Lab Culture Ep. 5: My Niece’s Positive Newborn Screen

My Niece's Positive Newborn Screen | www.APHLblog.org

My Niece's Positive Newborn Screen | www.APHLblog.orgFour years ago, as APHL joined with partners to celebrate the 50th anniversary of routine newborn screening in the United States, newborn screening hit more closely for APHL staff than it ever had before. Michelle Forman, manager of media and Lab Culture host, received a text that her new niece, Sloane, had a positive newborn screen. Her results were out of range for PKU. In this episode, Michelle interviews Sloane’s mom, Judith Forman, about that experience.

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Making Sense of Newborn Screening Cut-off Values

Making Sense of Newborn Screening Cut-off Values | www.APHLblog.org

Newborn screening is the practice of screening every baby in their first 24-48 hours of life for certain harmful or potentially fatal conditions that are not otherwise apparent at birth. For babies who have abnormal screens for one of these conditions, rapid identification and treatment makes the difference between health and disability – or even life and death. Every year more than 12,000 newborn lives are saved or improved through newborn screening. It is the largest and most successful health promotion and disease prevention system in the country.

How is a screening test different from a diagnostic test?

A screening test looks for abnormal levels that may indicate signs of a disease when no symptoms are present. It tells a patient their risk – normal levels indicate low-risk and abnormal levels indicate high-risk. A diagnostic test determines if, in fact, the disease is present allowing the healthcare provider to make a definitive diagnosis and initiate treatment.

Newborn screening is not a diagnostic test but rather a screening test – it determines whether the baby has a high or low risk of having that disease. If a baby has abnormal screening results, the baby’s levels were out of normal range. This immediately cues the healthcare provider to pursue additional diagnostic testing in order to know whether or not the baby has the disease in question.

If a baby has symptoms or family history of a disease, parents should not rely entirely on newborn screening to rule it out; healthcare providers should be consulted for additional diagnostic testing.

What are cut-off values?

As in many scientific tests, cut-off values are used to determine which levels are normal and abnormal. Newborn screening looks for markers of disease and the cut-off levels tell scientists if the amount of markers indicates high or low risk. Determining the precise cut-off values is extremely nuanced and always being evaluated.

How are cut-off values determined and why do they vary from state to state?

Every state newborn screening lab determines the optimal cut-off values for its population. The values are set using a number of factors and considerations such as:

  • The disease’s prevalence and severity in the state’s population,
  • Race and ethnic differences in the state (again, relating to a disease’s prevalence),
  • Environmental factors in the state (temperature or altitude, for example) which can affect testing,
  • Differences in the way the laboratory test is performed (methodology),
  • And other factors unique to the laboratory and its equipment.

For these reasons, a value in one state newborn screening lab cannot simply be compared to a value in another lab. The value associated with a normal screen in one state’s population may differ significantly from the value associated with a normal screening at another lab. That is, the line between normal and abnormal could be different in each state.

Making Sense of Newborn Screening Cut-off Values | www.APHLblog.orgFor example, Baby A gets a value of 14 which is normal in her state where the cut-off is 16. In a neighboring state, the cut-off is 10 so a 14 would be considered abnormal. However, because of differences in how cut-off values were determined and how the test was performed, Baby A’s sample would have screened at 8 in the neighboring state and been considered normal as well.

What are false positives and false negatives?

Sometimes newborn screening will show that a baby has abnormal levels of markers for a disease, but further diagnostic testing is negative. This is a false positive. In extremely rare cases, newborn screening will show normal levels of markers in babies who will eventually develop diseases. This is a false negative or delayed diagnosis.

False positives can be extremely stressful for families. In some cases, the diagnostic process can take several months leading to distress and hardship for the baby and family. False negatives, on the other hand, mean that a baby might begin experiencing symptoms of a condition before being diagnosed. Depending on the condition, these symptoms could cause life-long development delays, permanent disability or even death.

If cut-off values are thought of as a filter, state newborn screening programs work to find the optimal filter to catch as many babies as they can. That may mean catching more babies who are ultimately determined to be healthy to avoid missing others who may later receive positive diagnoses. . So while some false positives are necessary to avoid false negatives, states strive to keep them to a minimum.

