Assuring Laboratory Quality

​APHL collaborates with CDC to assure the proficiency of newborn screening laboratory testing. The association works in partnership with the CDC’s Newborn Screening Molecular Biology Branch to support the Newborn Screening Quality Assurance Program (NSQAP).

NSQAP is a voluntary, non-regulatory program to maintain and enhance the quality of newborn test results at state public health laboratories. It provides services to more than 85 US newborn screening laboratories, 31 manufacturers of diagnostic products and laboratories in 67 countries. NSQAP has served as the reputable source for newborn screening quality assurance services for over 33 years.

NSQAP sends coded specimens to participating laboratories to assess their testing proficiency. If a laboratory makes an error in identification, NSQAP works with the institution to identify the error and improve laboratory practices. The program also publishes quarterly reports to allow laboratories to benchmark practices against their peers.

Newborn Screening Analyte Interference List

The Newborn Screening Analyte Interference List is a compilation of published and observed analyte interferences of newborn screening assays. The list serves as a central, one-stop resource for all known newborn screening assay interferences. Users can both review and add interferences to the list. Categories include:

• Infant Conditions


NBS Analyte Affected	Root Cause	Effect on NBS Results
Acid α-glucosidase (GAA) (Pompe Disease) and other LSD's	High hematocrit	False negative
Butyrylcarnitine (C4)	Mild form of glutamate formiminotransferase deficiency	False positive for SCAD or IBD deficiency
DNA, PCR	Immunoglobulin G in plasma	Sample failure for CF, SCID and other molecular methods
DNA, PCR	Elevated hematocrit?	Sample failure for CF, SCID and other molecular methods
Elevated 17-OHP (?), amino acids, organic acids	Renal immaturity; renal disease
Elevated C3	Hyperbilirubinemia	False positive MMA/PA
Elevated IRT	Hypoxia	False positive for CF primary screen
Elevated tyrosine, methionine, galactose, depression of biotinidase enzyme activity	Liver disease
GALT activity	G6PD Deficiency	False positive for Galactosemia
Low T4, elevated TSH	Iodine deficiency	Transient hypothyroidism
Low T4, elevated TSH, elevated immunoreactive trypsinogen (IRT)	Acute illness	Transient hypothyroidism
Low T4, normal or low TSH	Central Hypothyroidism	False negative for CH if PTSH is used for screening
Low T4, normal TSH - followed by elevated TSH	Hypothyroxinemia of preterm birth	Transient hypothyroidism; Mild CH
Low T4, normal TSH and FT4	TBG (thyroxine-binding globulin) deficiency	False positive for CH
Low T4, normal TSH, delayed rise of TSH	Immature hypothalamic-pituitary thyroid axis	False negative for CH
Lower biotinidase activity levels inversely related to gestational age	Preterm
Lower biotinidase activity levels inversely related to gestational age	Preterm
Transient elevations of tyrosine	Vitamin C deficiency	Transient neonatal tyrosinemia
Transient elevations of tyrosine, methionine, and galactose, occasionally other amino acids	Liver enzyme immaturity
Varies (most if not all analytes, notably 17-OHP, TSH, IRT)	Baby screened too early after birth	False negative and false positive results
• Infant Treatment


