Why do we need Newborn Screening for Rare Diseases?
For more than 50 years, every newborn in the U.S. has been screened for a range of debilitating and deadly diseases through a dried blood spot taken by a heel prick.
Every year, 12,000 babies and their families benefit from newborn screening through the early detection of disease and the delivery of life-saving treatments. Newborn screening (NBS) is widely recognized as one of the largest and most successful disease prevention programs in U.S. history.
However, the federal law that supports NBS expired in 2019, threatening important infrastructure for federal and state programs. The federal advisory committee that reviewed evidence and made recommendations for adding new conditions to the national recommended screening panel was disbanded in April 2025. While the Secretary of Health approved the addition of two new conditions, Duchenne muscular dystrophy (DMD) and metachromatic leukodystrophy (MLD), to the list of federally recommended screening tests, the process for proposing future updates to these recommendations has not yet been defined.
The RARE Foundation is working with stakeholders and policymakers to advance evidence-based NBS programs at the state and federal level, with a goal of achieving greater consistency for babies born in every state of our nation.
Read about the Key Criteria for Newborn Screening Programs
Using the Roadmap
This Newborn Screening Resource Roadmap is designed to orient people new to newborn screening to key topics and resources to help them prepare to advocate effectively for NBS for one (or more) rare diseases in one (or more) states in the U.S.
1. Is the condition present in early childhood?
Yes
Go to Question 2!
No
If the condition is not understood to be present at birth or in early childhood, it is unlikely to be considered appropriate for inclusion in Newborn Screening programs.
If evidence were to begin to shift understanding about the condition being present and treatable in the newborn phase of life, it could be an opportune time to begin working to understand the NBS landscape and what evidence will be needed to advance NBS.
- Learn more about the assessment of public health impact for Newborn Screening
- Visit the Genetic and Rare Diseases Information Center (hosted by NIH)
- PubMed – a clearinghouse for medical publications
Unsure
If you’re unsure about whether the condition is biologically present in early childhood, consult with clinical experts for the condition and the published medical literature.
2. Is the condition considered medically serious and is it clinically well-defined?
Conditions that don’t meet both these basic criteria are unlikely to be considered appropriate for inclusion in newborn screening programs.
Yes
Go to Question 3!
No
If either the condition is not considered medically serious or it does not yet have a broadly agreed-upon case definition that describes the range of symptoms in newborns and children who would be identified through population-based screening, it’s likely best to focus on bringing together appropriate stakeholders to develop, publish, and foster adoption of a clinical case definition.
- Learn more about stakeholders
- Read a clinical case definition for PKU
- Read a clinical case definition for Infantile Krabbe Disease
Unsure
If you’re unsure about whether the condition is considered medically serious or if it has a broadly agreed-upon case definition that describes the range of symptoms in newborns and children who would be identified through population-based screening, consult with clinical experts for the condition and the published medical literature.
3. Is there an immediate intervention or standard of care for babies with the condition of interest?
A pillar of NBS programs is limiting screening to conditions that have an immediate intervention or standard of care that is expected to improve a baby’s health outcomes.
Yes
Go to Question 4!
Not Yet (Active Pipeline*)
If there is an active pipeline for one or more potential treatments that would be appropriate for use in babies, this could be an opportune time to begin working to understand the NBS landscape and the evidence needed to advance NBS. Recognize that it can take many years for a potential therapy to progress through the stages of clinical development and secure FDA approval. It can also take several years to develop the evidence to support NBS, so pursuing a parallel approach to the two processes may be pragmatic.
If treatment(s) in development are not yet being studied in young children, it may be beneficial to start by gaining a better understanding of how to incentivize studies that include children.
Review the American College of Medical Genetics and Genomics (ACMG) ACT Sheets and Algorithms to see if the condition of interest is listed. If not, engage with ACMG to learn more about whether it’s appropriate to develop materials about the condition at this time.
No (No Active Pipeline*)
If there is not an active pipeline for development of a therapy or treatment regimen for babies with the condition, it may be more practical to focus on bringing together appropriate stakeholders to advance research that could lead to one or more therapies beneficial for babies with the condition.
As the pipeline for pediatric treatment grows and progresses, begin working to understand the NBS landscape and the evidence needed to advance NBS. It can take many years for a potential therapy to progress through the stages of clinical development and secure FDA approval. It can also take several years to develop the evidence to support NBS, so a parallel approach may be useful as the pipeline becomes more robust and advances toward one or more FDA approvals.
Unsure
If you’re unsure about whether there is immediate intervention or standard of care for babies with the condition, consult with clinical experts for the condition and the published medical literature.
Review the American College of Medical Genetics and Genomics (ACMG) ACT Sheets and Algorithms to see if the condition of interest is listed. If not, engage with ACMG to learn more about whether it’s appropriate to develop materials about the condition at this time.
