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Newborn Screening Glossary


birth prevalence

the number of times a congenital disease is confirmed in a baby, as a fraction of the number of babies born alive

Project: NBS10

NOTE 1: “Incidence” is not the same as “birth prevalence,” because incidence refers to the occurrences of a disease over time; NOTE 2: “Birth prevalence” should not be confused with “prevalence,” which is a measure of the total number of existing cases of a disease or condition as a fraction of a defined population.


borderline result

a term sometimes used for an out-of-range screening test result that is close to a program-established screen-positive cutoff value and that indicates moderate risk/possible disease, rather than high risk/probable disease

Project: NBS02, NBS10

NOTE 1: A screen-positive result in the borderline range is typically followed up with a request for an additional screening specimen, rather than diagnostic testing or clinical evaluation; NOTE 2: Follow-up actions for a borderline result usually take additional time and should be restricted to diseases for which diagnosis and treatment are not time critical; NOTE 3: When a borderline result is obtained for the second time, the patient might be referred for diagnostic testing and/or clinical evaluation, rather than specimen collection for another screen; NOTE 4: See screen positive and repeat screening (requested); NOTE 5: In CLSI NBS10, see Figures 1 and 2.


central congenital hypothyroidism

congenital hypothyroidism caused by deficient secretion of thyroid-stimulating hormone by the pituitary gland, which may be due to a pituitary (ie, secondary congenital hypothyroidism) or hypothalamic (ie, tertiary congenital hypothyroidism) abnormality

Project: NBS10

NOTE: Central congenital hypothyroidism does not include secretion of a nonfunctioning thyroid-stimulating hormone molecule, which clinically resembles primary congenital hypothyroidism.


clinical sensitivity

(for newborn screening) the proportion of newborns in the screened population who have the target disease and who have positive screening test results

Alternate Term: diagnostic sensitivity

Project: NBS05, MM07, NBS09, NBS06, NBS07, NBS10

EXAMPLE: In screening for cystic fibrosis, newborns with meconium ileus should be included in the calculation of sensitivity: Sensitivity = a / (a + c), in which a = a true-positive result and c = a false-negative result; NOTE 1: The clinical disease must be defined by criteria independent of the test under consideration; NOTE 2: The term “clinical sensitivity” (United States) is equivalent to “diagnostic sensitivity” (Europe); NOTE 3: Sensitivity = a / (a + c), for which a = true-positive screening test results and c = false-negative screening test results; see table in screening outcome; NOTE 4: “Clinical sensitivity” is not the same as “analytical sensitivity”; NOTE 5: Proportion of truly diseased persons in a screened population who are identified as diseased by the screening test. Sensitivity is a measure of the probability of correctly diagnosing a case, or the probability that any given case will be identified by the test. Infants with meconium ileus should be included in the calculation of sensitivity. Sensitivity = a / (a + c) where a = a true-positive result and c = a false-negative result; NOTE 6: In programs in which meconium ileus is excluded from the clinical sensitivity calculations, this deviation from the typical practice should be noted; NOTE 7: Clinical sensitivity refers to the assay’s ability to detect subjects with the condition or disease; NOTE 8: Clinical sensitivity is the fraction of clinically true positives divided by the sum of clinically true-positive plus clinically false-negative classifications; NOTE 9: As used in NBS06, clinical sensitivity refers to the ability of the newborn screening algorithm to identify subjects with severe combined immunodeficiency; NOTE 10: As used in NBS07, clinical sensitivity refers to the ability of the newborn screening algorithm to identify individuals with any form of Pompe disease; NOTE 11: See acylcarnitine.


clinical specificity

(for newborn screening) the proportion of newborns in the screened population who do not have the target disease and who have negative screening results

Alternate Term: diagnostic specificity

Project: NBS09, NBS10

NOTE 1: The clinical disease must be defined by criteria independent of the test under consideration; NOTE 2: The term “clinical specificity” (United States) is equivalent to “diagnostic specificity” (Europe); NOTE 3: Specificity = d / (b + d), for which d = true-negative screening test results and b = false-positive screening test results; see table in screening outcome; NOTE 4: “Clinical specificity” is not the same as “analytical specificity”; NOTE 5: See positive predictive value.


