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Every state and U.S. territory routinely screens newborns for certain genetic, metabolic, hormonal and functional disorders. Most of these birth defects have no immediate visible effects on a baby but, unless detected and treated early, can cause physical problems, mental retardation and, in some cases, death.
Except for hearing screening, all newborn screening tests are done using a few drops of blood from the newborn's heel. Fortunately, most babies are given a clean bill of health when tested. However, in 2004, about 4,000 babies were found to have metabolic disorders and more than 12,000 to have hearing impairment (1, 2). In cases like these, early diagnosis and proper treatment can make the difference between healthy development and lifelong impairment.
Which newborn screening tests are most likely to be given to a baby?
This depends on where the baby is born. Currently each state or region operates by law its own newborn screening program. State programs vary widely in the number and types of conditions for which they test. Some states test for as few as 10 disorders, while others test for 50 or more (3).
Parents can find out which tests are routinely done in their state by asking their health care provider or state health department. They also can visit the National Newborn Screening and Genetics Resource Center Web site. This site also lists commercial and nonprofit laboratories that provide comprehensive newborn screening for parents considering having their baby tested for more disorders than those screened for by their state.
All states and U.S. territories screen newborns for phenylketonuria (PKU), hypothyroidism, galactosemia and sickle cell disease (3). The test for PKU was the nation's first newborn screening test. Developed with the help of the March of Dimes, it has been routinely administered since the 1960s. PKU affects about 1 baby in 25,000 (4). Babies with the disorder cannot process a part of protein called phenylalanine, which is found in nearly all foods. Without treatment, phenylalanine builds up in the blood stream and causes brain damage and mental retardation.
When PKU is detected early, mental retardation can be prevented by feeding the baby a special formula that is low in phenylalanine. This low-phenylalanine diet needs to be followed throughout childhood, adolescence, and generally, for life.
Women of childbearing age with PKU need to remain on the low-phenylalanine special diet before and during pregnancy. This will often prevent mental retardation in their children by avoiding fetal exposure to high maternal phenylalanine levels (5).
Congenital hypothyroidism is one of the most common disorders identified by routine newborn screening. It affects at least 1 baby in 5,000 (4). Congenital hypothyroidism is a thyroid hormone deficiency that retards growth and brain development. If it is detected in time, a baby can be treated with oral doses of thyroid hormone to permit normal development.
Galactosemia, which affects about 1 baby in 50,000, can cause death in infancy, or blindness and mental retardation (4). A baby with galactosemia is unable to convert galactose (a sugar in milk) into glucose, a sugar the body uses as an energy source. The treatment for galactosemia is to eliminate milk and all other dairy products from the baby's diet; this dietary restriction is lifelong (5).
Sickle cell anemia is an inherited blood disease that affects:
- About 1 in 400 African-Amerian babies (5)
- About 1 in 1,114 Hispanic babies in the eastern United States (5)
- At least 1 in 5,000 of all babies in the United States (4)
The disorder can cause anemia, bouts of pain, damage to vital organs and, sometimes, death in childhood. Young children with sickle cell anemia are especially prone to dangerous bacterial infections such as pneumonia and meningitis. Vigilant medical care and early treatment with penicillin, beginning in infancy, can dramatically reduce these serious complications and the deaths that can result from them.
Almost all states screen for congenital adrenal hyperplasia (CAH), biotinidase deficiency (BIO) and hearing loss. CAH is a group of disorders in which there is a deficiency of certain hormones, sometimes affecting genital development. It occurs in about 1 in 25,000 babies (4). In severe cases, CAH also can cause life-threatening salt loss from the body. Lifelong treatment with the missing hormones suppresses this disease.
Biotinidase deficiency , which affects about 1 baby in 75,000, can cause seizures, mental retardation, movement problems, hearing loss and, sometimes, coma and death (4). These symptoms result from an inherited lack of an enzyme that recycles the vitamin biotin. When detected in time, problems can be prevented with vitamin supplementation.
Hearing impairment affects about 2 to 3 in 1,000 newborns (2). Without testing, most babies with hearing impairment are not diagnosed until 2 or 3 years of age (2). By this time, they often have delayed speech and language development. Detection of hearing impairment in the neonatal period allows the baby to be fitted with hearing aids before 6 months of age, helping prevent serious speech and language problems.
