Newborn screening ‘ecosystem’ continues to improve

Maurizio Scarpa, MD, PhD, director of the Regional Coordinating Center for Rare Diseases of the European Reference Network for Hereditary Metabolic Diseases at Udine University Hospital in Udine, Italy, stands at the podium.

By Melanie Padgett Powers, writer

Newborn screening is known primarily as the heel stick a newborn gets to test their blood for certain genetic diseases. But that simple description understates the profound effect newborn screening has had on families, as public health celebrates 60 years since the beginning of routine newborn screening in the US.

“Newborn screening is one of the major achievements in the history of medicine, in public health,” said Maurizio Scarpa, MD, PhD, director of the Regional Coordinating Center for Rare Diseases of the European Reference Network for Hereditary Metabolic Diseases at Udine University Hospital in Udine, Italy. “The diagnosis of an asymptomatic child allows the choice of the best care and the best treatment. Newborn screening is indeed the way to go for a treatable disorder in order to limit the progression of the disease or the effect of the disease.”

Scarpa was one of four speakers at the 2023 APHL/ISNS Newborn Screening Symposium keynote session, “60 Years of Screening: A Time to Celebrate and a Time to Reflect,” in Sacramento, California in October. The keynote speakers examined newborn screening in a SWOT analysis framework—looking at the program’s strengths, weaknesses, opportunities and threats.

Newborn screening was created in 1963, after Robert Guthrie, MD, PhD, developed a blood test to screen for phenylketonuria (PKU) in New York. When discovered early, PKU can be treated with a lifelong specific diet and special nutritional supplement. Without treatment, children can develop permanent intellectual disabilities.

In the past 60 years, more than 750 million babies have been screened for PKU, Scarpa said, with 60,000 cases identified and treated. “An entire football arena can be filled up with all the children saved by [PKU] newborn screening,” he said.

Now PKU is one of more than 30 conditions recommended for US states to screen as part of their routine newborn screening programs. Most laboratory testing that supports state newborn screening programs is conducted by a public health laboratory.

Technological advancements in newborn screening

Newborn screening is so much more than that heel stick, said Jerry Vockley, MD, PhD, of the University of Pittsburgh Schools of Medicine and Public Health. Vockley maintained that the program is more of an “ecosystem.”

“It’s not just the test. It’s not just the follow-up. It’s not just the treatment,” Vockley said. “It’s actually a whole system of pieces that need to be in place for this to be successful.” This includes collaborations with multiple stakeholders, including patients, parents and regulatory agencies.

But as technology advances, the testing process is becoming more convoluted. Now, the addition of next-generation sequencing—which includes whole exome sequencing and whole genome sequencing—allows laboratories to examine the genetic information in a person’s DNA in a much shorter time. This is not a routine part of newborn screening, as laboratory professionals are still learning how to interpret and analyze results with this newer technology.

DNA sequencing can be helpful as a secondary test—after the initial newborn screening heel prick—to determine whether a screening was truly positive for a disease or whether it was a false positive, said Robert L. Nussbaum, MD, chief medical officer at Invitae, a genetic testing company.

In a true positive test, when biomarkers are ambiguous, DNA sequencing can help narrow down the diagnosis and determine what condition the newborn has, Nussbaum said. He cited a study that showed that DNA sequencing was helpful in determining whether there was an unknown genetic explanation for newborns struggling in neonatal intensive care units.

Another new technology that could benefit newborn screening is artificial intelligence, Scarpa said. “I think newborn screening should … start thinking about how to use artificial intelligence so newborn screening can be efficient, valid and with equity and equality for all the newborns that are tested.”

He pointed to one study with data from thousands of newborns in which computer algorithms were able to decrease the false positive rate of metabolic disorders by 25%. “We can indeed create algorithms that can help us in making our newborn screening even more precise, sensible and with an even bigger sensitivity to what we have now.”

However, he added, “We need to do this in a very passionate way, but in a very organized way. … But I think that this is a way that we cannot ignore, and we need to be prepared in order to add this kind of technology.”

Gene editing to cure sickle cell disease

Another advancement connected to newborn screening is gene editing to cure disease. Sickle cell disease (SCD) is one of the conditions included in newborn screening in all US states and territories. SCD is the most common inherited clinically significant blood disease in the country. It affects one in 400 African American newborns in the US.

The SCD survival rate to adulthood has improved significantly, thanks largely to the newborn screening process that detects SCD in the first week of a baby’s life. However, SCD can be incredibly painful and damage multiple organs.

Haydar Frangoul, MD, MS, shared how his team has successfully used CRISPR/Cas9 gene-editing technology to cure patients with SCD. He is the medical director of pediatric hematology/oncology at Sarah Cannon Pediatric Transplant and Cellular Therapy Program at TriStar Centennial in Nashville, Tennessee.

“Gene editing tools allow scientists to make very precise changes in the DNA,” Frangoul explained. “These tools allow genetic material to be disrupted, deleted, corrected or inserted at a precise location.”

Frangoul’s team is using gene editing to increase fetal hemoglobin. Before birth, a fetus’ hemoglobin is 95% fetal hemoglobin, he explained. These babies are born seemingly without SCD; their SCD symptoms arise only after their fetal hemoglobin is replaced by hemoglobin A a few months after birth. Previous studies have shown that those with SCD who also had higher rates of fetal hemoglobin as they aged—known as hereditary persistence of fetal hemoglobin—had less severe SCD symptoms.

Therefore, in the CLIMB SCD-121 trial, Frangoul and his team “basically turn patients with sickle cell disease into patients with hereditary persistence of fetal hemoglobin,” he said. To do the gene editing, the researchers collect a patient’s stem cells and “shock the cells” allowing CRISPR/Cas9 to enter. “I think the little kids really get a kick out of it when I say I’m going to electrocute their cells to fix them,” Frangoul said.

CRISPR/Cas9 breaks the DNA at the location needed. The patients undergo chemotherapy to destroy their bone marrow before the gene-edited cells are infused into them.

In the CLIMB SCD-121 trial, Frangoul’s team is using gene editing to decrease the BC11A gene. That suppression increases the production of gamma globin antibodies and increases fetal hemoglobin. The multicenter international trial started over four years ago. So far, 35 patients, ages 12 to 35, have undergone the gene editing. Before the treatment, the median number of vaso-occlusive crises—when SCD pain and other symptoms worsen—ranged from four to five per year. After the treatment, up to three years later, 94% of the patients had not had a SCD crisis or complication, and none of the patients were admitted to a hospital.

