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Overview of newborn screening

Overview of newborn screening
Literature review current through: Jan 2024.
This topic last updated: Jan 24, 2024.

INTRODUCTION — The goal of newborn screening is to detect disorders that are threatening to life or long-term health before they become symptomatic. These conditions include inborn errors of metabolism, endocrine disorders, hemoglobinopathies, immunodeficiency, cystic fibrosis, hearing loss, and critical congenital heart disease. Early treatment of these conditions may reduce morbidity and mortality in affected patients.

This topic provides an overview of the principles of newborn screening, screening policies, testing procedure, and follow-up.

Related topics include:

(See "Newborn screening for inborn errors of metabolism".)

(See "Newborn screening for inborn errors of immunity".)

(See "Screening the newborn for hearing loss".)

(See "Newborn screening for critical congenital heart disease using pulse oximetry".)

(See "Overview of the routine management of the healthy newborn infant".)

(See "Screening tests in children and adolescents".)

PRINCIPLES AND CRITERIA OF SCREENING — Screening tests are administered to all newborns to identify infants who have a serious but potentially treatable health problem. Screening tests do not provide a definitive diagnosis, but rather they identify newborns who require further testing. (See "Screening tests in children and adolescents", section on 'Overview'.)

Optimally, specific target conditions for universal screening should meet the following criteria:

The condition is serious (ie, without treatment it causes significant morbidity or death).

Effective treatment is available.

Treatment in the presymptomatic or early symptomatic period leads to better outcomes compared with usual care.

A screening test that is reliable and sensitive (ie, low false-negative rate) is available.

The screening test can be adapted for high output for the general neonatal population, and the cost of the test is acceptable relative to the potential benefit.

There is a process that ensures that the results of screening are communicated to the birth hospital or other responsible clinician(s) in a timely manner so that timely intervention can be provided. (See 'Communication of results' below.)

A definitive follow-up test should be readily available so that true positives can be distinguished from false positives.

Once the diagnosis is confirmed, ongoing treatment and follow-up care are readily available.

TARGET CONDITIONS

Core conditions that are commonly targeted by newborn screening programs – While newborn screening programs vary from region to region, the following conditions are routinely screened for in newborns in the United States. Most of these are discussed in detail in separate topic reviews.

Congenital hearing loss (see "Screening the newborn for hearing loss")

Critical congenital heart disease using pulse oximetry (see "Newborn screening for critical congenital heart disease using pulse oximetry")

The newborn blood spot panel includes tests for:

-Inborn errors of metabolism (eg, phenylketonuria, galactosemia, and many others (table 1)) (see "Newborn screening for inborn errors of metabolism")

-Inborn errors of immunity (eg, severe combined immunodeficiencies [SCID]) (see "Newborn screening for inborn errors of immunity")

-Congenital hypothyroidism (see "Clinical features and detection of congenital hypothyroidism", section on 'Newborn screening')

-Congenital adrenal hyperplasia (see "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Newborn screening')

-Hemoglobinopathies (eg, sickle cell anemia, thalassemia) (see "Diagnosis of sickle cell disorders", section on 'Newborn screening')

-Cystic fibrosis (see "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Newborn screening')

-Spinal muscular atrophy (see "Spinal muscular atrophy")

Other conditions that may be detected by newborn screening – There are a number of disorders with biochemical profiles that are similar to one or more of the core conditions listed above. These conditions (sometimes called secondary disorders) can be picked up by newborn screening even though they are not specifically targeted by newborn screening. For example, the newborn screening test for X-linked adrenoleukodystrophy, which detects abnormal levels of a particular very long chain fatty acid (specifically C26:0-LPC), can also pick up other peroxisomal disorders (eg, Zellweger spectrum disorder, acyl CoA oxidase 1 deficiency, D-bifunctional protein deficiency). (See "Peroxisomal disorders", section on 'Newborn screening'.)

Other examples of secondary conditions that can be detected through newborn metabolic screening are summarized in the table (table 1). (See "Newborn screening for inborn errors of metabolism", section on 'NBS for specific IEM'.)

In addition, because screening for critical congenital heart disease is based on finding hypoxemia by pulse oximetry, it can also detect other causes of hypoxemia, such as sepsis or persistent pulmonary hypertension. (See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Detection of other serious conditions'.)

