Newborn screening
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Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. Robert Guthrie is given much of the credit for pioneering the earliest screening for phenylketonuria in the late 1960s using blood samples on filter paper obtained by pricking a newborn baby's heel on the second day of life to get a few drops of blood. There were few federally sponsored government health programs in the 1960s and each state, and each Canadian province devised their own programs. Congenital hypothyroidism was the second disease widely added in the 1970s. The development of tandem mass spectrometry screening by Edwin Naylor and others in the early 1990s led to a large expansion of potentially detectable congenital metabolic diseases that affect blood levels of organic acids. Additional tests have been added to many screening programs over the last two decades but screening programs vary from state to state and have become a subject of political controversy.
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Disease qualification
Diseases are considered worth screening for if they meet the following criteria:
- A simple and reasonably reliable test
- A high enough frequency in the population to make it worthwhile
- A treatment or intervention that makes a difference if the disease is detected early
Newborn screening in the United States
The following tests are mandated (required to be performed on every newborn born in the state) in most of the United States and Canada. According to the U.S. Centers for Disease Control, approximately 3,000 babies with severe disorders are identified in the United States each year using newborn screening programs at current testing rates. States vary, and not all tests are required in every state, and a few states mandate more than this.
- Endocrine disorders: Congenital adrenal hyperplasia (CAH), Congenital hypothyroidism
- Blood cell disorders: Sickle cell anaemia (SS)
- Inborn errors of carbohydrate metabolism: Galactosemia
- Inborn errors of amino acid metabolism: Phenylketonuria (PKU), Maple syrup urine disease (MSUD), Homocystinuria
- Inborn errors of organic acid metabolism: Biotinidase deficiency
Usual procedures and responses to positive results
In nearly all of the United States, the newborn screening program is a division of the state health department. State law mandates collecting a sample by pricking the heel of a newborn baby to get enough blood (typically, two to three drops) to fill a couple of circles on filter paper labeled with names of infant, parent, hospital, and primary physician. It is usually specified that the sample be obtained on the second or third day of life, after protein-containing feedings (i.e., breast milk or formula) have started and the postnatal TSH surge subsided. Every hospital in the state as well as independent midwives supervising home deliveries is required to collect the papers and mail each batch each day to the central laboratory.
The state health department agency in charge of screening will either run a laboratory or contract with a laboratory to run the mandated screening tests on the filter paper samples. The goal is to report the test within a short period of time. If screens are normal, a paper report is sent to the submitting hospital and parents rarely hear about it.
If an abnormality occurs, employees of the agency, usually nurses, begin to try to reach the physician, hospital, and/or nursery by telephone. They are persistent until they can arrange an evaluation of the infant by an appropriate specialist physician (depending on the disease). The specialist will attempt to confirm the diagnosis by repeating the tests by a different method or laboratory, or by performing other corroboratory tests. Depending on the likelihood of the diagnosis and the risk of delay, the specialist will initiate treatment and provide information to the family. Performance of the program is reviewed regularly and strenuous efforts are made to maintain a system that catches every infant with these diagnoses.
Expanded screening and expanded controversies
With the development of tandem mass spectrometry in the early 1990s, the number of detectable diseases quickly grew, especially in the categories of fatty acid oxidation disorders and organic acidoses. Screening tests for the disorders listed below (and an increasing number of others) are now available, though not universally mandated. Laws have not kept up with this expansion, and there is considerable variability from state to state, and sometimes from hospital to hospital within a state. To make matters more confusing, some hospitals routinely obtain supplemental expanded screening (most of the tests below) on all infants even if not mandated by the state or requested by parents. In the last few years, expanded newborn screening with tandem mass spectrometry has become a profitable commercial venture (e.g., Pediatrix Screening, Inc (http://www.pediatrixscreening.com/index.cfm)), and offers parents a full screening test at a cost about four times the original charge to hospitals.