What other disorders can newborn screening detect?
Recent advances in technology, such as tandem mass spectrometry, now make it possible to screen for about 55 disorders. The March of Dimes would like to see all babies in all states screened for at least 29 specific disorders, for which effective treatment is available. This March of Dimes recommendation is based on endorsement of a report by the American College of Medical Genetics (commissioned by the Health Resources and Services Administration) urging screening for the 29 disorders (4). Almost 90 percent of newborns live in states that screen for 21 or more of these disorders. (In addition to these 29 disorders, the March of Dimes recommends that states report screening results of 25 “secondary target” conditions. Treatment for these additional disorders is generally not yet available.)
Treatment for the 29 disorders is likely to improve the health of children who are affected by them. The disorders are grouped into five categories:
Organic acid metabolism disorders: Each disease in this group of inherited disorders results from the loss of activity of an enzyme involved in the breakdown of amino acids, the building blocks of proteins, and other substances (lipids, sugars, steroids). When any of these chemicals is not properly broken down, toxic acids build up in the body. Without treatment, these disorders can result in coma and death during the first month of life. These disorders are:
- IVA (isovaleric acidemia)
- GA I (glutaric acidemia)
- HMG (3-OH 3-CH3 glutaric aciduria)
- MCD (multiple carboxylase deficiency)
- MUT (methylmalonic acidemia due to mutase deficiency)
- Cbl A,B (methylmalonic acidemia)
- 3MCC (3-methylcrotonyl-CoA carboxylase deficiency)
- PROP (propionic acidemia)
- BKT (beta-ketothiolase deficiency)
Fatty acid oxidation disorders: This group of disorders is characterized by inherited defects of enzymes needed to convert fat into energy. When the body runs out of glucose (sugar), it normally breaks down fat to support production of alternate fuels (ketones) in the liver. Because individuals with these disorders have a block in this pathway, their cells suffer an energy crisis when they run out of glucose. This most often occurs when an individual is ill or skips meals. Without treatment, the brain and many organs can be affected, sometimes progressing to coma and death. These disorders are:
- MCAD (medium-chain acyl-CoA dehydrogenase deficiency)
- VLCAD (very long-chain acyl-CoA dehydrogenase deficiency)
- LCHAD (long-chain L-3-OH acyl-CoA dehydrogenase deficiency)
- TFP (trifunctional protein deficiency)
- CUD (carnitine uptake defect)
Amino acid metabolism disorders: This is a diverse group of disorders with varying degrees of severity. Some individuals lack enzymes that are needed to break down the building blocks of protein called amino acids. Others have deficiencies in enzymes that help the body rid itself of the nitrogen incorporated in amino acid molecules. Toxic levels of amino acids or ammonia can build up in the body causing a variety of signs and symptoms, and even death. These disorders are:
- PKU (phenylketonuria)
- MSUD (maple syrup urine disease)
- HCY (homocystinuria due to CBS deficiency)
- CIT (citrullinemia)
- ASA (argininosuccinic acidemia)
- TYR I (tyrosinemia type I)
Hemoglobinopathies: These inherited diseases of red blood cells result in varying degrees of anemia (shortage of red blood cells) and other health problems. The severity of these disorders varies greatly from one person to the next. These disorders are:
- Hb SS (sickle cell anemia)
- Hb S/Th (hemoglobin S/beta-thalassemia)
- Hb S/C (hemoglobin S/C disease)
Others: This mixed group of disorders includes some diseases that are inherited and others that are not. The disorders vary greatly in severity, from mild to life threatening. These disorders are:
- CH (congenital hypothyroidism)
- BIOT (biotinidase deficiency)
- CAH (congenital adrenal hyperplasia due to 21-hydroxylase deficiency)
- GALT (classical galactosemia)
- HEAR (hearing loss)
- CF (cystic fibrosis)
How are screening tests done?
All of these disorders, except for hearing loss, are detected by a blood test. The baby's heel is pricked to obtain a few drops of blood for laboratory analysis. The same blood sample can be used to screen for 55 or more disorders. Usually, the baby's blood specimen is sent to a state public health laboratory for testing, and findings are sent to the health care professional responsible for the infant's care.
