Newborn Screening

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Newborn Screening

  1. 1. BY
  2. 2. WHAT IS NEWBORN SCREENING ?Newborn screening is a public health programdesigned to screen infants shortly after birthfor a list of conditions that are treatable butnot clinically evident in newborn period.
  3. 3. WHAT FOR NEWBORN SCREENING ?• “The goal of newborn screening is earlydetection of children at increased risk forselected metabolic or genetic diseases so thatmedical treatment can be promptly initiatedto avert metabolic crises and preventirreversible neurological and developmentalsequelae.”
  4. 4. HISTORY OF NEW BORN SCREENING• 1930’s George Jervis at NY identified 50 clientswith metal retardation attributed to PKU• 1963 Robert Guthrie, microbiologist-pediatrician at State University of New Yorkdevised simple inexpensive which allowedscreening for PKU• 1965 New York State law for newbornscreening, Public Health Law 2500
  5. 5. • 1970 -1980s: congenitalhypothyroidism, congenital adrenalhyperplasia, galactosemia• 1990s:DNA tests used as second tier – SickleCell Disease screening, Cystic Fibrosisscreening• 2000s : Tandem Mass Spectrometer (MS/MS)Many diseases, one test
  6. 6. CARDINAL PRINCIPLES OF SCREENING• The disorder has a relatively high incidence so that thecost per diagnosed individual is reasonable• An effective and not overly expensive treatment isavailable.• A relatively inexpensive screening test that is suitablefor high volume testing (preferably automatable)• The screening test has a very high sensitivity (very lowfalse negatives) and high specificity (low false positiveswhich require expensive follow-up)
  7. 7. CRITERIA FOR NEWBORN SCREENING• Disorder produces irreversible damage beforeonset of symptoms• Treatment is effective if begun early• Natural history of disorder is known
  8. 8. SCREENING PROCEDURE• SPECIMEN COLLECTIONBlood specimen is obtained from heel of infantIt should be obtained from medial or lateral sideof the heel
  9. 9. TIMING OF COLLECTION• Normal Term Newborn: Before nurserydischarge or 3rd day of life whichever is earlier.• Preterm or LBW: 2 wks of age or at dischargewhichever is earlier.• Newborn who is to receive blood transfusion,One specimen collected before transfusion &second specimen 2 days after transfusion.
  10. 10. SCREENING TESTS• BACTERIAL ASSAYS:Punching of small disc from Guthrie specimenDisc are place in agar or silica gel & containbacteria growth media & other necessary factorsEach bacterial plate are specified for response to aparticular metabolite.The amount of growth around the disc is directlyproportional to the concentration of metabolite inblood.They are used to screen for amino acid disorders.
  11. 11. • IMMUNOASSAYSRADIOIMMUNOASSAYFLUOROASSAYELISAUSED TO TESTEndocrinopathies: Congenital Hypothyroidism &CAHInfectious disease: Congenital toxoplasmosis, HIVCystic Fibrosis
  12. 12. Tandem Mass Spectrometer (MS/MS)
  13. 13. Tandem Mass Spectrometry (MS/MS) HighImpact and High Throughput• One disease, one test is not cost-effective• Many diseases, one test is cost-effective• MS/MS allows for rapid, simultaneous analysisand detection of many disorders of aminoacid, organic acid, and fatty acid metabolism• Sample set up determines which masses andtherefore which compounds are detected• 2 minute analysis time• Automated data processing for results
  14. 14. MS/MS Methodology – continuedCompounds analyzed are amino acids andacylcarnitines–Amino acids – to identifyPKU, MSUD, homocystinuria–Acylcarnitine – carnitine (vehicle) + fattyacid for identification of organic aciduriasand fatty acid oxidation disorders
