Newborn Screening Timeliness: Most States Had Not Met Screening Goals, but Some Are Developing Strategies to Address Barriers
Released: 2016-12-15T00:00:00

Letter

Background

Newborn Screening Overview

Newborn screening for heritable and other conditions begins with a provider collecting a blood specimen from a newborn within a few days of birth. The newborn’s heel is pricked to obtain a few drops of blood, which are placed and dried on a specimen collection card, and then sent to a state lab for testing. (See fig. 1 for an example of a collection card.) State departments of health may use their own lab to test newborn screening specimens or may contract with a private lab, a lab at a university medical school, or another state’s lab. After testing, lab staff notify providers of either normal results or presumptive positive results, which indicate that a newborn may have a heritable condition, subject to follow-up testing to determine if the condition is truly present. Lab staff may report presumptive positive results to providers by, for example, fax or phone call before sending all normal and presumptive positive results.

The newborn screening process involves collaboration between providers and other hospital staff, lab staff, and state newborn screening officials. Providers and other hospital staff are responsible for ensuring that newborn screening specimens are collected and sent to the state lab for testing. Lab staff and follow-up staff, such as nurses and social workers, are responsible for entering demographic data associated with the specimen into the state’s laboratory information management system (LIMS), testing the newborn screening specimen, and reporting results to providers. Newborn screening officials at state departments of health support providers and labs with education, data, and resources.

Advisory Committee’s Time-Frame Goals

HHS’s Advisory Committee on Heritable Disorders in Newborns and Children, which was chartered to recommend newborn screening improvements in states and provide technical information and advice about newborn screening to the Secretary of Health and Human Services, established a Recommended Uniform Screening Panel (RUSP), which is a list of conditions for which newborns should be screened. A 2005 report prepared for the advisory committee to make recommendations for the RUSP also identified time-frame goals for individual stages of the newborn screening process, such as from specimen collection to arrival at the lab, for the conditions on the RUSP. Subsequently, in response to a public comment during a committee meeting in September 2013, the advisory committee took additional steps to address newborn screening timeliness concerns: In 2014, the advisory committee designated 16 of 32 conditions on the RUSP as “time-critical” conditions. These are conditions for which acute symptoms or potentially irreversible damage could develop in the first week of life, and for which early recognition and treatment can reduce the risk of illness and death.

Also in 2014, the advisory committee, in conjunction with APHL, conducted a survey and issued its 2014 Newborn Screening Timeliness Survey Report, which included information on barriers to and strategies for newborn screening timeliness identified by newborn screening officials in 51 states.

In April 2015, the advisory committee sent a letter to the Secretary of Health and Human Services with new time-frame goals. For example, the 2015 letter included time-frame goals for the full newborn screening process (from birth to results reporting) rather than from specimen collection to results reporting. Additionally, the 2015 letter added different time-frame goals for time-critical and non-time- critical conditions, and shortened the time-frame goal for a specimen arriving at the lab from 3 days after collection to 24 hours after collection.

The advisory committee’s 2015 time-frame goals included recommended time frames for completing the full newborn screening process—that is, from birth to results reporting:

All newborn screening results should be reported for all conditions to a provider as soon as possible, but no later than 7 days after birth.

Presumptive positive results for time-critical conditions should be reported immediately to a provider, but no later than 5 days after birth.

Presumptive positive results for all non-time-critical conditions should be reported to a provider as soon as possible, but no later than 7 days after birth.

The advisory committee’s 2015 time-frame goals also include time frames for the first two newborn screening stages (from birth to specimen collection and from specimen collection to lab arrival) to help states achieve the goals for the full process; the committee did not identify a time-frame goal for the third newborn screening stage (lab arrival to results reporting): 1. Newborn screening specimens should be collected in the appropriate time frame for the newborn’s condition, but no more than 48 hours after birth. 2. Newborn screening specimens should arrive at the lab as soon as possible; ideally within 24 hours of collection.

Finally, the advisory committee encouraged states to benchmark progress by meeting each of these time-frame goals for at least 95 percent of specimens by 2017. (See fig. 2 for more information about the 2015 time-frame goals.)

HRSA’s Newborn Screening Efforts

HRSA’s Maternal and Child Health Bureau has responsibility for enhancing, improving, and expanding the ability of states to provide newborn screening. HRSA oversees a number of programs that provide resources to improve newborn screening quality and increase newborn screening education. Following the enactment of the Newborn Screening Saves Lives Reauthorization Act of 2014, some of these programs focused on newborn screening timeliness.

One of these programs is NewSTEPs, which is administered by APHL under a cooperative agreement. NewSTEPs began in 2012 to offer a forum for collaboration among state newborn screening officials and other stakeholders; to facilitate continuous quality improvement and data-driven outcome assessments through a data repository; and to create a national newborn screening technical assistance center that provides training, addresses challenges, and supports program improvement through partnerships with newborn screening stakeholders. In 2013, NewSTEPs launched its data repository to collect annual newborn screening data from participating states. To participate in the data repository, states must sign an MOU with APHL; 35 states had signed an MOU as of November 20, 2016, according to HHS.

In response to requirements in the Newborn Screening Saves Lives Reauthorization Act of 2014 for HRSA to support timely newborn screening, NewSTEPs updated the data repository to collect timeliness data from participating states that are consistent with the advisory committee’s 2015 time-frame goals. For example, a state’s data in the repository include the percentage of specimens for which all results for all conditions were reported within the advisory committee’s goal of 7 days after birth. NewSTEPs can use each state’s reported percentage for a given time-frame goal to monitor the state’s progress toward meeting the advisory committee’s 95 percent benchmark in a given year—that is, whether screening was completed within a time-frame goal (e.g., 7 days) for 95 percent of a state’s specimens. Most of the states with signed MOUs began entering timeliness data into the data repository in mid- 2016.

