Which of the following is a characteristic of the newborn screening test?

Summary and conclusion

The newborn screening program is a major accomplishment for public health in the United States. Every year, almost 4 million babies are screened for more than 29 different disorders. The expansion of the newborn screen in 2005 with tandem mass spectrometry has improved our understanding of some inborn errors of metabolism and their actual incidence and prevalence. Continuous optimization of the process is required; the success of the newborn screening program ultimately rests not only on the accuracy of testing, but also the infrastructure for adequate diagnosis, follow-up, and treatment. If we continue to add disorders to the screening programs without additional funding or human resources, the program could collapse, compromising the health of the patients already identified.

Several states are conducting research trials on newborn screening, adding disorders not yet recommended by the RUSP. These states are obtaining informed consent before filter card processing.

We need to be aware of an important distinction: the original goal of the newborn screening was to identify patients with disorders that were treatable or curable with available resources, versus the inclusion of disorders merely to obtain data on prevalence and incidence. In the latter case, the newborn screen changes its focus and calls for a continuous review of the supporting infrastructure and cost-effectiveness.

Timing of Collection

Newborn screening encompasses a gamut of conditions, each with its own ideal screening period during which there is the greatest chance of diagnosing the disorder and before onset of symptoms. As a result, it is worth noting that recommendations on the timing of specimen collection, although appropriate for the majority, may not be ideal for all conditions on the screening panel. In congenital adrenal hyperplasia, in which the symptoms can manifest within the first week of life, the optimal time for collection of the specimen is within 24 to 48 hours after birth. Formerly there was concern that with the newborn screening specimen collected early, often during the first day of life, some infants with metabolic disorders or CH might not have a sufficient degree of abnormality for identification. However, MS/MS methodology with its improved sensitivity and specificity has considerably improved the reliability of screening for metabolic conditions in early specimens (Chace and Naylor, 1999) and using thyroid-stimulating hormone (TSH) as the primary marker for CH, or as a second-tier test when T4 is the primary marker, has similarly allowed early screening for CH to be reliable.

Specimen collection timings vary around the world. In Europe and Australia, most screening specimens are collected within 48 to 72 hours, whereas specimens in the United Kingdom are not collected until the infant is 5 to 8 days old (U.K. Newborn Screening Progam Centre, 2008). In the United States, most screening specimens are collected within 24 to 72 hours after birth. The specimen should be obtained from every newborn infant before nursery discharge or by the third day of life, whichever is first. In infants whose initial specimen was obtained within the first 24 hours of life, as may happen with the practice of early nursery discharge, a second blood specimen should be obtained no later than 7 days of age to be certain that a diagnosis is not missed.

Special circumstances require specific attention to newborn blood specimen collection. Premature infants or those with very low birthweight, as well as infants who are sick and those in neonatal intensive care units (NICUs), are at a risk of unreliable screening owing to factors such as the unique physiology of the infant, therapeutic interventions, and a focus on critical activities in caring for the very sick neonate. Consequently, a single specimen is inadequate for screening in this subpopulation, and additional specimens should be collected for retesting. Serial screening with collection of three specimens—upon admission to the NICU, between 24 and 48 hours of life, and at discharge or at 28 days of life, whichever is sooner—has been proposed as an adequate and efficient protocol for this population (Clinical and Laboratory Standards Institute, 2009). In addition, some programs recommend screening every month until discharge for babies who continue to remain in the NICU.

A blood specimen should be collected from any infant who is being transferred to a different hospital or to a NICU, regardless of age. The first specimen should be collected before transfer, and a second specimen at the receiving hospital by 4 days of age. This dual collection policy covers the infant from whom a newborn specimen might not have been obtained in the turmoil that frequently accompanies the transfer of neonates.

In a newborn who is to receive a blood transfusion, a screening specimen should be collected before transfusion, and a second specimen should be collected 2 days after the transfusion. In addition, a third screening specimen should be obtained 2 months after the transfusion, when most of the donor red blood cells (RBCs) have been replaced. This practice ensures reliable testing for analytes present in RBCs, if a pretransfusion specimen has not been obtained.

Newborn screening tests are usually performed in a centralized state, provincial, or regional laboratory. In a regional program, the specimens may be received by the state program and then delivered to the regional state or private laboratory, or they may be sent directly to the regional laboratory. In either case, the individual state programs serve as the state data and follow-up centers.