collection device

(for newborn screening) a medical device used to collect blood spots for routine newborn screening

Alternate Term: specimen collection device

Project: NBS01, NBS09, NBS05, NBS10

NOTE 1: The collection device has two components: a section for recording demographic and other requested information and a blood collection (specified filter paper) section with preprinted circles to be filled with the newborn blood drops; NOTE 2: If a preprinted circle is not present, local requirements must define the quantity of blood considered acceptable; NOTE 3: Once the blood is collected, the collection device becomes the specimen (also referred to as “blood spot specimen” or “dried blood spot specimen”) and is no longer considered a collection device; NOTE 4: This specimen collection device is also commonly referred to as a “Guthrie card,” “filter paper,” or a “blood spot card”; NOTE 5: See dried blood spot.


confirmatory test

(for newborn screening) a test to prove or disprove the presence of a specific disease, group of diseases, or phenotypic difference suspected because of screening test results

Alternate Term: diagnostic test

Project: NBS03, NBS08, NBS09, NBS05, NBS02, NBS10

NOTE: For newborn screening and identity confirmation, confirmatory testing must be performed on a new specimen, rather than on any existing screening specimen.


dried blood spot

a specimen collected for laboratory testing, using an approved medical device composed of a specified filter paper, on which printed circles indicate the area to be filled with whole blood and air-dried for transport or storage

Project: NBS03, NBS02, NBS01, NBS07, NBS04, NBS09, NBS08, NBS05, NBS10

NOTE 1: Specimens collected using an approved medical device should yield a reproducible volume of blood per spot (typically 75 to 100 µL for a 12.5-mm circle, 35 to 50 µL for a 10-mm circle); NOTE 2: In newborn screening, the dried blood spot specimen is ideally collected directly from a heelstick using no anticoagulant agents, because anticoagulant agents, particularly heparin and EDTA, interfere with certain assays.


expected range

the range of values for a measurand in a typical healthy population

Project: NBS03, NBS05, NBS02, NBS01, NBS07, NBS09, NBS10

NOTE 1: The expected range is a population distribution, not an analytical parameter, that can be estimated by applying statistical methods to data from reference populations that are representative of the population being tested. The limits of the expected range might vary, depending on the reference population and the statistical methods used; NOTE 2: The expected range for newborn screening results might vary by calendar and gestational age; NOTE 3: For purposes of newborn dried blood spot screening, results within the expected range should exclude the presence of the congenital condition that the test is used to detect, while results outside of the expected range may need to be acted upon; NOTE 4: As used in NBS07, the range of acid α-glucosidase activity values measured in dried blood spot specimens from newborns without Pompe disease, as opposed to laboratory test results that show acid α-glucosidase activity values below the predetermined cutoff (ie, a result outside of the expected range, or an out-of-range result); NOTE 5: The analytically validated calibration range should ideally encompass the population expected range and the range surrounding the value used to distinguish screen-positive and screen-negative results; NOTE 6: Expected ranges may be specified separately for subpopulations such as full-term newborns, preterm and low birth weight newborns, and older infants; NOTE 7: As used in NBS07, the laboratory test result of any satisfactory dried blood spot specimen that shows acid α-glucosidase activity values at or above the predetermined cutoff is a screening result that is out of the expected range requiring follow-up (ie, a laboratory test result outside of the expected range of normal/negative testing results established for a particular condition, including carrier results, that indicates the need for additional testing); NOTE 8: As used in NBS09, the range of C26:0-lysophosphatidylcholine values measured in dried blood spot specimens from newborns without adrenoleukodystrophy disease, as opposed to laboratory test results that show C26:0-lysophosphatidylcholine values above the predetermined cutoff (ie, a result outside of the expected range, or an out-of-range result); NOTE 9: As used in NBS09, the laboratory test result of any satisfactory dried blood spot specimen that shows C26:0-lysophosphatidylcholine values at or above the predetermined cutoff is out of the expected range and requires follow-up; NOTE 10: Also called “reference range” and “normal range,” although the preferred terms are “biological reference interval” or “reference interval”; NOTE 11: See in-range and out-of-range.


