With all the prenatal screening, ultrasound, and diagnostic tests a mother has before childbirth, it’s easy to think you’re totally prepared for the birth of a healthy child. But even when baby looks normal, it can have a life-threatening genetic disorder that could result in serious, chronic disability or death if it goes undetected and untreated. That’s why all states now require newborn screening tests.
Here’s what to know about what they test for, how they test, and how accurate they are.
What Is Newborn Screening?
Newborn screening tests identify up to 50 debilitating genetic conditions from a tiny sample of the baby’s blood. While the conditions screened for vary by state, the focus is on conditions that can save the infant’s life, reduce the severity of the condition, or prevent it from arising altogether when diagnosed and treated early.
These screening tests search for certain genetic, endocrine, and metabolic disorders, as well as hearing loss and critical congenital heart defects. They are very sensitive tests but remember that they are screening tests, not diagnostic tests. They indicate the PPV (positive predictive value) the infant has a certain condition. A targeted diagnostic test is used to formally diagnose.
Newborn screening tests have been in use since the 1960s, when an American microbiologist named Dr. Robert Guthrie developed a test to screen infants for phenylketonuria (PKU), an inherited disorder that causes the amino acid phenylalanine to build up in the body because the body lacks the enzyme to break it down, resulting in intellectual disability and other health problems. By following a diet restricting phenylalanine, children with PKU were found at age 7 to be as healthy as siblings without the disease — a major win for public health [*].
As the technology has advanced, more conditions for which early treatment could make a difference were added to the screening [*]. Today, novel therapeutics and political advocacy also influence what is tested for in each state.
When Is Newborn Screening Performed?
Newborn screening is performed within 48 hours of birth, after the infant’s first feeding. In some states, your baby may also be required to be screened again 1-2 weeks later because the first screen can miss later-onset or milder forms of certain disorders. If you leave the hospital before 48 hours, or before your baby’s first feed, you may be required to return for screening.
Screening may be delayed if the infant has a low birth weight, is sick or needs a blood transfusion [*].
What Is Included in a Newborn Screening Test?
What conditions get screened for is influenced by federal public health recommendations, state laws, screening costs, the frequency of the disorder in the state, and the availability of health care providers with the ability to diagnose and effectively treat the disorder. Baby’s First Test lists each state’s screening protocols [*].
In 2002, some states screened for only 4 conditions while other states screened for as many as 50. By April of 2011, at least 26 disorders were screened for by all states. Screening for hearing loss increased from 46.5% of U.S. newborns in 1999 to 96.9% by 2008 [*].
Today, all states screen for at least 29 conditions [*]. The Recommended Universal Screening Panel (RUSP) created by The American College of Medical Genetics and The Advisory Committee on Heritable Disorders currently includes 35 specific conditions and 26 secondary conditions. The March of Dimes recommends all babies be screened for 35 conditions [*].
These conditions include metabolic disorders, endocrine disorders, blood disorders, and other disorders. Following is a brief overview; You can check exactly what your state screens for at Baby’s First Test [*].
Metabolic disorders occur when a genetic problem impairs a protein or enzyme critical to the metabolic process. Basically, the baby cannot break down food correctly.
In organic acid metabolism disorders, organic acids build up in the body; In fatty acid oxidation disorders, the infant cannot convert fat into energy (like MCAD) [*]; and in amino acid disorders (like PKU or maple syrup urine disease), the infant cannot metabolize certain proteins.
Endocrine disorders affect the glands that produce hormones. Hypothyroidism (affecting growth) is a disorder of the thyroid gland where the infant produces too little thyroid hormone. This can cause slow growth and intellectual disability. Congenital adrenal hyperplasia (affecting the body’s production of cortisol, androgens and mineralocorticoids) is a disorder of the adrenal glands [*]. Both are recommended for screening.
Disorders of the red blood cells screened for include sickle cell anemia, beta-thalassemia and SC disease, which can result in anemia severe enough to require blood transfusion or even a stem cell transplant [*].
Lyposomal Storage Disorders
People with lyposomal disorders cannot break down certain types of fats or complex sugars, causing a buildup in the body with deleterious symptoms. These include Pompe, Fabry, MPS I and MPS II, Niemann-Pick, and Gaucher.
Cystic fibrosis, congenital heart disease, SCID (severe combined immunodeficiency), HIV, X-linked adrenoleukodystrophy, galactosemia, (where the infant cannot metabolize the milk sugar galactose), biotinidase deficiency, and hearing loss are among the other disorders recommended for screening.
The list of screened conditions recommended for the RUSP is continually updated [*]. However, there has been pressure among parent advocacy groups to include other conditions that may not meet the criteria for inclusion because, for instance, the test isn’t complete, the disease mechanism isn’t well known, or there isn’t yet a treatment for it [*].
Parents who are concerned about a specific heritable condition not on their state’s screening list should ask their care team about supplemental screening options. State programs do not pay for supplemental screening; check with your insurance provider.
How Is Newborn Screening Done?
There are three components to newborn screening: the blood test, hearing screen and pulse oximetry.
1. Blood Test
A member of your care team will prick the baby’s heel for a few drops of blood that they collect on special paper. The paper is sent to a state lab that uses tandem mass spectrometry [*] to analyze the blood sample along with the infant’s vital statistics, including date and time of birth, sex, weight, date and time of heel stick collection and the date and time of its first feeding.
