A closer Look at newborn screening

A few drops of blood from a newborn can reveal so much about the health of a baby. The testing of those blood droplets, along with tests for hearing loss and critical congenital heart conditions, comprise a routine newborn screening. And while the hearing test and heart test are relatively simple evaluations, the blood screening is more complex.

In order to provide a more in-depth exploration of newborn screening, particularly the blood spot process, the December SCID Compass Lunch & Learn webinar featured newborn screening specialists: Dr. Mei Baker, co-director of the Newborn Screening Laboratory at the Wisconsin State Laboratory of Hygiene; Amy Gaviglio, public health and genetics contractor; and Ruthanne Sheller, senior specialist at Association of Public Health Laboratories. The trio presented “The Basics of Newborn Screening.”

Newborn Screening programs are state-based public health programs designed to detect treatable conditions. It is recommended that each baby in the U.S. undergo newborn screening shortly after birth. During the screening, medical providers evaluate the baby’s hearing, check the baby’s blood oxygen level, and prick the baby’s heel to draw a small amount of blood, which is collected on a card and sent to a state lab for analysis.

States screen the baby’s blood for endocrine, metabolic, and genetic disorders, including severe combined immunodeficiency (SCID), a life-threatening primary immunodeficiency characterized by low or no T cells, and a non-functioning immune system. A positive SCID screening is referred for confirmatory testing; a possible positive SCID screening or an inconclusive SCID screening is repeated. A negative SCID screening requires no further testing.

“I cannot emphasize enough. Newborn screening is a risk assessment. It’s different than taking someone to the hospital because they’re sick,” said Dr. Baker.

Ms. Gaviglio delved further into the differences between a screening test and a diagnostic test. Below are the three main contrasting points between the two:

• A screening test is offered to the entire population. A diagnostic test is only for those with symptoms or for those undergoing further workup after a positive screening.
• Results from a screening test estimate the level of risk and determine whether a diagnostic test is warranted. Results from a diagnostic test provide a definitive diagnosis.
• A screening test has high sensitivity cutoffs and an acceptance of false positives. A diagnostic test has cutoffs with high sensitivity designed for higher precision and accuracy.

The newborn screening blood spot analysis process can be broken down into three parts, explained Ms. Gaviglio, including the pre-analytical, the analytical, and the post-analytical.

In the pre-analytical stage of the blood spot process:

• Families should be provided education about screening before the sample is collected, including the prenatal period.
• Blood spot samples are recommended to be collected between 24 and 48 hours of age.
• Specimens are dried (on the card) horizontally for at least 3 hours prior to submission.
• Specimens should be sent to the screening program within 24 hours of collection.

In the analytical stage of the blood spot process:

• Specimens are logged, and demographic information is entered.
• Small punches are taken out of the blood spots, and testing is done in 96-well plates.
• For SCID, specimens are analyzed for T cell receptor excision circles (TRECs).
• Results are entered and verified by staff.

In the post-analytical stage of the blood spot process:

• Results should be available prior to seven days after birth.
• Normal results are provided back to the submitting birth facility and should be forwarded to the primary care provider.
• Positive results are given to the primary care provider/specialist.
• Families should be notified by the primary care provider/specialist as soon as possible.

When positive newborn screening test results are shared, the primary care provider/specialist should give educational information verbally and in writing to the family and offer them an opportunity to ask questions. Providers should also follow-up with the family shortly after the screening results to help reduce anxiety and increase knowledge retention.

Typical first follow-up tests for SCID include:

• Complete blood count
• T, B, and NK lymphocyte subset analysis
• Naïve and memory T cell quantification
• Recent thymic emigrant quantitation
• T cell proliferation PHA

In addition, genetic testing may be completed. There are more than 30 genes that may cause SCID, explained Ms. Gaviglio, and genetic results may help drive treatment options.

Supporting the public state health laboratories in their efforts to process newborn screening tests is the Association of Public Health Laboratories (APHL). APHL endeavors to strengthen the role of state labs in population screening and design strategies to address the changes in newborn screening.

Some states follow the RUSP, or the national Recommended Uniform Screening Panel, when deciding to take on a new disorder, and others take on a more active and state-centered role, explained Ms. Sheller. Once a new condition is added to the screening panel, states are responsible for obtaining appropriate screening equipment, training staff on how to use it, and working with specialists to report screening results.

“Newborn screening is constantly evolving. It’s a very exciting field, and states are constantly responding and adapting to demands from legislators, advocates, and the national advisory committee,” shared Ms. Sheller.

“Our goal at APHL is to help organize and facilitate a number of committees, workgroups, task forces, and national meetings that bring together the newborn screening programs from across the nation and allow them a platform to share best practices.”

An example of how state labs had to adapt their newborn screening practices was the introduction of SCID to the newborn screening panel. The effort began in 2008 when two states – Wisconsin and Massachusetts – began screening for SCID. Over the following years, other states followed suit.

Each state faced unique challenges, explained Ms. Sheller. Barriers included obtaining state legislated mandates and fees to support bringing on a new disorder.

SCID had some special challenges, she said. SCID was the first newborn screening disorder to use molecular technology as a first-tier screening test. The technology required new instrumentation and training for staff. States had to find funding for new equipment, and some had to find laboratory space.

Some states used the FDA approved testing, while others developed their own test. That resulted in some differences in the methodologies of the programs utilized and challenges in interpreting results.

“Overall, this new technology, coupled with limitations in funding, laboratory space, and technical expertise, proved to be challenging. SCID implementation required continuous changes to each program,” said Ms. Sheller.

“It also revealed areas for growth and collaboration. In fact, programs were able to convene multi-disciplinary teams, and they were able to support one another by sharing protocols, advice, and expertise.”

By 2018, after ten years of effort and advocacy by IDF and other partners, all 50 states had incorporated SCID into their newborn screening panels. Ms. Sheller quoted comments from a lab representative that she said expressed the success of the efforts to add SCID to the newborn screening panel.

“SCID implementation was one of the best examples of newborn screening programs supporting each other. People shared widely different protocols and advice, and there was a lot of communication,” she said.

To listen to the entire webinar, click here.