false-negative screening result

screen-negative result in an affected newborn

Project: NBS01, NBS09, NBS05, NBS03

NOTE 1: A screen-negative result indicating that an individual is not at increased risk for the primary target disease when the individual is found later to be affected; NOTE 2: For quantitative tests such as immunoreactive trypsinogen, this refers to an “in-range” result in an affected child; NOTE 3: For qualitative tests such as DNA analysis, this may include failure to detect cystic fibrosis transmembrane conductance regulator gene variants; NOTE 4: As used in NBS09, a screen-negative result of a laboratory screening algorithm (based on the detected C26:0-lysophosphatidylcholine concentration below the cutoff) reported for a newborn later diagnosed with adrenoleukodystrophy; NOTE 5: See primary target disease.


false-positive screening result

screen-positive result in an unaffected newborn

Project: NBS09, NBS01, NBS05, NBS03

NOTE 1: A screen-positive result indicating that an individual is at increased risk for a target disease when the individual is found later to be unaffected; NOTE 2: For quantitative tests such as immunoreactive trypsinogen, this refers to “out-of-range” results in an unaffected child; NOTE 3: For qualitative tests such as DNA analysis, this may include detection of cystic fibrosis transmembrane conductance regulator (CFTR) variants in a carrier or detection of CFTR variants that are not actually present; NOTE 4: As used in NBS09, a screen-positive result of a laboratory screening algorithm (based on the detected C26:0-lysophosphatidylcholine concentration above the cutoff) reported for a newborn who does not have adrenoleukodystrophy; NOTE 5: See primary target disease.


first-tier screen

(for newborn screening) a single assay, combination of assays, physiological measurement, or assessment performed on all newborns to screen for a disease, group of diseases, or phenotypic difference as the first step in the laboratory screening algorithm

Alternate Term: first-tier screening; first-tier testing

Project: NBS03, NBS08, NBS09, NBS10

NOTE 1: Also called “primary screening test”; NOTE 2: See laboratory screening algorithm, screening test, and second-tier screen.


follow-up

(for newborn screening) actions taken to ensure that a newborn whose specimen is unacceptable or whose screening result warrants additional action receives evaluation and/or intervention

Project: NBS05, NBS02, NBS09, NBS03, NBS10

NOTE: See intervention.


follow-up algorithm

(for newborn screening) documented process used to ensure that newborn screening results are communicated to the newborn’s specimen submitter and/or health care provider and that additional screening and/or diagnostic testing and clinical evaluation is completed. For affected babies, this process also includes ensuring that treatment is initiated and outcomes are monitored

Project: NBS07, NBS06, NBS02, NBS10

NOTE: See follow-up, short-term follow-up, and long-term follow-up.


gestational age

time since conception, measured in weeks and days or in completed weeks only

Project: NBS10

NOTE: Gestational age is most precisely estimated from in vitro fertilization information, followed by ultrasonographic metrics, followed by the time from the first day of the last menstrual period.


Graves' disease

hyperthyroidism caused by stimulating autoantibodies directed against the thyroid-stimulating hormone receptor of the thyroid gland

Project: NBS10


hyperthyroidism

excess of thyroid hormone, usually due to the overproduction of thyroid hormone by the thyroid gland

Project: NBS10

NOTE: Also called “overactive thyroid.”


hyperthyrotropinemia

a biochemical pattern of elevated serum thyrotropin (ie, thyroid-stimulating hormone) levels accompanied by in-range thyroid hormone levels

Project: NBS10


hypothyroidism

disease of the endocrine system in which the thyroid gland fails to produce sufficient thyroid hormone to meet the metabolic demands of the body

Project: NBS10

NOTE 1: Also called “underactive thyroid”; NOTE 2: See primary congenital hypothyroidism, central congenital hypothyroidism, subclinical congenital hypothyroidism, and transient congenital hypothyroidism.


hypothyroxinemia

low total thyroxine levels commonly observed in preterm, low birth weight, or sick newborns in the absence of elevated thyroid-stimulating hormone and not due to central congenital hypothyroidism