Other routine screening procedures performed in newborns – There are many other routine assessments and screening tests that are performed in newborns that are not formally overseen by public health officials and newborn screening programs. These screening procedures are beyond the scope of this topic review. Nevertheless, they are a routine part of newborn care in many hospitals. Examples include:

Screening for hyperbilirubinemia (see "Unconjugated hyperbilirubinemia in term and late preterm newborns: Screening")

Screening for hypoglycemia in at-risk newborns (eg, infants of mothers with diabetes and/or large for gestational age newborns) (see "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Screening')

Screening for developmental dysplasia of the hip (see "Developmental dysplasia of the hip: Clinical features and diagnosis")

Selective screening for cytomegalovirus in newborns who fail the newborn hearing screen (see "Screening the newborn for hearing loss", section on 'Screening for cytomegalovirus (CMV)')

PROGRAMS THROUGHOUT THE WORLD — Newborn screening is incorporated into the healthcare system in all developed countries. Several resources are available regarding newborn screening programs worldwide [1]:

Europe

United Kingdom

Asia Pacific region [2]

Australia

North America

Canada, Ontario

United States

There is substantial regional variability in the number and types of diseases screened and the methods and algorithms used. This is due to a variety of factors, including the birth prevalence of different diseases in the population, the newborn screening program's resources for screening (including laboratory requirements and follow-up needs), jurisdictional public health and healthcare system infrastructure, legislative priorities and mandates, and costs [3].

IMPLEMENTATION OF SCREENING IN THE UNITED STATES — This section will focus on newborn screening policy and process in the United States to illustrate how screening has been implemented.

State and regional policy — In the United States, all 50 states, the District of Columbia, Puerto Rico, the United States Virgin Islands, and Guam provide universal screening for the approximately four million infants born each year [3,4]. Newborn screening is operated at the state level and integrates screening policy and short-term follow-up after a positive screen [5]. For most conditions included in the newborn blood spot screening panel, sample collection and laboratory testing are centralized at the state level. Newborn screening for hearing loss and critical congenital heart defects are conducted at the birth center prior to discharge home.

Information regarding each state's newborn screening program and detailed descriptions of the selected conditions are available at the Baby's First Test website, a resource for information and education for healthcare providers and parents/caregivers about newborn screening.

To minimize variability across states, the United States Secretary of Health and Human Services has established the Recommended Uniform Screening Panel (RUSP), which is a list of conditions that are recommended for all newborn screening programs. These recommendations are informed by the Secretary's Advisory Committee on Heritable Disorders in Newborns and Children. The committee also welcomes nomination of additional conditions to be included in RUSP at the Advisory Committee's nomination webpage.

The role of the state is to design, coordinate, and manage an effective newborn screening system. However, the effectiveness of state newborn screening programs and their role in the follow-up of infants varies [6]. Clinicians should be aware of the level of services provided by the screening program in their area of practice. In each practice setting, proactive steps should be taken to ensure that the clinician can successfully communicate the results of the newborn screening tests to the family/caregivers and provide appropriate follow-up in a timely fashion [7]. These include having clinicians familiarize themselves with their state screening program, collecting state-specific contact information for regional medical subspecialists, and setting up a process to confirm that all newborns have been screened and that screening results have been received and communicated to the family/caregivers. (See 'Communication of results' below.)

Clinical laboratory quality assurance — In the United States, all clinical laboratories, including public health newborn screening laboratories, are required to meet general systems and personnel requirements according to the Clinical Laboratory Improvement Amendments (CLIA) regulations.

As the number of tests and their complexity increases, it has become increasingly challenging to meet the CLIA requirements. The Centers for Disease Control and Prevention (CDC) Newborn Screening Quality Assurance Program provides help to state health departments and their laboratories to maintain and enhance the quality of test results [8].

METHODS USED FOR TESTING — Newborn blood spot testing is performed with a variety of techniques, including tandem mass spectrometry (also referred to as MS-MS) and other techniques [9,10]. Increasingly, molecular methods are being incorporated into newborn screening.

Tandem mass spectrometry expanded the possibility for mass screening of multiple disorders from one small sample, and it remains the method used to detect most of the conditions included in the newborn screening panel (table 1). It detects molecules by measuring their weight and is a series of two mass spectrometers, which sort samples and identify and weigh the molecules of interest. It is best used when screening for inborn errors of organic acid, fatty acid, and amino acid metabolism. (See "Newborn screening for inborn errors of metabolism", section on 'NBS for specific IEM'.)