In addition to incorporating timeliness data in NewSTEPs’ data repository, HRSA oversees NewSTEPs 360, a program that provides technical assistance and collects monthly data on newborn screening timeliness through grants to states. Administered by the University of Colorado’s School of Public Health, in collaboration with APHL under a cooperative agreement with HRSA, NewSTEPs 360 aims to improve timeliness in newborn screening by providing quality improvement training. For example, according to officials involved in administering the program, NewSTEPs 360 holds monthly quality improvement coaching calls intended to help each participating state develop innovative strategies that focus on timeliness barriers. In addition, participating states enter monthly timeliness data into the data repository. Twenty-eight states were participating in this program, as of October 26, 2016.

Most States Had Not Met the Advisory Committee’s Benchmark for Newborn Screening Timeliness, but Data Challenges Limit a Full Understanding of Timeliness Trends

Most states that reported timeliness data to NewSTEPs had not met the advisory committee’s 95 percent benchmark for newborn screening timeliness. Missing data for several states and variations in data collection limit a full understanding of newborn screening timeliness trends, but HRSA has been taking steps to address these challenges.

Most States that Reported Timeliness Data Had Not Met the Advisory Committee’s Benchmark, but Improved Over Time

Most states that reported 2015 timeliness data (the most recent data available) to NewSTEPs had not met the advisory committee’s 95 percent benchmark for newborn screening timeliness for all conditions within 7 days. However, timeliness for completing this screening process improved over time for the majority of states.

Timeliness Data for Reporting All Results for All Conditions

Most states reporting 2015 timeliness data to NewSTEPs, which collects annual newborn screening data from states, had not met the advisory committee’s 95 percent benchmark for completing the full newborn screening process (stages 1 through 3) for all conditions within 7 days. According to the advisory committee’s benchmark, by 2017, states should report newborn screening results for all conditions within 7 days of birth, for at least 95 percent of specimens. In 2015, 5 of the 27 states reporting timeliness data for this measure met this 95 percent benchmark. (See fig. 3.)

States’ timeliness for completing the full newborn screening process for all conditions improved over time. The number of states meeting the benchmark was higher in 2015 compared to the previous 3 years. Likewise, the median percentage of specimens screened within 7 days was higher in 2015 than in the previous 3 years. (See table 1.) According to NewSTEPs, there were 21 states that demonstrated improvement from 2012 to 2015.

In 2015, states also had not met the advisory committee’s benchmark for timely reporting of presumptive positive results for time-critical conditions. According to this benchmark, by 2017, states should report these results for 95 percent of specimens within 5 days of birth. In 2015, none of the 16 states that reported on this measure met the 95 percent benchmark. (See fig. 4.)

The states’ data for reporting presumptive positive results for time-critical conditions did not indicate consistent improvement over time. The median percentage of specimens screened for time-critical conditions within 5 days increased from about 23 percent in 2012 to 28 percent in 2014, but decreased to about 24 percent in 2015. NewSTEPs noted that reporting results for time-critical conditions within 5 days of birth may be the most important time-frame goal, and while the data indicate that states had difficulty meeting this goal in 2015, the data from 2014 indicate that achieving timely reporting for a high percentage of specimens is possible. For example, in 2014, two states reported meeting the 95 percent benchmark for time-critical conditions. (See table 2.) NewSTEPs also noted that time-frame goals specifically for time-critical conditions were not in place before April 2015 (when the advisory committee recommended the current time-frame goals).

For non-time critical conditions in 2015, 2 of 16 states reporting on this measure had met the benchmark of reporting presumptive positive results within 7 days of birth for at least 95 percent of specimens. (See fig. 5.)

The states’ data for reporting presumptive positive results for non-time- critical conditions did not indicate consistent improvement over time. The median percentage of specimens screened for non-time-critical conditions within 7 days decreased from about 52 percent in 2012 to about 49 percent in 2013, but then increased to about 52 percent in 2014 and about 55 percent in 2015. (See table 3.)

States that reported timeliness data to APHL generally had not met the advisory committee’s 95 percent benchmark for stage 1. In 2015, 10 out of 35 states that reported timeliness data for this stage had 95 percent of specimens collected within 48 hours of birth—a stage 1 goal. An additional 5 states did not meet the benchmark, but were close. (See fig. 6.) The median percentage of specimens collected within 48 hours of birth was about 93 percent, meaning that half of the states reported having about 93 percent or more of the specimens collected within 48 hours. (See table 4.)

In contrast to stage 1, none of the 34 states that reported stage 2 data for 2015 approached the 95 percent benchmark. (See fig. 7.) The median percentage of specimens arriving at the lab within 24 hours of collection was about 7 percent, meaning that half of the states reported having 7 percent or fewer of the specimens arriving at the lab within 24 hours of collection. (See table 5.) The NewSTEPs August 2016 report noted that the advisory committee’s 24-hour goal for specimen arrival is ambitious. NewSTEPs also measured the percentage of specimens each state reported arriving at that lab within 48 hours of collection and found that the median percentage of specimens arriving at the lab within that more generous time-frame goal was higher (about 53 percent).

Missing Data and Variations in Data Collection Limit a Full Understanding of Newborn Screening Timeliness Trends, but HRSA Has Been Addressing These Challenges

Missing data for a number of states limit a full understanding of newborn screening timeliness trends. The NewSTEPs August 2016 report included annual timeliness data for 38 states, but did not include any data for 15 states. According to APHL officials, none of the states expressly declined to provide data to NewSTEPs for the August 2016 report; however, some states did not respond to the data request, and some states’ officials indicated that they were willing to provide data, but could not do so in time, citing resource constraints. In addition, the 38 states that provided data did not do so for all time-frame goals or all years (2012 through 2015). APHL officials told us that the lack of data for certain time- frame goals or years was due to factors such as competing priorities or limitations in states’ information systems, specifically in LIMS. For example, APHL reported that two states do not electronically capture the date and time that test results are reported to providers, and newborn screening officials in those states could not search paper records in time to provide the data. Additionally, a few states had recently changed their LIMS, which resulted in limited access to data for some years.