Project: NBS10


inconsistent result

results of two or more retests of the same newborn screening specimen that are sufficiently disparate from each other as to make the combined result uninterpretable


in-range result

test result that is within the expected range of testing results

Project: NBS06, NBS01, NBS09, NBS03, NBS05, NBS02, NBS10

NOTE: See expected range.


intervention

(for newborn screening) specific newborn screening follow-up activity (eg, clinical assessment, medical management, monitoring, treatments) aimed at preventing morbidity and mortality in at-risk or affected newborns

Project: NBS02, NBS03, NBS05, NBS10

NOTE: See follow-up.


jurisdiction

the area for which a newborn screening program has legal authority and/or responsibility

Project: NBS03, NBS10


laboratory screening algorithm

(for newborn screening) documented process for conducting laboratory-based screening tests, using a sequence of specified steps to determine the need for subsequent screening steps or actions and/or the final, reportable screening result and interpretation

Project: NBS06, NBS09, NBS02, NBS10


long-term follow-up

ongoing steps taken after diagnosis to prevent morbidity and mortality in affected individuals

Project: NBS02, NBS09, NBS03, NBS05, NBS08, NBS10

NOTE 1: In the context of public health, long-term follow-up most often involves periodic assessments of health outcomes as part of system evaluation. Other activities might include but are not limited to care coordination and assurance of access to treatments and/or other interventions; NOTE 2: See short-term follow-up and intervention.


lost to follow-up

(for newborn screening) status assigned to an individual for whom the newborn screening program has no record of completion of recommended follow-up testing and/or evaluation

Project: NBS03, NBS02

NOTE 1: This status might be assigned at a defined end point, even when all prescribed follow-up protocols have been completed; NOTE 2: Newborn screening programs might choose to further delineate this status (eg, unacceptable specimens vs screen-positive results) to better assess gaps in follow-up.


low birth weight

a birth weight of < 2500 g

Project: NBS03, NBS10

NOTE 1: In NBS03, references to low birth weight include very low birth weight and extremely low birth weight, unless otherwise noted; NOTE 2: See very low birth weight and extremely low birth weight.


newborn dried blood spot screening

process of collecting blood onto the blood collection (specified filter paper) section of a specimen collection device (for newborn screening), testing defined analytes by approved laboratory methods, and reporting results as appropriate

Project: NBS02, NBS03, NBS10


newborn hearing screening

the process of using a physiological measure of auditory function to detect hearing differences present in the newborn period that might interfere with the development of speech and language

Project: NBS02, NBS03


newborn screening program

a health program, which is one part of a greater newborn screening system, that operates with the goal of reducing morbidity and mortality in newborns with congenital diseases through early detection and intervention and consists of the jurisdiction’s health service components, which might include policies and regulations, planning and audits, specimen collection and transport, laboratory testing, and short- and long-term follow-up

Project: NBS03, NBS01, NBS02, NBS05, NBS09, NBS06, NBS07, NBS10

NOTE 1: In some jurisdictions, an entity is responsible for coordinating the health program elements essential to ensuring optimal health outcomes for screened newborns; NOTE 2: Newborn screening can be laboratory based or point of care based; NOTE 3: Most laboratory-based newborn screening uses dried blood spot specimens collected from heelsticks and analyzed by centralized laboratories that serve a region or jurisdiction; NOTE 4: See newborn screening system and newborn dried blood spot screening.


newborn screening system

a collaboration of newborn screening stakeholders, including public and private agencies, organizations, families, policy makers, health care providers, and other caregivers, working together to ensure that all newborns within a defined geographical area have access to newborn screening and that babies found affected are able to access appropriate care and optimize health outcomes

Project: NBS01, NBS02, NBS03, NBS09, NBS05, NBS06, NBS07, NBS10

NOTE: See newborn screening program.


out-of-range result

test result that is outside the expected range of testing results

Project: NBS07, NBS06, NBS05, NBS01, NBS09, NBS03, NBS02, NBS10

NOTE: See expected range.