There is growing interest in using molecular methods and genomic analysis for newborn screening. For example, molecular testing is used for newborn screening for spinal muscular atrophy using high-throughput molecular techniques that detect the causative molecular variant (homozygous deletion of exon 7 in the SMN1 gene). (See "Spinal muscular atrophy", section on 'Diagnosis'.)

Genetic sequencing (ie, whole exome or whole genome sequencing [WES or WGS]) holds promise as a tool for newborn screening [11-14]. However, it is costly and there are other challenges that need to be resolved before applying WES/WGS as a broad screening tool. These include uncertainty related to genotype-phenotype correlation for many disorders and the potential to identify other abnormalities in addition to the conditions that screening is targeting (eg, late-onset disorders, carrier status). (See "Next-generation DNA sequencing (NGS): Principles and clinical applications" and "Secondary findings from genetic testing".)

NEONATAL SCREENING PROCEDURE

Newborn hearing screen — Newborn hearing screening is performed during the birth hospitalization. The procedures for newborn hearing screening are summarized in the figures (for those in the newborn nursery (algorithm 1); for those in the neonatal intensive care unit (algorithm 2)) and described in detail separately. (See "Screening the newborn for hearing loss", section on 'Approach to screening during birth hospitalization'.)

Critical congenital heart disease screening — Newborn pulse oximetry screening for critical congenital heart disease is performed during the birth hospitalization. The procedure for newborn pulse oximetry screening is summarized in the figure (algorithm 3) and described in detail separately. (See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Approach to screening'.)

Blood spot panel

Timing of testing

Newborn nursery — For healthy newborns receiving routine care in the newborn nursery, the blood spot specimen should be obtained during the birth hospitalization at 24 to 48 hours after birth, as close to hospital discharge as possible. This timing optimizes the sensitivity of testing as it permits accumulation of abnormal compounds in the infant's blood and the best chance of obtaining a positive result if disease is present.

Blood samples are obtained by heel lance, warming the heel before puncture. Blood is collected on filter paper cards that are provided for this purpose. The designated circles should be completely filled with blood. Samples are then sent to a central laboratory for analysis. Appropriate documentation is completed, including the patient's name, time and date of birth, time and date of specimen collection, and contact information for the clinician who will provide follow-up. (See 'Follow-up of positive or equivocal results' below.)

Neonatal intensive care unit — For preterm or acutely ill neonates who are cared for in the neonatal intensive care unit (NICU), the approach to screening varies among screening programs with regards to the timing and number of screens performed. Newborns managed in the NICU usually require more than one screen. In some programs, the first blood spot test is obtained at the usual time (ie, 24 to 48 hours after birth) and then a second sample is obtained prior to discharge (or sooner if requested by the screening laboratory). However, other screening programs delay the first screen to reduce the risk of false-positives.

The variability in practice reflects the uncertainty about optimal timing of screening for this population. Earlier screening for these infants avoids delays in identifying and treating the target disorders. However, early screening in preterm and acutely ill neonates is associated with a high likelihood of false-positive findings, particularly for testing of amino acid and acylcarnitine profiles, likely related to the use of parenteral nutrition (PN) [15,16].

Out-of-hospital births — For newborns delivered out-of-hospital (ie, home births and birth centers), it is critical to ensure that newborn screening occurs [17]. Care providers in these situations should have screening protocols in place. If the primary healthcare provider cannot confirm that screening was performed in a newborn delivered out of the hospital, they should offer screening at the first well-baby visit. Primary care offices should contact their state or local newborn screening program to determine how best to obtain and send specimen to the appropriate laboratory.

Repeat screening — Repeat screening may be required if the initial specimen was insufficient or was obtained too early (ie, within the first 24 hours after birth). Preterm neonates often require repeat screening, as discussed above. (See 'Neonatal intensive care unit' above.)

In addition, some newborn screening programs use a two-screen protocol for all newborns. In states using two-screen protocols, the second blood spot screening panel is performed at the age of one to two weeks. This is typically done in the primary healthcare provider's office during a well-baby visit. The second screen increases the sensitivity (yield) of screening by mitigating initial false-negative screens related to normal physiologic changes and/or limited nutritional intake in the first days after birth [18].