- Check out Pubmed, a clearinghouse for medical publications
- Genetic and Rare Diseases Information Center
* The term “pipeline” refers to the status of one or more therapies in clinical development that may result in an approved treatment. In the context of NBS, it would reflect treatments being studied for potential use in very young children.
4. Is the condition listed on the federal newborn screening panel, referred to as “the RUSP”?
The Recommended Uniform Screening Panel (RUSP), is a list of disorders that the Secretary of the Department of Health and Human Services (HHS) recommends states screen for as part of their state-managed newborn screening (NBS) programs.
Yes, it is listed in on the RUSP.
If the condition you’re most interested in is already on the RUSP, but your state isn’t currently screening for it, consider engaging in state-focused “RUSP Alignment” efforts that aim to support testing of all RUSP conditions, including providing sources of funding for the addition of new conditions to state panels and increased ongoing screening costs.
- 68% OF BABIES NATIONWIDE ARE BORN IN RUSP ALIGNED STATES… THERE IS STILL MORE WORK TO DO! YOU CAN HELP IMPROVE THE CHANCE FOR ALL BABIES TO BENEFIT FROM NBS!
No, it is not listed on the RUSP.
Go to Question 5.
I’m not sure.
Review the core and secondary conditions included on the RUSP on the Health Resources & Services Administration’s website.
5. Is it currently being screened for by any US state?
Yes
If you identified one or more states that currently screen for the condition of interest, connect with their labs and learn what’s working well and what could be improved. You can also connect with other advocates who supported the addition in other states. Build that information into your plans.
- Recognize each stakeholder’s interest in Newborn Screening.
- Learn more about those states’ labs and other screening resources and contacts
Continue to Question 6.
No
Go to Question 6.
Unsure
NewSTEPs, a program of the Association of Public Health Laboratories, has an interactive dashboard that includes a US map you can search by disorder or by state. If the condition you’re interested in isn’t listed on this site, it’s probably not part of any state’s screening panel.
The US Health Resources and Services Administration (HRSA) hosts a guide to NBS that provides a full list of conditions screened for by each state, including conditions that are not on the RUSP.
Once identified if the condition is screened, continue to Question 6.
6. Do you understand your state’s process for adding new conditions?
Yes
If you’re confident in the your state’s process and funding sources, you might:
- Start gathering the evidence to support addition of the condition of interest to the state’s NBS program. If one or more pilot studies have been conducted, be sure to include that evidence
- Start developing a funding proposal to address the financial impacts. You may wish to draw on NBS legislation introduced and/or enacted by other states for potential models.
Continue to Question 7.
No or Unsure
States follow different processes to consider whether to add new conditions to NBS programs. They can be loosely grouped into the following categories:
States with state-prescribed nominating process clearly outlined on a state-managed website:
States that have an NBS-related advisory committee that may have a role in reviewing candidate conditions for NBS (without a prescribed nomination process)
States that generally add only those conditions included on the RUSP
States that use another state’s lab for processing dried blood spots (and generally follow the processing state’s approved list of conditions)
- Alaska, North Dakota, and South Dakota utilize Iowa’s state lab
- Maine, New Hampshire, Rhode Island, and Vermont utilize Massachusetts’ state lab
- Hawaii and Idaho utilize Washington’s state lab
- New Mexico utilizes Oregon’s state lab
- Montana utilizes Wisconsin’s state lab
- Wyoming utilizes Colorado’s state lab
States that contract for testing through Revvity, a third-party testing laboratory
- Delaware
- District of Columbia
- Mississippi*
- Nebraska
- Pennsylvania*
States whose nomination process is not publicly specified
- Connecticut
- Colorado
- Iowa*
- Kansas
- Kentucky
- Nevada
- New York
- North Carolina*
- South Carolina
- Tennessee*
- West Virginia
Continue to Question 7.
Helpful Resources
- See a Spreadsheet of State Based Newborn Screening Resources for Advocates
- Case Studies of States that Expanded Newborn Screening
* States that have passed RUSP Alignment legislation
Funding Sources for Expenses Related to Newborn Screening Panels
Funding sources and the amount charged for individual NBS tests vary by state. View NewSTEPs NBS Fees Report to learn more about how each state charges for NBS tests.
Adding a new test may require upfront investment, especially if the new test requires specialized laboratory equipment or training lab personnel to perform the test. Learn more about factors that labs must consider and prepare for, including:
- Personnel and training costs to perform and monitor new testing procedures and to provide notification of positive screens, referrals, etc. per state policies
- Upgrading or purchasing lab equipment and/or facilities
- Technology updates/upgrades for process changes to integrate testing, tracking and follow-up
- Costs for reagents, materials and specimen collection kits (in excess of current utilization)
What’s Next?
When you feel confident about your understanding of your state’s process and funding sources, you might start to gather the evidence to support addition of the condition of interest to the state’s NBS program
- If one or more pilot studies have been conducted, be sure to include that evidence.
