1 million.³⁷  These figures include both the direct cost of care as well as productivity losses, with the former comprising less than half of the total.  A recent review of the literature, however, suggests that many of the economic evaluations used to demonstrate that screening programs more than pay for themselves through reduced costs of care are inaccurate and that expansion of newborn screening programs should not be assumed to be cost-saving.³⁸  Furthermore, several recently published studies report conflicting conclusions about the cost-effectiveness of disorders screened by multiplex platforms.^{26, 37-41}  These discrepancies suggest there is still insufficient information available to support a claim of cost-effectiveness for increased screening.  It must be kept in mind, however, that newborn screening is a public health activity focused on saving lives, preventing disability, and improving quality of life. Its cost-effectiveness should not be considered only in terms of financial savings, but also in respect to reducing infant mortality and maximizing health improvements with limited resources.^{15, 27, 33}

A second prominent barrier to standardizing and/or expanding state newborn screening programs is the lack of resources, especially at the local level. Shortages are particularly acute with regard to medical expertise, testing laboratories, and coordinated activities between child care health professionals and subspecialists.¹⁵  Lack of resources also applies to the increased workload newborn screening presents to primary care physicians who must inform parents of test results and provide routine and acute care for affected infants.  As mentioned above, the HHS has established a network of Regional Genetics and Newborn Screening Collaboratives to address some of these resource issues.  These collaboratives are designed to help state and local health agencies provide screening services and follow-up care for newborns with heritable disorders and to offer education and genetic counseling to their parents.¹⁹  Promoting regional interactions will also help improve screening activity at the local level by reducing costs, ensuring long-term treatment and services, and decreasing variability.  While the resources provided by federal funding will help, there are concerns that physicians are unprepared to handle the increased workload that expanding newborn screening will generate.^15,43

In spite of the fact that newborn screening programs have been in place for more than 40 years in this country, much of the evidence demonstrating screening program effectiveness is based on expert opinion rather than randomized controlled trials.^28,44,45  In addition, there is a lack of formal evidence demonstrating clinical differences in outcomes that can be attributed to therapies initiated as a consequence of pre-symptomatic testing.  While preliminary results indicate that children identified by screening have fewer developmental and health problems than children identified clinically, an urgent need remains for long-term tracking of data to enhance understanding of health outcomes, clinical course of disease, and effective treatments.^27,28  While most states are required to report newborn screening results to the federal government, they often submit limited aggregate data and for only a handful of selected disorders.  Moreover, differences in screening methodologies used by states often make it difficult to compare data between programs.

To address these limitations, the NNSGRC recently developed an online data collecting system, referred to as the National Newborn Screening Information System (NNSIS), that should improve the data and surveillance infrastructure for newborn screening.²⁰  While most states have committed to using this system, its success remains tenuous since supplying data on newborn screening is still neither mandated nor a defined program responsibility in most states.  In addition, the NNSIS faces several challenges, including the fact that data definitions are not consistent from one state newborn screening program to another, staff shortages and turnover affect data entry into the system, the quality of the data from some state programs is difficult to validate, maintaining data on babies moving into a state or living on the border is often problematic, and obtaining accurate data on military births is difficult.  While none of these challenges is insurmountable in and of itself, together they hinder the federal government’s efforts to gather reliable data that can be used to more accurately define disease incidence and health outcomes.

While some states perform adequate short-term follow-up on their newborn screening and report this information to the federal government, data on long-term follow-up are rarely tracked as completely.  Long-term follow-up is essential to understand morbidity/mortality, treatment efficacy, natural history of the disorder, psychological effects of the disorder, barriers to care, and the cost of care.  The fact that states are implementing similar technology (eg, tandem mass spectrometry) in newborn screening provides an opportunity to collect comparable long-term follow-up data from different programs.  Collecting this type of information, however, requires a tool for data collection, and a system to pool data to share nationally and internationally.  In 2002, the CDC awarded grants to Oregon and Iowa to develop a tool for collecting long-term follow-up data on newborns diagnosed with certain congenital metabolic disorders.  This database system is now being implemented in clinics in these states and being used to collect long-term follow-up data on newborns diagnosed with 26 disorders and on the newborns’ siblings.²⁰

Summary

Newborn screening programs now exist in every state, but the programs vary dramatically in the number of tests they offer.  The federal government and recognized stakeholders acknowledge the need for states to retain strong oversight of their public health screening programs to ensure appropriate delivery of testing and associated services.  A need clearly exists, however, for national guidelines and standardized policies that will help eliminate disparities between states and also improve the overall quality of screening programs.  A substantial challenge is to find a balance between costs and the need to perform uniform, comprehensive screening on all newborns, regardless of where they are born in the United States.

A great deal of effort has been put forth by various expert committees to increase the uniformity among state newborn screening programs.  The most recent efforts by HRSA in conjunction with the AAP15 and ACMG6 are steps in the right direction to eliminate differences and create a national set of guidelines and policies.  The ACMG in particular, should be commended for its efforts to generate a standardized screening panel along with a decision-making tool that states can use to more effectively evaluate and update their programs.  Its proposed core panel provides a foundation for progress in the creation of a national newborn screening panel.  Several states are already using the ACMG recommendations to consider and implement testing for an increasing number of disorders.  Continued discussions, which fully address the impact of screening and the potential benefits on a condition by condition basis and carefully consider issues relating to negative impacts, costs, and ethical concerns of newborn screening, will facilitate the establishment of a standardized panel agreed upon by the numerous medical specialties and government entities involved in newborn screening.

Recommendations

The following statements, recommended by the Council on Science and Public Health, were adopted by the AMA House of Delegates as AMA policy and directives at the 2006 AMA Annual Meeting:

1. The AMA recognizes the need for uniform minimum newborn screening (NBS) recommendations. (Policy)
2. The AMA will encourage continued research and discussions on the potential benefits and harms of NBS for certain diseases. (Directive)
3. The AMA will monitor developments in the effort to implement a uniform minimum newborn screening panel, including status of the pending Health Resources and Services Administration report entitled Newborn Screening: Toward a Uniform Screening Panel and System, and the ongoing expansion of required tests by each state. (Directive)

References 

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Resolution 530, introduced by the Medical Student Section at the 2005 American Medical Association (AMA) Annual Meeting and referred to the Board of Trustees, asks:

That the AMA support and recognize a need for uniform minimum newborn screening (NBS) recommendations; and

That the AMA encourage continued research on the benefits of NBS for certain diseases and the development of new NBS technology; and

That the AMA recommend the adoption of a national minimum uniform screening panel for newborns by establishment of model state legislation and encouragement of legislation for adoption by Congress, pending completion and a review of the evaluation by the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children.

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