Variations in data collection also limit a full understanding of newborn screening timeliness trends. According to APHL officials, the data in the NewSTEPs August 2016 report generally represent with accuracy the time taken to screen specimens in reporting states, but there are a number of limitations, including the following examples:

Although the advisory committee’s time-frame goals apply to first specimens only, some states’ data did not distinguish a lab’s receipt of a first specimen from receipt of a subsequent specimen, which can result in the appearance of longer screening times (that is, longer times from birth to specimen collection and birth to reporting results) for such states.

Variation exists in how state labs define specimen arrival at the lab, which can be the time a specimen is delivered by a courier, the time lab staff record receipt of the specimen in LIMS, or the time lab staff initiate testing of the specimen. This variation can affect the data reported for stage 2 (specimen collection to lab arrival).

Many states’ LIMS do not allow lab staff to record separate dates for when results for time-critical conditions and results for non-time- critical conditions from the same specimen card were reported to providers, even though time-critical results may be reported earlier. These systems typically include data entry fields that capture only the date that all results (presumptive positive and normal) for all conditions (time-critical and non-time-critical) were reported to providers, which can result in the appearance of longer newborn screening times for states with such systems.

With HRSA’s support, NewSTEPs has been taking steps to improve the completeness and consistency of the annual newborn screening timeliness data that states submit to the data repository. APHL officials told us that they expect to have all 53 states sign the MOU and enter data into the data repository. As participation in the data repository increases and data definitions are used more consistently across states, NewSTEPs can more accurately assess timeliness in states across the country. Steps taken by NewSTEPs include Increasing participation in the data repository. According to HHS, as of November 20, 2016, 35 out of 53 states had signed an MOU with APHL to provide annual data to the data repository for future analysis, and, therefore, receive data-related technical assistance from NewSTEPs. APHL officials told us they have been working with the remaining 18 states to address issues, such as confidentiality concerns, in an effort to have the MOUs signed. APHL officials say they have been reaching out to achieve buy-in from the remaining states through a variety of methods, including sending emails; making phone calls; conducting in-person meetings; incorporating reminders in webinars on newborn screening; and engaging with organizations, such as the American Academy of Pediatrics. APHL officials told us that while the data in the NewSTEPs August 2016 report provide a meaningful understanding of timeliness in a large number of states, they expect this understanding to improve as more states sign MOUs and submit data to the data repository.

Clarifying data definitions. NewSTEPs has also reviewed the data definitions used for the data repository to address variability in data collection and reporting among states. APHL officials said that, as a result of this review, NewSTEPs revised guidance documents for its data dictionary to, for example, more clearly separate screening timeliness data for first specimens from data for subsequent specimens. NewSTEPs is working with states participating in the program to help ensure they use these revised definitions consistently when submitting timeliness data to the data repository.

APHL officials told us they plan to publish state-specific reports on the NewSTEPs website by early 2017 to promote continuous quality improvement by allowing states and others an opportunity to review states’ progress toward meeting the advisory committee’s benchmarks. According to these officials, each state will be able to track its progress on a specific time-frame goal over time, as well as examine how its timeliness compares to that of other states.

States Identified Numerous Barriers Affecting Timeliness, and a Variety of Strategies Have Been Developed to Address Them

State newborn screening officials identified numerous barriers to timeliness in each of the three stages of the newborn screening process and developed a variety of strategies to address these barriers. HRSA, through its cooperative agreement for NewSTEPs 360, has been funding activities to provide technical assistance to states to address barriers and improve the timeliness of newborn screening.

States Identified Numerous Barriers to Timeliness throughout the Newborn Screening Process and Some States Have Developed Strategies to Address Them

Newborn screening officials from 51 states who responded to the advisory committee’s 2014 survey identified numerous barriers to timeliness in each of the three stages of the newborn screening process. Examples of barriers include a lack of understanding of the importance of timely screening among providers performing out-of-hospital births (stage 1), limited courier availability (stage 2), and insufficient lab operating hours (stage 3). Newborn screening officials in selected states told us they developed a variety of strategies to address these barriers.

Stage 1: Birth to Specimen Collection

Newborn screening officials who responded to the 2014 survey identified barriers to timely collection of newborn screening specimens. Barriers included nursing protocols that are not always consistent with advisory committee time-frame goals, lack of feedback to hospitals on timeliness performance, and lack of understanding of the importance of timely screening for out-of-hospital births. (See table 6.) Newborn screening officials in the four selected states we interviewed reported developing strategies to address the barriers.

Newborn screening officials from selected states reported that following nursing protocols that are inconsistent with the advisory committee’s time- frame goals can cause delays. For example, according to newborn screening officials in one state, nursing protocols often dictate that specimen collection be performed as late as possible prior to the baby’s discharge from the hospital. According to these officials, this protocol can result in late collection of some specimens; for example, among newborns born via Caesarean-section, who often have longer hospital stays. To improve the timeliness of specimen collection, this state recommended that hospitals make nursing protocols consistent with the advisory committee goal to collect specimens within 24 to 48 hours of birth, and has developed educational strategies to advise providers to aim for collection to take place within 24 hours of birth.

