A Primer on Newborn Screening

Kristin Gatrell Bryant, RN, BSN, MSN; Kimberly M. Horns, RNC, NNP, PhD; Nicola Longo, MD, PhD; Julieanne Schiefelbein, MappSc, RNC, MA (Ed), RM, PNP, NNP


Adv Neonatal Care. 2004;4(5) 

In This Article

Profile of Commonly Screened Disorders

Every state screens for at least 3 disorders:

  • Hyperphenylalaninemia

  • Congenital hypothyroidism

  • Galactosemia

Others may screen for up to 40 different disorders.[14,16,27] It is important for health care providers to understand the guidelines and tests done in their state.

The 4 most commonly screened metabolic disorders in the nation and their incidence rates are listed in Table 3 .[16,28] Hyperphenylalaninemia is an autosomal recessive disorder caused by the lack of the enzyme phenylalanine hydroxylase, needed to break down the amino acid phenylalanine.[16,19] Accumulation of phenylalanine in the brain impairs development of the central nervous system. If left untreated, it results in seizures and severe mental retardation.[19] With early recognition and treatment, individuals with hyperphenylalaninemia increasingly reach adulthood and reproduce.

Women are encouraged to maintain stricter diet control prior to becoming pregnant. If their diet is not strictly controlled during pregnancy, maternal hyperphenylalaninemia can cause microcephaly, retardation, and congenital heart disease in their offspring.[19] Treatment consists of a lifelong low-phenylalanine diet and regular monitoring of serum phenylalanine levels.[16,19] The National Institutes of Health Consensus Developmental Panel suggests monitoring serum phenylalanine once a week for the first year of life, twice a month until age 12, and then monthly thereafter.[29]

Congenital hypothyroidism, the most common preventable cause of mental retardation, was added to some state newborn screening programs in the 1970s.[9,11,17] Present at or before birth, it is the result of the body's inability to produce adequate amounts of thyroid hormone, which is manifested by an elevated thyroid stimulating hormone (TSH or thyrotropin) and/or low thyroxine (T4).[16]

Understanding the normal physiological transitions of infants is integral for health care providers, as changes in TSH occur shortly after birth.[19] False-positive results may be due to early screening or prematurity.[19] Classic clinical signs of hypothyroidism, which may not manifest for several weeks, include lethargy, hypothermia, poor feeding, small stature, poor growth, prolonged jaundice, constipation, hypotonia, and a hoarse cry.[19] Early screening and regular monitoring are necessary to prevent irreversible brain damage and mental retardation. Alterations in the development of the heart, lung, and other tissues may also occur if untreated.[30] Consultation with a pediatric endocrinologist is recommended.

Early treatment with thyroid hormone is critical in reducing the incidence of developmental disabilities. Delays in treatment may negatively impact intelligence quotient (IQ).[9] Prior to widespread newborn screening, 75% of infants diagnosed with congenital hypothyroidism who were not treated until 6 to 9 months of age had an IQ of <80.[9] Even with early diagnosis and adequate treatment, there is still a trend toward slightly lower IQ scores, as illustrated in a case of identical twins (one with congenital hypothyroidism and the other euthyroid).[9] The affected twin had a lower IQ score despite optimal treatment.[9]

Galactosemia is an inherited disorder characterized by a deficiency in 1 of 3 enzymes: galactose-1-phosphate uridyl transferase (GALT), galactokinase, or uridine diphosphate-galactose-4-epimerase, which are required to break down galactose into glucose.[5,16,19] Symptoms of this disorder usually appear within 2 weeks of life and may include vomiting, diarrhea, seizures, hepatomegaly, jaundice, and Escherischia coli sepsis.[19]

Historically, false-positive results were higher in humid climates during hot summer months, and false-negative results occurred in infants fed soy formulas.[19] These problems are now circumvented by measuring enzyme activity directly in red blood cells. Treatment consists of a galactose-free diet. Failure to treat this disorder may result in failure to thrive, mental retardation, liver disease, cataracts, and even death from sepsis or bleeding.[2,16,19]

Congenital adrenal hyperplasia (CAH) was added to newborn screening programs in 1997.[17] This disorder of steroid biosynthesis is characterized by deficiency of enzymes in the adrenal gland that are necessary to synthesize cortisol and aldosterone.[2,16] There are 5 different types of CAH due to specific enzyme deficiencies necessary to convert cholesterol into cortisol. The most common form of CAH, 21-hydroxylase deficiency, accounts for 90 to 95% of cases.[2,5,19] The increased synthesis of androgens may be manifested by ambiguous genitalia.[19]

If CAH is undiagnosed and untreated, death may occur from salt wasting. The infant may present as early as 5 days of life, before newborn screening results are available. Although symptoms may occur any time in the first few months of life, most infants present by 10 days of life with a life-threatening adrenal crisis.[5] Other clinical manifestations may include hypoglycemia, vomiting, weakness, cardiac arrhythmias, and failure to thrive.[2] Consultation with a pediatric endocrinologist is essential.[2] Treatment usually consists of replacing cortisol and, in most cases, mineralocorticoids to suppress excessive production of corticotropin.[2]


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