- Develop a funding proposal to address the financial impacts. You may wish to draw on NBS legislation introduced and/or enacted by other states for potential models.
7. How prepared are you to meet typical evidence requirements for adding a new test?
Generally, there should be evidence to support the following statements:
✓ The condition is medically serious.
✓ The condition has a well-defined case definition that describes the range of symptoms in newborns and children.
✓ The condition has well-defined treatment protocols and approved therapies available to treat babies.
✓ There is a valid screening test that is reasonable to implement in a newborn screening program that is sensitive enough not to miss any newborns, while having a low rate of false negatives.
✓ The screening process is specific enough to detect newborns who have the condition and will most likely benefit from treatment.
✓ There is existing data to support how well the population-based screening works to find newborns, often referred to as “pilot studies.”
Of all the evidence needed to advance a NBS screening proposal, data from one or more pilot studies using a validated screening test can be the most challenging to collect.
Is there a validated screening test for the condition of interest?
If yes…
Work toward development of a comprehensive evidence package. Engage with clinical experts in the state to define treatment protocols when the condition is identified pre-symptomatically (if no treatment guidelines currently exist).
Become familiar with evidence packages that many states will require:
- Evidence package for metachromatic leukodystrophy (MLD).
- Evidence package for Duchenne muscular dystrophy.
- Recording of the NBS evidence review workshop for MLD
- Recording of the NBS evidence review workshop for Duchenne
Prepare to address common technical questions like those in the full RUSP nomination form about screening tests and algorithms, including presenting data from pilot studies.
Engage with clinical experts in the state to define treatment protocols when the condition is identified pre-symptomatically (if no treatment guidelines currently exist).
If no or you’re unsure…
Support the development of a validated NBS test with minimal false positives and agreement about how to confirm the diagnosis after a positive newborn screen.
- Engage with the NBS test developer to support test validation efforts, if needed.
- Become familiar with common technical questions like those in the full RUSP nomination form about screening tests and algorithms, including presenting data from pilot studies.
- Engage with clinical experts in the state to define treatment protocols when the condition is identified pre-symptomatically (if no treatment guidelines currently exist).
Case Studies From Other Advocates
Learn from other case studies and connect with advocates who have navigated the process for adding a condition to one or more states’ NBS programs
Learn from RARE Foundation’s newborn screening training program, Newborn Screening Bootcamp.
Participate in RARE Foundation’s Community Congress – Newborn Screening and Diagnostics Working Group.
Are you fully prepared to meet the NBS evidence requirement right now?
If yes, continue to Question 8.
If not, this does not mean you will never be ready! Return to an earlier step in the Roadmap.
8. Are you familiar with your state’s advisory councils, legislature, and calendar?
No or Unsure
Learn more about the state government’s rare disease and/or NBS advisory councils (if either exists), relevant state legislative committees (especially majority party leaders), key advocates’ legislative representatives.
- Explore the directory of existing state rare disease councils and establish relevant connections.
- Become familiar with the state’s NBS advisory committee (if one exists).
Yes
Establish a relationship with the state government’s rare disease and/or NBS advisory councils, relevant state legislative committees (especially majority party leaders), key advocates’ legislative representatives.
- Connect to state legislature websites through this Congress.gov directory.
- Browse state-based NBS resources.
- Review primer on state legislative processes
- Learn more about enacted state legislation since 2017 related to Maternal and Child Health (can filter specifically for newborn screening)
When ready, continue to Question 9.
9. Have you identified other potential allies to support a request to add this condition?
Yes
Strategize with allies to support this legislation, including state-based rare disease organizations, healthcare systems, expert HCPs, pharmaceutical companies, testing companies, etc.
No
Identify and then strategize with potential allies to support this legislation, including state-based rare disease organizations, healthcare systems, expert HCPs, pharmaceutical companies, testing companies, etc.
Next Steps
- Recognize each stakeholder’s interest in NBS.
- Review these tips for working with others on NBS.
- Identify any possible objections or opponents to this effort and collectively develop strategies to overcome barriers and opposition.
- Review case studies
Continue to Question 10.
10. Do you feel ready to submit a nomination or advocate for legislation to add this condition?
Yes
Review legislation for single-condition additions to NBS panels successfully passed in other states and identify legal and/or legislative support to help develop a draft for your state
- Make sure you’ve engaged with the state’s NBS program staff and/or NBS advisory committee so any legislative proposal reflects their input
- Review State Newborn Screening Bills
- Review recent evidence packages to use as a guide
- Evidence package for metachromatic leukodystrophy (MLD)
- Evidence package for Duchenne muscular dystrophy
- Recording of the NBS evidence review workshop for MLD
- Recording of the NBS evidence review workshop for Duchenne
No or Unsure
If you are not yet ready, return to an earlier step and explore additional resources.