A lack of feedback from state newborn screening officials to hospitals was also identified as a barrier to timely specimen collection, according to newborn screening officials who responded to the 2014 survey, because providers may be unaware that they are not meeting timeliness goals. Officials we interviewed from three states reported developing or improving methods of providing feedback to hospitals through online quality reports or report cards. For example, newborn screening officials in one state we interviewed said they provide feedback to hospitals through report cards that evaluate hospital performance based on the advisory committee’s goal for timely specimen collection. The report cards are disseminated monthly and include an outlier report that alerts facilities when specific specimens do not meet the timeliness goal. According to the officials, these outliers showed problems with timeliness at neonatal intensive care units (NICU). As a result, the state began reporting NICU timeliness separately on the report cards; subsequently, newborn screening officials reported that NICU timeliness has improved.

Arizona’s Efforts to Address Barriers to Timely Screening for Out-of-Hospital Births Newborn screening officials in Arizona have focused on improving the timeliness of newborn screening for out-of-hospital births. Generally, according to newborn screening officials, babies born outside of a hospital—such as in birthing centers (freestanding facilities separate from hospitals) and home births—have higher rates of delayed specimen collection. Newborn screening officials in Arizona attributed this to a variety of causes, including a lack of understanding among providers about the importance of timely screening, and a lack of standardization of protocols for birthing centers and home births. For example, for healthy, low-risk deliveries outside of hospitals, midwives often leave 4 hours after the baby is born and may not follow up during the period when specimen collection should occur. Since 2011, Arizona has provided education and basic background training on newborn screening to midwives individually and through the state’s midwifery association to help address this barrier. Newborn screening officials explained that following the increased outreach and training, newborn screening timeliness for out-of-hospital births has improved, but noted that midwives continue to have problems seeking reimbursement for newborn screening services.

Stage 2: Specimen Collection to Lab Arrival

Newborn screening officials who responded to the 2014 survey identified a variety of barriers that may delay the arrival of newborn screening specimens at the state lab, including hospitals and other providers waiting to send specimens to the lab in batches, insufficient lab operating hours, and a lack of courier services for transporting specimens. (See table 7.)

One barrier to timely completion of stage 2 (collection to lab arrival) identified by officials responding to the 2014 survey was providers waiting to send specimens to the lab in batches. To address this practice, known as batching, officials from selected states reported employing strategies that involved providing feedback and training to providers at hospitals. According to newborn screening officials in one state, when specimens take more than 3 days from birth to arrive at a lab—which corresponds with the combined time-frame goals for stage 1 and stage 2—hospitals are asked to review those cases and avoid batching in the future.

Another barrier identified by officials responding to the 2014 survey is that lab staff are not always available to receive newborn screening specimens, because the lab’s operating hours do not align with courier service, mail, or other delivery service times. In three of the selected states, state officials told us that they addressed this barrier by having lab staff available on Saturday to receive and test specimens or to ensure they can be tested first thing Monday morning. Officials in one of these states also reported developing a process for cases in which a geneticist believes a baby’s specimen is likely positive for a time-critical condition. Under this process, the baby’s physician calls the state newborn screening program, and a courier or a state health official will pick up the specimen within 2 hours for transport to the lab for immediate testing.

Colorado’s Efforts to Expand Courier Service to Mitigate Geographic Challenges Newborn screening officials in Colorado told us that they expanded courier service to all hospitals in 2015 to address barriers to timely arrival of specimens at the state lab after specimen collection. According to these officials, prior to 2015, rural hospitals facing geographic challenges, such as long distances to the state lab, relied on mail services to transport newborn screening specimens to the lab. Beginning in April 2015, the newborn screening program’s courier service was expanded to all hospitals in the state, including these rural hospitals. Newborn screening officials explained that courier service is particularly beneficial for hospitals located long distances from the state lab, because it can include direct transport from the hospital to a nearby airport, a flight, and direct transport from the airport to the lab. In addition, courier service was expanded to have pick-up 6 days per week for all hospitals. This increase in courier service provides additional opportunities for timely specimen pick up from the hospital for transporting to the lab. According to Colorado newborn screening officials, these efforts have reduced specimen transport time for some facilities by up to 3 days.

Stage 3: Results Reporting

Newborn screening officials who responded to the 2014 survey identified barriers to timely results reporting, such as insufficient lab operating hours and labs’ reliance on the mail to communicate results. (See table 8.)

In addition to affecting timely specimen arrival at the lab, a lab’s operating hours may also affect how quickly staff are available to test specimens and report results. Officials from one state told us that their strategy to address this barrier included expanding lab operating hours to 6 days a week: specimens are processed Monday through Saturday, allowing the lab to report results for time-critical conditions to providers on Sunday instead of waiting until Monday.

Additionally, according to some state newborn screening officials we interviewed, another barrier to timely reporting is that some labs report results to providers via mail; as a result, providers could wait up to a week to receive results after they are sent. Newborn screening officials in one state told us that they updated provider records to include fax numbers and began faxing newborn screening results to providers. Newborn screening officials in two other states told us that they are beginning or planning to report presumptive positive results electronically prior to sending them by mail; for example, seven hospitals in one of these states are piloting a program that allows providers to electronically access results as soon as screening tests are completed at the lab.

Wisconsin’s Efforts to Improve Its Laboratory Information Management System Newborn screening officials in Wisconsin reported updating their laboratory information management system (LIMS) to align with newborn screening quality indicators to provide better feedback on newborn screening timeliness to hospitals, and to allow electronic messaging between hospitals and labs in the future, increasing record accuracy and reducing the need for manual entry. State newborn screening officials told us that to align LIMS with newborn screening quality indicators, they added new fields to LIMS to accurately measure time taken to complete the stages of the newborn screening process. For example, they explained that by adding a field in LIMS to record the time a specimen was received at a lab they can more accurately measure the amount of time between specimen collection and receipt at the lab. Newborn screening officials said that with this feedback, hospitals should be able to better identify changes needed to improve timeliness. Wisconsin also reported updating its LIMS to meet Health Level 7 standards, known as HL7, which provide a framework for health information retrieval and exchange from one information system to another (in this case from hospitals’ information systems to LIMS). Wisconsin newborn screening officials are working with hospitals to standardize information in their electronic health information systems so that newborn screening tests can be ordered electronically and LIMS can automatically retrieve and exchange demographic and other information from hospital systems, reducing the need for manual entry of information and increasing accuracy. Finally, Wisconsin officials told us that they are creating a web portal that allows providers to access the newborn screening results in LIMS for their patients online in real-time, reducing the amount of time taken to report newborn screening test results.