NBS Analyte Affected	Root Cause	Effect on NBS Results
Carnitine, hemoglobin A, unsuitable for Galactosemia	Intrauterine or postnatal RBC transfusion	False positive CUD; inconclusive hemoglobin result; unsuitable for Galactosemia
Carnitine, hemoglobin A, unsuitable for Galactosemia	Intrauterine or postnatal RBC transfusion	False positive CUD; inconclusive hemoglobin result; unsuitable for Galactosemia
Elevated acylcarnitines	Carnitine supplementation	Can mask carnitine transport disorders; False negative CUD
Elevated isovaleryl 2-methylbutyryl carnitine	Pivalic acid, antiobiotic therapy	Unknown (varies, dependent on half-life of antibiotic)
Elevation of multiple amino acids	Parenteral Nutrition (PN)	False positive for multiple amino acid disorders
Immunoreactive trypsinogen (IRT)	Meconium ileus	False negative NBS result for CF
Low T4, high TSH	Iodine exposure with povidone/iodine preps	Transient hypothyroidism
Masks absence or presence of enzymes and proteins intrinsic to RBC	Red cell transfusion & extracorporeal life support (ECLS) -pre- and postnatal transfusions	False negatives for hemoglobinopathies and (possibly) Galactosemia
Masks absence or presence of enzymes intrinsic to serum	Red cell transfusion & extracorporeal life support (ECLS) -pre- and postnatal transfusions	Possible false negative for biotinidase deficiency
Suppressed levels of 17-OHP, TSH and T4	Steroids	False negative for CH and CAH
Suppressed levels of 17-OHP, TSH and T4	Steroids	False negative for CH and CAH
Suppressed levels of TSH	Dopamine	False negative for CH
• Maternal Conditions


NBS Analyte Affected	Root Cause	Effect on NBS Results
	Hypothyroidism treated with carbamazepine
Elevated 17-OHP	Maternal Congenital Adrenal Hyperplasia	False positive result
Elevated C5OH, low free carnitine	Maternal 3-MCC deficiency	False positive 3-MCC
Elevated even-chain acylcarnitines	Fatty liver of pregnancy or HELLP syndrome	False positive, associated with LCHAD
Elevated phenylalanine	Maternal PKU or moderate hyperphenylalaninemia (uncontrolled)	Transient hyperphenylalaninemia
Elevated propionylcarnitine (C3)	Maternal vitamin B12 deficiency	False positive PA/MUT/Cbl A, B/Cbl D, E
Elevated TSH	Autoimmune (Hashimoto's) thyroiditis	Mild CH or Transient hypothyroidism
Low carnitine levels	Maternal carnitine deficiency	False positive for CUD
Low free carnitine, elevated C5DC	Maternal GA-1	False positive for CUD
Low or normal 17-OHP	Steroids: prednisone, betamethasone/dexamethasone	False negative for CAH
Low T4, high TSH	Hyperthyroidism treated with PTU and Methimazole	Transient hypothyroidism
Low T4, high TSH	Radioactive iodine treatement during pregnancy after 8 weeks gestation
None	Radioactive iodine treatment during pregnancy before 8 weeks gestation	Hypothyroidism
• Special Diets


NBS Analyte Affected	Root Cause	Effect on NBS Results
Amino acids Leucine, Methionine, Phenylalanine and others	Highly concentrated infant formula feeding of baby	May elevate some amino acids and/or free carnitine
• Specimen in Treatment


NBS Analyte Affected	Root Cause	Effect on NBS Results
17-OHP	Blood collection with EDTA	False positive for CAH
DNA, low TREC	Blood collection with heparin	Sample failure for CF, SCID and other molecular methods
Immunoreactive trypsinogen (IRT)	Blood collection with EDTA	False negative for CF by IRT
Isovalerylcarnitine (C5)	Nipple-fissure cream containing neopentanoate esters	Elevated C5
Malonylcarnitine (C3DC)	Use of Sani-Wipes	False positive for C3DC
Phenylalanine (Phe)	Benzocaine skin treatment prior to collection	False elevation of phenylalanine, false positive for PKU
Prevent extraction of analytes/degrade protein markers	Heat and/or Humidity	False-positives and false-negatives for many disorders (see Analyte Disruption Description field)
TSH, T4	Blood collection with EDTA	False negative for CH

How to Nominate an Interference

To nominate an interference, please review the example and/or the reported analyte interferences above.

• Select " Nominate an Interference"
• Enter your data. Note that some fields are mandatory. Important: You must enter all your data at one time. It is not possible to save your data and return to it later. Locate your information prior to starting the entry.
• Select Submit to send analyte interference to the QA/QC subcommittee for review.