The ongoing impact of newborn screening

Gene editing to cure diseases, DNA sequencing to discover the cause of mystery illnesses, and artificial intelligence to improve screening results: all of these extraordinary promises of medical diagnosis and treatment would not have been possible without the creation of newborn screening 60 years ago.

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

The Newborn Screening Symposium, co-sponsored by APHL and the International Society for Neonatal Screening, was held in Sacramento, California, and online October 15-19, 2023.

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Advocates work to expand newborn screening worldwide

One person speaks at a podium during the 2023 APHL/ISNS Newborn Screening Symposium while another panelist sits and listens.

By Melanie Padgett Powers, writer

Over the past 60 years, newborn screening has led to early diagnoses and treatments for millions of babies with genetic health conditions, saving and improving lives. However, the existence of newborn screening programs around the world is not equal.

Globally, nearly 40 million babies are screened annually, but that’s only about 28% of infants born every year, said James Bonham, MSc, PhD, CSci, FRCPath, president of the International Society for Neonatal Screening (ISNS) during the 2023 APHL/ISNS Newborn Screening Symposium in Sacramento, California, in October.

“There is much to celebrate after 60 years, but much to do after 60 years,” said Bonham, who led off the two-part half-day session, “The Development of Newborn Screening in Low- and Middle-Income Countries.”

While mortality rates for children under five have improved substantially over the past 20 years, death from birth defects for children under five has increased, now a cause of about 20% of the deaths in these young children, according to Bonham. That fact led the World Health Organization to convene an assembly in 2010 on birth defects, recognizing that primary prevention of childhood disease was going to be crucial to decrease infant mortality and under five mortality.

That goal “is really a platform for newborn screening, not just biochemical newborn screening as we see it now, but the wider concept of checking a baby out shortly after birth,” Bonham said.

In 2021, the International Federation of Clinical Chemistry and Laboratory Medicine, partnering with ISNS, created the Global Task Force on Newborn Screening, of which Bonham is co-chair. APHL is also involved in the efforts, which aim to help develop appropriate screening programs worldwide, including in low- and middle-income countries.

“I really do emphasize the word ‘appropriate,’” Bonham said. “We’re not inflicting high-tech programs on countries where that would make little practical benefit for the children. We’re finding out what is really needed and then attempting to support that.”

The task force established objective selection criteria to choose the countries to reach out to first. In early 2023, task force representatives visited the first three countries: South Africa, Dominican Republic and Romania.

Setting up screening in the Dominican Republic

In the Dominican Republic, newborn screening is only offered through private labs and occasionally through private insurance. There is no organizational support and no data on follow-up or the number of conditions discovered, said Van Leung-Pineda, PhD, DABCC, FAACC, director of clinical chemistry and clinical mass spectrometry at Children’s Healthcare of Atlanta. Leung-Pineda, who is originally from Panama, was part of the team that traveled to the Dominican Republic.

The Dominican Republic has a population of about 11 million people, with 170,000 to 200,000 births each year. It is designated as one of 20 countries in Latin America with mid to high revenues. However, it has an insufficient investment in public health, Leung-Pineda said.

The country had already achieved several steps along the way to create a national newborn screening program. Local leaders had completed a feasibility study and proposed starting with six disorders. Four maternity units were selected to start the program, and a media awareness campaign was launched. Primary goals were established, a site was selected to build a laboratory and clinical protocols for follow-up were developed, Leung-Pineda said. But all that came to a halt when the COVID-19 pandemic hit in 2020.

While the task force has lent its expertise and assistance, working with local champions and gaining federal support have been key to moving the program along, he said. A federal bill that had passed one of the two houses of Congress of the Dominican Republic in 2014 had expired. But since the task force’s visit in February 2023, local advocates were able to get a new bill introduced, which passed the Senate and is now awaiting review in the other house, the Chamber of Deputies. The health minister—with whom the task force met—has also received approval for funds from the World Bank. And the laboratory construction is underway.

Learning from a growing program in India

Lessons learned were also shared from a program already underway in the state of Kerala in India. Newborn screening began in Kerala with metabolic screening in 2012; hearing screening was added in 2014 and nurse screening of visible birth defects was added in 2016. In 2018, the Kerala program became the first in India to add universal pulse oximetry screening. That same year, all these programs were brought under the umbrella of a new newborn screening program  called Shalabham, which means “butterflies,” said Sreehari Madhavankutty Nair, PGD DN, PGD QM, MBA, medical officer in the Department of Health Services in Thiruvananthapuram, Kerala.

Because guidelines recommend women stay in the hospital after birth for 48 hours, the local newborn screening team focused on that time frame, Nair said. Visible birth defects are confirmed in the hospital within 24 hours, and pulse oximetry is confirmed in the hospital within 24-48 hours. Hearing results are sent to the nearest audiology center, while infant heel pricks are done within 48 hours and the dried blood spots are sent to a nearby laboratory.

However, the health department noticed there were several delays in the pipeline: Sometimes samples were kept too long in the hospital before being sent to the laboratory, while other times there was a delay in notifying the parents of results recommending they return for more testing.

Sample quality was another challenge, Nair said. Up to 12% of samples from some hospitals were rejected by the laboratory. New samples were needed, but when patients were recalled to collect a new sample, fewer than 20% returned to the hospital.

To improve the issues, the health department updated the processes and systems to reduce delays, retrained staff on procedures and the importance of timeliness, and added more nurses to the program.

These challenges were discovered due to the collection of appropriate data. The program developed an Android app that allows staff to easily capture and report data. “When we started looking at visible birth defect screening, there was around 150 different clinical conditions that were going to be screened by the nurses,” Nair explained. “It was really challenging for them to learn all these names with the correct spelling.” But the app now allows them to simply tap on an image of a child, in the appropriate area of the body, and various conditions and information pop up.

The app and its accompanying dashboard are “very useful for the program managers, to see how the system is moving, if there is a derailment that can be adjusted at the earliest point,” Nair said.

The team also updated its parent education, explaining in the hospital why the screening was so important and why it was important to return if notified. “Sometimes parents are not aware of why the sample is taken, and that is the reason why they don’t come back,” Nair said. Beyond that, the team updated the app to text parents when they need to return with their baby for follow-up. The app also texts results to the baby’s doctor, who can notify the parents directly.

Adopting appropriate technology for the community has been critical to the program, Nair said. Another key component has been establishing linkages with other systems in place and with the community nurses. “The processes should align with the existing health system,” he said. “Otherwise, it’s going to be an additional burden to the people who are managing it.”

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

The Newborn Screening Symposium, co-sponsored by APHL and the International Society for Neonatal Screening, was held in Sacramento, California, and online October 15-19, 2023.