HRSA Has Started Supporting States through Technical Assistance to Help Address Timeliness Barriers

HRSA, through its cooperative agreement for NewSTEPs 360, has recently focused on improving newborn screening timeliness by funding activities to provide technical assistance to and information sharing among states. According to officials involved in administering NewSTEPs 360, since January 2016, they have held telephone calls to provide coaching to 20 of the 28 states participating in the program; these officials said they expect to begin coaching calls with the remaining 8 states by January 2017. The goal of these coaching calls is to help states achieve the advisory committee’s benchmark of timely reporting of newborn screening results for 95 percent of newborn screening specimens by 2017. According to newborn screening officials from two states that participate in NewSTEPs 360, the coaching calls help states prioritize their efforts to improve newborn screening timeliness and help states hold themselves accountable for meeting milestones, because they report on progress made during each monthly call. In addition, these officials said that participating in NewSTEPs 360 allows them to learn about strategies developed by other participating states. For example, officials in one state told us that they formed a small group of officials from states working to update their LIMS to meet Health Level 7 standards (known as HL7) for electronic health information exchange. (These standards provide a framework for health information retrieval and exchange from one information system to another—in this case from hospital information systems to LIMS.) According to these officials, participation in this small group helped them identify milestones to break their project into manageable pieces. The officials participating in the small group also said that they compared and shared strategies for meeting both these short- term milestones and their overall goal for updating LIMS.

Officials involved in administering NewSTEPs 360 told us the program has started taking steps to analyze and share information about barriers and strategies gathered from states that enter monthly timeliness data, and receive technical assistance through the program in order to help identify and promote the use of successful strategies. According to program officials, these steps include the following examples:

Sharing NewSTEPs’ August 2016 report on newborn screening timeliness, which contained information on activities that some NewSTEPs 360 states had undertaken to improve timeliness. The report included, for example, strategies for improving newborn screening education for providers.

Sharing information on lessons learned (such as factors that may predict newborn screening timeliness in hospitals) through an online video and presenting strategies at the 2016 APHL Newborn Screening and Genetic Testing Symposium.

Sharing information in messages sent to states through a listserv. For example, in September 2016, NewSTEPs 360 sent a message summarizing a new cystic fibrosis newborn screening timeliness initiative. For this initiative, NewSTEPs 360, in collaboration with the Cystic Fibrosis Foundation, convened stakeholders to identify strategies for reporting test results for cystic fibrosis in a more timely way.

Analyzing monthly timeliness data from states participating in NewSTEPs 360. According to APHL officials, as of November 16, 2016, 20 of 28 states participating in NewSTEPs 360 had entered monthly timeliness data into the data repository and the program had begun analyzing these data to track any progress in these states. These officials told us they expect that the remaining states will begin submitting monthly timeliness data by mid-December 2016.

Coding transcripts from the monthly coaching calls for states participating in NewSTEPs 360 to categorize and track barriers experienced by states and strategies developed to address them. As calls are completed over time, officials involved in administering NewSTEPs 360 believe this will allow them to compare the resulting data with the monthly timeliness data to measure the impact of developing a given strategy. These officials told us that they expect to present results from this analysis to all states (regardless of participation in NewSTEPs 360) in 2018.

In addition, HRSA also funded targeted technical assistance to help nurses improve newborn screening timeliness through NewSTEPs 360. Under a sub-award from NewSTEPs 360, the Genetic Alliance started providing training to nurses on the importance of timely screening. This includes, for example, free education on newborn screening specimen collection through an online training portal. According to an official at Genetic Alliance, the organization is also involved in identifying barriers that contribute to newborn screening delays and strategies to address such barriers. Based on information gathered in focus groups with nursery and NICU nurses held in June 2016, Genetic Alliance drafted a number of recommendations for hospitals and nurses to help address barriers to timely newborn screening. These recommendations include working with nurses to better integrate updated newborn screening guidance—such as the advisory committee’s 2015 time-frame goal for collecting newborn screening specimens—into nurses’ protocols for newborn screening.

It is too soon to determine which strategies, if any, developed through HRSA-supported technical assistance have a measurable impact on improving timeliness in states participating in NewSTEPs 360, and whether these strategies could be effective in additional states. The program began collecting monthly timeliness data from participating states in January 2016, and not all states have started entering data; eight states that were selected to participate in NewSTEPs 360 in October 2016 have not yet started participating in monthly coaching calls. In addition, Genetic Alliance has not yet issued its recommendations to hospitals and nurses. According to HRSA officials, the agency will be conducting annual monitoring of NewSTEPs 360, and a final report that includes performance measures for NewSTEPs 360 is required to be completed by late 2018. HRSA officials told us that the report will capture the extent to which states’ timeliness improved as a result of technical assistance received through the program.

Agency Comments and Our Evaluation

We provided a draft of this report to HHS for review and comment. In its written comments, reproduced in appendix III, HHS generally agreed with our data-supported findings, but noted two concerns about the conclusions we have drawn from the findings.