Communication of results — The newborn blood spot panel typically takes five to seven days to result. Thus, unless a medical issue keeps the infant in the hospital (eg, preterm birth), most newborns will have been discharged from the birth hospital by the time results are available. For this reason, it is critical for newborn screening programs to have a reliable protocol in place for notifying the primary healthcare provider and parents/caregivers about abnormal results.

State and local public health agencies — The mechanism of communicating test results, including the role of state and local public health agencies, varies widely [1,5]. In some states, the testing laboratory is assigned the responsibility of communicating test results to the healthcare provider and/or birth hospital. In other states, the role of locating infants and communicating test results is assigned to local health department staff.

Most state programs require that a healthcare provider be notified of results. However, this may be the clinician of record at the infant's birth hospital and not the primary healthcare provider. In cases of positive screening results that require urgent follow-up (eg, highly abnormal screening test for a metabolic disorder), newborn screening programs will actively seek parents/caregivers to inform them and to expedite diagnosis and treatment.

Primary care clinician's role — The primary healthcare provider (eg, pediatrician, family practitioner, nurse practitioner) should be aware of the system in their state or region to ensure timely notification of abnormal results to parents/caregivers. Ideally, healthcare providers should also inform parents/caregivers when the results of screening are normal, but this is less critical and less time sensitive. (See 'Normal screening results' below.)

A successful screening program requires collaboration among all healthcare professionals involved in newborn care [7]. This begins with the obstetric provider, who should educate expectant parents about newborn screening and the importance of identifying the medical home for the newborn. Additional information about newborn screening should be provided during the birth hospitalization. Identifying the medical home for the newborn is an important criterion for discharge. Discharge documentation should clearly indicate whether or not screening was performed, the name of the clinician responsible for the birth hospitalization, and the name of the primary care provider. (See "Overview of the routine management of the healthy newborn infant", section on 'Discharge criteria'.)

Primary care providers should be familiar with local pediatric subspecialty care resources so that appropriate referrals can be made when an infant is diagnosed with a specific disorder [7]. Genetic counseling, testing of other family members, and family/caregiver support services should be facilitated [5,7]. (See 'Follow-up of positive or equivocal results' below.)

Primary care clinicians are often underprepared to provide initial counseling and subspecialty referral for infants with positive newborn screening results. This was illustrated in a survey of general pediatricians and family practitioners in the United States that demonstrated many responding clinicians did not feel competent to discuss the results of a positive newborn screen [19]. Continued efforts are required to ensure that primary care clinicians are adequately trained and supported to deliver appropriate follow-up care of these infants and their families/caregivers.

When screening identifies a carrier state (eg, sickle cell trait), communication to the parents/caregivers can be challenging because it does not usually have health consequences for the newborn. Nevertheless, the finding may have health implications during adulthood and it is important for future reproductive planning for the newborn's parents. (See "Sickle cell trait", section on 'Screening'.)

Additional resources for healthcare providers and families/caregivers about newborn screening, including information about specific diseases, are provided below. (See 'Resources' below.)

FOLLOW-UP OF POSITIVE OR EQUIVOCAL RESULTS

Confirmatory testing — Positive or equivocal results from newborn screening should have a repeat and/or confirmatory test performed as quickly as possible. In most newborn screening programs, positive results are communicated to the primary healthcare provider (or to the birth hospital staff if the newborn has not yet been discharged) who then assumes the responsibility for the appropriate follow-up care. (See 'Communication of results' above.)

For newborns with abnormal hearing screen or abnormal pulse oximetry screening, the approach to follow-up testing is discussed separately. (See "Screening the newborn for hearing loss", section on 'Follow-up' and "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Assessment of newborns with positive screens'.)

For infants with abnormal findings on the newborn blood spot panel, the appropriate follow-up testing and care depends on the specific abnormality identified. The specifics of this testing for each condition on the newborn blood spot panel are beyond the scope of this topic. These details are provided in separate topics:

Inborn errors of metabolism – The American College of Medical Genetics and Genomics (ACMG) website provides one-page action sheets and laboratory testing algorithms to inform clinicians about the implications of a screening result, the urgency of follow-up, as well as the basic and specialized laboratory tests that are necessary to clarify a potential differential diagnosis or identify a false-positive screening result (table 1). (See "Newborn screening for inborn errors of metabolism", section on 'NBS for specific IEM'.)

