neonatal screening


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neonatal screening

  1. 1. ‫الرحيم‬ ‫الرحمن‬ ‫هللا‬ ‫بسم‬
  2. 2. Newborn ScreeningBy Dr: Eman Mohamed Habib
  3. 3. • Is a public health program designed to screen infants shortly after birth for a list of conditions that are treatable, but not clinically evident in the newborn period. • Some of the conditions are only detectable after irreversible damage has been done • In some cases sudden death is the first manifestation of the disease Neonatal screening
  4. 4. Second screen strongly recommended between 7 and 14 days of age 2 3 Third screen recommended for sick and premature infants Washington State law requires that every newborn be tested within five days of age1 Who is screened?
  5. 5. • Most babies with metabolic disorder look normal at birth. • By the appearance of signs and symptoms, irreversible consequences are already present. • So screening is essential as it allows early intervention and prevention of irreversible damage. Why do newborn screening?
  6. 6. 1 Important condition 2 Acceptable treatment available 3 Facilities for diagnosis and treatment 4 Difficult to recognize early 5 Suitable screening test Criteria for Newborn Screening 6 Natural history known Cost-effective to diagnose and treat 7 Wilson & Jungner, 1968
  7. 7. Sample coleection Testing workup TECHNIQUE
  8. 8. • Using the heel prick method, a few drops of blood are taken from the baby’s heel • Blotted on a special absorbent filter card • Blood is dried for 4 hours and sent to the Newborn Screening Center SAMPLE COLEECTION
  9. 9. The filter paper is often attached to a form containing required information about the infant and parents. This includes: • Date and time of birth. • Date and time of sample collection. • The infant's weight and gestational age. • Information about whether the baby has had a blood transfusion • Any additional nutrition the baby may have received (TPN).
  10. 10. Tandem Mass Spectrometer (MS/MS)
  11. 11. MS/MS Plasma Amino Acids
  12. 12. 3. Enzyme assays are used to screen for galactosemia and biotinidase deficiency 4.Immunoassays measure thyroid hormones for the diagnosis of congenital hypothyroidism and 17- hydroxyprogesterone for the diagnosis of congenital adrenal hyperplasia. 5. Molecular techniques are used for the diagnosis of cystic fibrosis and severe combined immunodeficiency.
  13. 13. B. bedside testing for hearing loss using evoked auditory potentials and congenital heart defects using pulse oximetry.
  14. 14. Results Reporting • Immediately reported by phone and fax to baby’s physician/nurse • Phone calls made by genetic counselors and/or clinicians who are familiar with the disorders together with the pediatrician and the primary heath care provider for immediate assessment and early intervention.
  15. 15. The conditions included in newborn screening programs around the world vary greatly, based on Legal requirements Prevalence of certain diseases within a population political pressure and availability of resources for both testing and follow-up of identified patients. Which disorders should be identified?
  16. 16. 2002 Maternal and Child Health Bureau commissioned ACMG Recommend a core panel to create uniform NBS across all states through scoring system. Which disorders should be identified?
  17. 17. Incidence of condition Sign & Symptoms clinically identifiable in the first 48 hours Burden of disease (natural Hx if untreated) Does a sensitive AND specific screening test currently exist Test characteristics ( Yes= apply score; no = zero) Availability of treatment Cost of treatment Potential efficacy of existing treatment Benefits of early intervention (individual outcome) Benefits of early identification (family & society) Benefits diagnosis and treatment prevent mortality Availability of diagnostic confirmation Acute management Simplicity of therapy
  18. 18. 1 Amino acid disorders 2Fatty acid oxidation disorders 3 Endocrinopathies 4Hemoglobinopathies 5 Organic acidemias 6Cystic fibrosis 7 Urea cycle disorders 8Hearing loss 9 Congenital heart defects 10Severe combined immunodeficiency 11 Other conditions Target Disorders
  19. 19. Amino Acid Disorders • PKU: severe, permanent ID • MSUD: ID, hallucinations, ataxia • HCY: connective tissue damage (joints, heart), ID, psychiatric disturbances • ASA: brittle hair, liver disease ID • TYR I: acute or chronic liver disease, liver cancer, neurologic pain crises • Diagnosed by plasma amino acids, urine amino acids, and/or urine organic acids .
  20. 20. PKU Phenylalanine -------------------//----------------------- Tyrosine (substrate) phenylalanine hydroxylase (product) Disorder of phenylalanine hydroxylation leading to accumulation of this amino acid. Patients have progressive developmental delay up to severe mental retardation, seizures and autistic-like behavior .
  21. 21. PKU
  22. 22. MSUD
  23. 23. A diet with minimal levels of the amino acids leucine, isoleucine, and valine must be maintained in order to prevent neurological damage
  24. 24. Homocysteine
  25. 25. Diagnosed by plasma acylcarnitines, and urine organic acids can be helpful • MCAD: Medium-chain acyl-CoA dehydrogenase deficiency • VLCAD: Very long-chain acyl- CoA dehydrogenase deficiency • LCHAD: Long-chain L-3-OH acyl-CoA dehydrogenase deficiency • TFP: Trifunctional protein deficiency • CUD: Carnitine uptake defect Fatty Acid Disorders
  26. 26. Medium chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common fatty acid oxidation disorder which had been implicated in several cases of sudden infant death syndrome. MCCAD
  27. 27. Organic acids are breakdown products of protein and fatty acid metabolism. Defects in breakdown lead to: Vomiting, metabolic acidosis, elevated ammonia in crises ID, motor delay, ataxia, cardiac/renal/pancreatic problems Diagnosed by urine organic acids and/or plasma acylcarnitines IVA: Isovaleric acidemia GA I: Glutaric acidemia type I HMG: 3-OH 3-CH3 glutaric aciduria MCD: Multiple carboxylase deficiency MUT: Methylmalonic acidemia (mutase deficiency) 3MCC: 3-Methylcrotonyl-CoA carboxylase deficiency Cbl A,B: Methylmalonic acidemia PROP: Propionic acidemia BKT: Beta-ketothiolase deficiency Organic Acid Disorders
  28. 28. * * * * * * C2 100% Intensity * internal standards Control Intensity 100% * * * * * * MCAD C2 C16 C8 C10:1 C6 MS/MS Plasma Acylcarnitines
  29. 29. Endocrinopathies • The most commonly included disorders of the endocrine system are congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH). • Congenital hypothyroidism • Breathing problems, anemia, slow heart rate, delayed milestones, poor weight gain and growth, hearing loss, jaundice • Screening for CH is done by measuring thyroxin (T4), thyrotropin (TSH) or a combination of both analytes
  30. 30. • CH was added to many newborn screening programs in the 1970s, often as the second condition included after PKU. • The most common cause of CH is dysgenesis of the thyroid gland • Early hormonal substitution can control the condition.
