Most industrialized countries of the world require screening of newborns to detect congenital and metabolic disorders within the first week of life. In the United States, only three disorders—phenylketonuria (PKU), congenital hypothyroidism (CH), and GAL—are screened in all states. Some states have expanded screening using tandem mass spectrometry (MS/MS) technology to screen for more than 20 genetic metabolic disorders. Providing and performing the testing and following up on all abnormal results are the responsibility of state health departments. For those babies with a confirmed congenital disorder, genetic counseling, treatment, and long-term care are also provided in most states (e.g., special dietary formula for PKU children). Recently, pilot programs have been undertaken to develop protocols to screen for severe combined immune deficiency (SCID), which affects 1 in 100,000 newborns. SCID is often fatal, characterized by no immune response because of a defect of the white blood cell. If identified within a few weeks of birth, 95% of cases can be cured by bone marrow transplantation.

Screening for congenital hearing loss has become a standard of care for all newborns in the United States. The prevalence of permanent hearing loss is about 1–3 of every 1000 live births. Before implementation of newborn hearing screening, most children were typically older than 2 years before congenital hearing loss was detected. Unfortunately, by this age, children have difficulty developing speech and language skills. However, when identified at a much earlier age and with intervention, by 6 months, these children can develop language skills equal to children with normal hearing.

1. Newborn blood is sampled using a heel-stick procedure in the first week of life (see Chapter 2).

2. Apply the blood drops (less than 0.5 mL in total) to a piece of special filter paper, which usually contains three to five printed circles.

3. Fill all the printed circles with blood, which in most cases can be done with one drop of blood per circle.

4. Be sure the attached coverslip does not come into contact with the blood until completely dry. Do not permit the blood-soaked portion of the collection kit to come in contact with another surface (e.g., desktop, absorbent paper). Proper collection procedures are based on Clinical Laboratory Standards Institute document LA4-A5: Blood Collection on Filter Paper for Newborn Screening Programs; Approved Standard—6th Edition.

5. In addition to the filter paper, the collection kit also contains a multipart form requesting information regarding the baby’s name, mother’s name, birth date and time, specimen collection data and time, birth weight, and so forth. It is important that this form be filled out completely because the information is critical for the laboratory staff in the interpretation of test results. For example, differentiating normal from abnormal thyroid-stimulating hormone results for potential hypothyroidism may be dependent on the age (in hours) of the infant at the time of specimen collection.

6. After the specimen is collected, allow the blood card to air-dry in a horizontal position for a minimum of 3 hours at room temperature. After the blood is dried, the specimen should be forwarded (e-mail or courier) to the screening laboratory within 24 hours.

7. Although the process may vary among newborn screening laboratories, most testing begins by punching a ⅛-inch blood spot into a 96-well microplate (or some other vessel such as a test tube or dimple tray).

   1. Basic chemistry procedures are completed, such as measurement of phenylalanine or galactose metabolites.

   2. Electrophoresis technology or liquid chromatography is used to separate hemoglobin fractions.

   3. Immunochemistry (e.g., antigen–antibody reactions) is used to measure thyroid hormones (hypothyroidism), 17-hydroxyprogesterone (congenital adrenal hyperplasia), and immunoreactive trypsinogen enzyme (cystic fibrosis).

   4. Gene mutation analysis is used to detect the genetic mutation causing the disorder (e.g., cystic fibrosis, abnormal hemoglobin). Mutation analysis is used as a second-tier assay to improve the specificity of the primary assay.

   5. MS/MS technology has allowed newborn screening programs to expand significantly the number of disorders screened. The disorders fall into four groups: fatty acid oxidation (FAO), organic acidemia (OA), urea cycle (UC), and aminoacidopathies (AA). The FAO and OA disorders are detected by measuring acylcarnitine (an intermediate compound containing fatty acids or organic acids combined with carnitine that occurs from blocked metabolic pathways), and the UC and AA disorders are determined by measuring a specific set of amino acids. At least 30 different disorders can be detected by this technology.

8. Urine samples can also be collected using dried urine filter paper strips. Because the collection of liquid urine from neonates is difficult and transportation of frozen urine is expensive, the use of filter paper strips is more convenient.

9. Hearing can be tested using otoacoustic emissions (OAEs) or automated auditory brain stem responses (ABR). With OAEs, an earphone is placed in the infant’s ear canal and emits certain tones or clicks. Sounds subsequently produced by the inner ear are recorded. Alternatively, ABR also requires an earphone being placed in the ear canal; however, three electrodes on the head, neck, and shoulder record neural activity in response to tapping noises emitted from the earphone. The infant is asleep during these procedures.

Chart 11.4 is a list of disorders that currently can be detected through newborn screening. It should be noted that the information provided is generally not considered all-inclusive, and results are considered presumptive (requiring confirmation before a formal diagnosis is made and treatment implemented). The State Public Health Laboratory or Health Department in specific states or regions can provide information about the status of newborn screening in a particular state or region. Most screening programs have two levels of abnormal results. The first level of abnormal results are considered borderline. The likelihood of such results being indicative of a disorder is low, and most are resolved by repeating the newborn screen. The second level of abnormal results are those considered urgent. These results are highly indicative of a disorder and require immediate follow-up and confirmation, usually at a clinic specializing in the disorder. Abnormal values represent the absence of expected enzyme activity, elevated or decreased hormone values, presence of abnormal or variant hemoglobins, abnormal levels of amino acids, or presence of a genetic mutation.

1. Most of the congenital disorders are autosomal recessive genetic disorders (the exception being hypothyroidism). This means that for the baby to have one of these disorders, both the mother and father have to carry the abnormal gene that causes the disorder. If the mother and father are carriers, there is a one-in-four chance that with each pregnancy, the couple will have an affected baby.

2. Although the disorders can be quite varied in clinical expression, there are common issues. All the disorders are relatively rare. The most frequently detected disorder is CH, which occurs in 1 of 3000 births in most states or regions. Some disorders have a frequency rate of 1 in 100,000 or less.

3. All of the disorders, if not detected early and treated promptly, will cause severe medical complications. These complications include intellectual disability, neurologic problems, or death.

4. All of the disorders can be detected by laboratory tests in the first few days of life before there are any clinical symptoms.

5. If a disorder is detected early and promptly treated, the baby’s quality of life can be significantly improved.

6. The treatments are relatively simple and inexpensive when compared against a lifetime of medical care. For example, several of the metabolic disorders are treated by changes in diet and vitamin supplements.

Pretest Patient Care

1. Explain the significance of timing and importance of newborn screening to the parents. Provide the parents with educational brochures regarding newborn screening.

2. Explain to the parents that most states do not require informed consent to perform newborn screening and have limited reasons for parental refusals. Have the parents sign a waiver if they refuse to have the newborn screened and the reason is valid under specific state criteria.

3. Complete the form associated with the newborn screening blood collection kit. Be sure the name on the blood collection card matches the newborn whose blood is being drawn.

4. Collect the newborn screening specimen before discharge from the hospital. If the initial specimen was collected before 24 hours of age, obtain a repeat in about 14 days as recommended by the American Academy of Pediatrics.

5. For premature and sick infants, collect an initial specimen as soon as medically possible but no later than the first week of life. Be familiar with your local newborn screening laboratory procedures and policies regarding initial and repeat testing.

6. Collect initial specimen before transfusion, if possible. Be familiar with your local newborn screening laboratory procedures and policies regarding repeat testing when a newborn has been transfused.

7. Record the date the specimen was sent to the screening laboratory.