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APHL and ISNS Honor 2023 Newborn Screening Award Winners

Group photo of all 2023 APHL Newborn Screening Award winners posing with their awards.

For Immediate Release

Sacramento, CA, October 19, 2023 – At the 2023 Association of Public Health Laboratories (APHL)/ International Society for Neonatal Screening (ISNS) Newborn Screening Symposium, APHL presented awards to leaders in the field of newborn screening. Additionally, ISNS honored those from around the globe for their commitment to the field of newborn screening. The winners were announced during a ceremony on Wednesday, October 18. Congratulations to all award winners!

The following APHL awards were presented:

The George Cunningham Visionary Award in Newborn Screening is given to someone who has made the greatest contribution to expanding or improving the screening of newborns by public health agencies in one or more states. This year’s award recipient is:

  • Rachel Lee, PhD, medical screening unit director, Laboratory Services Section, Texas Department of State Health Services

The Judi Tuerck Newborn Screening Follow-up and Education Award honors someone who has made significant and outstanding contributions in one or more of the following areas: enhancing the caliber of the newborn screening system; improving follow-up and education; developing creative short term follow-up strategies that significantly reduce the time to diagnosis and treatment of affected infants; developing or enhancing long term follow-up strategies; establishing novel approaches or methods for managing the integration of new technologies in newborn screening; translating novel approaches or methods into best practices or guidelines for follow-up and education; providing innovative newborn screening follow-up training/education for best practices; or improving practices to ensure timely detection, reporting, intervention and treatment for newborns detected with disorders/conditions. This year’s award recipient is:

  • Carol Johnson, newborn screening follow-up coordinator, Iowa Newborn Screening Program, State Hygienic Laboratory at the University of Iowa

The Everyday Life Saver Award in Newborn Screening highlights the meaningful, ongoing ways the recipient contributes to the morale of their team and/or operations of their program on a daily basis. This year there are two recipients:

  • Kimberly Blake, newborn screening manager, North Carolina State Laboratory of Public Health
  • Ron Hardy, owner (retired), Central Delivery Services of Iowa

The Harry Hannon Laboratory Improvement Award in Newborn Screening award honors someone who has made significant contributions in one or more of the following areas: assuring the quality of testing, enhancing the specificity of tests, establishing new creative laboratory approaches and technologies, providing laboratory training/education for new technologies and tests, or improving the detection of newborn disorders/conditions. This year’s recipient is:

  • Patrick Hopkins, newborn screening project specialist, Missouri State Public Health Laboratory

The Clinician Champion Award honors someone involved in patient care and who has made significant contributions in one or more of the following areas: ensuring newborns receive adequate screening and appropriate follow-up; assuring timely and effective communication of screening results to patients and families; and contributing to efforts to strengthen the impact of the public health newborn screening system by being directly involved in follow-up care, community affairs, newborn screening advocacy and/or community activities. This year there are two recipients:

  • Philip Farrell, MD/PhD, emeritus dean and professor, Departments of Pediatrics and Population Health Sciences, UW School of Medicine and Public Health
  • Paul Levy, MD, director, Inherited Metabolic Disease Specialty Care Center, Montefiore Medical Center

The Achievements in Public Health Informatics Award honors a person working in any aspect of newborn screening worldwide and has made significant contributions in one or more of the following areas: enhancing implementation practices for electronic messaging; developing strategies for achieving effective data management; improving laboratory capability for health information data exchange; or providing new and creative approaches to communicate findings through data visualization. This year’s recipient is:

  • Craig Newman, PhD, Public Health Interoperability Subject Matter Expert, Altarum Institute

The ISNS awardees are:

The Robert Guthrie Award is given annually to honour a member of ISNS who has made an outstanding contribution to newborn or other population-based screening which is recognized as such worldwide. The awardees are:

  • 2019 Awardee: R. Rodney Howell, MD, FAAP, FACMG; Professor and Chairman of Pediatrics, Emeritus; Emeritus Member, Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine
  • 2020 Awardee: Georg F. Hoffmann, MD, Univ.-Prof. Dr. med., Prof. h.c. mult. (RCH); Chairman/Department of Pediatrics, University of Heidelberg
  • 2021 Awardee: Joanne Mei, PhD; Chief, Newborn Screening Quality Assurance Program, Newborn Screening and Molecular Biology Branch, Centers for Disease Control and Prevention
  • 2022 Awardee: Michael Gelb, PhD; Professor and Boris and Barbara L. Weinstein Endowed Chair in Chemistry; Adjunct Professor of Biochemistry, Department of Chemistry, University of Washington

The Jean Dussault Medal for young investigators is given annually to honour a member of ISNS who has made a significant contribution to neonatal or other population-based screening which is recognized as such. The awardees are:

  • 2019 Awardee: Stephan Borte, MD, PhD; Head of Department of Laboratory Medicine, Hospital St. Georg Leipzig
  • 2020 Awardee: Francyne Kubaski, MSc, PhD; Staff Scientist, Biochemical Genetics Laboratory, Greenwood Genetic Center
  • 2021 Awardee: Ulrike Mütze, MD; Metabolic Pediatrician, PI Long-term outcome metabolic newborn screening; Metabolic Center Heidelberg, Metabolic Laboratory, Center for Pediatric and Adolescent Medicine, Heidelberg University Hospital
  • 2022 Awardee: Amy M. Gaviglio, MS, CGC; Genetics and Public Health Consultant, Connetics Consulting

The Gerard Loeber Award for Contributions to Newborn Screening Expansion in Developing Countries (NBS Development Award) is given every third year at the occasion of the ISNS international symposium. The awardee is:

  • 2023 Awardee: Kate Armstrong, DrPH, B Med, DCH, MPH, FAFPHM; President and Founder, Caring & Living as Neighbors (CLAN)

APHL and ISNS congratulate all award winners, and we thank them for their contributions to advancing the essential work of newborn screening.

Learn more about the APHL/ISNS Newborn Screening Symposium.

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The Association of Public Health Laboratories (APHL) works to strengthen laboratory systems serving the public’s health in the US and globally. APHL’s member laboratories protect the public’s health by monitoring and detecting infectious and foodborne diseases, environmental contaminants, terrorist agents, genetic disorders in newborns and other diverse health threats. Learn more at www.aphl.org.

Contact Michelle Forman at 240-485-2793 or michelle.forman@aphl.org

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Families share their stories with newborn screening

Photo of the Parent/Patient Panel at the 2023 APHL/ISNS Newborn Screening Symposium.

