A Primer on Newborn Screening

Kristin Gatrell Bryant, RN, BSN, MSN; Kimberly M. Horns, RNC, NNP, PhD; Nicola Longo, MD, PhD; Julieanne Schiefelbein, MappSc, RNC, MA (Ed), RM, PNP, NNP


Adv Neonatal Care. 2004;4(5) 

In This Article

Comparisons of National Screening Practices

The wide state-to-state variation in screening practices (Fig 1)[14] may be attributable to community values, political environment, technological capabilities, and/or economic environments.[8] In 2000, the American Academy of Pediatrics (AAP) and the Federal Health Resources and Services Administration (HRSA) sponsored a national Newborn Screening Task Force of health care experts to discuss the need for uniformity among states and emphasize the importance of implementing current technology.[8] Further, AAP and HRSA set guidelines for examining the addition of potential screening tests prior to making the tests mandatory ( Table 1 ).[8,11,15] They acknowledged that there are limited data related to the validity of specific tests and the impact of screening on health outcomes.[8] Despite this consensus conference, there is still no real consensus regarding mandated testing and what constitutes a "treatable" disorder.

State newborn screening as of February 26, 2004.[14] PKU, hyperphenylalaninemia; CH, congenital hypothyroidism; GAL, galactosemia; MS/MS, tandem mass spectrometry; +, other disorders screened for nationally. (Created by Russell K. Gatrell.)

Some of the variability may be attributed to costs. In 1 survey, the differences in screening costs ranged from no charge in 8 states to $10 to $60 (U.S.) in the other remaining states.[16] The fees may be collected from the healthcare professional, the parent, or the birth hospital, or may be paid by a third party.[8] Some state programs bundle the cost of genetic counseling, follow-up care, treatment, and education into the screening costs, while other program costs include only laboratory fees.[17]

By the end of the year 2000, 8 states required infants to have repeat screening at a later date, while the remaining states require a repeat screening test only if the initial screening was before 24 or 48 hours[17]; the AAP also reiterates the importance of a second screening with hospital stays <48 hours.[18]

The timing of the repeat screen varies from 7 to 14 days of life to 2 to 6 weeks of age.[17] For example, Massachusetts repeats the screening in all infants screened prior to 24 hours of life and also for those who weigh <1500 grams or are in the newborn intensive care unit (NICU) at 2 weeks of age.[17] The rationale for repeat screening may include infants' lack of adequate protein intake early in life and the potential for false-negative test results for hyperphenylalaninemia.[11]

Repeat screening may also be indicated for infants who were transfused prior to the initial screening test, infants who received antibiotics or other interfering substances which may limit the interpretation of results, premature infants, heat-damaged specimens, or if the screening test was inadequate or the results inconclusive.[17] Some testing modalities assay enzyme activity in red blood cells; false-negative results can occur if screening occurs after transfusion.[5] Antibiotic treatment can also affect results by inhibiting bacterial growth in the Guthrie assay method.[19]

Repeat screening is also necessary to ensure accurate diagnosis of certain disorders in which metabolic accumulation occurs,[11] or to detect disorders that are influenced by transplacental transport. The timing of the newborn screening test may improve the accuracy of diagnosing certain metabolic disorders ( Table 2 ).[12,13,20]

Notification of screening results varies by state. Abnormal results may be reported by a letter, fax, phone call, or lab report, and are usually reported to the birth hospital.[3,17]

Normal results are reported in all but 2 states. Typically they are reported to the birth hospital, though they may also be reported to the infant's primary care provider or parents.[21]

Almost 80% of pediatricians who were involved in a newborn screening survey indicated that no report implied the results are negative, assuming that "no news is good news." This is a major, and potentially dangerous, fallacy.[3] Healthcare providers must proactively seek verification of the test results for every infant under their care so that timely follow-up can occur.

A positive screening test does not equate to diagnosis of disease.[11] Rapid follow-up of a screen-positive infant should be the highest priority.[2] Each abnormal result triggers further diagnostic testing to confirm or exclude diagnosis of a disorder.[2,19]

Although each state reports abnormal results, the timing of that report may vary between states. The national standard for reporting of screen-positive infants is 5 to 7 days.[2,3] Simply reporting results to birth hospitals may be ineffective; some sick or premature infants may be transferred to another facility, resulting in a potential for delayed diagnosis and treatment. An effective communication system must be in place to link state programs directly to the current healthcare provider in order to maintain a successful newborn screening program.[3,22]

Once an abnormal screen is reported, most states confirm that treatment was initiated; annual follow-up of diagnosed infants occurs in >60% of states.[17] Conversely, approximately 35 to 40% of states do not follow-up to ensure treatment of diagnosed cases.[17]

The AAP strongly recommends that parents and infants be linked to a medical home, defined as accessible care which is comprehensive, family-centered, coordinated, compassionate, and culturally effective.[22] This recommendation ensures access to appropriate care and treatment and also provides for continuity of care. Infants and families at highest risk are those who fail to establish a primary care provider, those at high social risk, and/or migrant populations who move in and out of communities.