What happens when there is a delayed diagnosis (aka, false negative)?

While delayed diagnoses (aka, false negatives or missed cases) are extremely rare, they are not nonexistent. State newborn screening program staff work to save babies’ lives and they take this job extremely seriously. It takes just one delayed diagnosis reported to a newborn screening program to trigger a comprehensive examination of the system. Every effort is made to understand why the case was missed and what, if any, changes can be made to prevent additional delayed diagnoses.

When a delayed diagnosis is reported to the state newborn screening program, the laboratory scientists begin repeating the test to see if they get different results. They retest the baby’s bloodspot if it is still available and revalidate the testing equipment to make sure it is functioning properly. If everything is still the same upon retesting, newborn screening laboratory scientists will reevaluate the state cut-off values for the condition, consider altering the sensitivity of the testing equipment and/or determine whether the baby’s biology (fluctuating hormone levels, for example) may have affected the screen.

What has been done to prevent delayed diagnoses? Is there more than can be done?

Making Sense of Newborn Screening Cut-off Values | www.APHLblog.orgMany states have implemented processes to prevent delayed diagnoses while keeping false positives to a minimum. In most states, when a baby’s newborn screening results are abnormal, the test is performed again to confirm that the results are consistent. In cases where the value is abnormal but is close to the cut-off, second tier testing may be used. Second tier testing employs a more sensitive test that can eliminate some false positives and delayed diagnoses. But second tier tests are also more expensive, more complex and take more time than the primary method of testing. For these reasons, they are reserved for supporting or refuting a borderline abnormal result.

Additionally, newborn screening short-term follow-up program staff review reports from clinicians of babies’ final diagnoses. This information, even if consistent with the baby’s newborn screening results, helps the program continue to improve the quality of their testing.

Newborn screening programs around the nation routinely evaluate and examine their processes from beginning to end. There is always room for improvement, and newborn screening programs will continue to seek new advances in technology and methodology while looking to other scientists, clinicians and parents for input.

To learn more:

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Addition of lysosomal storage disorders to newborn screening panels is complex and highly emotional

Addition of lysosomal storage disorders to newborn screening panels is complex and highly emotional | www.APHLblog.org

By Michelle Forman, senior specialist, media, APHL

When it comes to newborn screening, the primary goal, simply stated, is to save or improve the lives of babies who otherwise may have died or been severely disabled. While the goal of the program is rather straightforward, achieving that goal can be very complicated. The addition of lysosomal storage disorders (LSDs) to newborn screening panels fully exemplifies how complex and emotional this critical public health program can be.

While newborn screening is a program managed by each state, there is a federal panel that reviews and recommends conditions to be added to state screening panels. The Secretary of the US Department of Health and Human Services’ Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) uses strict criteria when considering which conditions should be recommended for addition to the Recommended Uniform Screening Panel (RUSP). Disorders added to the RUSP are evaluated based on scientific evidence that demonstrates:

  • The potential benefit of routinely screening all newborn babies,
  • Public health laboratories’ ability to perform the test and
  • Availability of effective treatments for the disorder.

LSDs consist of 50 rare metabolic diseases that are characterized by vital enzyme deficiencies which cause build-up of toxic materials in a person’s tissues and organs. If left untreated, the patient’s physical and mental functions will begin to deteriorate, likely leading to death. Krabbe, Pompe, Niemann-Pick A/B, MPS I and Fabry are all part of this group of diseases, and they have all been considered as potential additions to the RUSP. As of February 16, 2016, only Pompe and MPS 1 have been approved. The other conditions have not been formally recommended to the Secretary for consideration because they don’t meet the requirements listed above. Most often, the committee cited the lack of a perfected test and/or a lack of effective treatment for the condition.

However, some states have gone beyond the RUSP and have added or are planning to add certain LSDs to their newborn screening panels. On June 1, 2015, after a nearly seven month long pilot program, Illinois became one of three states to implement testing for LSDs joining New York and Missouri. Statewide testing in Illinois was implemented for five LSDs (Gaucher, Fabry, MPS I, Niemann-Pick A/B and Pompe) – state law requires two additional conditions, MPS II and Krabbe, which will be added at a later date.