point-of-care screening

in vivo monitoring or testing of physiological parameters performed in a hospital, clinic, ambulatory health care facility, or other alternate site outside a central laboratory environment, generally nearer or at the site of the patient

Project: NBS03, NBS02

NOTE: As applied to newborn screening, “point-of-care screening” describes practices in which results are obtained at the bedside, with oversight from a public health agency, to detect diseases specified for a jurisdiction (eg, hearing screening, pulse oximetry for critical congenital heart disease detection).


positive predictive value

(of newborn screening) the probability that an individual with a screen-positive result has a program-defined target disease

Project: NBS09, NBS05, NBS10

NOTE 1: Positive predictive value = a / (a + b), for which a = confirmed cases that were screen positive (ie, true-positive screening test results) and b = any screen-positive results for which additional follow-up showed that the newborn does not have the program-defined target disease (ie, false-positive screening test results); see table in screening outcome; NOTE 2: A program might report multiple positive predictive values, depending on which disease, group of diseases, and/or other medically relevant findings are defined and included as true-positive or false-positive screening test results; NOTE 3: See screening outcome.


primary biomarker

analyte or ratio of analytes that is typically out of range (high or low, present or absent, depending on the marker) in a particular disease, disease form, or phenotype

Alternate Term: primary marker

Project: NBS09

NOTE 1: In newborn screening, this analyte and/or ratio of analytes is typically assessed first in all newborns to determine whether additional testing or secondary biomarker analysis is needed; NOTE 2: See biomarker and secondary biomarker.


primary congenital hypothyroidism

thyroid hormone deficiency that is present at birth and that is caused by a problem with thyroid gland development (ie, dysgenesis) or with thyroid hormone biosynthesis (ie, dyshormonogenesis)

Project: NBS10


primary target disease

(for newborn screening) a disease, disease form, or phenotype that the newborn screening test is designed to detect

Project: NBS06, NBS09, NBS07

NOTE 1: Primary target diseases typically meet the following minimum criteria: the disease can be identified by newborn screening of most affected newborns before clinical presentation; a suitable screening test is available; and the benefits of early detection and intervention, as well as efficacious treatments for the disease, have been documented; NOTE 2: Target diseases can also be referred to as “target conditions” or “target disorders”; NOTE 3: See secondary target disease.


recall rate

the percentage of tested newborns for whom additional action is requested (eg, requested repeat screening or clinical evaluation) to complete the screening process

Project: NBS10

NOTE 1: Additional action might be needed because the initial specimen was unacceptable, screen inconclusive, and/or screen positive; NOTE 2: Recall rate = (a + b) / (a + b + c + d); see table in screening outcome; NOTE 3: Repeat screens that are collected as a part of routine screening practices (eg, routine second screens, serial screening protocols for preterm, low birth weight, or sick newborns) do not factor in to the recall rate calculation.


re-collection

(for newborn screening) collection of another dried blood spot specimen from the same patient, owing to an unacceptable initial specimen or an out-of-range initial screening test result

Project: NBS01, NBS09, NBS10

NOTE 1: Some newborn screening programs are mandated to collect second and third specimens from all newborns, which is different from re-collection; NOTE 2: Many newborn screening programs collect second and third specimens from preterm, low birth weight, or sick newborns because of the high risk of an initial false-negative result in this population; NOTE 3: See repeat screening (requested).


repeat screening (requested)

any subsequent screening test(s) performed on an additional specimen that was collected because the previous screening specimen had an out-of-range or screen-inconclusive result or was deemed unacceptable for testing

Project: NBS03, NBS02, NBS10

NOTE: See screen inconclusive and specimen acceptability.


repeat screening (routine)

any subsequent screening test(s) performed on an additional specimen that was collected as part of the screening program’s routine practices

Project: NBS02, NBS03, NBS10

NOTE: Routine repeat screening might be performed by two-screen programs, as well as by programs that routinely collect multiple specimens (eg, from low birth weight newborns).


retest

the same test applied to a punched sample from the same dried blood spot specimen to obtain replicate results as part of the activity within the newborn screening laboratory process

