Office of Newborn Screening

Testing & Specimen Collection

Our office is responsible for all newborn screening in Arizona and includes both bloodspot and hearing. This section deals with best practice guidelines related to bloodspot collection using a filter paper collection device (e.g., a kit).

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Special Considerations

For a baby in the NICU, a first bloodspot specimen should be collected prior to transfusion, parenteral nutrition, and other therapies, even if it means the specimen will have to be collected prior to 24 hours of age. The CLSI Guideline for preterm, low birth weight, and sick newborns recommends collection of the first screen on admission to the NICU so that it can be obtained prior to any intervention. This guideline recommends a second screen between 48 and 72 hours of age and a third on day 28 or prior to discharge, whichever comes first.

Arizona rules do not have modified requirements for NICU collection. However, they do require the hospital to collect the second screen between 5 and 10 days of age and before discharge if a baby is still hospitalized at 5 days of age. If a baby is transferred to another hospital prior to 48 hours of age, the receiving hospital is required to collect a first screen, unless the first screen has been collected by the sending hospital.

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The following factors affect test results and/or interpretation of test results:

Transfusions

According to the Arizona Administrative Code (R9-13-204A), the first newborn screening test should be collected prior to any transfusion, unless specified otherwise by a physician. This is necessary to avoid false negative results for most disorders.

Any transfusion of red blood cells (whole blood, packed RBCs or ECMO) can cause false negative results for galactosemia and hemoglobinopathies and this effect lasts until the donor red blood cells have been replaced (3-4 months after the last transfusion). Rescreening then would be necessary unless a previous screen had been collected prior to transfusion. For both of the above disorder groups a specimen collected prior to 24 hours of age is valid and yields reliable results.

Transfusions of whole blood or ECMO (or plasma, for biotinidase deficiency screening) can cause false negative results for all screened disorders for 4-72 hours after the transfusion (except for galactosemia and hemoglobinopathies where the effect lasts for 3-4 months).

Parenteral Nutrition

Parenteral nutrition (PN) can cause false positives for amino acids and fatty acids. Multiple amino acid abnormal results can be an indication of excess free amino acids from the parenteral nutrition solution or liver problems (immature enzymes or illness so that liver enzymes can't handle the amino acids fast enough to prevent a rise in amino acid concentration in the blood). Medium chain fatty acids are also added to parenteral nutrition solutions and can be present in higher amounts in the blood. Prolonged PN can lead to carnitine depletion. A false positive result for IVA (elevated C5) is also possible.

A repeat screen should be collected 24-72 hours after PN is stopped, if a previous screen had abnormal results.

Maternal Conditions

A mother with hyperthyroidism treated with PTU can deliver a baby with transient hypothyroidism (elevated TSH on the newborn screen). Positive results will occur until the drug clears the newborn's system - between 7-14 days after birth. A repeat screen or other thyroid testing should be done around two weeks of age.

A mother with CAH can deliver a baby with a false positive result for 17-OHP. The newborn should be rescreened between 3 and 7 days after birth.

Transient hyperphenylalaninemia in the newborn is a result of a mother with uncontrolled PKU (high phenylalanine levels). This effect will normalize within 12-24 hours, unless the baby also has PKU.

A mother treated with steroids during pregnancy can deliver a baby with a false negative result for CAH since steroids can suppress fetal adrenal function. The length of the effect depends on the class of steroid and the dose and is unknown but estimated at 1-2 weeks after birth. A repeat screen done later than 2 weeks of age would be needed.

Maternal carnitine or Vitamin B12 deficiencies can cause false positive results for C0 (carnitine) and C3 (Vitamin B12). The effects can last several days depending on the nutrition provided to the newborn (for B12 deficiency) and the duration of the effect of carnitine deficiency is unknown).

Carnitine supplementation can cause false negative results for C0 (Carnitine uptake defect) during supplementation and for some weeks afterwards. It can also cause false positives for other acylcarnitines. This effect lasts approximately 4 days.

A mother with 3MCC can have an unaffected baby with elevated C5OH. The duration of this false positive effect is unknown.

Sick or Stressed Infant

A sick or stressed newborn can have elevated 17-OHP and IRT (false positives for CAH and CF) until recovered. Liver disease and jaundice can cause false positives for many disorders (tyrosinemia, homocystinuria, PKU, CF, biotinidase deficiency)

Pre-Term or Low Birth Weight Infant

Elevated tyrosine and 17-OHP and low biotinidase are common results for preterm or low birth weight babies (false positives for tyrosinemia, CAH and biotinidase deficiency).

False positives for amino acids disorders are a result of immature liver enzymes.

A false negative result for hypothyroidism caused by an immature hypothalamic/pituitary/thyroid axis where TSH does not rise in response to low T4 levels can last for more than a month after birth. Since the newborn screen now measures only TSH, this possibility should be considered for all preterm and low birth weight babies, even though the hypothyroidism is usually transient.

Steroid or Antibiotic Treatment

Dopamine therapy suppresses TSH and can cause false negative results for hypothyroidism until the drug is discontinued.

Steroid therapy (including dexamethasone) suppresses TSH and can cause false negative results for hypothyroidism as well as false negative results for CAH. This effect can last for 1 to 2 weeks after therapy has been stopped.

Antibiotics conjugated with pivalic acid (for example, pivampicillin) can elevate C5 (false positives for IVA). This effect lasts until the drug clears the baby's system (at least 24 hours after discontinuing therapy).

Early Collection

False positives for hypothyroidism and CAH are possible because of the normal hormone surge after birth. False negatives for amino acidopathies and organic acid disorders are possible with early collection but specimens collected shortly after 24 hours of age are reliable.

Late Collection

Collection of a first screen after 48 hours of age can show false negative results for fatty acid oxidation disorders. A well fed state can mask indications of a FAOD so it is important that a first screen be collected between 24 and 36 hours if at all possible.

If a baby has an abnormal result for any FAOD on a first screen and then has a normal result on the second, that second result cannot be taken to mean that the baby had a false positive on the first screen. All babies with abnormal results on first screens should have diagnostic testing done to confirm or rule out the possibility of a disorder even though their second screen is normal. Very few false positive results for fatty acid oxidation disorders ever occur.

Late collection is also not helpful in identifying disorders that have early crises since results will not be available when symptoms start to appear. Disorders which can have serious consequences if not diagnosed early include galactosemia, MSUD, salt-wasting CAH, urea cycle disorders, organic acid disorders and some fatty acid oxidation disorders.

Parental Refusal of Screening

It is important to convince parents of the value of newborn screening so that they get their babies screened during the best window of time to detect the disorders.

Providers are required to order newborn screening tests but parents may refuse testing. If after explaining the benefits of newborn screening and the risks involved in refusing testing, and parents still wish to refuse, they should sign a waiver in which they accept responsibility for adverse consequences.

You should check to see that the waiver you ask parents to sign has been reviewed and approved by your legal counsel. You can print a sample form to be used as a template for preparing a customized form for your use.

This refusal should be fully documented in the baby's medical record. The demographic information on a newborn screening kit should be fully filled out and submitted to the State Lab with no blood and the Parent Refused Testing box in the lower right hand corner of the form checked.

Note: Files are PDF format unless otherwise stated.