Addition of lysosomal storage disorders to newborn screening panels is complex and highly emotional | www.APHLblog.orgAdding LSDs to newborn screening programs requires extensive work. The Illinois newborn screening program chose to use the most common testing platform, tandem mass spectrometry (MS/MS), for LSD screening because it lends itself to multiplexing (screening for multiple conditions at once) and high specimen throughput (screening lots of samples quickly). In order to accommodate these instruments, the Illinois public health laboratory needed to undergo renovations such as adding higher voltage outlets and additional air conditioning units. The renovations combined with the cost of renting the MS/MS instruments and other necessary equipment, buying reagents, staff labor and laboratory overhead totaled $1.45 million just to get the laboratory portion of the program off the ground. The follow-up costs are close to $150,000 annually. (The Illinois newborn screening program increased fees to cover this cost. Every state handles costs differently. Within each of the state profiles on NewSTEPs’ website, you can see how they handle fees.)

There is still controversy surrounding LSD screening. One concern is that the results aren’t necessarily straight-forward. An abnormal result could mean the baby is an asymptomatic carrier, will experience late onset with milder symptoms, needs treatment immediately to prevent serious outcomes, or other possibilities depending on the condition. In order to fully understand what abnormal results mean and to provide a definitive diagnosis, further diagnostic and genetic testing is required. However, in Illinois many insurance companies won’t cover that additional testing. For some families, paying for genetic testing out of pocket (often around $2,000) simply isn’t an option. Some families have refused.

As of January 2016 (over a year since the pilot program began), Illinois has screened over 110,000 specimens. Of those, 276 babies had abnormal results. Here is a breakdown of those newborns:

  • After undergoing further testing, 17 were diagnosed with a lysosomal storage disease. Most of these cases were Pompe and MPS I.
  • Fewer than 10 have refused additional genetic testing. That means there was enough information to warrant additional testing, but without it there is no official diagnosis.
  • There are still 74 cases pending. Some of these cases are awaiting additional testing while some are trying to determine how they will pay for that testing; there are many possible reasons for these pending cases.

While speaking with staff in the Illinois newborn screening program, their strong desire to help newborn babies and their families was abundantly clear. They were driven to perform their job as they were expected and as best they could. But the challenges they faced were also clear. For example, one of the conditions on their LSD panel is Niemann-Pick A/B, a neurological disorder that has no FDA approved treatment yet; the outcome for the baby is typically death. This makes it extremely hard to explain the results and what it means for the family.

Illinois is paving the way for other states to implement similar testing when the time is right. Many of their peers look to them for guidance on this issue.

Articulating the value of newborn screening can be very simple when discussing metabolic conditions for which we have been screening for decades and treatments are readily available. But newborn screening for LSDs is still very new, just as PKU screening once was. And just like with PKU, the desire to perfect LSD testing in order to save babies’ lives is eminently clear.

 

Have questions about newborn screening and genetics? Now is your chance to ask!

Have questions about newborn screening and genetics? Now is your chance to ask! | www.APHLblog.org

Next Monday, APHL will kick off the 2016 Newborn Screening and Genetic Testing Symposium in St. Louis, Missouri! Held every 18 months, this conference brings together newborn screening lab scientists, pediatricians, genetic counselors, follow-up coordinators and other professionals working on population genetics. Together, they will address state, national and international newborn screening and genetic testing issues that are important to public health.

Whether you are attending the symposium or not, you can follow the conversation on Twitter using #NBSGTS.

We are extremely excited to have NPR science correspondent, Joe Palca, join our keynote panel! Dr. Palca will present as one of the panelists during this session entitled, “Expanding the Newborn Screening Gateway: Considerations, Applications and Future Implications for Genomics and Precision Medicine.” He will also moderate the Q&A portion of this session.

This year we want to invite you to submit questions to be answered by Dr. Palca and our other highly regarded panelists.

Below is a list of the panelists and their presentation topics, as well as information on how to submit your questions. It is going to be a great discussion!

If you have a question about newborn screening and whole genome sequencing, genetics or genomics, please send them to us by Friday, February 26 at 5:00pm ET. Here’s how:

We might not be able to respond to every question, but we will try our best! If we can’t answer your question during the session, we will work to have an APHL newborn screening team member provide an answer after the symposium.