Inborn errors of immunity (eg, severe combined immunodeficiency [SCID]). (See "Newborn screening for inborn errors of immunity", section on 'Follow-up testing'.)

Congenital hypothyroidism. (See "Clinical features and detection of congenital hypothyroidism", section on 'Interpretation and follow-up'.)

Sickle cell disease. (See "Diagnosis of sickle cell disorders", section on 'Approach to a positive result from newborn/infant screening'.)

Cystic fibrosis. (See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Newborn screening'.)

Congenital adrenal hyperplasia. (See "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Confirmatory serum testing'.)

Spinal muscular atrophy. (See "Spinal muscular atrophy", section on 'Diagnosis'.)

Newborns with a confirmed disorder — When an infant is diagnosed with a specific disorder, referrals should be made for appropriate subspecialty care. Often, earlier consultation with a subspecialist is warranted to guide the diagnostic evaluation. Depending on the specific diagnosis, genetic counseling and testing of other family members may be warranted.

Of the four million infants who are screened each year in the United States, approximately 12,900 are ultimately diagnosed with one of the core conditions of the uniform screening panel, resulting in a detection rate of 34 per 10,000 live births [3,4,20].

The four most commonly diagnosed conditions are [4]:

Hearing loss (17 per 10,000 live births) (see "Screening the newborn for hearing loss")

Primary congenital hypothyroidism (6 per 10,000 live births) (see "Clinical features and detection of congenital hypothyroidism", section on 'Newborn screening')

Sickle cell disease (5 per 10,000 live births) (see "Diagnosis of sickle cell disorders", section on 'Newborn screening')

Cystic fibrosis (2 per 10,000 live births) (see "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Newborn screening')

Early identification through newborn screening allows for earlier intervention, which reduces long-term morbidity and mortality [21].

False positives — Because of the rarity of the conditions included in newborn screening, most positive newborn screens turn out to be false positives. However, given the serious nature of the conditions, it is important to provide timely and appropriate care after all positive newborn screens.

False-positive hearing screen – The most common reason for a false-positive result on the hearing screen using otoacoustic emissions testing is fluid or vernix in the ear. This is discussed in greater detail separately. (See "Screening the newborn for hearing loss", section on 'Comparison of AABR and OAE'.)

False-positive pulse oximetry screen – Most newborns who fail the pulse oximetry screen do not have congenital heart disease. However, some of these newborns may have other serious neonatal conditions associated with hypoxemia. This is discussed separately. (See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Detection of other serious conditions'.)

False-positives of the blood spot panel – The estimated false-positive rate for the newborn blood spot panel is approximately 1 to 2 percent, though it varies somewhat depending on the specific panel of tests included [22]. The false-positive rate is approximately five to six times higher than the true positive rate [3,4,20]. This means that for every newborn diagnosed with a disorder, five to six newborns will have false-positive results.

False-positive results on the blood spot screening panel can happen for a many reasons. For example, false positives are common in acutely ill or preterm neonates, particularly those receiving parenteral nutrition (PN) [22]. False positives for hypothyroidism and congenital adrenal hyperplasia can occur if the specimen is obtained early (ie, within 24 hours after birth).

The impact of false-positive results can be significant for families (eg, need for additional testing, parent/caregiver stress and anxiety) [23,24]. It is important for healthcare providers to inform parents/caregivers about the possibility of a false-positive result at the time of testing. Nevertheless, given the seriousness of the conditions on the newborn blood spot panel, clinicians should take all positive newborn screens seriously and have systems in place to ensure timely and appropriate follow-up.

NORMAL SCREENING RESULTS — If the newborn has no abnormal findings on any of the screening tests, parents/caregivers should be notified that the results were normal and that no additional testing is required. However, healthcare providers and parents/caregivers should be aware that a negative screening result does not completely rule out the disorder since false-negative screening results can occur.

Thus, primary care providers must remain vigilant to the development of symptoms of these conditions, even if screening was negative.

False-negative results are more likely in infants born prematurely, in those who received blood transfusions or dialysis therapy, or in those who were tested too early (less than 24 hours of age).