First, the department noted concern with our use of the advisory committee’s benchmark, which it encouraged states achieve to by 2017, to assess whether states screened newborns in a timely manner. We report that data provided by 38 states for 2012-2015 showed that states generally had not met the advisory committee’s recommended 2017 benchmark of meeting each time-frame goal for at least 95 percent of specimens. Our analysis is of the most recent data available, and our report states clearly that the advisory committee recommended states achieve these goals by 2017. Time-frame goals for completing newborn screening were initially identified in 2005, and concerns about the timeliness of screening date back to at least late 2013. Our analysis indicates that substantial work remains for the majority of states to achieve the recommended benchmark by 2017, based on the latest available information.

HHS also commented that our findings were limited by not including point-of-care screening within the definition of newborn screening. In the report, we include information on the 2 conditions—critical congenital heart disease, and hearing loss—that use point-of-care screening, and note that these are 2 of the 32 conditions on the RUSP. However, since these two conditions are not subject to the advisory committee's time- frame goals (which apply to newborn screening using a blood specimen), and NewSTEPs' August 2016 report did not include data on timeliness for these two conditions, we did not include them in the timeliness data in our report or in the description of barriers and strategies.

In addition, HHS provided technical comments, which we incorporated as appropriate.

We are sending copies of this report to the Secretary of Health and Human Services, and appropriate congressional committees. In addition, the report will be available at no charge on GAO’s website at http://www.gao.gov.

If you or your staff have any questions about this report, please contact me at (202) 512-7114 or at crossem@gao.gov. Contact points for our Office of Congressional Relations and Office of Public Affairs can be found on the last page of this report. Other major contributors to this report are listed in appendix IV.

Appendix I: Scope and Methodology

To examine what is known about the timeliness of newborn screening for heritable conditions, we reviewed timeliness data from states included in an August 2016 report from the Newborn Screening Technical assistance and Evaluation Program (NewSTEPs). NewSTEPs is administered by the Association of Public Health Laboratories (APHL), in collaboration with the University of Colorado’s School of Public Health, through a cooperative agreement with the Health Resources and Services Administration (HRSA), an agency within the Department of Health and Human Services (HHS). The August 2016 report included data collected from states through a data repository maintained by APHL under NewSTEPs.

The data repository includes (but is not limited to) annual timeliness data collected from states participating in NewSTEPs. These annual timeliness data are based on time-frame goals recommended by HHS’s Advisory Committee on Heritable Disorders in Newborns and Children in April 2015 and data definitions developed by a workgroup composed of newborn screening experts and stakeholders convened by APHL. For individual newborn screening stages (e.g., specimen collection to lab arrival) or the full newborn screening process, the data measure the percentages of a state’s specimens screened within the advisory committee’s time-frame goals. For example, the data measure the percentage of specimens for which all results for all conditions were reported within the advisory’s committee’s goal of 7 days after birth. For the August 2016 report, NewSTEPs requested annual timeliness data from all 53 states, and 38 states submitted data that were included in this report. (See table 9.) Of the 38 states reporting timeliness data included in the report, 20 states entered data directly into the data repository and 18 additional states did not have a signed memorandum of understanding (MOU) and submitted equivalent data using a spreadsheet provided by NewSTEPs. For all 38 states included in the report, NewSTEPs determined the percentages of specimens screened within each of the committee’s 2015 time-frame goals (for the full newborn screening process or individual stages) in 2012, 2013, 2014, and 2015. The NewSTEPs report also included the median, quartiles, minimum, and maximum percentage meeting the 2015 time-frame goal in each year.

We assessed the reliability of the annual data in the NewSTEPs August 2016 report for the purposes of examining what is known about the timeliness of newborn screening by taking several steps. For example, we reviewed spreadsheets sent to states without an MOU and confirmed that the spreadsheets were based on the same definitions as the data repository (used by states with signed MOUs). We also confirmed that the spreadsheets had a built-in mechanism to mitigate data entry errors, such as automatic calculation of percentages. We interviewed officials from APHL and the University of Colorado’s School of Public Health to confirm that the data repository also had mechanisms to reduce risks of error. For example, these officials said the data repository can automatically calculate percentages and identify obvious data errors, such as values over 100 percent. These officials also noted that the data combined from the data repository and spreadsheets were based on common data definitions and that the data were carefully reviewed and searched for outliers before being reported. Based on these steps, we determined that these data were sufficiently reliable for the purposes of our report. The timeliness data for the states providing data for the NewSTEPs August 2016 report are not generalizable to other states, but provided valuable insight on what is known about newborn screening timeliness in the reporting states.

In addition to reviewing the annual timeliness data in the August 2016 report, we reviewed time-frame goals from the advisory committee included in an April 2015 letter to the Secretary of Health and Human Services, as well as results from the committee’s 2014 survey, which analyzed timeliness for specimens screened from January through May 2014. We also reviewed documents obtained from APHL officials that describe the data repository, quality indicators, and methods for entering data. We interviewed officials from APHL and the University of Colorado’s School of Public Health to learn about their activities related to timeliness, including how they manage the data repository, and to discuss the August 2016 report. We also interviewed these officials to describe any plans to track newborn screening timeliness in the future. We interviewed newborn screening stakeholders identified by APHL and on HRSA’s website to learn about efforts to track newborn screening timeliness. These stakeholders included a member of the advisory committee who co- chaired a timeliness workgroup, a member of the advisory committee who conducted research related to newborn screening barriers, and officials from associations (Association of Maternal & Child Health Programs, Association of State and Territorial Health Officials, Genetic Alliance, and March of Dimes). Stakeholders stated that NewSTEPs’ work in tracking timeliness through the data repository represented the most comprehensive source of information available for describing what is known about newborn screening timeliness.

