Master's in Genetic Counseling (MGC)

Timing of Specimen Collection

The timing of specimen collection is very important for proper testing of many of the disorders on the newborn screening panel. Blood obtained during the first hours of life can be used to detect enzyme abnormalities and hemoglobinopathies in the plasma or red blood cells such as biotinidase deficiency, abnormal hemoglobin, or galactose-1-phosphate uridyl transferase deficiency. However, detection of disorders by abnormal metabolite levels, such as PKU and MSUD, requires that there be an accumulation of metabolites in order to be detected. This accumulation does not occur until after a period of protein intake, such that if the specimen is collected too early, disorders such as PKU and MSUD may not be detected.

In "Issues in Newborn Screening" (Pediatrics 1992;89:345-349), the American Academy of Pediatrics has provided the following recommendations regarding the collection of specimens for newborn screening:

• The specimen should be obtained as close as possible to the time of discharge from the nursery for the full-term, well neonate, and in no case later than 7 days of life.

• Cord blood is not adequate for detection of PKU or other disorders with metabolite accumulation after birth.

• If an infant requires transfusion or dialysis prior to the routine time for acquisition of the newborn screening specimen, and if the clinical status of the infant permits, it is optimal to obtain the sample prior to transfusion or dialysis. If a sample cannot be obtained before dialysis or transfusion, the pediatrician should ensure that an adequate repeat specimen is obtained at the appropriate time when the plasma and/or red blood cells will again reflect the child’s own metabolic processes or phenotype.

• If the initial specimen is obtained before 24 hours of age, then a second specimen should be obtained at 1 to 2 weeks of age to decrease the probability that PKU and other disorders with metabolite accumulation will be missed as a consequence of testing on the first day of life.

Timing/Feeding Considerations For Each Disorder:

Biotinidase Deficiency: Screening for biotinidase deficiency is an enzyme assay and is not dependent on the age of the infant or on the amount of protein intake.

Congenital Hypothyroidism: Infants less than 24 hours of age may have low T4 levels with or without an associated elevation of TSH. These low T4 levels will increase to normal in normal infants. Protein intake does not influence screening for congenital hypothyroidism.

Galactosemia: Galactosemia screening tests that measure galactose-1-phospahte uridyl transferase enzyme activity (i.e. Beutler test) are accurate at any time regardless of age or lactose ingestion. Screening tests that measure galactose accumulation (i.e. Paigen or Hill test) require adequate ingestion of lactose containing milk.

Hemoglobinopathies: Screening for hemoglobinopathies is not dependent upon the age of the infant or upon protein intake.

Homocystinuria: Accurate screening for homocystinuria is dependent upon adequate protein ingestion. Affected infants screened prior to 48 hours may be missed.

Maple Syrup Urine Disease: In affected infants, plasma leucine levels begin to rise immediately after birth. However, the sensitivity of testing for MSUD is at its greatest after 24 hours of protein feeding.

Phenylketonuria: Infants with classical PKU may show abnormal blood phenylalanine levels, even without protein ingestion, as early as 4 hours after birth. However, 24 hours of protein feeding will result in more accurate screening.

Tyrosinemia: Optimal screening for tyrosinemia requires 48 to 72 hours of protein feedings.