27.5.7 Urea Cycle Disorders

Routine neonatal screening currently can identify three of the six urea cycle disorders. These include citrullinemia and argininosuccinic acidemia, both identified by increased citrulline in newborn screening, and arginase deficiency, identified by increased arginine. Detailed discussion of these disorders can be found elsewhere in this book (Chapter 92). The urea cycle is responsible for metabolizing ammonia released during the turnover of amino acids, which results from the ingestion and endogenous turnover of protein. A deficiency in any of the six urea cycle enzymes blocks this metabolic pathway and produces hyperammonemia as well as a reduction in urea. The hyperammonemia is extremely toxic to the brain and can produce life-threatening cerebral edema. Citrullinemia (argininosuccinic synthetase deficiency) and argininosuccinic acidemia (argininosuccinic lyase deficiency) may present acutely in the neonate or have a later onset with a chronic course. Mild citrullinemia has been reported as benign (59), and argininosuccinic acidemia may also have a relatively benign or completely benign phenotype (60,61). Arginase deficiency usually has a clinical phenotype very different from the other urea cycle disorders in that the hyperammonemia is milder and the patients have a chronic neurologic picture characterized by spastic diplegia and developmental delay. A rare patient with arginase deficiency, however, has been described with an acute lethal neonatal course (62).

A second form of citrullinemia has recently been reported. This form, called citrullinemia type II or citrin deficiency, is also identified in neonatal screening by increased citrulline in the newborn specimen. The primary defect is in citrin, a mitochondrial carrier protein primarily located in the liver. The most frequent neonatal feature has been intrahepatic cholestasis that often results in a secondary increase in galactose, methionine, phenylalanine, and/or tyrosine, elevations that may also be detected in newborn screening (63).

Several newborn screening programs also screen for decreased citrulline. This allows for the identification of the proximal urea cycle disorders NAGS deficiency, CPS deficiency, and OTC deficiency (14). These three disorders can have a life-threatening neonatal presentation with profound hyperammonemia and, if so, require immediate and dramatic therapy.

Treatment of the urea cycle disorders requires immediate measures for the acute hyperammonemic neonatal course. These include discontinuation of protein intake and administration of intravenous fluids with very high caloric value. In addition, “scavenger” medication such as sodium benzoate and sodium phenylacetate are administered to aid in waste nitrogen removal. Hemodialysis may be required. The chronic therapeutic regimen consists of a low-protein diet supplemented by the organic acid medications.

1.7 Newborn Screening

NBS is a very important act for the earliest diagnosis of patients with IEM and is of significant importance to initiate early treatment to prevent morbidity and mortality. The first NBS effort was for PKU in 1959 and was done by Dr. Robert Guthrie. The test was a bacterial inhibition assay and has been used for NBS for many years in many countries. In the countries which implemented obligatory NBS for PKU, a significant reduce in mental retardation rate was noticed. At the beginning of 1990s, the introduction of tandem mass spectrometry has brought revolutionary changes. This technology provided the screening for more than 30–40 diseases at the same time using a single DBS, which only requires 0.3 mL of whole blood. Many countries today started doing “expanded NBS” by this accurate and rapid technology (Table 22). In the populations where some IEM are prevalent, carrier screening is also an important tool for preventing IEM [99–102].

Table 22. The Methodology Used for Newborn Screening for Some IEM

Disease or Disease GroupMethodologyAmino acid disorders (general)Tandem mass spectrometryFatty acid oxidation defectsTandem mass spectrometryOrganic acidemiasTandem mass spectrometryBiotinidase deficiencyEnzyme assayLysosomal storage disordersEnzyme assayClassical galactosemiaEnzyme assay

Newborn Screening

Newborn screening (NBS) was established as a public health initiative in the 1960s to identify infants at a higher risk for certain disorders, who would benefit from early diagnosis and management. Most disorders identified by NBS, although not apparent at birth, would cause death or permanent disability if left untreated. Therefore, early treatment depends on early detection.

In the mid-1970s, it was demonstrated that a screening test for DMD could be performed on the dried blood spots already collected by the established NBS program.34 Serum CK levels are elevated in newborns with DMD, but can also be elevated in other muscle conditions, including traumatic muscle damage during the birth process. For this reason, testing the newborn CK level detects all infants with DMD, but also generates many false-positive results.35

There have been several trials of NBS for DMD, and it is currently offered for newborn boys with parental consent in some countries, including Wales, Canada, and Belgium. The German infant screening program ended in November 2011 (G. Scheuerbrandt, personal communication, December 7, 2011).

There are currently four hospitals in the USA that offer optional NBS for DMD, through a research study funded by the Centers for Disease Control and Prevention (CDC) and conducted by investigators at the Columbus Children’s Research Institute in Ohio.36 In the past, NBS was offered in other parts of the USA, including parts of Pennsylvania (Pittsburgh), New York, Oregon, Iowa, and Texas, as well as parts of Brazil, France, New Zealand, and Puerto Rico.

As treatments for muscular dystrophies continue to be developed, the need for earlier treatment may arise, which would support NBS to identify individuals with muscular dystrophy presymptomatically. Even now, there is strong support for NBS for DMD among families affected by DMD, mainly because of the potential to help them to prepare for the future care of their child.

Which of the following is not part of the newborn screening quizlet?

Which screening tests are most appropriate for newborns?

What is the importance of newborn screening?

What are the most common newborn screening disorders?