History and Overview of Newborn Screening

Newborn Screening


Newborn screening is recognized internationally as an essential, preventive public health program for early identification of disorders in newborns that can effect their long term health. Early detection, diagnosis, and treatment of certain genetic, metabolic, or infectious congenital disorders can lead to significant reductions of death, disease, and associated disabilities. 


Newborn screening programs in the US began with the work of Dr. Robert Guthrie, who in the 1960's developed a screening test for phenylketonuria. 

When Dr. Guthrie also introduced a system for collection and transportation of blood samples on filter paper, cost effective wide scale genetic screening became possible. 

The federal Maternal and Child Health Bureau (MCHB), a branch of the Health Resources and Services Administration (HRSA) has been involved in the evolution of newborn screening from the beginning, and it now funds many different activities dedicated to strengthening and expanding newborn screening programs. 

Current Status and Scope

States routinely test blood spots collected from newborns for up to thirty metabolic and genetic diseases of which the four most commonly included are phenylketonuria (PKU), congenital hypothyroidism (CH), galactosemia (GAL), and sickle cell disease (SS, SC etc.). Many states are also tasked with providing follow-up to infants identified through newborn screening programs, including ensuring appropriate diagnosis, treatment, and ongoing evaluation. In many cases, education (professional and consumer) is also a program responsibility along with counseling and provision of other ancillary services.

The panel of newborn disorders screened for varies from state to state, and decisions for adding or deleting tests involve many complex social, ethical,  and political issues. Usually, newborn population screening disorders are tied to issues such as disorder prevalence, detectability, treatment availability, outcome, and overall cost effectiveness. It is possible to screen for many disorders at birth and soon more will be possible. Currently, improvements in tandem mass spectrometry screening procedures allow detection of up to 30 additional metabolic disorders.

The role and scope of newborn screening is expanding. While traditional newborn screening was only concerned with a few inborn errors that led to mental retardation, programs now include disorders that can cause premature death, infectious diseases, hearing disorders and even heart problems.

Future Challenges

In the last decade many technological changes have occurred that have the potential for improving the sensitivity, specificity and scope of newborn screening services. DNA research and the human genome project have the potential for allowing genotyping, not only as a secondary confirmation of many newborn screening conditions as is now the case, but also as a routine primary screen. It may also soon be possible to detect many adult onset disorders at birth. 

As technology improves, the definition of screening shifts closer to diagnosis and in the wake of these advances, it is essential that public health policy makers take advantage of opportunities for newborn screening program improvement in a timely and effective way. To that end, a National Newborn Screening Task Force, organized by the American Academy of Pediatrics and funded by the Health Resources and Services Administration, was convened to review the issues and challenges faced by newborn screening programs, and to offer recommendations to strengthen and standardize these programs. The Task Force report may be viewed at: Newborn Screening Taskforce: Full Report

Routine Disorders Included in Newborn Screening

Listed in alphabetical order. Click on title for additional information

Biotinidase Deficiency

Biotinidase deficiencyis caused by the lack of an enzyme called biotinidase, resulting in an inability to liberate biotin from a bound form so that it can be used by the body. Without sufficient biotin, several other critical enzyme systems are unable to function properly. Biotinidase deficiency can lead to seizures, developmental delay, eczema, and hearing loss. Newborns with the disorder appear normal, but develop critical symptoms after the first weeks or months of life. Symptoms include hypotonia, ataxia, seizures, developmental delay, hair loss, seborrheic dermatitis, hearing loss and optic nerve atrophy. Metabolic acidosis can result in coma and death. Biotinidase deficiency is treated with daily biotin supplement, and with early diagnosis and treatment, all symptoms can be prevented.

Congenital Adrenal Hyperplasia (CAH)  

CAH is a group of disorders caused by the deficiency of an adrenal enzyme resulting in decreased cortisol (and sometimes aldosterone) production. Without sufficient cortical and aldosterone the affected newborn may appear normal, but can quickly develop symptoms including lethargy, vomiting, muscle weakness and dehydration. In severe cases death may occur within a few weeks if left untreated. Infants with milder forms of the disorder are at risk for reproductive and growth difficulties.  If detected early and maintained on appropriate doses of medication, infants diagnosed with CAH should have normal growth and development.

Congenital Hypothyroidism (CH) 

CH is the result of an inability to produce adequate amounts of thyroid hormone. Left untreated, this congenital deficiency of thyroid hormone can result in mental retardation and stunted growth. Newborns may appear normal  up to three months of age. If detected early (before three weeks) and maintained on appropriate levels of thyroid hormone medication, infants diagnosed with CH should have normal growth and development. 