Project: NBS06, NBS07, NBS10

NOTE: The new sample may be punched from the same or different dried blood spot on the original dried blood spot specimen. However, it should be of the same diameter and from the same relative location within a dried blood spot, because samples taken from different locations within a dried blood spot may produce different analytical results.


screen inconclusive

a final, reportable result, based on the newborn screening result(s) and laboratory screening algorithm for a screened disease, group of diseases, or phenotypic difference, indicating the inability to accurately interpret the screening result, typically leading to a request for a repeat dried blood spot specimen

NOTE: See repeat screening (requested).


screen negative

a final, reportable result for a disease, group of diseases, or phenotypic difference, based on the newborn screening result(s) and laboratory screening algorithm, indicating that the risk for that disease, group of diseases, or phenotypic difference is low and that no additional newborn screening follow-up is needed

Project: NBS06, NBS05, NBS07, NBS09

NOTE 1: Also referred to as a “negative screening result”; NOTE 2: In the T-cell receptor excision circle assay, a final, reportable T-cell receptor excision circle result that is above the preset T-cell receptor excision circle cutoff value; NOTE 3: In the acid α-glucosidase activity assay, a final, reportable acid α-glucosidase activity result that is above the preset acid α-glucosidase activity cutoff value.


screen positive

a final, reportable result for a disease, group of diseases, or phenotypic difference, based on the newborn screening result(s) and laboratory screening algorithm, indicating that the risk for that disease, group of diseases, or phenotypic difference is higher and that additional follow-up is needed

Project: NBS06, NBS05, NBS07, NBS09

NOTE 1: Also referred to as a “positive screening result” or a “presumptive positive result”; NOTE 2: An out-of-range result might not be equivalent to a screen-positive result when more than one screening test (eg, both a first-tier test and a second-tier test) is used in a laboratory screening algorithm to determine the final, reportable result; NOTE 3: A final screen-positive result might necessitate either a repeat screening request (eg, if a program considers borderline results to indicate “possible” [vs “probable”] disease) or referral for diagnostic testing and/or clinical evaluation; NOTE 4: Individual newborn screening programs might use differing definitions of the term “screen positive” internally (eg, they might include both results indicating the need for additional clinical follow-up and results indicating that a repeat newborn screening specimen needs to be requested); however, using a consistent definition of “screen positive” across programs enables consistent comparison of screening metrics; NOTE 5: Newborn screening algorithms determine under which circumstances a positive screening result requires immediate clinical evaluation and/or a repeat newborn screening specimen; NOTE 6: In the severe combined immunodeficiency newborn screening assay, a final, reportable T-cell receptor excision circle result that is below the previously determined T-cell receptor excision circle cutoff value; NOTE 7: In the acid α-glucosidase activity assay, a final, reportable acid α-glucosidase activity result that is below the previously determined cutoff value; NOTE 8: See re-collection and repeat screening (requested).


screen results

false-negative screening result – screen-negative result in an affected newborn; NOTE: A screen-negative result indicating that an individual is not at increased risk for the primary target disease when the individual is found later to be affected.

false-positive screening result – screen-positive result in an unaffected newborn; NOTE: A screen-positive result indicating that an individual is at increased risk for a target disease when the individual is found later to be unaffected.

screen inconclusive – a final, reportable result, based on the newborn screening result(s) and laboratory screening algorithm for a screened disease, group of diseases, or phenotypic difference, indicating the inability to accurately interpret the screening result, typically leading to a request for a repeat dried blood spot specimen; NOTE: See repeat screening (requested).

screen negative – a final, reportable result for a disease, group of diseases, or phenotypic difference, based on the newborn screening result(s) and laboratory screening algorithm, indicating that the risk for that disease, group of diseases, or phenotypic difference is low and that no additional newborn screening follow-up is needed; NOTE: Also referred to as a “negative screening result.”

