Section 661.30  Interpretation of Results

Although the majority of infants affected by disorders included in the newborn screening panel will be identified by this screening, due to genetic variabilities and variations in health status, specimen quality, and timing of specimen collection, not all infants affected by such a disorder may be identified.  As with any laboratory test, false positive and negative results are possible.  Newborn screening test results are insufficient information on which to base diagnosis or treatment.

a)         Phenylketonuria

1)         Normal phenylalanine levels shall be established using accepted statistical techniques.

2)         When the blood phenylalanine level is deemed to be abnormal, the Department shall recommend a repeat newborn screening test or referral of the infant to a designated consultant for a quantitative phenylalanine determination and other diagnostic studies as determined by the consultant.

b)         Primary Hypothyroidism

1)         Neonatal levels for thyroid stimulating hormone (TSH) vary with gestational age, birthweight, time of collection and in response to concurrent medical problems.  Normal TSH and normal thyroxine (T4) levels shall be established using accepted statistical techniques.

2)         When the TSH level or the T4 level is deemed to be abnormal, the Department shall recommend a repeat newborn screening test or referral of the infant to a designated pediatric endocrinologist for further evaluation for primary hypothyroidism and additional serum testing for thyroid function.

c)         Galactosemia

1)         Laboratory tests for galactosemia may be performed by testing for total galactose (galactose and galactose-1-phosphate) or a deficiency of the galactose-l-phosphate uridyl transferase enzyme.  Normal test results indicate a normal level of total galactose or the presence of the enzyme.  Test results are abnormal when the level of total galactose is above the normal range or the presence of the enzyme is not detected.  Normal ranges shall be established using accepted statistical techniques.

2)         When the galactose or enzyme levels are deemed abnormal, recommendations may be given to change the diet of the infant to a galactose free diet.  The Department shall recommend a repeat newborn screening test or referral of the infant to a designated consultant for further diagnostic studies.

d)         Congenital Adrenal Hyperplasia (secondary to 21-hydroxylase deficiency)

1)         Neonatal levels for 17-hydroxyprogesterone vary with gestational age, birthweight, time of collection and in response to concurrent medical problems.  Normal 17-hydroxyprogesterone levels shall be established using accepted statistical techniques.

2)         When the 17-hydroxyprogesterone level is deemed to be abnormal, the Department shall recommend a repeat newborn screening test or referral of the infant to a designated pediatric endocrinologist for further evaluation for congenital adrenal hyperplasia.

e)         Biotinidase Deficiency

1)         Laboratory tests for biotinidase deficiency are designed to detect a deficiency of the biotinidase enzyme.  Normal test results indicate the presence of the enzyme.  Test results are abnormal when the presence of the enzyme is not detected.

2)         When the determination of the enzyme is deemed abnormal, the Department shall recommend a repeat newborn screening test or referral of the infant to a designated consultant for a quantitative determination of the biotinidase enzyme and further diagnostic studies.

f)          Sickle Cell Disease/Trait and Other Hemoglobinopathies

            Qualitative testing will determine the presence of A, F, S, C and other hemoglobins.

1)         When F and S hemoglobins, but no A hemogolobin, are detected on the same specimen, the Department shall recommend referral to a designated consultant for follow-up and genetic counseling.

2)         When F, S and C hemoglobins, but no A hemogolobin, are detected on the same specimen, the Department shall recommend referral to a designated consultant for follow-up and genetic counseling.

3)         When F, A and C hemoglobins or F, A and S hemoglobins are detected on the same specimen, the Department shall recommend parental testing and genetic counseling by the attending physician or another qualified counselor.

4)         When A hemoglobin is detected as the predominant hemoglobin, and the specimen was collected at less than 2 months of age, it will be assumed that the infant received a blood transfusion and a report indicating such will be made.  A repeat newborn screening specimen should be drawn from all such infants 3 months post transfusion.

g)         Phenylketonuria (PKU) and other amino acid, organic acid, and fatty acid oxidation disorders

            (Note: PKU testing is described in Section 661.30(a)).

1)         Analysis shall be performed by MS/MS.  The patient metabolite distribution patterns shall be compared to normal populations.  Pattern analysis, and internal metabolite ratios relative to normal populations, shall be calculated using accepted statistical techniques.

2)         When blood levels or ratios are found to be abnormal, indicating the possibility of a metabolic condition harmful to the infant, the Department shall recommend a repeat newborn screening test or referral of the infant to a designated consultant for appropriate definitive testing and diagnostic studies.

h)         Cystic Fibrosis (CF)

1)         CF is indicated by elevated neonatal levels of immunoreactive trypsinogen (IRT) that can be detected in dried blood spots by immunoassay or other techniques.  The normal IRT range shall be established using accepted statistical techniques.

2)         When elevated levels of IRT are detected, testing by genetic mutation analysis shall be performed in order to decrease false positive results.  Because there are over 1,000 mutations in the CF transmembrane conductance regulator (CFTR) gene, testing will yield only 90 to 95 percent sensitivity.

3)         When IRT levels and/or mutation analysis are found to be abnormal, thus indicating the possibility of CF, the Department shall recommend referral of the infant to a designated consultant for appropriate definitive testing and diagnostic studies.

4)         To establish normal IRT range and validate the mutation analysis, the Department shall conduct, through February 2008, a phase-in project requiring CF screening of all babies born at the following Illinois birthing hospitals:  Advocate Lutheran General Children's Hospital, Advocate Hope Children's Hospital, Prentice Women's Hospital, Carle Hospital Foundation, Evanston Hospital, St. Alexius Hospital, Loyola University Medical Center/Foster McGaw Hospital, Rush University Medical Center, University of Chicago Hospitals, St. Francis Medical Center (Peoria), Methodist Medical Center, Proctor Hospital, St. John's Hospital, and Memorial Medical Center (Springfield).  At the conclusion of the phase-in project, all specimens submitted to the DPH Newborn Screening Laboratory will be tested for CF.

(Source:  Amended at 31 Ill. Reg. 13203, effective August 28, 2007)