To examine the barriers identified as contributing to delays in newborn screening for heritable conditions, and strategies being used to address them, we reviewed the advisory committee’s 2014 Newborn Screening Timeliness Survey Report, which included findings from a survey of states intended to assist with assessing policies and practices related to the timeliness of newborn screening. The committee, in conjunction with APHL, fielded the survey in the summer of 2014 to identify barriers to and strategies for timely newborn screening, among other things. The survey asked respondents to identify (1) the extent to which certain barriers (identified by newborn screening experts prior to the survey) impacted the newborn screening timeliness in their state, and (2) the strategies that were ongoing in their state to help the newborn screening system meet the recommendations for timely newborn screening. State officials indicated whether a number of barriers for each stage of the newborn screening process identified in the survey had a “major impact,” “moderate impact,” “minor impact,” or “no impact” on timeliness in their state. State officials could also include in written responses additional barriers impacting timeliness not previously identified. The advisory committee obtained survey responses from newborn screening officials in 51 states, although not all states responded to all questions.

We selected certain barriers for which we collected more detailed information from states. To select these barriers, we reviewed state responses in the advisory committee’s 2014 survey report, published presentations from APHL’s 2016 Newborn Screening and Genetic Testing Symposium, and a 2015 report by the Association of State and Territorial Health Officials. We selected the barriers most frequently indicated by survey respondents as having a major or moderate impact on timeliness, as well as additional barriers that were frequently reported in the survey’s written responses, which were grouped into categories in the survey report. We also selected barriers from the survey report that fewer respondents indicated as having a major or moderate impact on timeliness, but which were highlighted by a number of state newborn screening officials in published presentations and reports. We combined barriers that were similar into broader topics. For example, for stage 1, we included barriers related to staff training and turnover into one topic related to staffing issues.

We interviewed officials from four selected states to collect more detailed information on the barriers we selected from the survey report. These selected states were Arizona, Colorado, Minnesota, and Wisconsin. We selected these states because, according to our review of documents from APHL and the Association of State and Territorial Health Officials, they were focusing on activities related to newborn screening timeliness, which would allow them to provide in depth information on barriers and strategies. In addition, these four states’ activities related to a range of barriers and strategies. For example, one state focused on improving timeliness for out-of-hospital births, while another state focused on improving its laboratory information management system to provide better feedback to hospitals. Through a combination of written responses and interviews, officials from these states provided more detailed information on how the identified barriers may have contributed to delays in their states, and described strategies they had developed or planned to develop to address these barriers. The results of our review of states are not generalizable to other states, but provided insights on these issues.

In addition to collecting information from states on barriers and strategies for timely newborn screening, we reviewed documents from APHL and the University of Colorado’s School of Public Health involved in NewSTEPs and NewSTEPs 360, including NewSTEPs’ August 2016 report (which contained information on activities that some states had undertaken to improve timeliness) and interviewed these officials to clarify or elaborate on information about barriers to timely newborn screening and strategies to address such barriers. Similarly we also reviewed information and interviewed newborn screening stakeholders identified by APHL officials and on HRSA’s website to elaborate on barriers and strategies. These stakeholders included a member of the advisory committee who co-chaired a timeliness workgroup, a member of the advisory committee who conducted research related to newborn screening barriers, and officials from associations involved in efforts to improve newborn screening (such as the Association of State and Territorial Health Officials and Genetic Alliance).

Appendix II: Heritable and Other Conditions on the Recommended Uniform Screening Panel (RUSP) as of March 2015

Frequency

Inability to process the amino acid leucine, leading to low blood sugar and accumulations of several organic acids, especially after illness or missed meals. Untreated, can lead to brain damage, mental retardation, coma, and death. Treatment includes a diet low in protein and fat, and high in carbohydrates.

Buildup of argininosuccinic acid and ultimately ammonia, leading to brain swelling, coma, and sometimes death. Treatment consists of a low-protein diet, frequent meals, medications to prevent ammonia buildup, nutritional supplements, and sometimes a liver transplant.

Periodic episodes of acid buildup, often triggered by illness, which can lead to coma, brain damage, and death. Intravenous treatment to regulate blood sugar and blood acid levels can permit normal development.

Buildup of citrulline and ultimately ammonia, which untreated can lead to seizures, coma, brain damage, and death. Treatment with low-protein diet, medications to prevent ammonia buildup, and nutritional supplements to allow normal development.

Lack of the liver enzyme needed to convert galactose, a major sugar in milk, into glucose (blood sugar). Galactose then accumulates in and damages vital organs, leading to blindness, severe mental retardation, infection, and death. Milk and other dairy products must be eliminated from the baby’s diet for life. This greatly improves the outlook for affected infants, but risk of mild developmental delays remains.

A group of inherited disorders resulting from deficiencies of hormones produced by the adrenal gland. Severe forms of CAH, if undetected and untreated, cause life-threatening salt loss via urine. Treatment includes hormone replacement.

Inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxyl- lysine, and tryptophan, which are building blocks of protein. Often unrecognized for up to 18 months until childhood illness triggers onset of symptoms. Without early diagnosis and prompt treatment when needed, can lead to brain damage, low muscle tone, cerebral palsy-like symptoms, and death.

A condition in which the body is unable to break down proteins and carbohydrates. People with this condition have trouble using biotin, a vitamin that helps turn certain carbohydrates and proteins into energy for the body. It can lead to a harmful buildup of organic acids and toxins in the body. Early detection and treatment with biotin supplements can prevent the severe outcomes of MCD.

Inability to process the amino acid leucine. Can cause coma, brain damage, or death in infancy, or emerge later in childhood after infectious illness. Early diagnosis and treatment with low-protein diet and nutritional supplements allow most children to develop normally.

Description Inability to convert certain fats to energy. Symptoms such as feeding difficulties, low blood sugar, and lack of energy can begin soon after birth, and people with this condition may experience heart problems, difficulty breathing, liver failure, and sudden death. Treatment includes a high-carbohydrate, low-fat diet, nutritional supplements, and frequent meals. <1 in 100,000 Genetic metabolic disorder with mild to severe symptoms, which can lead to mental retardation or death. Treatment consists of a special diet, continued indefinitely.