screen positive – a final, reportable result for a disease, group of diseases, or phenotypic difference, based on the newborn screening result(s) and laboratory screening algorithm, indicating that the risk for that disease, group of diseases, or phenotypic difference is higher and that additional follow-up is needed; NOTE 1: Also referred to as a “positive screening result” or a “presumptive positive result”; NOTE 2: An out-of-range result might not be equivalent to a screen-positive result when more than one screening test (eg, both a first-tier test and a second-tier test) is used in a laboratory screening algorithm to determine the final, reportable result; NOTE 3: A final screen-positive result might necessitate either a repeat screening request (eg, if a program considers borderline results to indicate “possible” [vs “probable”] disease) or referral for diagnostic testing and/or clinical evaluation; NOTE 4: Individual newborn screening programs might use differing definitions of the term “screen positive” internally (eg, they might include both results indicating the need for additional clinical follow-up and results indicating that a repeat newborn screening specimen needs to be requested); however, using a consistent definition of “screen positive” across programs enables consistent comparison of screening metrics; NOTE 5: See re-collection and repeat screening (requested).

true-negative screening result – screen-negative result in an unaffected newborn.

true-positive screening result – screen-positive result in an affected newborn.

Project: NBS02, NBS10


screening model

the test or combination of tests used to screen for a disease and the actions taken based on the results

Project: NBS10


screening outcome

the combined results of the entire screening process in terms of epidemiological parameters; see table below

Final Screening Result

Affected

Unaffected

Total

Positive

True positive (a)

False positive (b)

Screen positive (a + b)

Negative

False negative (c)

True negative (d)

Screen negative (c + d)

Total

Total affected (a + c)

Total unaffected (b + d)

Total screened (a + b + c + d)

(Table reprinted with permission from the International Society for Neonatal Screening, Lexicon of Terms to be used in newborn screening. https://www.isns-neoscreening.org/wp-content/uploads/2016/06/Lexicon8.pdf)

Project: NBS09, NBS05, NBS02, NBS10

NOTE: See clinical sensitivity, clinical specificity, positive predictive value, recall rate, screen negative, screen positive, and screen results.


screening test

the systematic application of determinations (ie, measurement procedures, physiological evaluations, or assessments) among a defined population (eg, newborns) with the goal of detecting individuals at sufficient risk for a specific disease, group of diseases, or phenotypic difference to merit additional investigation or guide preventive action

Project: NBS02, NBS03, NBS05, NBS09, NBS10

NOTE 1: Although sometimes used in a more generalized sense, in NBS02, the term “screening test” refers specifically to the determination(s), not to the other elements of the newborn screening system; NOTE 2: See first-tier screen, second-tier screen, third-tier screen, and newborn screening system.


secondary biomarker

analyte or ratio of analytes that, if out of range in a particular disease, disease form, or phenotype, increases the specific risk when combined with an out-of-range primary biomarker result

Alternate Term: secondary marker

Project: NBS09

NOTE 1: Analyte ratios are often considered secondary biomarkers in newborn screening; NOTE 2: A secondary biomarker alone might not indicate a specific risk for the disease or condition in question; NOTE 3: Secondary biomarkers are typically analyzed only when the primary biomarker(s) is out of range; NOTE 4: See biomarker and primary biomarker.


secondary target disease

(for newborn screening) a disease form or a specific phenotype of the primary target disease or a different disease altogether that might be detected during the process of screening for a primary target disease

Project: NBS09

NOTE 1: Secondary target diseases typically do not meet all of the criteria for a primary target disease; NOTE 2: Secondary target diseases often have clinical manifestations that, if diagnosed, can be ameliorated with treatment; however, it is not the aim of the newborn screening program to detect these diseases; NOTE 3: Target diseases can also be referred to as “target conditions” or “target disorders”; NOTE 4: See primary target disease.


second-tier screen

(for newborn screening) additional assay, physiological measurement, or assessment, performed as a second step in a laboratory screening algorithm on a subset of newborns, that uses the initial screening specimen (ie, specimen re-collection not necessary) when first-tier screening results are out of range

Alternate Term: second-tier screening; second-tier testing

Project: NBS03, NBS04, NBS07, NBS08, NBS09, NBS10

NOTE 1: A second-tier screen generally uses or assesses a different method, technology, and/or biomarker than the first-tier screen and often defines the final, reportable result; NOTE 2: Because of its higher specificity, a second-tier screen is typically used to reduce the number of false-positive screening results; NOTE 3: Also called “reflex testing”; NOTE 4: See laboratory screening algorithm, screening test, and first-tier screen.