The keynote session is on Monday, February 29 from 1:30-3:30 PM CT (2:30-4:30 ET)! Be sure to follow #NBSGTS for live tweets from conference attendees!

Have questions about newborn screening and genetics? Now is your chance to ask! | www.APHLblog.org

Newborn screening saved these babies. How are they doing now?

By Michelle Forman, senior media specialist, APHL

In 2012 and 2013, as we celebrated the 50th anniversary of newborn screening, APHL began gathering stories from families who had a child born with a condition detected with this invaluable little heel prick. When we first spoke, some of those families were still in their first and second years of managing these diseases. The news that their newborn had a potentially devastating condition that would need to be managed with a strict lifelong diet or an invasive surgery was still very fresh. Today those infants and toddlers are happy, healthy, growing kids! I checked in with their moms to see how they’re doing and to get some new photos.

Evan’s Greatest GiftNewborn screening saved these babies. How are they doing now? | www.APHLblog.org

Evan is now four-and-a-half and a big brother!! His little sister was born healthy. We had newborn screening done right away to confirm that she does not have MSUD. Evan loves his little sister and takes the role of big brother seriously. He just started preschool and loves it! He played tee ball this summer, learned to swim, and learned to ride a bike! Of course all of these activities come with bumps and bruises, but we love watching him live and enjoy life!!

No Story is the Best StoryNewborn screening saved these babies. How are they doing now? | www.APHLblog.org

Maren is such a wonder and joy. Sometimes I wonder what she could have been like without newborn screening. But, sadly, I know. She wouldn’t be here today…at all. Thank you to newborn screening for letting us keep this beautiful gift!

On the Verge of a Coma, Baby Carter’s Life was SavedNewborn screening saved these babies. How are they doing now? | www.APHLblog.org

Carter is now two – almost three – and recently started preschool. He is a rambunctious little boy who loves sports and can usually be found with some kind of ball in his hand. He is a very charming boy who flirts with all the girls and wins over all the guys. We have been able to effectively manage his disease so Carter is thriving and hitting all of his developmental milestones. Although MSUD is a serious disease, we now feel our main health concerns are around Carter doing something crazy and breaking a bone, as opposed to anything MSUD-related. Carter never ceases to amaze us and every time we see happiness across his face we are thankful for newborn screening and all it has allowed, and will allow our little guy to do.

Raising Baby Caroline: Life With PKUNewborn screening saved these babies. How are they doing now? | www.APHLblog.org

Caroline will be four in February! Wow! Time goes by so fast and each day I am so thankful for her newborn screen. I cannot even imagine what our lives would be like if she didn’t have that test. This picture represents our Caroline. She is full of life. Full of energy. She loves to color, play Go Fish, loves her Daddy, she loves Princess Sofia, Minnie Mouse, and could stay outside for hours. We still have our struggles as she grows more independent and wonders why her diet is so different from others. If it weren’t for the newborn screen, we would have a completely different toddler on our hands. Caroline would have developed irreversible brain damage if we didn’t catch it and couldn’t treat her PKU. We are forever grateful! I wish I could go back and talk to that mom (me) you interviewed almost three-and-a-half years ago. I would tell her that everything is going to be OK. Your baby is going to grow up and be a smart toddler and she is going to teach you so many things about yourself. And it’s all because of that one heel prick.

Despite Galactosemia, Ella Grace is a Healthy Baby GirlNewborn screening saved these babies. How are they doing now? | www.APHLblog.org

Ella was born on June 6, 2012 with Classic Galactosemia. Despite being very sick those first weeks today she is a happy, healthy, smart, spunky 3 year old. She loves dance, soccer, school, and her big brothers!

Remembering Dr. Kenneth Pass, a newborn screening champion

It is with great sadness that we share the news of the passing of our dear friend and colleague, Dr. Kenneth Pass. Ken was a passionate man whose heart was always in the right place.

Dr. Pass served as the New York State Newborn Screening Program Director for over 28 years and was Chief of the Laboratory of Genetics Services where he was responsible for the state’s newborn screening program. During his time there, he guided the program as it expanded from a screening panel of four conditions to one of 28, and performed more than 7 million tests each year on New York’s newborns.