By Melanie Padgett Powers, writer

Elizabeth Whyte and her husband were living in Dubai, United Arab Emirates, when their first child, Henry, was born. A colleague told Whyte she would be asked if she wanted the heel prick “extra test” and that she would need to pay for it. Whyte consented to this newborn screening, but she wasn’t really sure what it was for.

About five days after Henry was born, when the family was back home, the hospital called to let Whyte know that one of her baby’s results “was out of range.” She was told she needed to bring in Henry for a repeat test. The second test was negative, so she was ready to move on. But friends in the UK encouraged her to get follow-up testing. So, the couple sent a sample of Henry’s blood to a laboratory in Germany.

Henry tested positive for glutaric aciduria type 1 (GA-1), a genetic disease in which the body can’t break down certain amino acids, the building blocks of proteins. People with the disease need to follow a strict low-protein diet to prevent a metabolic crisis.

Whyte shared her family’s story by video during the Parent/Patient Panel at the 2023 APHL/ISNS Newborn Screening Symposium in Sacramento, California, in October. The event celebrated 60 years since the beginning of routine newborn screening in the US.

The case of Henry, who is now a first grader, illustrates the benefits of newborn screening but also several challenges, including the different testing regimens from country to country—and in the US, from state to state—as well as the scattered education and awareness of newborn screening. In fact, this life-changing intervention is not yet available to more than 100 million babies born annually in low- and middle-income countries.

Whyte consented to screening for her newborn primarily because a colleague told her about it, and she followed up with testing because trusted friends and family in the UK encouraged her to. She and her husband were able to find a consultant in Dubai for Henry, but it was one person, not a team. Plus, it was difficult in Dubai to access the medication and special formula Henry needed.

The family decided to move back to England for Henry’s medical care. In 2020, they had another son, Jude. They waited to test him for GA-1 until after he was born. He too tested positive for GA-1, although his concurrent regular newborn screening showed a false negative for GA-1.

“It obviously posed a lot of questions,” Whyte said. “What would have happened if we hadn’t have had Henry in Dubai and been tested within the 48 hours, instead of that additional time that it is in the UK, which is from five days onwards?” Whyte said she understands that the screening in the UK is done later because of other conditions, but, she said, “I can’t help but feel that our outcome would likely have been very different should Henry not have been born in Dubai.”

Today, because of newborn screening, a special diet and access to treatment in the UK, Whyte said, “Both boys are doing fantastically. … We’re so grateful that we live in a time that we have the support and awareness of these metabolic conditions.”

Systematic parent education needed

In the US, newborn screening is often thought of as that heel prick, which takes a sample of the newborn’s blood for testing in a laboratory. But newborn screening also includes a heart screening and a hearing test.

Also on the panel was Michelle John, who shared her experience with her three children’s births. Her oldest, Tyson, was born deceased but revived after 17 minutes. After six weeks in a critical care facility, Michelle said he was sent home “to die.”

To this day, John has no idea if her son had a heel prick or heart test. But she was told, despite all his medical issues, that he had to have a required hearing test before he left the hospital. He failed the test, but a clinician told John that her baby probably just had fluid in his ears.

Later, an otolaryngologist (an ear, nose and throat doctor, commonly called an ENT) wasn’t sure if Tyson could hear. John got the sense that no one wanted to focus on Tyson’s hearing because he had so many other potentially fatal medical conditions. Finally, an audiologist took the issue seriously. Tyson was retested, and they learned he was Deafblind plus, which refers to people with vision and hearing loss as well as an intellectual impairment.

Tyson lived. He’s now 10 years old. John and her husband also have two other children: Trinity, age 7, and Lane, age 5. All three kids were born by Cesarean delivery in a non-critical care facility in New Hampshire.

“I have no idea if any of my children had newborn screening,” John said. “I know my oldest failed the hearing; I have no further information than that.” After her daughter was born, John was told at one point, “We’re going to take your daughter to check on her.” John assumed that meant newborn screening, but “she came back, no information was given, and I’ve never heard another word since.” The situation repeated itself after her youngest son was born.

Newborn screening “wasn’t brought up during [my obstetric] appointments. It wasn’t brought up after birth; it wasn’t brought up before going home. None of these things were discussed,” John told attendees.

“Somewhere along the line, something went a little wonky,” she said. Newborn screening needs to be explained to parents several times throughout the pregnancy and delivery, she stressed. “It’s not to scare them. … It’s just to be honest. … It’s critical that this becomes a natural part of the process. It has to be engrained, and it has to start long before the baby is born.

“I have three amazing kids. One is Deafblind plus. I’m here because of him, but I’m actually here to represent the fact that, especially in rural communities, information is maybe not quite as open as it needs to be. And it’s really critical that it becomes a lot more transparent with everyone involved.”

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

The Newborn Screening Symposium, co-sponsored by APHL and the International Society for Neonatal Screening, was held in Sacramento, California, and online October 15-19, 2023.

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The promise of whole genome sequencing faces privacy concerns

Panelists at the APHL 2022 Newborn Screening Symposium during a session called, "The Next Frontier of Genetics and Privacy: Newborn Screening at the Intersection."

By Melanie Padgett Powers, writer

As technology continues to advance rapidly, the newborn screening community is having a robust conversation to address privacy concerns while still being able to advance the diagnosis of rare diseases that saves babies’ lives.

Speakers during the session “The Next Frontier of Genetics and Privacy: Newborn Screening at the Intersection,” during the APHL 2022 Newborn Screening Symposium in October, specifically addressed whole genome sequencing (WGS), which could be the next step for newborn screening programs.

Newborn screening programs exist in all 50 states. Conducted when an infant is only a day or two old, newborn screening checks a baby for rare, serious and mostly treatable health conditions such as sickle cell disease, cystic fibrosis, phenylketonuria, hypothyroidism and more. It is done through a blood test by pricking a baby’s heel to get a few drops of blood. A hearing test and heart screening are also conducted.

Whole genome sequencing — which maps out an individual’s entire DNA sequence — can be used to diagnose a disease in a sick child, but is also used in healthy newborns to look for potential issues. It is not routinely done as part of newborn screening. But will that change in the future? And what are the potential privacy consequences?

“We are at a time where newborn screening is sitting between changing technologies, changing panels, the use of whole genome and exome sequencing in both families experiencing rare disease and in healthy newborns. … At the same time, on the other side, we have an increased concern among families and communities around genetic privacy,” said session co-moderator Aaron Goldenberg, PhD, MPH, professor and vice chair in the bioethics department at Case Western Reserve University and the co-director for Case Western’s Center for Genetic Research Ethics and Law.