Seemingly well infants suddenly develop seizures due to low blood sugar. People with this condition are at risk of seizures, breathing difficulties, liver problems, brain damage, coma, and sudden death. Treatment includes nutritional supplements and frequent meals.

Defect in processing four amino acids, resulting in illness in first week of life. Severity varies, but death during first month and lifelong brain damage are common. Treatment includes low-protein diet, vitamin B12 injections, and nutritional supplements.

Defect in the processing of four amino acids leading to illness in newborns including brain damage, coma, and death. Even with treatment, which includes a low-protein diet and nutritional supplements, some children have development delays, seizures, increased muscle tone, frequent infections, and heart problems.

Seemingly healthy infants can die of what appears to be sudden infant death syndrome. Other infants may develop low muscle tone, seizures, heart failure, and coma, often following illness. Treatment based on frequent meals, a low-fat diet, and nutritional supplements.

Inability to convert certain fats to energy. Unless treated, infants often develop heart and liver failure, dying before age one. Treatment includes a high-carbohydrate, low-fat diet, nutritional supplements, frequent meals, and limiting exercise.

Defect in processing the amino acid leucine, leading to brain damage, seizures, liver failure, and infant death, or sometimes no symptoms until adulthood. Symptoms may develop after childhood illness. Treatment includes a low-protein diet.

An inherited disorder resulting in lack of the enzyme that recycles the vitamin biotin. May cause frequent infections, uncoordinated movement, hearing loss, seizures, and mental retardation. Undiagnosed and untreated, can lead to coma and death. If condition is detected soon after birth, problems can be prevented with oral high-dose biotin. <1 in 100,000 Cells cannot readily absorb carnitine, needed to transfer fatty acids into mitochondria (which supply cells with energy). Results include low blood sugar and sudden death in infancy. Older children may present with progressive heart failure. High-dose carnitine permits normal development.

Description Inability to process the essential amino acid phenylalanine, which accumulates and damages the brain. Can lead to severe mental retardation unless detected soon after birth. Treatment includes a special formula and a low-protein diet, continued indefinitely.

A group of seven heart defects. Babies born with CCHD are at significant risk of disability or death if not diagnosed soon after birth.

A common inherited disorder, resulting in lung and digestive problems, and death by age 35, on average. Early diagnosis and treatment may improve the growth of babies and children with CF.

Babies with Pompe disease have trouble breaking down a large sugar called glycogen. Too much glycogen can keep certain organs and tissues, like the heart and muscles, from working properly. Treatment includes enzyme replacement therapy, physical therapy, and respiratory therapy.

Sickle cell disease is an inherited disease of red blood cells. Individuals with sickle cell disease have abnormal hemoglobin, the protein inside red blood cells that carries oxygen to every part of the body. Hb S/BTh is a form of sickle cell anemia, in which the child inherits one sickle cell gene and one gene for beta thalassemia, another inherited anemia. Symptoms are milder than for Hb SS, though severity varies. Routine treatment with penicillin may not be recommended for all affected children Sickle cell disease is an inherited disease of red blood cells. Individuals with sickle cell disease have abnormal hemoglobin, the protein inside red blood cells that carries oxygen to every part of the body. Hb S/C is another form of sickle cell disease, in which the child inherits one sickle cell gene and one gene for another abnormal type of hemoglobin. Hb S/C tends to be milder than Hb SS; therefore, treatment with penicillin may not be recommended.

Without early testing, most babies with hearing loss are not diagnosed until age two or three. By then, they often have delayed speech and language development. Early diagnosis allows use of hearing aids by six months, helping prevent serious speech and language problems.

Lack of an enzyme that converts the amino acid homocysteine into cystathionine, needed for normal brain development. Untreated, leads to mental retardation, eye problems, skeletal abnormalities, and stroke. Treatment consists of a special diet, one or more vitamins (B6 or B12), and other supplements.

Inherited vitamin metabolism defect. Can lead to buildup of acids in blood, brain damage, seizures, paralysis, coma, and death. Treatment includes B12 injections and a low-protein diet.

Thyroid hormone deficiency that severely retards growth and brain development. Treatment includes thyroid hormone replacement therapy with dietary restrictions.

A group of rare inherited disorders characterized by defects in two critical immune system cells that are normally mobilized by the body to combat infections. SCID has also been referred to in the popular media as the “bubble boy disease.” Without treatment, infants with SCID are more susceptible to and can develop recurrent infections, leading to failure to thrive and often death.

Sickle cell disease is an inherited disease of red blood cells. Individuals with sickle cell disease have abnormal hemoglobin, the protein inside red blood cells that carries oxygen to every part of the body.

Description Lack of an enzyme that causes the byproducts of the amino acid tyrosine, particularly a very toxic compound (succinylacetone), to build up in the liver. Fatal liver and kidney failure may result. Treatment includes dietary restrictions and medication to help protect the brain, liver, and kidneys.

In 2014, the advisory committee identified 16 of 32 conditions as “time-critical” conditions. These are conditions in which acute symptoms or potentially irreversible damage could develop in the first week of life, and for which early recognition and treatment can reduce the risk of illness and death.

Appendix III: Comments from the Department of Health & Human Services

Appendix IV: GAO Contact and Staff Acknowledgments

GAO Contact

Staff Acknowledgements

In addition to the contact named above, Kim Yamane (Assistant Director), Hernan Bozzolo (Analyst-in-Charge), Emily Binek, Jazzmin Cooper, Drew Long, Vikki L. Porter, and Jennifer Whitworth made key contributions to this report.