Newborn screening 768605 223062748 2008-07-02T11:54:06Z DOI bot 6652755 Citation maintenance. Formatted: pages, doi. You can [[WP:DOI|use this bot]] yourself! Please [[User:DOI_bot/bugs|report any bugs]]. '''Newborn screening''' is the process of testing newborn babies for treatable [[genetic disorder|genetic]], [[endocrinology|endocrinologic]], [[inborn error of metabolism|metabolic]] and [[hematology|hematologic]] diseases.<ref name="pmid17679658">{{cite journal | author = Tarini BA | title = The current revolution in newborn screening: new technology, old controversies | journal = Archives of pediatrics & adolescent medicine | volume = 161 | issue = 8 | pages = 767–72 | year = 2007 | pmid = 17679658 | doi = 10.1001/archpedi.161.8.767 }}</ref><ref name="pmid17402600">{{cite journal | author = Kayton A | title = Newborn screening: a literature review | journal = Neonatal network : NN | volume = 26 | issue = 2 | pages = 85–95 | year = 2007 | pmid = 17402600 | doi = }}</ref> [[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. <ref name="pmid11728413">{{cite journal | author = Clague A, Thomas A | title = Neonatal biochemical screening for disease | journal = Clin. Chim. Acta | volume = 315 | issue = 1-2 | pages = 99–110 | year = 2002 | pmid = 11728413 | doi = 10.1016/S0009-8981(01)00716-1 }}</ref> [[Congenital hypothyroidism]] was the second disease widely added in the 1970s.<ref name="pmid4137217">{{cite journal | author = Klein AH, Agustin AV, Foley TP | title = Successful laboratory screening for congenital hypothyroidism | journal = Lancet | volume = 2 | issue = 7872 | pages = 77–9 | year = 1974 | pmid = 4137217 | doi = }}</ref> 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 disease]]s that affect blood levels of organic acids.<ref name="pmid14578311">{{cite journal | author = Chace DH, Kalas TA, Naylor EW | title = Use of tandem mass spectrometry for multianalyte screening of dried blood specimens from newborns | journal = Clin. Chem. | volume = 49 | issue = 11 | pages = 1797–817 | year = 2003 | pmid = 14578311 | doi = 10.1373/clinchem.2003.022178}}</ref> Additional tests have been added to many screening programs over the last two decades. Newborn screening has been adopted by most countries around the world, though the lists of screened diseases vary widely. ==Disease qualification== Common considerations in determining whether to screen for disorders: # A disease that can be missed clinically at birth # A high enough frequency in the population # A delay in diagnosis will induce irreversible damages to the baby # A simple and reasonably reliable test exists # A treatment or intervention that makes a difference if the disease is detected early ==Newborn screening in the United States and Canada== 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. The first test to be universally mandated across the U.S. was the [[Guthrie test]] for phenylketonuria (PKU), and in many areas and hospitals, the newborn blood test is often erroneously referred to as a "PKU test", even though all states now universally test for congenital [[hypothyroidism]], [[galactosemia]], and increasing numbers of other diseases as well. *Endocrine disorders: [[Congenital adrenal hyperplasia]] (CAH), [[Congenital hypothyroidism]] *Blood cell disorders: [[sickle-cell disease]] (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]] For a recent state-by-state list, see [http://genes-r-us.uthscsa.edu/ U.S. National Newborn Screening and Genetics Resource Center]. According to this resource, the only tests mandated in every state are the following: * CH - Congenital hypothyroidism * H-HPE - Benign hyperphenylalaninemia * PKU -- Phenylketonuria/hyperphenylalaninemia * HEAR - Hearing * GALT - Transferase deficient galactosemia ===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 few circles on [[filter paper]] labeled with names of infant, parent, [[hospital]], and [[primary care physician|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 [[infant formula|formula]]) have started, and the postnatal [[Thyroid-stimulating hormone|TSH]] surge subsided. Every hospital in the state as well as independent [[midwife|midwives]] supervising [[home delivery|home deliveries]] are 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 results 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. Guidelines for newborn screening and follow up have been published by the [[American Academy of Pediatrics]].<ref>Newborn Screening Expands: Recommendations for Pediatricians and Medical Homes-Implications for the System. Pediatrics121:1 192-217 January 2008[http://www.pediatrics.org/cgi/doi/10.1542/peds.2007-3021]</ref> ===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 disorder]]s and [[organic aciduria|organic acidoses]]. Screening tests for the disorders listed below (and an increasing number of others) are now available, though not universally mandated. There is considerable variability from state to state, and sometimes from hospital to hospital within a state, on disease that are screened. To make matters more confusing, some hospitals routinely obtain supplemental screening (most of the tests below) on all infants even if not mandated by the state or requested by parents. In recent years in the United States, expanded newborn screening with tandem mass spectrometry has become a profitable commercial venture. 