Challenges and lawsuits have popped up against the storage and use of infants’ dried blood spots, which DNA can be extracted from. Some states store dried blood spots taken for newborn screening for years and use them for quality assurance, quality control and implementation of new screening tests. Any time a new disorder is added to the recommended uniform screening panel (RUSP), newborn screening programs do a population study to determine how best to detect that condition. Population studies require thousands and thousands of samples – so without the stored dried blood spots, population studies would become much harder to conduct and would slow down progress to implementing new screening tests. 

In a Michigan lawsuit, lawyers argued that the existing consent form —which is required from parents before their baby’s blood can be used for research — was vague and that parents were not sure what they actually signed. In New Jersey, privacy concerns were highlighted when it was uncovered that law enforcement used an infant’s dried blood spots to identify a criminal suspect related to that child.

Session presenter Rachel Lee, PhD, HCLD, medical screening unit director in the Laboratory Services Section of the Texas Department of State Health Services, outlined the health department’s experience in Texas, which was sued and settled the lawsuit in 2009. The lawsuit said the storage and use of newborn screening blood spots violated the Fourth Amendment, which prohibits unreasonable searches and seizures.

Texas had begun destroying all its blood spot samples before the settlement; 5.3 million specimens were destroyed between 2002 and 2009, Lee said.

Before the lawsuit, Texas didn’t require parental disclosure. That changed after the settlement, when the state passed multiple laws to address privacy concerns. The state now requires disclosure of specimen storage and use for other purposes. Initially, a 2009 law allowed parents or adults to request destruction of samples; in 2011, a new law changed that opt-out process to an opt-in requiring parental consent to store and use their infant’s blood spot. The new law also limited use to only public health purposes.

The health department had to consider and develop new processes for request and approval, destruction, storage and documentation, Lee said. “We also did a lot of engagement and education and communication to stakeholders, the public and parents, hoping they understand why these specimens were valuable to us,” she said.

Since the new laws, about 40% of parents allow storage, while 17% require the specimens be destroyed. The remaining 43% do not return the decision form. “We do have educators trying very hard to reduce that number,” Lee said.

Without the specimens, it’s more difficult for the public health laboratory to ensure the testing process is performing as well as it should be, she said. It also makes it challenging to add new conditions to the NBS panel.

Whole genome sequencing can save babies’ lives

Presenter Wendy Benson, MBA, outlined the important findings that WGS can uncover. Benson is chief strategy and innovation officer at Rady Children’s Institute for Genomic Medicine in San Diego. The institute works with 83 children’s hospitals to conduct WGS on severely sick children in intensive care units to determine what rare disease they might have. In the institute’s eight years, it has sequenced about 3,500 genomes and has a 40% diagnostic rate.

“This journey has been so humbling,” Benson said. “We work with really smart medical geneticists, but it’s amazing how much we don’t know.”

For example, the institute uncovered 13 Kabuki syndrome cases in San Diego. Kabuki syndrome is a rare, multisystem disorder; the symptoms and severity differ among individuals.

“These don’t look like your normal Kabuki [cases],” Benson explained. “These kiddos are in the ICU; they have wires and tapes and all sorts of tubes coming in and out of them, so the phenotype doesn’t look like Kabuki. There’s obviously stuff we don’t know about Kabuki because we’re finding so many of them so early.”

Benson outlined a study that showed the critical need for WGS. The San Diego Study of Outcomes in Mothers and Infants San Diego County used the county’s 20 years of collected blood spots to study unknown deaths among babies younger than one year old. Among 45 infant deaths, WGS showed that 31% had a genetic disease; of those, 57% had an effective treatment available if the children had been diagnosed.

The institute is starting a study that will conduct WGS on 50 infants, looking at 400 disorders. As the institute scales the project and builds its partnerships, its goal is to sequence more than 1 million babies, Benson said.

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

APHL 2022 Newborn Screening Virtual Symposium was held in Tacoma, Washington, and online October 16-20, 2022. 

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Sickle cell disease patients lack access to appropriate care after newborn screening and diagnosis

Julie Kanter, MD, director of the adult SCD program at the University of Alabama, Birmingham and president of the National Alliance for Sickle Cell Centers, speaks at the APHL 2022 Newborn Screening Symposium.

By Melanie Padgett Powers, writer

Sickle cell disease (SCD) was first identified in 1910. In 1972, Congress recognized SCD as a significant public health concern, passing the National Sickle Cell Anemia Control Act to establish education, screening, testing, counseling, research and treatment programs. Despite that, it wasn’t until 1998 for the first treatment, a medication called hydroxyurea, to be approved in the US.

“That’s relatively appalling. Almost no other disorders in the room have that kind of tragic history,” said Julie Kanter, MD, director of the adult SCD program at the University of Alabama, Birmingham and president of the National Alliance for Sickle Cell Centers, which was created in 2020.

It took another 21 years for the next drugs to be approved. And today, Kanter said, more than 50% of adults with SCD are not being treated by SCD experts.

Kanter’s presentation was part of the keynote session, “Improvements to Technology, Testing and Treatments: Progressing towards Universality in Newborn Screening,” during the APHL 2022 Newborn Screening Symposium in October.

She illustrated how much more needs to be done to improve SCD treatment and the quality of life for patients—particularly overcoming political and financial barriers to care and engaging families soon after a baby’s newborn screening.

People with SCD, which can be a very painful disease, have abnormal hemoglobin in their red blood cells that causes the cells to become hard and sticky and die early causing a shortage of red blood cells. Kanter pointed out SCD is a multi-system vascular disease—it’s not only about the red blood cells. “All that damage to the endothelium and the inside of the blood vessel means there’s not a single organ that remains unaffected by this disease,” she said.

SCD is the most common inherited clinically significant blood disease in the US, Kanter said, affecting approximately 120,000 people. The survival rate to adulthood has improved from less than 50% in 1970 to nearly 95% in 2010, thanks largely to the newborn screening process that detects SCD in the first week of a baby’s life. SCD was first included on the newborn screening panel in 1975, starting in New York. By 2006, it was on all 50 state panels, which is considered a major public health success story.

However, Kanter illustrated that while many newborns are diagnosed early, they are not receiving appropriate care or being seen by a SCD specialist throughout their lives. She illustrated the problem through the case of her SCD patient Janelle (not her real name), age 29. By the time Kanter saw Janelle as an adult, she had several complications including fatigue, chronic pain, death of bone tissue in two joints and alloimmunization, meaning her body’s immune system put up a fight against the red blood cell transfusions that should have helped her.