His work in New York had worldwide significance, and was always driven by his passion for saving babies. He was an innovative, driven leader and a strong voice for the newborn screening community and for families.

We are forever thankful for Ken’s contributions to newborn screening programs across the world. APHL has lost a good friend. He will be missed but never forgotten.

 

Q&A with NewSTEPs: Bringing routine CCHD newborn screening to every state

The latest release of CDC’s Morbidity and Mortality Weekly Report (MMWR) highlights the rapidly expanding program to routinely test all newborns for critical congenital heart disease (CCHD). In September 2011, CCHD was added to the HHS secretary’s Recommended Uniform Screening Panel (RUSP) for all newborns in the United States. Currently, the vast majority of states require CCHD screening for newborns while others have policies in the pipeline.

Read how this simple test saved Baby Dylan’s life

As noted in the MMWR, in 2014 CDC began partnering with the Newborn Screening Technical assistance and Evaluation Program (NewSTEPs), a program of APHL in collaboration with the Colorado School of Public Health. NewSTEPs is a national newborn screening program designed to provide data, technical assistance and training to state newborn screening programs across the country.

Sikha Singh, manager of NewSTEPs (APHL), and Marci Sontag, associate director of NewSTEPs (Colorado School of Public Health), answered some questions about bringing routine CCHD screening to all 50 states.

A primary role for NewSTEPs in the success of the CCHD newborn screening program has been data collection. Why is data collection a key contributor to this program’s success?

As with all newborn screening, it is important to have continuous quality assurance programs for CCHD screening. Data shows us what is working and where improvements can be made. At the public health level (as opposed to clinical care), we are always asking these questions:

– How many newborns were screened?
– Were there any newborns who were not screened but should have been?
– How many newborns had abnormal screening results and what happened to them?
– Did the newborns who had abnormal results receive the appropriate follow-up and care?
– Is the testing algorithm being appropriately implemented?
– Can changes be made to the algorithm to decrease inaccurate results?

CCHD newborn screening is done right in the hospital with a pulse-oximeter that is placed on the baby’s foot. No sample is sent to a public health laboratory like with other newborn screening tests. So why is APHL involved in this aspect of the newborn screening program?

Q&A with NewSTEPs: Bringing routine CCHD newborn screening to every state | www.APHLblog.orgAPHL and NewSTEPs are a newborn screening resource, so we are responsible for supporting that system. CCHD screening is one of two point-of-care newborn screening tests that are not laboratory- based (hearing loss detection is the other.) In many cases, newborn screening program staff are covering all aspects of the state’s newborn screening program. If our members and partners are focused on the entire system, we need to be as well.

Why was the addition of CCHD testing so significant for the newborn screening program?

Addressing CCHD screenings is very different from other newborn screens because abnormal results mean a baby requires immediate follow-up care prior to leaving the hospital. Abnormal results would indicate a dire situation and, in many cases, the solution is open heart surgery. CCHD screening therefore sets off a completely different chain of events than other newborn screens.

From the direct perspective of NewSTEPs, the exchange of information is different. With laboratory- based newborn screening, data is typically sent from the state public health laboratories to birthing facilities. With CCHD, we are working to get data from birthing facilities to newborn screening programs, which poses significant financial and logistical challenges.

More broadly speaking, the addition of CCHD to newborn screening panels has expanded public health’s commitment to addressing severe conditions in the very early stages of life before permanent damage can be done. While newborn screening once referred only to metabolic conditions, it now includes many other types of heritable diseases as well. The addition of both CCHD and hearing loss detection brought newborn screening into completely new territories but under the same goal of saving and improving babies’ lives.

What needs to happen to have all 50 states routinely screening every newborn for CCHD?

As the MMWR indicates, we are very close to having all states routinely screening for CCHD. In fact, additional states have begun mandatory CCHD screenings since the MMWR was written. NewSTEPs works closely with each state to evaluate the best mechanism for moving routine CCHD screening forward. In some states, legislative action has been necessary to move CCHD screening forward, but other states have mandated screening through regulatory action, and yet other states have implemented statewide screening absent a legislative or regulatory mandate. Through our ongoing data collection and analysis, along with the help of partner organizations and parent advocates, we have the tools and the momentum necessary to ensure that CCHD newborn screening becomes the standard of care in all states.