  15. 15. SECONDARY TEST• An abnormal finding on newborn screeningtest is not diagnostic of a disorder.• Additional tests should be performed tosubstantiate the original finding.• Also the original specimen is retested for theanalyte that is abnormal.
  16. 16. • In screening for congenital hypothyroidism,Low T4TSH ImmunoassayLow TSH Normal TSHCongenital Transient low T4Hypothyroidism
  17. 17. DISORDERS MOST COMMONLYSCREENED• PHENYLKETONURIA• CONGENITAL HYPOTHYROIDISM• GALACTOSEMIA• HOMOCYSTINURIA• MAPLE SYRUP URINE DISEASE• CONGENITAL ADRENAL HYPERPLASIA• SICKLE CELL DISEASE
  18. 18. PHENYLKETONURIA• INCIDENCE: 1 IN 12000 live births• Untreated: Mental retardation & neurologicalabnormalities• Screening is done by MS/MS• Screening test is positive if phenylalanine levelis > 6mg/dl• Liver disease, Galactosemia & Tyrosinemiatype 1 can also produce phenylalanine levels.
  19. 19. CONGENITAL HYPOTHYROIDISM• INCIDENCE: 1 in 3000 to 5000 newborn• UNTREATED: Growth retardation & delayedcognitive development• Two Screening approaches are usedPrimary screening for low T4 with secondaryscreening for high TSHPrimary screening for high TSH
  20. 20. • FALSE POSITIVELow T4: Premature infants, Thyroxin bindingglobulin deficiencyHigh TSH: Perinatal stress• FALSE NEGATIVENormal T4: In first 24hrs of life.Normal TSH: In premature infants with CH it maytake 2 or more wks for TSH elevation to develop
  21. 21. GALACTOSEMIA• INCIDENCE: 1 in 62000• MANIFESTATIONS: Failure tothrive, vomiting, Liver disease & death fromsepsis due to E.Coli• 2 Screening TestSPECIFIC ENZYME ASSAYMeasures activity of Galactose 1 Phosphate UridylTransferraseIdentifies only galactosemia
  22. 22. METABOLITE ASSAY Measures total Galactose(galactose & galactose 1phosphate)Identifies other galactose metabolic disorders likeGalactokinase & Epimerase deficiencyPOSITIVE SCREENING TESTRAPID CONFIRMATORY TESTTESTING OF URINE FOR REDUCING SUBSTANCES
  23. 23. URINE CONTAINS REDUCING SUBSTANCESDISCONTINUATION OF BREAST OR FORMULA FEEDSSUBSTITUTION WITH NON LACTOSE FORMULA Eg, SOYENZYME ASSAY FOR RBC GALT ACTIVITY
  24. 24. HOMOCYSTINURIA• INCIDENCE: 1 IN 344,000 births• UNTREATED: Ectopia lentis, OsteoporosisThromboembolism, Mental Retardation• SCREENING MARKER: Plasma Methioninelevels.• MS/MS is used for screening
  25. 25. • Isolated Hypermethioninemia may occur inMAT Deficiency,Tyrosinemia type 1Liver disease• HOMOCYSTINURIAHomocysteine is detectable in plasma & urinePlasma total Homocysteine & MethioninePlasma cysteine is reduced
  26. 26. • ISOLATED HYPERMETHIONINEMIAPlasma Methione markedlyNo detectable homocysteine in plasma or urineNormal plasma cysteine levels
  27. 27. MAPLE SYRUP URINE DISEASE• INCIDENCE: 1 IN 185,000 births• FULMINANT DISEASE: SevereKetoacidosis, Vomiting & lethargy & mayprogress to coma & death• SCREENING MARKER: 4 fold elevation ofplama leucine in NB
  28. 28. • Confirmatory plasma & urine specimensobtained• Plasma shows marked increase in leucine,isoleucine & valine (branched chain aminoacids)• Urine is strongly positive for ketones• Maple syrup odor appears earliest in cerumen& later in urine. Can be detected by cottontipped swab inserted into infant’s ear.
  29. 29. • CONGENITAL ADRENAL HYPERPLASIAScreening Marker: Increased levels of 17OHP• SICKLE CELL DISEASEScreening is by means of Hemoglobinelectrophoresis.It also identifies sickle cell trait & other abnormalhemoglobins.
  30. 30. OTHER DISORDERS DETECTED BYNEWBORN SCREENING• BIOTINIDASE DEFICIENCY• OTHER AMINO ACID DISORDERS: EgCitrullinemia• LONG CHAIN & MEDIUM CHAIN ACYL CoADEHYDROGENASE DEFICIENCY• CYSTIC FIBROSIS• NEUROBLASTOMA

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