Janelle had also tried one of the only SCD medications at that time, hydroxyurea, but she didn’t take it regularly because she wasn’t sure why she was supposed to be taking the drug, Kanter said. Janelle was among those who lived into adulthood with SCD. However, she was on disability, had to drop out of college, felt she couldn’t leave her house for long periods and had been hospitalized five times in the previous year.

“This is why we’re not there yet. We’ve improved childhood mortality—great. … But we haven’t improved mortality overall, specifically in our young adults,” Kanter said. Recent data show adults with SCD die on average at age 43 for women and 41 for men.

In 2015, Kanter restarted Janelle on hydroxyurea—and explained to her why she needed it—and created an individualized care plan for her. Those interventions decreased her hospitalizations to twice a year, but she still had very frequent acute pain. In 2017, she was given a new drug, crizanlizumab, which significantly decreased her acute crises. Her last hospitalization was in 2018, though she still seeks treatment at Kanter’s clinic for frequent pain.

Janelle later asked to be considered for gene therapy, but an evaluation showed that she had more antibodies in her blood than Kanter had ever seen. This meant there were no blood units available that she would need to have blood transfusions as part of gene therapy. Because Janelle had not been cared for appropriately and had not previously seen a SCD specialist, she could not undergo gene therapy, Kanter said.

How to improve sickle cell disease care

While SCD is more prevalent than hemophilia and cystic fibrosis combined, there are only half as many comprehensive adult SCD centers in the US compared to more than 130 each for the other two diseases, according to Kanter.

Until recently, SCD had no coordinated network of centers; they were all operating in siloes. And there was no clear definition of what a sickle cell center was. There is no SCD registry to collect long-term data, and there is an insufficient number of centers with experts focused on adult SCD care.

“How’d you know if you went to a sickle cell center versus someone who hung their shingle up and said, ‘yes, we can take care of you with sickle cell disease’?” Kanter explained.

And the drugs now available to treat SCD are used by less than 50% of the people who need them. The rise in mortality occurs in the early adult years, ages 20 to 24, which often puts the blame on the transition from pediatric to adult care. But Kanter said that’s not the full story. She undertook a study of 421 SCD patients to see when patients were lost to follow-up care.

“The most common predictor for whether or not they made it to my adult center was whether they were seen after 15 years of age. … These patients were lost to follow-up long before transition [to adult care],” she said.  

To prevent this, Kanter called for early engagement with families from sickle cell centers, right after newborn screening leads to a SCD diagnosis. Recent data show that early childhood-specific treatments are not being done. Penicillin prophylaxis is given continuously to fewer than 30% of children ages 1–5 with SCD. There is currently no standardized protocol for SCD diagnosis via a newborn screening program and no definition for when the program resolves and closes the case.

“This clearly suggests to us that there’s some insufficient, poorly standardized newborn screening follow-up programs because some of these kids just aren’t getting to care,” she said.

“As a result,” she added, “there’s no assurance that a child diagnosed with sickle cell disease will ever see a sickle cell disease specialist.”

Kanter invited newborn screening programs to join her ENHANCE Study, an APHL-funded quality improvement project to study and develop an optimized protocol for notifying SCD families and a definition of “case resolution” for newborn screening departments. Kanter is also leading the RECIPE study, which aims to identify and link underserved adults with SCD to specialists. The RECIPE study will adapt the concept of “linkage coordinators” used successfully in HIV care.

“I can’t tell you the number of 30- to 50-year-olds who walk into my clinic that haven’t been seen by a sickle cell specialist,” she said. “Many of them don’t even know we exist, much less how to get there or make an appointment.”

Kanter acknowledged that newborn screening for SCD has resulted in amazing improvements in care and reduced childhood mortality. “But despite these improvements, many children and adults are not getting guideline-based care for sickle cell disease.” Although several “amazing” therapies are being developed, without access to SCD centers, patients will never receive the right treatments, she said.

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

APHL 2022 Newborn Screening Symposium was held in Tacoma, Washington and online October 16-20, 2022. 

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APHL Celebrates 2022 Newborn Screening Award Winners

The six APHL Newborn Screening Award winners pose with their awards.

For Immediate Release

Tacoma, WA, October 19, 2022 – At the Association of Public Health Laboratories (APHL) 2022 Newborn Screening Symposium, APHL presented awards to six leaders in the field of newborn screening.

“Through their work, all recipients have directly improved the quality of life of newborns and their families,” said Scott J. Becker, MS, chief executive officer, APHL. “We commend the exceptional and innovative work of all those who were nominated.”

The following awards were presented in a ceremony during the Symposium today in Tacoma, WA:

The George Cunningham Visionary Award in Newborn Screening is given to someone who has made the greatest contribution to expanding or improving the screening of newborns by public health agencies in one or more states. This year’s award recipient is:

  • Sylvia Mann, MS, CGC, genomics section chief, Children with Special Health Needs Branch, Hawaii Department of Health

The Judi Tuerck Newborn Screening Follow-up and Education Award honors someone who has made significant and outstanding contributions in one or more of the following areas: enhancing the caliber of the newborn screening system; improving follow-up and education; developing creative short term follow-up strategies that significantly reduce the time to diagnosis and treatment of affected infants; developing or enhancing long term follow-up strategies; establishing novel approaches or methods for managing the integration of new technologies in newborn screening; translating novel approaches or methods into best practices or guidelines for follow-up and education; providing innovative newborn screening follow-up training/education for best practices; or improving practices to ensure timely detection, reporting, intervention and treatment for newborns detected with disorders/conditions. This year’s award recipient is:

  • Natasha F. Bonhomme, founder, Expecting Health; chief strategy officer, Genetic Alliance

The Everyday Life Saver Award in Newborn Screening highlights the meaningful, ongoing ways the recipient contributes to the morale of their team and/or operations of their program on a daily basis. This year’s recipient is:

  • Mei W. Baker, MD, director, Newborn Screening Laboratory, Wisconsin State Laboratory of Hygiene

The Harry Hannon Laboratory Improvement Award in Newborn Screening award honors someone who has made significant contributions in one or more of the following areas: assuring the quality of testing, enhancing the specificity of tests, establishing new creative laboratory approaches and technologies, providing laboratory training/education for new technologies and tests, or improving the detection of newborn disorders/conditions. This year’s recipient is:

  • Andreas Rohrwasser, PhD, MBA, director, Utah Public Health Laboratory

The Clinician Champion Award honors someone involved in patient care and who has made significant contributions in one or more of the following areas: ensuring newborns receive adequate screening and appropriate follow-up; assuring timely and effective communication of screening results to patients and families; and contributing to efforts to strengthen the impact of the public health newborn screening system by being directly involved in follow-up care, community affairs, newborn screening advocacy and/or community activities.