More than 95% of infants will have residual blood specimens; this facilitates repeat testing.[8] Most states have policies regarding specimen disposal.[17] One state keeps the blood specimen just until testing is complete; others keep the specimen indefinitely.[17] There have been considerable concern and debate regarding use of leftover blood specimens and the potential violation of privacy and autonomy.[21]

Newborn screening programs must evolve to manage a population-based genomic database while addressing ongoing issues of patient confidentiality.[21] Some states store blood for possible uses such as repeat testing, future testing, research, epidemiologic research, testing requested by parents, and clinical or forensic testing.[8,21] In 4 states, researchers do not need to obtain approval to examine data in newborn screening programs, as program data are open to the public.[21] Others require institutional review board approval from the state laboratory and/or the director of the newborn screening program to obtain access to program data.[21]

The AAP and HRSA emphasize the need for state policies and protocols regarding storage and use of residual blood.[8] Ethical challenges include developing guidelines for use of residual blood for purposes other than those for which they were originally obtained while protecting privacy and confidentiality for infants and their families.[8] The potential for use and misuse is expanding[8]; to date there have been no published reports of misuse. While residual blood samples may be of value for research, it is of utmost importance to protect the interests of the infants from whom they are obtained.[8]

Additional testing, beyond mandated state screening, may be done at the parents' discretion. Supplemental screening does not replace state newborn screening requirements. Other disorders which may be screened for include biotinidase deficiency, congenital adrenal hyperplasia, cystic fibrosis, and glucose-6-phosphate dehydrogenase deficiency.[5,19]

Tandem mass spectrometry technology, often used for supplemental screening, detects disorders of amino acids, organic acids, and fatty acid oxidation Additional biochemical techniques, such as qualitative colorimetric assay and quantitative fluorimetric assay, may also be used.[5] Abnormal results are reported immediately to the primary care provider, and normal results are mailed.[10] As with newborn screening, additional diagnostic testing is indicated for unusual or abnormal results.[10]

While some states may not offer additional testing, private for-profit companies provide supplemental screening for a fee,[10,16] ranging from $25 for 35 disorders to $98.50 for 55 disorders.[10] Approximately 1 in every 1500 infants will have a disorder detected with the addition of supplemental comprehensive newborn screening.[10] Parents are informed of optional testing for additional disorders not included in their state's routine newborn screening program in fewer than 25% of the states.[16]

Tandem mass spectrometry (MS/MS) was first applied to newborn screening in the 1990s; currently, 35 states have implemented this technology to screen for disorders.[20,23,24] A tandem mass spectrometer is referred to as MS/MS because it is composed of 2 mass analyzers separated by a collision chamber (Fig 2).[13,20,23] It requires a few droplets of blood on filter paper. After the specimen is dry, 4 small circular punch-outs are made and prepared. Next, the sample is injected into the spectrometer where it is ionized, sorted, and given a molecular weight in the first analyzer.[23] The ions then enter the collision chamber where they are broken into smaller fragments.[12] The fragments enter the final chamber where they are resorted and weighed.[23] The information detected is then plotted on a histogram for interpretation.[12] This technique can identify and quantify most amino acids and generate an acylcarnitine profile to screen for disorders of fatty acid oxidation and organic acidemias.[23]

A tandem mass spectrometer is a type of analytical instrument used in some state laboratories to screen newborns for a series of disorders included in mandatory and supplemental screening programs.

Current estimates are that MS/MS will detect an IBEM in 1 in 4000 to 1 in 5000 infants.[13,25] Over 20 different disorders can be identified from a single blood spot and can be reliably analyzed in about 2 minutes ( Table 2 ).[12,13,20,25,26] The advent of this technology has allowed for an expansion of newborn screening to include disorders of fatty acid oxidation and organic acid metabolism.[20,23] The number of specimens that can be interpreted has increased from approximately 33,000 per year in 1993 to 500,000 per year during 2000.[20]

The MS/MS technology is quicker and has better sensitivity to detect IBEM than earlier techniques. It has improved both the sensitivity and specificity of detecting disorders already screened for, such as hyperphenylalaninemia.[23] Improved sensitivity results in the positive identification of most affected infants while achieving acceptably low rates of false-positive tests.[26]

Infants in the NICU may be at particularly high risk for false-positive results, which may be caused by prematurity, medium chain triglyceride (MCT) oil supplementation, carnitine supplementation, and hyperalimentation.[13] To take advantage of the speed of this technology, specimens must get to the laboratory in a timely manner, ideally within 24 hours of collection.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: