The medical community has an opportunity to update its approach to newborn screening (NBS) to be prepared for emerging technological advancements that will help diagnose children with rare diseases from their first weeks of life, according to an editorial from a leading Children’s National Hospital researcher published in JAMA Pediatrics.
“In health care, we are seeing ways in which we can identify more children who have rare diseases even earlier, in the newborn period, rather than waiting for children to develop symptoms or experience irreversible changes,” said Beth Tarini, M.D., M.S., M.B.A., associate director of the Center for Translational Research. “We have continued innovations in screening technology – with more on the way – that can be added to the screening programs overseen by all 50 states. Updating how we approach newborn screening presents an incredible opportunity for doctors and their patient-families.”
Why it matters
Newborn screening happens before the baby leaves the hospital, generally with a prick of the heel to take a small sample of blood to look for several dozen rare, debilitating disorders such as sickle cell disease, congenital hypothyroidism and cystic fibrosis. The current screening system has grown successfully for roughly 60 years and creates a network of state programs. Along the way, researchers have had extensive debates about which disorders to include, based on whether there are treatments and options for patients.
Dr. Tarini, a pediatrician who has done extensive research on NBS and related policies, said that the existing screening programs across all 50 states should be modernized, with federal research support and funding, to create a unified “learning newborn screening system” that derives information from the 4 million babies born each year and provides feedback to the medical community about best practices for babies who are diagnosed with a rare disease or at risk for developing one.
“A new approach will require resources and infrastructure, but as the technology advances, we should change our system to leverage the experience of doctors, patients, and NBS programs across the country,” Dr. Tarini said. “We have the will, the experience and the ability to transform the care for children with rare disease.”
Children’s National received a grant to investigate the impact of newborn screening on families who receive an uncertain prognosis.
The National Institutes of Health (NIH) awarded Children’s National Hospital a $3.7 million grant to investigate the impact of newborn screening on the growing population of families who leave the testing with an uncertain prognosis.
Following the families longitudinally allows for a real-time view of the experiences of these children, sometimes referred to as “patients in waiting.”
Newborn screening is part of a universal, mandatory state health program that helps to identify inherited conditions that can affect a child’s health and survival. Millions of babies are screened annually for genetic, metabolic and endocrine disorders, using a few drops of blood from a prick to the heel; additional tests are done at the bedside such as hearing and heart screening. Sometimes, however, the results create medical odysseys and flag conditions that may never result in symptoms.
“For its first 50 years, newborn screening presented relatively consistent outcomes,” said principal investigator Beth Tarini, M.D., M.S., M.B.A., who serves as the associate director of the Center for Translational Research at Children’s National. “However, in the 21st century, new screening tests have created more ambiguous findings. As a result, we cannot accurately predict what type of symptoms a child may develop, when or if they will develop them, or how severe they will be. This is a lot to ask parents to deal with after the birth of a new child who appears otherwise healthy.”
Why it matters
The uncertainty can take a significant toll on parents by creating fear, anxiety and the medicalization of a child. However, to date, little long-term data exist to inform the care for these children. Ethically, that gap leaves clinicians unsure of how to weigh the benefit and harm of mandatory newborn screening programs. From a policy perspective, the drought of information leads to questions about how best to add disorders to newborn screening panels – an issue that will likely only grow as technology allows us to test for more conditions.
“We have a new group of children growing up and wondering when – or if – they will ever develop signs or symptoms of a disease,” Dr. Tarini said. “For some families, the information is an opportunity. For others, it becomes a burden. We owe it to these families to understand their experience and chart a sensible path forward to help them.”
What’s next
The four-year study will bring together researchers at Children’s National and Case Western University to analyze data and patient interviews from families in Virginia, Iowa and Oregon. The research team will include experts in newborn screening, genetics, health services, genetic counseling, psychology, bioethics and biostatistics.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2022/10/baby-getting-heel-prick-CNRI-feature.png385685Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2022-10-05 10:39:252022-10-05 10:39:25Researchers study murky findings in newborn screening panels with $3.7m NIH grant
Two Children’s National Hospital cardiac care leaders received prestigious recognition awards from the American Academy of Pediatrics (AAP) during that organization’s virtual National Conference and Exhibition in October 2021.
Gil Wernovsky, M.D., cardiac critical care specialist at Children’s National Hospital, received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery, celebrating his 30-plus-years as a clinician, educator, mentor and leader in the field.
Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award, in recognition of his work to establish the use of pulse oximetry to screen newborn infants for critical congenital heart disease in the first 24 hours of life.
Dr. Wernovsky: 2021 Maria Serratto Master Educator Award, AAP Section on Pediatric Cardiology and Cardiac Surgery
Gil Wernovsky, M.D., received the 2021 Maria Serratto Master Educator Award from AAP Section on Pediatric Cardiology and Cardiac Surgery.
The Master Educator Award is presented each year to a pediatric cardiologist or cardiothoracic surgeon who exemplifies excellence as an educator, mentor and/or leader in the field.
A practicing cardiac critical care specialist with more than 30 years’ experience in pediatric cardiology, Dr. Wernovsky trained and mentored more than 300 fellows in pediatric cardiology, cardiac surgery, neonatology, critical care medicine and cardiac anesthesia, in addition to countless residents and fellows. He also organizes national and international symposia to share expertise around the world. During the COVID-19 public health emergency, for example, he co-founded the Congenital Heart Academy (CHA). The CHA provides content from an international faculty of cardiac care to more than 26,000 practitioners in 112 countries and includes a thriving YouTube channel.
Dr. Wernovsky is also a founding member of several international societies focused on bringing together clinicians, researchers and students across sub-specialties of pediatric cardiology and cardiac surgery for knowledge exchange and best practice sharing. These include: the Pediatric Cardiac Intensive Care Society, World Society for Pediatric and Congenital Heart Surgery, the International Society of Pediatric Mechanical Circulatory Support and the Cardiac Neurodevelopmental Outcome Collaborative.
Dr. Wernovsky received the award on October 10 at the virtual Scientific Sessions of the 2021 American Academy of Pediatrics National Conference and Exhibition.
Dr. Martin: AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award
Gerard Martin, M.D., FAAP, FACC, FAHA, C. Richard Beyda Professor of Cardiology, Children’s National Hospital, received the AAP Section on Advances in Therapeutics and Technology (SOATT) Achievement Award.
The Section on Advances in Therapeutics and Technology (SOATT) educates physicians, stimulates research and development and consults on therapeutics and technology-related matters for the AAP. The Achievement Award recognizes someone who has shown leadership in applying innovative approaches to solve pressing problems.
Dr. Martin is the C. Richard Beyda Professor of Cardiology and has cared for children at Children’s National for more than 30 years. As an advocate for congenital heart disease efforts nationally and internationally, he played an integral role in the development of an innovative use of existing hospital technology—the pulse oximeter—to detect critical congenital heart disease in newborn babies.
Today, Dr. Martin and colleagues across the United States and around the world have worked to make this screening method a standard of care for newborns everywhere. It is a part of the Health Resources and Services Administration (HRSA) Recommended Uniform Screening Panel and has become law in every state. They continue to conduct research to refine the recommendations and hone-in on the most effective ways to harness these tools.
Dr. Martin was selected for this award in 2020. He accepted it and offered remarks during the 2021 virtual AAP National Conference and Exhibition on Monday, October 11, 2021.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2021/10/Wernovsky-and-Martin.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2021-10-11 12:20:092021-10-18 10:14:45Cardiac care leaders recognized for mentorship and innovation at AAP
There are concerns about implementing whole-exome sequencing since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease.
It is still premature to standardize an innovative methodology known as whole-exome sequencing (WES) as part of state newborn screening programs, argues Beth A. Tarini, M.D., M.S., associate director for the Center of Translational Research at Children’s National Hospital, in a new editorial published in JAMA Pediatrics.