Of the three tests, the blood test is the most time sensitive. If the sample is drawn before the infant is 24 hours old, certain conditions may go undetected. If it is drawn past the 48-hour mark, it could result in a life-threatening delay in treatment.
2. Hearing Screen
There are two hearing tests that can screen for hearing loss in newborns. Both are non-invasive and quick. The otoacoustic emissions test (OET) uses tiny earphones to measure the echo of a sound in the baby’s ear canal. The auditory brain stem response test (ABR) evaluates how the ear carries sound to the brain and the brain’s response to that sound using earphones and tiny electrodes placed along the baby’s head.
3. Pulse Oximetry Test
A painless sensor placed on the baby’s skin measures how much oxygen is in the blood. Low oxygen can point to congenital heart disease.
When Are the Results Ready?
Results of your baby’s blood screen should become available 5-7 days after birth. The results will either be in-range (negative/normal/low risk), out-of-range (positive/abnormal/high risk), or borderline (inconclusive/medium risk). If your newborn is experiencing trouble breathing, feeding or moving, don’t wait for your screening results to contact your care provider.
The hearing screen and pulse oximetry yield results upon testing.
What Happens if a Newborn Screening Test Comes Back Positive?
Your care team will contact you regarding an out-of-range result and advise you on the second-tier screening or diagnostic tests needed to confirm or rule out the condition caught by the initial screening.
If diagnostic tests confirm the disorder, you may be advised to see a specialist to learn more about the disorder and how to manage it effectively. You may also be referred to a genetic counselor in the event you plan to have more children.
How Accurate Are Newborn Screening Tests?
The blood screening tests are very sensitive and can have a high rate of false positives, so first of all, don’t panic. False positive results are those that show an out-of-range result but are later confirmed to be incorrect with another screening or diagnostic test.
False positives can occur for a number of reasons, including the collection and handling of the sample; incorrect data on the screening card as to the timing of the birth or collection of the sample; or screening performed outside the recommended time frame. The bulk of false positives occur with premature babies [*].
The results, even when debunked, can linger with parents and cause undue stress, or cause them to not take seriously a finding at another time that indicates a risk to their child.
To combat the controversial and emotional issue of false positives, the Mayo Clinic developed a screening program in 2004 called Region 4 Stork (R4S) designed to improve the quality of tandem mass spectrometry results. It compares the infant’s results to a massive database of true-positive cases and offers on-demand access to post-analytical tools to better interpret the blood data. A 2014 study found that R4S could reduce California’s false positive cases by up to 90% [*].
The next generation of this remarkable tool is CLIR (Collective Laboratory Integrated Reports), which, with 54 sites worldwide participating, has the reference population to adjust for demographic covariates such as age, birth weight and sex. Any site can use these tools as long as they contribute their data so the tool can continue to improve its accuracy.
Can Parents Decline Newborn Screening?
It depends on your state. Some states only allow parents to decline newborn screening for religious reasons, some states let them refuse for any reason, and a few states do not allow parents to refuse at all [*].
Newborn Screening FAQ
Why is newborn screening mandatory?
The CDC regards newborn screening among the 10 greatest public health achievements in the United States [*]. It saves thousands of lives each year and profoundly reduces the impact of inherited genetic diseases for which early treatment can mean the difference between a normal life and a life of chronic disability or death.
What is the difference between NIPT and newborn screening?
While both noninvasive prenatal testing and newborn screening seek to detect certain genetic abnormalities, the source material is totally different. NIPT uses cells from the mother’s placenta. Newborn screening uses the baby’s blood. NIPT screens primarily for trisomy while newborn screening tests for a wide range of heritable disorders.
How many disorders can newborn screening detect?
At least 50 disorders can be identified in newborn screening as of this writing. Some may only be available through supplemental newborn screening.
What is the difference between core and secondary conditions in the RUSP?
Core conditions are what the newborn screening is targeted to identify. These are conditions there is a specific and sensitive test for, and for which the health outcomes and treatments are understood and effective. Core conditions are also those that may affect the future reproduction decisions for a family [*].
Secondary conditions are those that may be identified unintentionally in the course of screening for a core condition or as a result of diagnostic testing after a false-positive result for a core condition.
How often is any disorder detected by newborn screening?
The ACOG says about 1 in every 300 babies — 13,000 babies each year — have a health condition identified by newborn screening, and these babies usually come from families that do not have a history of the disorder.
What is the most common disorder in newborn screening?
Hearing loss, hypothyroidism, cystic fibrosis, sickle cell disease and other hemoglobin disorders and MCAD deficiency are most commonly detected, according to the ACOG.
Will my baby be screened if I don’t have insurance?
Yes. Fees vary by state, but all babies receive screening. For eligible families, the State Children’s Health Insurance Program or Medicaid can pay the fees for newborn screening.
Can newborn screening detect autism?
Not exactly, but there is some promising research. Autism Spectrum Disorder (ASD) isn't usually diagnosed until children are 3-4 years old, and one of the tests checks their brain response to sound. A 2020 study of almost 140,000 newborns looked at ABR testing scores at birth and children later diagnosed with ASD to see if there was a correlation. They found that children diagnosed with ASD had slower brain response to sounds on the ABR test as newborns [*].
Cord Blood and Genetic Disorders
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Newborn screening can mean the difference between life and death for some infants, and its accuracy continues to improve with access to more sophisticated data programs.
Yes, it can deliver false positives — or false negatives — but it remains the first line of defense in the event your newborn does have a potentially debilitating disorder.