  31. 31. Congenital adrenal hyperplasia • Elevated 17-hydroxyprogesterone (17OHP) is the primary marker used when screening for CAH, most commonly done using enzyme-linked immunosorbant assays, tandem mass spectrometry test to reduce the number of false positive results. • Classic CAH is caused by a deficiency of the enzyme steroid 21-hydroxylase, and comes in two forms - simple virilizing and a salt-wasting form. • Treatement is steroids.
  32. 32. Haemoglobinopathies Scikle cell disease • A sickle cell test is a blood test done to screen for sickle cell trait or sickle cell disease. • The red blood cells deform because they contain an abnormal type of hemoglobin, called hemoglobin S, instead of the normal hemoglobin.
  33. 33. Penicillin has been used in children with sickle cell disease, blood transfusions for patients identified with severe thalassemia.
  34. 34. Cystic fibrosis Also known as mucoviscidosis, is an autosomal recessive genetic disorder. It affects most critically the lungs, and also the pancreas, liver, and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions. • CF is caused by a mutation in the gene for the protein cystic fibrosis transmembrane conductance regulator (CFTR)
  35. 35. • The newborn screen initially measures for raised blood concentration of immunoreactive trypsinogen. Infants with an abnormal newborn screen need a sweat test . • People with CF have increased amounts of sodium and chloride in their sweat. In contrast, they have less thiocyanate and hypothiocyanite in their saliva and mucus. CF can also be diagnosed by identification of mutations in the CFTR gene.
  36. 36. • No cure for cystic fibrosis but early diagnosis can improve the codition • The cornerstones of management are proactive treatment of airway infection, and encouragement of good nutrition and an active lifestyle. • Recently therapies such as transplantation and gene therapy aim to cure some of the effects of cystic fibrosis
  37. 37. Urea cycle disorders Disorders of the distal urea cycle, such as citrullinemia, argininosuccinic aciduria and argininemia are included in newborn screening programs in many jurisdictions that using tandem mass spectrometry to identify key amino acids. Proximal urea cycle defects, such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase deficiency are not included in newborn screening panels because A. They are not reliably detected using current technology B. Severely affected infants will present with clinical symptoms before newborn screening results are available.
  38. 38. Some regions claim to screen for HHH syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria) based on the detection of elevated ornithine levels in the newborn screening dried blood spot
  39. 39. 1 SCID has not been added to newborn screening 2 It requires PCR is not commonly used 3 Follow-up and treatment of affected infants also requires skilled immunologists, 4 Treatment for SCID is a stem cell transplant Severe combined immunodeficiency
  40. 40. Others recently added disorders Duchenne muscular dystrophy • X-linked disorder caused by defective production of dystrophin. • Many jurisdictions around the world have screened for DMD using elevated levels of creatine kinase measured in dried blood spots
  41. 41. Galactosemia • Galactosemia occurs when an enzyme galactose-1-phosphate uridyl transferase deficient or not woking properly. • (Coagulopathy, sepsis, severe jaundice, developmental delay • Treatment Restrict milk products
  42. 42. Biotinidase Deficiency Caused by a lack of the enzyme biotinidase Seizures Developmental delay Progressive hearing loss Skin problems – eczema Treated with biotin
  43. 43. • Screening for G6PD: by measuring the level of the enzyme can prevent haemolytic crisis especially if family history is present. • Screening for diabetes: by measuring the level of IGF-1. • Screening for hyperbilirubinaemia: by measuring total and direct serum bilirubin.
  44. 44. Summary
  45. 45. Refuse screening2 3 Confidentiality and privacy protections Be informed about screening 1 Parents, on behalf of their children, have the right to Parents and consumers must be involved in all parts of the policy-making and implementation process
  46. 46. Pitfalls of Newborn Screening
  47. 47. Pitfalls of Newborn Screening • Not collecting newborn screening sample prior to transfusion because the baby is “too young” or has not yet been fed – Transfusions and feeding history alter results of some, but not all of the newborn screening tests. – Card has place to list transfusions, time of first feeding, antibiotics, overall health and birthweight. • Meaningful interpretation of test results takes all those bits of information into account.
  48. 48. • Not collecting an adequate newborn screening sample – Most newborn screening tests are quantitative. • More or less blood means higher or lower values and may lead to false positives or negatives. • Diagrams of correct circle filling are meant to ensure that the appropriate amount of blood is on the filter paper, and that there is no evidence of dilution (with alcohol, for example)
  49. 49. • Assuming that an abnormal newborn screen is a false positive because the baby is well and/or because factors known to be associated with a false positive are present. – This runs counter to the whole purpose of newborn screening, which is to pick up kids BEFORE they are symptomatic
  50. 50. Thank you