RESOURCES

Baby's First Test is a website that provides information and education for healthcare providers and families/caregivers about newborn screening. Information is available regarding each state's newborn screening program, as are detailed descriptions of the conditions included in newborn screening. This resource also provides support for families/caregivers of children with a condition identified through newborn screening.

The American College of Medical Genetics and Genomics (ACMG) website provides one-page action sheets and laboratory testing algorithms to inform clinicians about the implications of a screening result, the urgency of follow-up, as well as the basic and specialized laboratory tests that are necessary to clarify a potential differential diagnosis or identify a false-positive screening result.

ONGOING CHALLENGES AND CONTROVERSIES — There are many areas of challenge and debate in newborn screening, including:

Use of the residual dried blood spot specimen – Researchers can use anonymized dried blood spots to develop new screening tests. However, some families/caregivers are concerned about the risk to privacy. The rules regarding the use of anonymized dried blood spots for research and the length of time that newborn screening programs save residual dried blood spots vary by state.

Identification of late-onset disease – Some newborn screening tests that detect significant illness in childhood will also identify individuals who might not develop illness until adulthood. Assessing the benefit versus harm of early identification of late-onset disease is challenging.

Identification of conditions for which treatment has not been established – Identifying newborns with serious conditions in the presymptomatic period may be important to develop new treatments. Some families/caregivers might want to know early about serious health conditions in their children, even in the absence of therapy. This can help avoid unnecessary diagnostic evaluation and allow families/caregivers to make plans for the affected child and make informed reproductive decisions.

Identification of carriers – Newborn screening can identify carriers for many of the targeted conditions. There is uncertainty and debate about how best and when to inform families and these children about their carrier status to inform future reproductive decisions [25].

Cascade testing of family members – After diagnosis through newborn screening of certain conditions (eg, X-linked adrenoleukodystrophy), it is reasonable to test first-degree family members to see whether they are carriers or affected by the condition. A number of ethical and psychosocial issues apply to genetic testing, including the consequences for the family, issues related to testing children who are unaffected, and concerns about genetic discrimination. Clinicians must consider the benefits and risks of genetic testing, including the possibility of false-positive and false-negative results. (See "Genetic testing".)

Provision of long-term care – Early identification of most of the conditions included in newborn screening allows modification of the condition from being associated with significant morbidity and mortality in infancy to a long-term chronic illness. Developing systems to assure that these individuals have access to chronic disease management, including medications or nonpharmacologic therapy (eg, specific diet), is challenging [26]. The Newborn Screening Translational Research Network has developed the Longitudinal Pediatric Resource, a tool to register conditions identified by newborn screening.

Resource allocation – Public health agencies have limited resources, and assuring comprehensive newborn screening is costly. Often the cost of the screening test is coalesced into the cost of operating the newborn screening program and does not include resources to assure appropriate follow-up care. Policy makers therefore need to consider all costs related to the adoption of newborn screening for each condition.

FUTURE DIRECTIONS — Newborn screening is expanding and adapting globally. Potential future advances in newborn screening include:

Adaptation of screening programs at the state or local level to target specific high-risk conditions in the region.

Rapid improvements in scientific knowledge and testing techniques, which continue to increase the number of disorders that can be detected.

The potential for creating newborn screening archives (ie, storage of residual dried blood spots so that they can be analyzed well after the newborn period), which may inform future epidemiologic studies [27].

Advances in prenatal screening, which may decrease the need for some newborn screening tests. (See "Preconception and prenatal panethnic expanded carrier screening".)

It is important for local, national, and international policy makers to keep pace with these changes and to address the ethical, legal, and financial challenges involved.

SUMMARY AND RECOMMENDATIONS

Importance – The goal of newborn screening is to detect treatable disorders that are threatening to life or long-term health before they become symptomatic. Screening tests are administered to all newborns to identify infants who have a serious but potentially treatable health problem. (See 'Introduction' above and 'Principles and criteria of screening' above.)

