Newborn Screening

The newborn screen is sometimes referred to as the newborn blood-spot screen because it involves blotting a small amount of each newborn’s blood onto a piece of filter paper that is sent to a government lab. This public health initiative screens for treatable genetic conditions at day 1 or 2 after birth. The goal of newborn screening is to diagnose these conditions and initiate treatment before irreversible health effects occur.

The specific diseases included in the newborn screen vary by state and country, and some countries may not perform the screening at all. For information on conditions screened by state, see the Newborn Screening Clearinghouse. Conditions that are screened in the United States fall into the following categories:

Disorders Detected by the Newborn Screen in the United States

Category	Disorders
Metabolic	Urea cycle disorders Amino acid disorders Organic acid disorders Fatty acid oxidation disorders Galactosemia Biotinidase deficiency Storage disorders (recently added; screening exists for only a few)
Endocrine	Congenital hypothyroidism Congenital adrenal hyperplasia
Hematologic	Sickle cell disease Thalassemia
Pulmonary	Cystic fibrosis
Immunologic	Severe combined immunodeficiency (SCID)

It is important to be aware of certain disorders that are not presently screened for in newborns so that a normal newborn screening test result doesn’t dissuade you from considering such conditions in the differential diagnosis for a sick child.

Some diseases that are not currently included in the newborn screen:

glycogen storage disorders
metabolic disorders detectable in the cerebrospinal fluid (CSF) but not the blood
mitochondrial disorders
most lysosomal storage disorders

A positive newborn screen prompts a notification from the newborn screening lab to the pediatrician, who then refers the family to a specialist (e.g., metabolic geneticist, hematologist). Like all screening tests, sensitivity is valued more than specificity so as not to miss any affected infants. This, coupled with the low pretest probability of any one of these rare conditions, means that false-positive results occur. The specialist will order subsequent lab tests, as well as repeat newborn screening, to determine whether a child is in fact affected, and if so, to identify the specific disorder.

Newborn screening does occasionally fail to diagnose a child. Thus, if there is a clinical suspicion for a condition in a child who had normal newborn screening, consider that a false-negative screen might have occurred.

For information on newborn screening and immunodeficiency, see Immunodeficiency in the Pediatric Allergy/Immunology rotation guide.

For more information on newborn screening, see Prevention and Screening in Preventive/Well Child rotation guide.

Research

Landmark clinical trials and other important studies

Research

The role of exome sequencing in newborn screening for inborn errors of metabolism

Adhikari AN et al. Nat Med 2020.

Found whole exome sequencing alone to be insufficiency sensitive or specific for most newborn screen inborn errors of metabolism, but found that as a second tier test for infants with abnormal multiple spectroscopy results it could reduce false-positive results, decrease the time to diagnosis, and in some cases suggest a more appropriate or specific diagnosis than was initially obtained