OUP user menu

Newborn Screening in Preterm, Low Birth Weight, and Sick Babies

DOI: http://dx.doi.org/10.1309/LMRM9NEPH5DQE5JP 653-655 First published online: 1 November 2009

CLSI Develops Best Practices

When his mother developed life-threatening HELLP (hemolysis, elevated liver enzymes, low platelets) syndrome, Baby B was rushed into the world at 36 weeks’ gestation. As a premature newborn, Baby B was immediately taken to the hospital’s Special Care Baby Unit (SCBU), sometimes referred to as the neonatal intensive care unit. There, neonatal specialists quickly converged on his incubator. Assessments were made, treatments ordered, and interventions begun, all within the baby’s first hour of life.

In a rapidly developing situation like this, where does newborn screening (NBS) fit into the care plan for the infant? In your facility, are the blood specimens taken immediately after birth, 24 hours after birth, or maybe 2 days later? Do you test just 1 blood sample, or is serial testing part of your NBS protocol? And finally, how much difference does any of this really make? For Baby B, as you will later learn, the difference was life-changing.

The challenges inherent in planning any NBS program are many, from deciding which tests will be performed to identifying when and how many (serial) samples should be collected. Considering the sheer number of conditions for which screening is now available, more than 50 in some NBS programs, and realizing each analyte has its own ideal screening window, the complexities inherent in identifying “best practices” in an NBS protocol become readily apparent.

With preterm, low birth weight (LBW), and sick babies, numerous variables are added to the NBS equation. The multilayered health and developmental issues of this population can affect both specimen collection and result interpretation of NBS tests. Repeatedly collecting even small amounts of blood, for example, can be problematic for a fragile baby whose blood volume is already very low. Then, too, the delayed development of some metabolic systems in preterm newborns can cause inaccuracy in NBS tests for some conditions. Even life-saving infused nutritional support can create confusion in the interpretation of metabolic NBS results.

Clinical and Laboratory Standards Institute (CLSI) published a new document, Newborn Screening for Preterm, Low Birth Weight, and Sick Newborns; Appro ed Guideline (I/LA31-A), which focuses on the best practices for NBS of preterm and other at-risk newborns in SCBUs. A team of international experts in neonatology, NBS, endocrinology, metabolism, hematology, hearing loss, genetics, and cystic fibrosis collaborated to research and develop this comprehensive guideline. The intent of the document’s recommended best practices is to help caregivers perform NBS on SCBU infants with the highest degree of reliability in the shortest period of time and with the fewest number of specimens.

Christina Valentine, advisor to the CLSI subcommittee, noted the effects of nutritional support on NBS testing. “Pre-term and sick newborns receive varying levels of nutritional support,” she explained. “It’s one of the biggest issues that complicate newborn screening in these babies. To avoid malnutrition, we start specialized nutritional support right after delivery, which is different from past practices. The amino acids that are infused at this very early stage prevent malnutrition and promote growth.” However, she added, “They can also complicate the interpretation of test results when some of these amino acid metabolites appear in the blood and mimic the screening of an infant who is at metabolic risk.”

Recognizing the complexity of treatments such as parenteral nutrition with amino acids, the committee developed tables for inclusion in the document listing not only the effect a treatment has on NBS results but the duration of those effects. The document includes 7 tables in all, which, along with charts supplied in the appendix, distill a vast amount of complex data into easy-to-follow guidelines. For instance, Table 4 focuses on various infants’ conditions—the best screening window for the detection of these conditions, and the ways in which they can affect NBS panels. Special considerations for many known or suspected conditions such as cystic fibrosis and sickle cell disease are detailed in Appendix B. Maternal conditions, like vitamin B12 deficiency, are addressed in Table 1 and Appendix A. This document, organized in a logical and sequential format, may well be the most comprehensive compilation of this type of information available to clinicians and laboratory professionals today. (See Sidebars)

I/LA31-A Tables

Table 1. Maternal Conditions Affecting the Newborn Screening Results

Table 2. Treatments Used in Special Care Baby Units and Effects on Newborn Screening Results

Table 3. Conditions of the Infant Affecting Newborn Screening Tests

Table 4. Conditions Included in NBS Panels and Factors Affecting Newborn Screening Tests

Table 5. Rising Serum Thyroxine Levels in Cord Blood with Increased Gestational Age

Table 6. Follow-up Load for SCBU Infants Screened on Admission or < 12 Hours Old

Table 7. Special Considerations for Specific Conditions

I/LA31-A Appendices

Appendix A. Summary of Factors in Preterm/Sick Infants Affecting Reliability of Newborn Screening Results

Table A1. Maternal Conditions

Table A2. Treatments Given to the Infant

Table A3. Conditions of the Infant

Appendix B. Summary of Conditions Included on Screening Panels

The timing of blood specimen collection, a basic tenet of NBS, varies widely from state to state and country to country. Committee member Dianne Webster noted that, internationally, some programs use cord blood for NBS, while others use capillary blood collected from a few hours of age to 5–10 days.