Congenital Toxoplasmosis 

Congenital toxoplasmosis is caused by infection of the fetus with the protozoan parasite Toxoplasma gondii, typically by active infection of the mother during pregnancy. The mothers can become infected by eating raw or undercooked contaminated meat, or by accidentally ingesting cat oocysts in feces or in contaminated soil or unwashed vegetables. Signs of congenital infection may be present at birth or develop over the first few months of life. Newborns may show signs of central nervous system disorders, enlargement of the liver and spleen, blindness, and mental retardation. Early diagnosis and drug therapy will greatly reduce the risk of serious complications. 

Cystic Fibrosis (CF) 

CF results from an altered synthesis of a protein involved in the transport of chloride ions. The major clinical consequences are the production of abnormally thickened mucous secretions in the lungs and digestive systems of affected newborns. With early detection and lifelong comprehensive treatment plans, infants diagnosed with CF can be expected to live longer and in a better state of health than in the past.

Galactosemia (GAL)

GAL results from a deficiency in the enzyme needed to metabolize galactose in milk sugar. Newborns typically appear normal, however, within a few days to two weeks after initiating milk feedings, vomiting, diarrhea, lethargy, jaundice and liver damage develops. Untreated, the disorder may result in developmental retardation, hepatomegaly, growth failure, cataracts, and in severe cases death. With early detection and strict adherence to a galactose-free diet, infants diagnosed with GAL can be expected to achieve satisfactory general health. However, since some galactose can be produced in the body and cause negative effects, close developmental monitoring and assessment is recommended. 


This disorder is caused by an enzyme deficiency that blocks the metabolism of homocysteine to cystathionine. The major clinical features include optical dislocation (affecting 80% of homocystinurics by age 15), mental retardation, osteoporosis and thromboembolism (causing death in 50% of homocystinurics by age 20, and 75% by age 30). With early detection, strict dietary management, and vitamin supplements, growth and development should be normal.

Maple Syrup Urine Disease (MSUD)

MSUD is a disorder due to a deficiency of the branched-chain ketoacid decarboxylase enzyme affecting the metabolism of amino acids. Newborns typically appear normal, but by the first week of life can present with feeding difficulties, lethargy, and failure to thrive. Left untreated, the disorder can lead to progressive neurological problems, acidosis, seizures, and sudden apnea that can rapidly lead to coma and death. Treatment consists of strict dietary management and supplements along with close developmental monitoring and assessment. With early detection and treatment, infants diagnosed with MSUD can avoid many of the severe effects of the disease and lead normal lives. 

Medium-Chain Acyl-CoA Dehydrogenase Deficiency (MCAD)

MCAD is a rare hereditary disease that results from the lack of an enzyme required to convert fat to energy. Complications typically arise when the affected infants have long periods between meals, requiring the body to use it's own fat reserves to produce energy. When this action is blocked by the lack of the necessary enzyme, serious life threatening symptoms and even death can occur. MCAD causes no apparent symptoms at birth, but low blood sugar, seizures, brain damage, cardiac arrest and serious illness can occur very quickly in infants who are not feeding well. Treatment for the disorder requires close monitoring of the infant to determine "safe" time periods between meals, and adhering to a strict feeding schedule. With early detection and monitoring, and avoidance of fasts, children diagnosed with MCAD can lead normal lives particularly as the "safe" time between meals expands as they mature.

Phenylketonuria (PKU)

PKU is the result of an inability to break down the amino acid, phenylalanine, which is found in the protein of foods. Infants may appear normal in the first few months of life, but left untreated, PKU can cause mental and motor retardation, microcephaly, poor growth rate and seizures. With early detection and proper dietary treatment, growth and development should be normal. 

Sickle Cell Diseases (SCD) 

Sickle cell diseases are inherited abnormalities in the function of hemoglobin. "Sickling" is the term referring to changes in the red blood cell causing them  to become hard, sticky and crescent shaped. These changes prevent them from moving smoothly through the body. The most catastrophic abnormal hemoglobin conditions are sickle cell anemia and sickle beta thalassemia. Affected newborns will appear normal, but anemia develops in the first few months of life, followed by increased susceptibility to infection, slow growth rates and the possibility of life threatening splenic sequestration. With appropriate medical care including penicillin prophylaxis, appropriate vaccinations, and long term management, the complications of sickle cell disease can be minimized. 

Note: Infants identified with sickle cell "trait" typically will have few or no clinical symptoms. 

For information on additional newborn screening disorders available through supplemental screening, visit the University of Massachusetts New England Newborn Screening Program.