About 4 million infants are born annually in the United States. Newborn screening is a mandatory state-run public health program that screens infants for inherited diseases in the first days of life so they can receive treatment before irreversible damage occurs. Several of these screening tests are done on blood drawn from an infant’s heel.
WES holds the potential to screen infants for thousands of disorders and traits, including those that appear in adulthood. But there are concerns about implementing WES since it takes away the child’s right to decide if they want to know — or not — about their specific inherited disease. There is also the unknown effect that it could have on their ability to obtain health insurance.
“As caretakers for their children, parents have the challenge of deciding what kind of information, including genetic, will be valuable for their child,” says Dr. Tarini. “As a society, we have the responsibility of deciding where the healthcare dollars get the best return – especially when it comes to children. We need to start that conversation for universal genomic sequencing of newborns sooner rather than later.”
The Pereira et al. study, appearing in the new edition of JAMA Pediatrics and referenced in Dr. Tarini’s editorial, is the first to demonstrate no significant harm in the initial 10 months of life after performing WES under the best conditions of access to resources and a controlled environment.
While the Pereira et al. study has limited data on the effects of WES on families from underrepresented backgrounds, Dr. Tarini notes that it does provide a critical first step in this area of pediatric genomic research and for policy decision-making about the widespread implementation of WES in newborns.
“Moving forward, the U.S. will have to make a collective decision about the value of WES for newborns,” says Dr. Tarini. That value calculus cannot be made without consideration of the general state of healthcare for infants. As she points out, “This is not an easy question to answer in a country whose infant mortality ranks 34th according to the Organization for Economic Co-operation and Development (OECD).”
Dr. Tarini’s research identifies ways to optimize the delivery of genetic services to families and children, particularly newborn screening. She has also chaired state newborn screening committees and served on several federal newborn screening committees.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2018/02/Smiling-baby-boy.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2021-08-23 10:48:592021-09-03 11:35:58Could whole-exome sequencing become a standard part of state newborn screening?
Run at the state-level, mandatory newborn screening (NBS) programs detect a host of hereditary disorders so that infants can be treated before further damage, or even death, occurs.
Newborn screening (NBS) programs are critical to public health. Run at the state-level, mandatory NBS programs detect a host of hereditary disorders so that infants can be treated before further damage, or even death, occurs.
While much attention is paid to testing technology, programs must still meet basic minimum requirements to reliably identify and treat all affected individuals including minimum reporting requirements, case surveillance and a dedicated short-term follow-up program. In newborn screening, success is systematic.
A new report “How a baby with classic galactosemia was nearly missed: When the test succeeds but system fails,” published in the American Journal of Medical Genetics, takes a look at an individual case that almost slipped through the cracks of a local NBS program.
One disorder detected by NBS is classic galactosemia (CG), which arises from a deficiency in the galactose-1-phosphate uridyltransferase (GALT) enzyme, leaving infants unable to metabolize galactose-1-phosophate, a monosaccharide abundantly present in milk. CG can result in fatal liver failure, sepsis and coagulopathy if the affected infant is not switched to soy-based formula within the first week of life.
CG can be detected through a combination of enzyme assay, DNA analysis and galactose quantification. However, NBS programs differ in testing protocols for CG by state, and not all NBS programs conduct all of these tests. This is of particular relevance to the Washington, D.C., metropolitan area, a regional nexus where crossing state and district lines for medical care is common.
The report describes how a D.C.-born infant was screened for CG through all three tests. While his galactose levels were normal, his GALT was low and DNA testing revealed homozygosity for a CG mutation known as K285N. In tandem, the latter two indicators constitute a true positive result for CG, and necessitate the proper issuance of referrals, precautions and follow-up, which failed to occur in this case.
The infant breastfed and displayed notable lethargy, and parents were directed to a local emergency department in a neighboring state which does not screen for CG with DNA testing.