Admittedly, knowing the best time to collect blood samples for NBS can be very complicated in any newborn and certainly more so in SCBU infants. Subcommittee Co-chair Judi Tuerck cited 1 example. “Hypothyroidism in this population can be missed entirely because the preterm infant’s hypothalmic-pituitary-thyroid (HPT) axis is immature. As a result, the infant cannot increase the thyroid-stimulating hormone level in response to a decreasing thyroxine. It can take several weeks for the infant’s HPT axis to mature, and only serial NBS will identify these infants, who may or may not all be preterm or low birth weight.” This example illustrates the importance of following the I/LA31-A guidelines for the timing of sample collection.

Tuerck also saw “a dichotomy between the complex analytical interpretations of the metabolic specialists and the busy neonatologists who need a simple screening algorithm they can easily understand and quickly apply to a rapidly evolving situation in the SCBU.”

The point is well taken. Not every birthing center has a team of neonatologists and newborn screening specialists to make well-researched decisions about NBS results and follow-up testing. The subcommittee devised an SCBU screening algorithm, presented as an easy-to-follow flow chart detailing collection and follow up from birth to 28 days of life. By using current literature and case studies, the committee was able to produce an algorithm that, according to Dr. Valentine, “really helps the busy practitioner be able to just say, ‘Okay, let’s do the test on this day.’” Nursery staff and laboratory technologists will also find the algorithm and document’s tables invaluable aids in understanding the complicated issues surrounding NBS in these at-risk infants.

Although I/LA31-A will serve as a comprehensive resource to birthing centers with an SCBU, it has application possibilities in all facilities where babies are born. Preterm, LBW, and sick babies are born in all birthing centers. Before transferring newborns to another center, physicians and medical staff should be aware of the recommended NBS practices for this special population and have an understanding of how the treatments they initiate immediately following delivery may affect the NBS results.

What about Baby B whose preterm birth was a result of his mother’s developing HELLP? He was born in Oregon, where the NBS protocol includes “admission screening” for all infants admitted to the SCBU, 1 of the “best practices” recommended in I/LA31. Baby B’s first NBS blood specimen was collected before he was 1 hour old.

The initial screening showed a significant elevation of all the long-chain acylcarnitines, indicating possible long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency. The metabolic specialist, consultant to the Northwest Regional Newborn Screening Program, immediately contacted the neonatologist and recommended frequent feeding and follow-up confirmatory testing, for which blood was then collected.

When Baby B was 7 days old, before confirmatory testing was complete, a second NBS specimen was collected. (The recommended “best practice” in I/LA31-A calls for a 48–72-hour recollection.) The screening at 7 days was completely normal; the LCHAD disorder was by now masked by the baby’s adequate caloric intake. Had the facility’s protocol not included “on admission” NBS, the disorder may not have been identified.

Thirteen days after his birth, Baby B’s neonatologist received a second call from the metabolic specialist, confirming the diagnosis of LCHAD deficiency, and treatment for the disorder was immediately initiated, thanks to NBS “on admission.”

Subcommittee Co-chair Julie Miller summed up the benefits of I/LA31-A by saying, “This document should help programs harmonize their follow-up protocols to ensure reliable screening for newborns in SCBUs. Many babies get transferred across borders, and the more similar these neighboring jurisdictions are in their practices, the less risk there will be in missing an affected newborn.”

Dr. Valentine added, “I think a copy of the I/LA31-A newborn screening guideline should be placed in both the laboratory and nursery of birthing facilities.” Although NBS challenges that information unique to SCBU babies is the primary focus of this document, Dr. Valentine believed the information is useful for the screening of non-SCBU newborns as well, when she said, “It reviews in detail the most up-to-date newborn screening guidance and complements other CLSI newborn screening guidelines.”

As for the international application of CLSI NBS guidelines, Dr. Webster believed the importance of having such guidance developed by CLSI is directly related to the process creating it. As 1 of 3 international committee members, she believed, “The expert advice and the robust review process ensure that the documents have high credibility. Even when local practices or legislation and regulations differ from CLSI documents, the documents provide a framework for the assessment of screening and other clinical and laboratory processes.”

For Baby B and the other preterm, LBW, and sick babies born every year, NBS is a very personal matter. The effects of unrecognized LCHAD deficiency in Baby B could have meant feeding difficulties, lethargy, muscle weakness, and liver problems as he developed, and possibly put him at risk for serious heart problems and even sudden death.

Without the standardization of practices such as those researched in the development of I/LA31-A, a certain number of metabolic disorders in SCBU babies will surely be missed every year. By creating this thoroughly researched set of recommendations for “best practices,” the subcommittee hopes to help ensure the best possible quality of life for all infants who require care in an SCBU.

Appendix

The Experts

Julie Miller, BS, Program Manager, Newborn Screening and Genetics, Nebraska Department of Health and Human Services

Judi Tuerck, MS, BS, RN, retired from the Metabolic Clinic at Oregon Health & Science University; now a Newborn Screening consultant

Christina J. Valentine, MD, MS, RD, The Ohio State University, Nationwide Children’s Hospital and representative of the American Society for Parenteral and Enteral Nutrition,

Dianne Webster, PhD, Director of the National Testing Center, Auckland, New Zealand

Notes

Jon DeMartino is a freelance medical writer and training course designer. He can be reached atjonde1{at}juno.com.

CLSI is a global, nonprofit organization promoting the development and use of voluntary consensus standards and guidelines within the health care community.

References

View Abstract