short-term follow-up

steps taken to ensure a final screening outcome for newborns with actionable screening results

Project: NBS02, NBS03, NBS05, NBS08, NBS09, NBS10

EXAMPLES: Request for a repeat specimen and confirmation of its receipt, notification of a screen-positive result, and the steps taken to obtain a final screening outcome; NOTE: See long-term follow-up, repeat screening (requested), and screen positive.


specimen acceptability

(for newborn screening) determination of a specimen’s fitness for use, based on criteria for acceptability and unacceptability:

acceptable dried blood spot specimen – a dried blood spot specimen with a quantity and quality of blood, along with complete demographic and clinical data, that meet program criteria; NOTE 1: A specimen can be determined to be acceptable for all newborn screening tests or for only a portion of tests, with a repeat specimen needed to complete all screening tests; NOTE 2: See dried blood spot and re-collection.

unacceptable dried blood spot specimen – a dried blood spot specimen with a suboptimal quantity and/or quality of blood or with missing demographic or clinical data, according to program criteria; NOTE 1: A specimen can be determined to be unacceptable for all newborn screening tests or for only a portion of tests. In both scenarios, a repeat specimen is needed to complete all screening tests; NOTE 2: If a program chooses to test unacceptable dried blood spot specimens, the results might be unreliable or inaccurate, and the screening results report should include a disclaimer, with a request for a repeat specimen; NOTE 3: An unacceptable specimen is also commonly referred to as an “unsatisfactory specimen”; NOTE 4: See dried blood spot and re-collection.

Project: NBS01, NBS02


subclinical congenital hypothyroidism

a biochemical pattern of slightly elevated thyroid-stimulating hormone levels accompanied by in-range thyroid hormone levels

Project: NBS10

NOTE: See hyperthyrotropinemia.


third-tier screen

(for newborn screening) additional assay, physiological measurement, or assessment, performed as a third step in a laboratory screening algorithm on a small subset of newborns, that uses the initial screening specimen (ie, specimen re-collection not necessary) when first- and second-tier screening results are out of range

Alternate Term: third-tier screening; third-tier testing

Project: NBS09

NOTE 1: A third-tier screening test might define the final, reportable result or might be used to provide additional relevant information to health care providers; NOTE 2: In newborn screening, third-tier testing is typically molecular, usually involving gene sequencing or multigene panels; NOTE 3: See laboratory screening algorithm, screening test, first-tier screen, and second-tier screen.


thyrotropin

an anterior pituitary gland hormone that stimulates thyroid hormone (ie, thyroxine and triiodothyronine) synthesis and secretion by the thyroid gland

Alternate Term: thyroid-stimulating hormone

Project: NBS10


thyroxine

an iodine-containing hormone, produced by the thyroid gland as a product of the cleavage of thyroglobulin, that increases metabolic rate and is used to treat thyroid diseases

Project: NBS10

NOTE 1: Free thyroxine is the biologically active form that is not bound to a binding protein, whereas bound thyroxine attaches to proteins, preventing it from entering body tissues; NOTE 2: Laboratory tests measure total thyroxine (both the free and bound forms) or free thyroxine only, which is generally considered to more accurately reflect biological thyroid hormone status; NOTE 3: 1 µg/dL = 12.87 nmol/L.


transient congenital hypothyroidism

a temporary condition in which thyroid hormone levels are low at birth but return to in range over the first months to years of life

Project: NBS10

NOTE: “Transient” is sometimes used to refer to screen-positive results in newborns without confirmed congenital hypothyroidism, but that definition does not apply in NBS10.


triiodothyronine

a biologically active metabolite of thyroxine formed by removal of an iodine atom in the outer ring of thyroxine

Alternate Term: 3, 5, 3′-triiodothyronine

Project: NBS10

NOTE: 1 ng/dL = 10 ng/L = 0.0154 nmol/L.


true-negative screening result

screen-negative result in an unaffected newborn


true-positive screening result

screen-positive result in an affected newborn


 

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