The providers there were unfamiliar with the DNA results, and after new labs came back normal, the NBS results were deemed as “likely falsely positive” for CG. Fortunately, a provider at the community hospital forwarded the NBS results to the Children’s National Rare Disease Institute (CNRDI). Upon review, CNRDI metabolic specialists immediately sought to rectify the situation by reaching out to the family with proper instructions and arranging a clinical evaluation, which occurred 10 days after birth.
While this case had a fortunate ending, the report highlights the potential deficiencies in NBS programs, which have historically been among America’s most successful public health initiatives. The proper and timely functioning of NBS systems is contingent upon the functioning of its constituent parts, including testing, diagnosis, follow-up, management and stakeholder education.
While test results were accurate in this case, systemic shortcomings left a patient in danger. As the authors state, “Programs must keep in mind that the true success of newborn screening extends beyond just the test itself…to improve safety and care outcomes we must focus on the system.”
https://innovationdistrict.childrensnational.org/wp-content/uploads/2019/11/Newborn-baby-laying-in-crib.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2020-04-28 10:13:102020-07-20 09:26:33How a baby with classic galactosemia was nearly missed: When the test succeeds but system fails
Stephen Monaco with his brother before a life-changing incident in 2001.
Jana and Tom Monaco have four children and two, Stephen and Caroline, were born with isovaleric acidemia (IVA) and secondary carnitine deficiency, a rare metabolic disorder. This genetic condition prevents the body from producing enzymes to break down the amino acid leucine, found in many proteins – from nuts and beans to chicken and fish. If undetected, the condition, which affects about one in 250,000 children, can be fatal. IVA can also lead to autism or severe brain damage. Fortunately, newborn screenings in every state now detect most IVA cases.
Eighteen years ago, a series of events happened with Stephen, age 3.5 at the time, which led to his diagnosis of having IVA and secondary carnitine deficiency. He celebrated his grandmother’s birthday with a family dinner on Memorial Day. The next day he woke up with symptoms of a stomach virus, which the family treated as such. The following morning he didn’t wake up at all. Jana went to his room to check on him and realized something was wrong. She called an ambulance and within 24 hours Stephen fell into a coma in her arms. He was immediately put on life support at a Virginia hospital.
Amy Lewanda, M.D., a geneticist, and Craig Futterman, M.D., an intensivist, both of whom now work at Children’s National Health System, delivered news about the condition: IVA is an inability for the IVD gene to create enzymes to break down protein. Within a 24- to 48-hour period, Stephen’s body flooded with isovaleric acid it couldn’t break down. Once the acid reached his brain he was paralyzed. Jana mentions you could find him in the emergency department of the hospital by following the odor: He reeked of ketones and isovaleric acid, which accumulated in his blood and body tissue. His blood glucose level was so low that he was practically in a diabetic coma.
Jana and Stephen Monaco, at a charity golf tournament established in Stephen’s honor to raise awareness about and support for isovaleric acidemia (IVA).
If the Monaco family was able to get his blood checked locally at the hospital – which the clinicians did not yet have the ability to do because this condition is so rare – they may have been able to receive an early diagnosis, enabling them to intervene in infancy, as they did with their youngest daughter, Caroline.
After the diagnosis, in hindsight, Jana and Tom recognized Stephen’s symptoms as a toddler: picky eating, anemia, rejection of protein-rich foods, such as favoring jelly over peanut butter on a PB&J sandwich, opting for easy carbs, since they are easier for those with IVA to process, and breastfeeding longer, since breast milk is lower in protein. He had a peculiar odor trailing from his diaper, a common symptom of this condition. They also remembered he had a harder time recovering from a stomach virus, which left him weak and floppy, compared to one of his brothers, who had the same flu but bounced back faster. As parents, they did everything they could to promote healthy growth and development for their children – from properly installing car seats to staying up-to-date on vaccines and enrolling everyone in activities, like Little League. They only wished they could have detected this condition earlier.