Learn more about NewSTEPs

Newborn Screening: This Tiny Test is a Big Job That’s Always Improving

By Scott J. Becker, executive director, APHL

Newborn screening saves or improves lives – 12,000 each year, to be specific. Every year over four million babies born in the United States have their heels pricked during the first days of life to check for certain devastating conditions that are not otherwise apparent at birth. The small number of babies who test positive for those conditions may suffer serious and irreversible damage without early detection. Newborn screening enables health professionals to identify and, in most cases, treat those babies allowing them to grow up to live healthy, normal lives. The newborn screening program is one of our nation’s greatest public health achievements, but that doesn’t mean it is perfect.

Newborn Screening: This Tiny Test is a Big Job That’s Always Improving | www.aphlblog.org

Last year a series in the Milwaukee Journal Sentinel drew public attention to some of the areas in which the newborn screening program needed to improve. That story and a recent editorial in USA Today focused on the amount of time between specimen collection, testing and reporting of results. Timeliness is critical for the newborn screening program to be a success, and we acknowledge the valuable contribution these articles have made.

Continual quality improvements – including timeliness – have been and continue to be a priority for public health laboratories, the agencies responsible for identifying and reporting positive newborn screening test results. In fact, APHL recognized the efforts of many state programs during the 2014 Newborn Screening and Genetic Testing Symposium. Many state newborn screening programs have conducted hospital site visits; conducted targeted outreach to lagging performers and publicly recognized top performers; provided hospitals and other specimen submitters with guidelines for collection of specimens; reinforced regulatory requirements; and provided training for use of overnight courier shipping software. Program changes like these in states around the country have significantly improved specimen transit times.

APHL and its members have collaborated with the Department of Health and Human Services Discretionary Advisory Committee on Heritable Disorders in Newborns and Children to develop updated recommendations on timeliness guidelines. These activities occur in tandem with a series of other quality improvement activities including proficiency testing, evaluation of emerging technologies and implementation of quality practices pertaining to screening, confirmation and results reporting.

I am proud of the work state newborn screening programs are doing every day. We do not take the public health laboratories’ role in this life-saving program lightly, and I thank the staff for their dedication to improving it. Our focus is on the babies – it always has been and always will be.

Family Stories are the Best Way to Grasp the Value of Newborn Screening

By Michelle M. Forman, senior media specialist, APHL

Family Stories are the Best Way to Grasp the Value of Newborn Screening | www.aphlblog.org

Did you know that September is National Newborn Screening Awareness Month? Even though this simple test is performed routinely on all babies born in the United States, it is still important to understand what it tests for and what to do if your baby has abnormal results. There is no better way to grasp the value of newborn screening than through the stories of families who have lived it.

I have gone through the newborn screening process twice, once with each of my children. The nurse came, whisked the baby away for a quick test and brought her/him back with a bandage on their heel. If I didn’t work in this field, I probably wouldn’t have asked. There was just too much going on during those days in the hospital. But I did ask – and I asked the pediatrician for their results. Fortunately, my children’s results were both normal.

Yes, newborn screening is looking for conditions that are extremely rare. Yes, the odds are that your baby does not have one of these hereditary conditions. But it is possible that they do and, if caught early by this amazing public health service, they can be treated and go on to live a healthy life.

After coming to know the families who shared their stories with me, seeing my baby taken to the nursery for that little heel prick was of immense comfort. Below is a list of all of the personal and family stories we have on our blog sorted by condition. They are stories of fear, stories of close-calls and many are stories of joy. Were it not for newborn screening, these families would have dramatically different lives than they do now. But instead, they are watching their children reach milestones, win awards, graduate and even start families of their own.

Thank you to the nurses, doctors, laboratorians and advocates working on newborn screening every day!

3-methylcrotonyl-CoA carboxylase deficiency (3-MCC)

Biotinidase Deficiency

Congenital Hypothyroidism

Critical Congenital Heart Disease (CCHD)

Cysitic Fibrosis

Galactosemia

Isovaleric Acidemia

Malonic Aciduria

Maple Syrup Urine Disease (MSUD)

Phenylketonuria (PKU)

Propionic Acidemia

Severe Combined Immunodeficiency (SCID)

Sickle Cell