Conditions that are screened for – While newborn screening programs vary from region to region, the following conditions are routinely screened for in newborns in many settings (See 'Target conditions' above.):

Inborn errors of metabolism (table 1) (see "Newborn screening for inborn errors of metabolism")

Severe combined immunodeficiencies (SCID) (see "Newborn screening for inborn errors of immunity")

Endocrine disorders (eg, congenital adrenal hyperplasia and hypothyroidism) (see "Clinical features and detection of congenital hypothyroidism", section on 'Newborn screening' and "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Newborn screening')

Hemoglobinopathies (eg, sickle cell anemia, thalassemia) (see "Diagnosis of sickle cell disorders", section on 'Newborn screening')

Cystic fibrosis (see "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Newborn screening')

Spinal muscular atrophy (see "Spinal muscular atrophy")

Congenital hearing loss (see "Screening the newborn for hearing loss")

Critical congenital heart disease (see "Newborn screening for critical congenital heart disease using pulse oximetry")

In the United States, the Department of Health and Human Services has established a Recommended Uniform Screening Panel (RUSP), which includes all the screening tests listed here. However, screening programs vary from state to state, and clinicians should familiarize themselves with the system in their state. (See 'Implementation of screening in the United States' above.)

Screening procedure

Hearing and critical congenital heart disease screening – These screening procedures are summarized in the figures (algorithm 1 and algorithm 2 and algorithm 3) and discussed in detail separately. (See "Screening the newborn for hearing loss", section on 'Protocols' and "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Approach to screening'.)

Blood spot screening panel – The blood spot screen is obtained during the birth hospitalization at 24 to 48 hours after birth, as close to hospital discharge as possible. Blood samples are collected on filter paper from puncture of the newborn's warmed heel. The blood spot cards are then sent to a central laboratory for analysis. (See 'Blood spot panel' above.)

Follow-up of positive or equivocal screening results

Confirmatory testing – Abnormal screening results require repeat and/or confirmatory testing. The urgency and type of follow-up testing depends on the specific abnormal finding. (See 'Confirmatory testing' above.)

Follow-up testing for abnormal metabolic screening is summarized in the table (table 1) and discussed separately. (See "Newborn screening for inborn errors of metabolism", section on 'NBS for specific IEM'.)

Confirmatory tests for other conditions are discussed in separate topic reviews:

-(See "Screening the newborn for hearing loss", section on 'Follow-up'.)

-(See "Newborn screening for critical congenital heart disease using pulse oximetry", section on 'Assessment of newborns with positive screens'.)

-(See "Newborn screening for inborn errors of immunity", section on 'Follow-up testing'.)

-(See "Clinical features and detection of congenital hypothyroidism", section on 'Interpretation and follow-up'.)

-(See "Diagnosis of sickle cell disorders", section on 'Approach to a positive result from newborn/infant screening'.)

-(See "Cystic fibrosis: Clinical manifestations and diagnosis", section on 'Newborn screening'.)

-(See "Clinical manifestations and diagnosis of classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency in infants and children", section on 'Confirmatory serum testing'.)

-(See "Spinal muscular atrophy", section on 'Diagnosis'.)

True positives – If follow-up testing confirms the diagnosis of a specific disorder, referrals should be made for appropriate subspecialty care. The detection rate of the core newborn screening conditions is approximately 30 to 40 per 10,000 live births. The four most commonly diagnosed conditions are congenital hearing loss, congenital hypothyroidism, sickle cell disease, and cystic fibrosis. (See 'Newborns with a confirmed disorder' above.)

False positives – Most newborns with abnormal newborn screening results are not ultimately diagnosed with a disorder. The false positive rate is approximately 1 to 2 percent. Nevertheless, given the seriousness of the conditions on the newborn screening panel, clinicians should take all positive newborn screens seriously and have systems in place for timely and appropriate follow-up. (See 'False positives' above and 'Follow-up of positive or equivocal results' above.)

Normal screening – If the newborn has no abnormal findings on any of the screening tests, no additional testing is required. However, healthcare providers and parents/caregivers should be aware that a negative screening result does not completely rule out the disorder since false-negative screening results can occur. Thus, primary care providers must remain vigilant to the development of symptoms of these conditions, even if screening was negative. (See 'Normal screening results' above.)

Challenges – Although newborn screening is incorporated into healthcare systems around the world, ongoing challenges and controversies remain. These include resource allocation, identification of conditions that are late-onset or have no established treatment, and identification of disease carriers. (See 'Ongoing challenges and controversies' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Lori Sielski, MD, who contributed to earlier versions of this topic review.

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Topic 4980 Version 51.0

References

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