A second chance arrived six months after Stephen was diagnosed with IVA: Jana and Tom learned they were pregnant with Caroline. From studying Stephen’s condition, they knew Caroline had a 25 percent chance of having IVA and secondary carnitine deficiency. (Jana and Tom are recessive carriers for a mutated IVD gene, but remain asymptomatic.) They scheduled an amniocentesis, a prenatal test that provides information about a baby’s health from sample amniotic fluid, which can diagnose genetic defects and fetal infections. Caroline was just 16 weeks in utero, but abnormal metabolites from the amniotic fluid sample confirmed she had IVA and secondary carnitine deficiency.
Caroline, a healthy teenager with IVA, is an example of the benefits of newborn screenings and early-life medical interventions.
Having advance knowledge about the condition enabled doctors and geneticists to create a plan for her delivery, which made a difference between her long-term prognosis and Stephen’s. After birth, she was transferred to the neonatal intensive care unit at Children’s National. She was fed a formula that prevented excess isovaleric acid build-up, part of an hour-by-hour protocol to ensure she stayed healthy. Caroline is now 16. She plays the viola in her school orchestra, rides horses and excels in school.
When Stephen was born, the state of Virginia, where the Monaco family lives, screened for eight prenatal conditions, such as PKU, a rare but more common condition. The state now screens for 31 conditions, thanks in part to Jana, Stephen and Caroline. The list grows as research evolves. Jana started advocating for these efforts in Richmond and on Capitol Hill when Caroline was 2. Her approach: Take Stephen and Caroline to her state capitol and to the U.S. Capitol to push for statewide newborn screenings – visually showing the same condition, but with two very different outcomes. How could anyone say no?
She worked with the Virginia Genetics Advisory Council and with the Health and Human Services Secretary Advisory Committee to pass the legislation, which helped detect other organic acidemias – inherited conditions that prevent babies from breaking down amino acids found in protein, creating potentially toxic situations, similar to Stephen’s. They advocated for adding other conditions to the panel, like severe combined immunodeficiency, commonly referred to as “bubble boy” syndrome. Stephan was the only newborn screening advocate in attendance with a disability. Now all 50 states have implemented these screenings.
The Monaco family raised $100,000 for the genetics division and ongoing IVA research at Children’s National Health System.
The family isn’t done yet. On Oct. 26, Stephen will celebrate his 22nd birthday and a fifth-annual golf tournament, created in his honor, to raise awareness about and support for IVA and similar conditions. The Monaco family started this tradition in 2015 on Stephen’s 18th birthday and have raised $100,000 for the genetics division at Children’s National. They hope Stephen’s legacy will leave others with a message they keep framed in their Virginia home: Learn from yesterday, live for today and hope for tomorrow.
They educate Caroline along the way, noting the annual golf tournament and their advocacy supports ongoing IVA research and care – ensuring that she and others with these rare metabolic conditions continue to live a long, healthy life, echoing their longstanding partnership with Children’s National to help children grow up stronger.
https://innovationdistrict.childrensnational.org/wp-content/uploads/2019/05/Jana-and-Stephen.png300400Innovation Districthttps://innovationdistrict.childrensnational.org/wp-content/uploads/2023/12/innovationdistrict_logo-1-1030x165.pngInnovation District2019-05-24 07:00:362021-03-02 10:16:44Prenatal screening: the story of two siblings
Sarah Viall, PPCNP, coordinator for the Newborn Screening Program at the Children’s National Rare Disease Institute (CNRDI), has been invited to serve on the Education and Training Workgroup of the Health Resources & Services Administration’s (HRSA) Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC).
Established under the Public Health Service Act, the ACHDNC focuses on reducing morbidity and mortality in newborns and children who have, or are at risk for, genetic disorders. The Committee currently recommends that all newborn screening programs include a Uniform Screening Panel that monitors for a total of 34 core disorders and another 26 secondary disorders.