  • Susan A. Berry, MD, professor, Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota

The Achievements in Public Health Informatics Award honors a person working in any aspect of newborn screening worldwide and has made significant contributions in one or more of the following areas: enhancing implementation practices for electronic messaging; developing strategies for achieving effective data management; improving laboratory capability for health information data exchange; or providing new and creative approaches to communicate findings through data visualization.

  • Brendan Reilly, program specialist VI / health informaticist III, Biochemistry and Genetics Branch, Laboratory Services Section, Texas Department of State Health Services

“We congratulate all award winners and thank them for their contributions to advancing the essential work of newborn screening,” Becker said.

Learn more about the APHL Newborn Screening Symposium.

# # #

The Association of Public Health Laboratories (APHL) works to strengthen laboratory systems serving the public’s health in the U.S. and globally. APHL’s member laboratories protect the public’s health by monitoring and detecting infectious and foodborne diseases, environmental contaminants, terrorist agents, genetic disorders in newborns and other diverse health threats. Learn more at www.aphl.org.

Contact Michelle Forman at 240-485-2793 or michelle.forman@aphl.org

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Importance of newborn screening for early detection and treatment emphasized by patients and families

Three panelists share their stories during the APHL 2022 Newborn Screening Symposium.

By Melanie Padgett Powers, writer

At six weeks old in the early 1970s, Kendra Hogenson was adopted. But her new parents quickly realized that instead of cooing and wiggling around, all their baby did was cry and beat her head against the wall. They had no idea what was wrong with their daughter and took her from doctor to doctor seeking help.

As Hogenson, now age 51, told her story as part of the Parent/Patient Panel during the APHL 2022 Newborn Screening Symposium in October, she began to cry. “One doctor even said, ‘put her away in an institution; she’ll never amount to anything,’” she recalled. But Hogenson’s mom said, “I know she’s in there.”

Finally, a pediatrician suspected sickle cell anemia and had the baby tested. The results were positive. Sickle cell anemia is part of a group of inherited disorders known as sickle cell disease (SCD). People with SCD have abnormal hemoglobin in their red blood cells that causes the cells to become hard and sticky and die early, according to the Centers for Disease Control and Prevention. The red blood cells can also get stuck in small blood vessels, causing severe pain and other serious health problems.

Routine newborn screening in the US will celebrate its 60th anniversary next year, and as of 2011 all 50 US states were screening for at least 26 disorders. Through a simple heel prick in the hospital when a baby is one to two days old, newborn screening tests an infant for rare but serious disorders that can be treatable.

If Hogenson, born in Washington, had received newborn screening when she was born, SCD would not have been included in the panel. New York was the first state to screen for the disease beginning in 1975. It wasn’t until 2006 that universal newborn screening for SCD was in place in all 50 states, Puerto Rico and the US Virgin Islands.

As a child, Hogenson was in and out of Seattle Children’s Hospital, which she referred to as her “second home.” She’s had meningitis three times which caused brain damage; strokes that led to learning disabilities; more than 20 surgeries; and 32 years of routine exchange blood transfusions, which she credits with saving her life.

Despite her challenges, Hogenson said she “exceeded all their expectations.” She graduated high school even though it was difficult: “Me and math still don’t get along.” She drives and has held a full-time job. “I wasn’t supposed to live this long; here’s to proving them wrong,” she said.

She thanked Symposium attendees for now screening every infant for SCD, “so their families don’t have to go what mine went through to find out what was wrong.”

Hogenson and fellow panelist Denise Bazemore, a 63-year-old woman who also has SCD, will soon be living in a new “sickle cell house” in Seattle called the “HUB,” which was developed by the Metro Seattle Sickle Cell Task Force, a grassroots organization.

HUB, which stands for healing, use and belonging, will offer people with SCD massage, yoga, acupuncture, reflexology and other therapies. It will offer educational and occupational workshops and offer a safe place for those with SCD to connect and support each other.

Improving newborn screening education

Susan Mays and daughter, Indie, share their story at the APHL 2022 Newborn Screening Symposium.
Susan Mays and daughter, Indie, share their story at the APHL 2022 Newborn Screening Symposium.

Also speaking on the panel were Susan Mays and her daughter, Indie, age 9. Thanks to the newborn screening program, Indie was diagnosed with maple syrup urine disease (MSUD) a few weeks after she was born. MSUD is a condition in which the body cannot process certain amino acids, requiring a strict low-protein diet.

Susan Mays said she didn’t really know what newborn screening was until her baby’s second-week follow-up appointment with her pediatrician, when she was told her daughter needed a second screening test.

“It makes me cringe to think about it now, but at the time I questioned why a second test was necessary, simply being clueless as to its importance,” she said. Indie wasn’t showing symptoms of MSUD, making the second test all that more important because that’s what led to her diagnosis. She had a confirmatory test a few days later.

Now Indie is a happy little girl who loves soccer, French fries and reading. She’s limited to 12-15 grams of protein a day and drinks four to five servings a day of medical formula.

While Mays said the process of getting tested and notified was “textbook,” she pointed out that she doesn’t remember being told about newborn screening during her pregnancy. She didn’t understand what it was for, causing her to push back a bit on that second test.

Mays said there’s an opportunity to explain what newborn screening is “far earlier than when the mom is pregnant,” perhaps even teaching about it as part of high school sex education classes. And it should certainly be emphasized in birthing classes and by pregnant women’s health care providers, she said.

It’s also important for families like hers to continue to share their stories about how newborn screening saved their babies’ lives and led to earlier treatment, she said. “I think all of us who have been impacted have a responsibility and an opportunity to help educate, starting with your friends, your family, using social media. I don’t think it relies on any one person or any part of the puzzle. Certainly, there’s a big opportunity for an understanding of why it’s done and why it’s important.”

The presentation concluded with a powerful video of other families sharing how newborn screening saved their babies’ lives. Afterward, attendees and panelists, and other families affected by newborn screening, gathered for a mixer in the exhibit hall.

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

APHL 2022 Newborn Screening Symposium was held in Tacoma, Washington, and online October 16-20, 2022. 

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How to improve inequalities in newborn screening

Photo of a newborn baby

By Melanie Padgett Powers, writer

Every year in the US, nearly 4 million babies receive newborn screening for a variety of health conditions within the first 24–48 hours of birth. Newborn screening was developed almost 60 years ago on the basis of equality—screening all babies for the same conditions.