Newborn screening tests have become a subject of political controversy in the last decade. It is difficult to resist the appeal of screening when a single child injured by a treatable disease can be shown to the news media and legislature. A prime recent example is the so-called "tale of the two Zacharys." Two California babies, Zachary Wyvill and Zachary Black, were both born with Glutaric acidemia type I. Wyvill's birth hospital only tested for the four diseases mandated by state law, while Black was born at a hospital that was participating in an expanded testing pilot program. Black's disease was treated with diet and vitamins; Wyvill's disease went undetected for over a year, and during that time the damage from the enzyme deficiency became irreversible. Birth-defects lobbyists pushing for broader and more universal standards for newborn testing are using the tale of the two Zacharys as powerful persuasion.
Why would anyone be reluctant to support the new, expanded screening programs? As the number of diseases and their rareness has increased, the cost to screen each infant and the cost to detect each case has risen dramatically. If one assumes that state budgets for child health are constrained and finite, dollars spent detecting the 1-in-a-million diseases exceed the costs saved by treating it and reduce resources available to other potentially lifesaving programs such as care for the uninsured or liability insurance for infant immunizations. The issue may be determined by juries deciding whether hospitals must routinely offer expanded newborn screening or risk multimillion dollar malpractice verdicts. Can another US$50-100 for each newborn infant be added to the cost of care or obtained from the state legislatures?
Conditions and disorders
The following list includes most of the disorders detected by the expanded or supplemental newborn screening by mass spectrometry. This expanded screening is not yet universally mandated by most states, but may be privated purchased by parents or hospitals at a cost of approximately US$80. Perhaps one in 5,000 infants will be positive for one of the metabolic tests below (excluding the congenital infections).
Blood cell disorders
Inborn errors of amino acid metabolism
Inborn errors of organic acid metabolism
- Glutaric acidemia type I
- Glutaric acidemia type II
- HHH syndrome (Hyperammonemia, hyperornithinemia, homocitrullinuria syndrome)
- Hydroxymethylglutaryl lyase deficiency (HMG lyase)
- Isovaleric acidemia
- Isobutyryl-CoA dehydrogenase deficiency
- 2-Methylbutyryl-CoA dehydrogenase deficiency
- 3-Methylcrotonyl-CoA carboxylase deficiency (3MCC deficiency)
- Beta-methyl crotonyl carboxylase deficiency
- 3-Methylglutaconyl-CoA hydratase deficiency
- Methylmalonyl-CoA mutase deficiency
- Methylmalonic aciduria (MMA)
- Beta-ketothiolase deficiency
- Propionic acidemia
- Adenosylcobalamin synthesis defects
- Multiple-CoA carboxylase deficiency
Inborn errors of fatty acid metabolism
- Carnitine palmityl transferase deficiency type 2 (CPT)
- Long-chain acyl-CoA dehydrogenase deficiency (LCAD)
- Long-chain hydroxyacyl-CoA dehydrogenase deficiency (LCHAD)
- Short-chain acyl-CoA dehydrogenase deficiency (SCAD)
- Short-chain hydroxy Acyl-CoA dehydrogenase deficiency (SCHAD)
- Medium-chain acyl-CoA dehydrogenase deficiency (MCAD)
- Very-long-chain acyl-CoA dehydrogenase deficiency (VLCAD)
- Carnitine/acylcarnitine Translocase Deficiency (Translocase)
- Multiple acyl-CoA dehydrogenase deficiency (MADD)
- Trifunctional protein deficiency (TFP Deficiency)
Congenital infections
Miscellaneous multisystem diseases
Newborn screening by other methods than blood testing
Newborn screening programs worldwide
Newborn screening has also been adopted by most countries in Europe and around the world, though the lists of screened diseases vary widely.
See also
External links
- U.S. National Newborn Screening and Genetics Resource Center (http://genes-r-us.uthscsa.edu/)
- About Newborn Screening (http://www.aboutnewbornscreening.com/)
- Pediatrix Screening, Inc. (http://www.pediatrixscreening.com/index.cfm) (Commercial company that pioneered some of the screening procedures and offers testing directly to parents. Excellent set of links to other sites about metabolic diseases and screening.)
- Waldholz, Michael, "A Drop of Blood Saves One Baby; Another Falls Ill," Wall Street Journal, 17 June 2001, p. A1 (52k PDF) (http://www.huntershope.org/pdf/wsj_nbs_article.pdf)