In addition to developing recommendations on national newborn screening guidelines, the ACHDNC also advises the U.S. Department of Health and Human Services Secretary on the most appropriate application of newborn screening technologies, tests, policies and standards. The Committee provides technical information that helps develop Heritable Disorders Program policies and priorities that enhance the ability of local and state health agencies to provide screening, healthcare services and counseling for newborns and children affected by genetic disease.
Viall had previously spent a year observing meetings for the ACHDNC Education and Training Workgroup.
“I am thrilled to be an official member that can contribute to the important work of educating communities about newborn screening,” says Viall.
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Several experts, including Gerard R. Martin, M.D., recently published recommendations for the use and standardization of pulse oximetry screening for critical congenital heart defects in newborns.
The European Pulse Oximetry Screening Workgroup recently published recommendations for the use and standardization of pulse oximetry screening for critical congenital heart defects in newborns. Children’s National Medical Director of Global Services Gerard R. Martin, M.D., was among the experts that compiled the recommendations.
Approximately 1 in 500 babies is born with a critical congenital heart defect (CCHD). Because these conditions can cause serious, life-threatening symptoms, early detection and intervention is essential. Pulse oximetry screening (POS) – a method that measures oxygen saturation – is regarded as a simple, quick and reliable tool for early detection of CCHD, and was recommended for use in screening by the American Academy of Pediatrics and the American Heart Association in 2011.
In Europe, although POS is being used by an increasing number of hospitals, few countries have issued national guidelines recommending universal POS. To remedy this situation, neonatologists, experts in CCHD screening, and representatives from major scientific pediatric societies across Europe came together to create recommendations for the use and standardization of POS for early detection of CCHD across Europe.
Their recommendations, which were published in The Lancet, are as follows:
POS for critical congenital heart defects should be recommended for all European countries
POS should be done with new-generation equipment that is motion tolerant
Screening should occur after 6 hours of life or before discharge from the birthing centre (preferably within 24 hours after birth)
Screening should be done in two extremities: the right hand and either foot
Each country should consider the advantages and disadvantages of the two available protocols and use that which best suits their population
In 2011, screening for critical congenital heart defects (CCHD) became the second point-of-care newborn screening test added to the Recommended Uniform Screening Panel, and it has since been widely adopted. Heart defects are the primary targets for CCHD screening, which often require evaluation by echocardiogram. An original list of seven conditions represented the most common critical lesions which routinely present with hypoxemia for newborns. Endorsed by the American Academy of Pediatrics and four other professional medical societies, the CCHD screening using pulse oximetry is required by law in all but two states. Remaining challenges include national data collection and outcomes analyses at the population level.
What’s New
An expert panel including Gerard R. Martin, MD, a cardiologist at the Center for Translational Science at Children’s National Health System, reviewed current practices in newborn screening for CCHD and identified opportunities for improvement. The panel’s study expanded the list of core conditions to 12 to emphasize the importance of other potentially critical, yet treatable secondary conditions. Roughly 79 percent of “positive” screens for CCHD identify secondary conditions, such as sepsis and pulmonary diseases. The study found algorithm misinterpretation was common in states collecting outcomes data, emphasizing needs for proper training and quality-assurance feedback mechanisms. Public health surveillance varied dramatically, with nearly one-fifth of states neither actively collecting data nor planning to do so. Additional CCHD screening research in special settings like the NICU, out-of hospital settings, and areas with high altitude may result in adaptations to screening protocol. Future improvements to the current screening algorithm and analyses of the impact on CCHD outcomes will rely on further investment in a national data repository.
Questions for Future Research
Q: What will be the impact on present screening for CCHD on outcomes of non-CCHD secondary conditions? Q: What is the optimal algorithm for CCHD based on screening and testing ease of use, costs, resource utilization, and sensitivity for different treatment settings? Q: What will be the impact on present screening for CCHD on outcomes of non-CCHD secondary conditions?