Babies are screened for hearing loss with one of two tests that measure how the baby responds to sounds. These tests are done in the newborn hospital nursery, using either a tiny soft earphone or microphone that is placed in the baby's ear. If either of these tests shows abnormal results, the baby needs more extensive hearing testing to see if he does have hearing loss.
How soon after birth should screening tests be done?
A blood specimen should be taken from every newborn before hospital release, usually at 24 to 48 hours of life. Some of the tests may not give accurate results if they are done too soon after birth. Because of early hospital discharge, some babies are tested within the first 24 hours of life. In order to avoid missing cases, some states now routinely screen twice: in the newborn nursery and again about two weeks later. Hearing tests are usually performed before the baby is discharged from the hospital. Babies born outside the hospital should have newborn screening tests done before the seventh day of life.
What does an abnormal test result mean?
Parents should not be overly alarmed by abnormal test results, as the initial screening tests give only preliminary information that must be immediately followed by more precise testing. Most babies with abnormal newborn screening test results prove normal in further testing (6, 7).
What should a parent do if his child is diagnosed with one of the conditions?
The child may need follow-up treatment at a pediatric center that specializes in children with metabolic or genetic conditions. It is essential for the child's healthy development that parents follow the health care provider's treatment recommendations. As the child grows, he or she may need careful, continued evaluations and monitoring.
If one child has a disorder, will other children in the same family have it?
For most of the disorders detected by newborn screening, when one child in a family is affected, the chance of the same birth defect occurring in a sibling is 1 in 4. The chances remain the same with each pregnancy. Parents who have a baby with one of these disorders can discuss their risk of having another affected child with their health care provider or a genetic counselor. These disorders are inherited when both parents have the same abnormal gene and pass it on to their baby. A parent who has the abnormal gene, but not the disease, is called a carrier. The health of a carrier is rarely affected.
Congenital hypothyroidism usually is not inherited from parents (5). The siblings of those who have this disorder are seldom affected.
Hearing loss can be passed on through parents' genes. However, other causes of hearing loss, such as infections that are passed on to the baby during pregnancy or birth, are unlikely to recur in another pregnancy.
Does the March of Dimes fund research and other programs on newborn screening?
The March of Dimes has long supported research, professional and consumer education, and advocacy related to newborn screening. In the 1960s, a March of Dimes grantee developed the first PKU screening test. Other grantees developed screening tests for biotinidase deficiency and congenital adrenal hyperplasia and contributed to the development of testing for hypothyroidism. The March of Dimes also funds research aimed at improving the treatment of children with a number of the screened disorders.
For many years, the March of Dimes has worked to expand and improve newborn screening programs through its advocacy efforts. For example, the March of Dimes was instrumental in the passage of of the 2008 Newborn Screening Saves Lives Act. The law lays the groundwork to establish national guidelines that will specify the conditions for which testing should be done and authorizes funding for states to strengthen their existing programs.
References
- Overview of the NBS Programs: States of the States. Briefing Presented at the First Meeting of the Advisory Committee on Heritable Disorders and Genetic Diseases in Newborns and Children, June 7-8, 2004, Washington, D.C.
- Centers for Disease Control and Prevention (CDC). Early Hearing Detection and Intervention Program. July 3, 2008.
- National Newborn Screening and Genetics Resource Center. U.S. National Screening Status Report. Updated 3/4/08.
- American College of Medical Genetics. Newborn Screening: Toward a Uniform Screening Panel and System. Final Report, March 8, 2005.
- American Academy of Pediatrics Committee on Genetics, Newborn Screening Fact Sheets. Pediatrics, volume 118, number 3, September 2006.
- American Academy of Pediatrics Newborn Screening Authoring Committee. Newborn Screening Expands: Reommendations from Pediatricians and Medical Homes, Implications for the System. Pediatrics, volume 121, number 1, January 2008, pages 192-217.
- McCabe, L.L. and McCabe, E.R.B. Expanded Newborn Screening: Implications for Genomic Medicine. Annual Review of Medicine, 2008, volume 59, pages 163-175.
August 2008