However, public health professionals recognize that disparities exist across the newborn screening system. A panel of experts outlined these disparities and recommended actions that public health laboratories can take to improve the system, during the 2022 APHL Annual Conference May 18 session, “Exploring Equity Across the Newborn Screening System: From Discourse to Action.”

Newborn screening is “an interesting use case because newborn screening has historically been heralded as this universal program, a great equalizer among diagnoses for rare congenital diseases in newborns,” said Amy Gaviglio, MS, CGC, a genetic consultant based in Minneapolis.

The most obvious disparity, Gaviglio said, is the differences in conditions screened for from state to state, despite what is recommended by the US Recommended Uniform Screening Panel (RUSP). She said the RUSP did a great job at level-setting the panels in 2009—with all programs screening for at least 20 of the core conditions. However, as the complexity of diseases has grown, so have the disparities.

Gaviglio outlined three problem areas within newborn screening programs at public health laboratories:

  1. Lack of tiered testing. Using tiered testing can reduce referral rates, which can improve follow-up screening and diagnosis.
  • Programs vary in their incorporation of molecular technologies. Use of such technology can reduce the lack of access to genetic testing that some groups face, including Hispanic people, uninsured people, non-citizens and people with lower education levels.
  • All babies may not be screened in the best possible way. This is often discussed in relation to cystic fibrosis, which often uses a CFTR variant panel, which was created using white individuals.

The APHL NewSTEPs data showed that time to diagnosis and to intervention for cystic fibrosis was longer for Black and African American babies than for Asian and white babies, according to Gaviglio. The program also studied hemoglobinopathies such as sickle cell disease, which largely affect Black and African American people.

“Despite this condition being considered more of an African American condition, there was no real statistical difference in time to diagnosis or time to intervention,” Gaviglio said. “What was important with this work … was to indicate that the universality of newborn screening really does fall short when we call results out. These babies and these families succumb to the disparities in our health care system, and this is an area we’re going to have to focus on to make sure all of our babies are receiving similar care post-newborn screening.”

Involving families at every step

It’s important to recognize that different groups have varying access to resources, skill sets and opportunities to get their condition and causes “on the radar,” said Natasha Bonhomme, founder of Expecting Health and director of Baby’s First Test, the nation’s newborn screening resource center.

When it comes to educating communities about newborn screening and various conditions in recent years, the public health community has done better in providing materials in multiple languages, listening to feedback to inform new projects, using images that reflect the community and considering rural versus urban issues, Bonhomme said.

However, she said, the areas in which public health must improve include taking into account different learning styles; creating a consistency in language, terminology and descriptions; acknowledging people’s health care experiences; and considering an individual’s hierarchy of needs.

A person’s hierarchy of needs, Bonhomme said is “where there’s all these ‘nice to haves’ and things we wish people would understand are important, but we also need to listen to families who say: ‘I know that’s important, but I need this to get through today, to get through this week.’”

That’s a different starting-off point and must be incorporated as we educate people about the importance of public health issues, Bonhomme said.

In the advocacy arena, the newborn screening community has improved in addressing learning opportunities, sharing stories and perspectives, and informing policy and sharing across groups. However, the newborn screening system needs to build an infrastructure for policy and developing long-term data, while also expanding partnerships and providing more leadership opportunities, she said. It’s critical that the newborn screening system keeps families central and continually asks for their input.

Bonhomme said she often hears from families who say: “I went to a conference and I told my story and people cried or said ‘you’re so strong,’ and ‘that’s amazing,’ and then I never heard from them again. I want to help.”

She ended her presentation with a quote: “Equality is giving everyone a shoe. Equity is giving everyone a shoe that fits.”

“There are a lot of barriers,” Bonhomme said. “We work in a lot of systems that are not flexible, but what can we do, bit by bit, day by day, to get to that shoe that actually fits?”

Melanie Padgett Powers is a freelance writer and editor specializing in health care and public health.

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Maximizing next-generation sequencing in newborn screening through bioinformatics

A baby sleeps with his dad

by Samantha Marcellus, MPH, APHL-CDC Newborn Screening Bioinformatics Fellow

We live in the era of rapid access to near limitless information, over-the-counter DNA testing, and emerging gene therapies. As genetic testing, technology, and treatments advance, newborn screening must broadly utilize bioinformatics to keep up with the ever-changing rare disease arena and other areas of public health. Infectious diseases groups have widely adopted bioinformatics and next-generation sequencing over the last decade, and many laboratories have the capability to sequence and interpret the whole genome of a pathogen in hours or days. Through bioinformatics, cases can be linked via their specific strains and outbreaks can be declared more rapidly than ever before.

For the states that have harnessed the power of next-generation sequencing and bioinformatics for second- or third-tier screens, test times have been reduced and more detailed genetic information is presented to the providers. Continued and widespread implementation of bioinformatics in NBS is vital for programs to keep up with advances in technology and to offer providers and parents a more complete picture of the newborn’s risk profile.

Getting Started in Texas
In spring 2019, APHL and the Newborn Screening and Molecular Biology Branch at the US Centers for Disease Control and Prevention (CDC) selected the inaugural class of Newborn Screening Bioinformatics Fellows—myself and three others. We were matched with state public health laboratories to enhance or implement bioinformatics in their NBS programs.

At the Texas Department of State Health Services Laboratory we are building a bioinformatics program from the ground up. We are developing and refining a program to efficiently and accurately analyze and interpret severe combined immunodeficiency (SCID) next generation sequencing data. The public health bioinformatics community has already developed many great pipelines and analysis tools, so we plan to draw from those tools while adding some of our own programs to best fit the needs of Texas newborns. While all states utilize bioinformatics in different ways, we can still learn a great deal from our collective experiences.

In Texas, geneticists and consultants from around the state have shown interest in receiving sequencing information from the newborn screening program. The results from next-generation sequencing can be used to complement currently available newborn screening results and provide parents with a more complete picture of their child’s risk for a screened disease. As gene therapy is developed for an increasing number of disorders and those diseases are added to the Recommended Uniform Screening Panel (RUSP), the need for rapid DNA sequencing may increase in kind.

Looking Forward
With in-house bioinformaticians, laboratories will be able to process and analyze next-generation and Sanger sequencing data more rapidly and with programs that are designed to fit the state’s specific needs. These capabilities can allow for faster test times, higher accuracy and precision in results, and quicker result reporting. In the case of newborn screening, that could mean referring a baby to a specialist more quickly and with more complete information. Through programs such as the APHL/CDC Newborn Screening Bioinformatics Fellowship, state laboratories have the opportunity to develop staff and infrastructure to meet the evolving needs of newborn screening programs and public health in general.

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