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 six months, 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? Instituting MS/MS screening often requires a sizable up front expenditure. When States choose to run their own programs the initial costs for equipment, training and new staff can be significant. To avoid at least a portion of the up front costs, some states such as [http://www.savebabies.org/states/mississippi.php Mississippi] have chosen to contract with private labs for expanded screening. Others have chosen to form [http://www.umassmed.edu/nbs/ Regional Partnerships] sharing both costs and resources. But for many states, screening is an integrated part of the department of health which can not or will not be easily replaced. Thus the initial expenditures can be difficult for states with tight budgets to justify. Screening fees have also increased in recent years as healthcare costs rise and more states add MS/MS screening to their programs. [http://www2.uthscsa.edu/nnsis (See Report of Summation of Fees Charged for Newborn Screening, 2001 - 2005)] Dollars spent for these programs may reduce resources available to other potentially lifesaving programs. It has been recommended that one disorder, Short Chain Acyl-coenzyme A Dehydrogenase Deficiency, or SCAD, be eliminated from screening programs, due to a "spurious association between SCAD and symptoms. <ref>Newborn Screening for Metabolic Disorders. [[Journal of the American Medical Association]] 2006 PMID 16926360</ref> However, recent studies suggest that expanded screening is cost effective (see [ftp://ftp.hrsa.gov/mchb/genetics/screeningdraftforcomment.pdf ACMG report page 94-95] and articles published in ''Pediatrics'' <ref>Expanded Newborn Screening for Inborn Errors of Metabolism by Electrospray Ionization-Tandem Mass Spectrometry: Results, Outcome and Implication PMID 12777559 [http://pediatrics.aappublications.org/cgi/reprint/111/6/1399]<</ref>'<ref>Cost-Benefit Analysis of Universal Tandem Mass Spectrometry for Newborn Screening. Pediateics 2002 PMID 12359795 [http://pediatrics.aappublications.org/cgi/reprint/110/4/781]</ref>. Advocates are quick to point out studies such as these when trying to convince state legislatures to mandate expanded screening. Expanded newborn screening is also opposed by among some health care providers who are concerned that effective follow-up and treatment may not be available, [[false positive]] screening tests may cause harm, and issues of [[informed consent]]. (see [http://www.newbornscreening.info/felsi.html Financial, Ethical, Legal, and Social Issues]) The issue may ultimately be determined by juries, deciding whether hospitals must routinely offer expanded newborn screening or risk the threat of multimillion dollar malpractice suits. ==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). The 29 marked with a "@" were recommended as "core panel" by the 2005 report of the American College of Medical Genetics (ACMG). The incidences reported below are from [ftp://ftp.hrsa.gov/mchb/genetics/screeningdraftforcomment.pdf their report], pages 143-307, though the rates may vary in different populations. (WARNING: The file is a very large PDF.) ===[[Blood cell]] disorders=== * [[Glucose-6-phosphate dehydrogenase deficiency]] (G6PD) * [[Sickle cell anemia]] (Hb SS) > 1 in 5,000; among [[African-Americans]] 1 in 400 * [[Sickle-cell disease]] (Hb S/C) > 1 in 25,000 * Hb S/Beta-[[Thalassemia]] (Hb S/Th) > 1 in 50,000 ===Inborn errors of [[amino acid]] metabolism=== * [[Tyrosinemia I]] (TYR I) < 1 in 100,000 * [[Tyrosinemia II]] * [[Argininemia]] * [[Argininosuccinic aciduria]] (ASA) < 1 in 100,000 * [[Citrullinemia]] (CIT) < 1 in 100,000 * [[Phenylketonuria]] (PKU) > 1 in 25,000 * [[Maple syrup urine disease]] (MSUD) < 1 in 100,000 * [[Homocystinuria]] (HCY) < 1 in 100,000 ===Inborn errors of [[organic acid]] metabolism=== * [[Glutaric acidemia type I]] (GA I) > 1 in 75,000 * [[Glutaric acidemia type II]] * [[HHH syndrome]] (Hyperammonemia, hyperornithinemia, homocitrullinuria syndrome) * [[Hydroxymethylglutaryl lyase deficiency]] (HMG) < 1 in 100,000 * [[Isovaleric acidemia]] (IVA) < 1 in 100,000 * [[Isobutyryl-CoA dehydrogenase deficiency]] * [[2-Methylbutyryl-CoA dehydrogenase deficiency]] * [[3-Methylcrotonyl-CoA carboxylase deficiency]] (3MCC) > 1 in 75,000 * [[Beta-methyl crotonyl carboxylase deficiency]] * [[3-Methylglutaconyl-CoA hydratase deficiency]] * [[Methylmalonyl-CoA mutase deficiency]] (MUT) > 1 in 75,000 * [[Methylmalonic aciduria]], cblA and cblB forms (MMA, Cbl A,B) < 1 in 100,000 * [[Beta-ketothiolase deficiency]] (BKT) < 1 in 100,000 * [[Propionic acidemia]] (PROP) > 1 in 75,000 * [[Adenosylcobalamin synthesis defects]] * [[Multiple-CoA carboxylase deficiency]] (MCD) < 1 in 100,000 ===[[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) > 1 in 75,000 * [[Short-chain acyl-CoA dehydrogenase deficiency]] (SCAD) * [[Short-chain hydroxy Acyl-CoA dehydrogenase deficiency]] (SCHAD) * [[Medium-chain acyl-CoA dehydrogenase deficiency]] (MCAD) > 1 in 25,000 * [[Very-long-chain acyl-CoA dehydrogenase deficiency]] (VLCAD) > 1 in 75,000 * [[Carnitine/acylcarnitine Translocase Deficiency]] (Translocase) * [[Multiple acyl-CoA dehydrogenase deficiency]] (MADD) * [[Trifunctional protein deficiency]] (TFP) < 1 in 100,000 * [[Carnitine uptake defect]] (CUD) < 1 in 100,000 ===[[Congenital]] infections=== * [[Congenital toxoplasmosis]] * [[HIV]] ===Miscellaneous multisystem diseases=== * [[Cystic fibrosis]] (CF) > 1 in 5,000 * [[Maternal vitamin B12 deficiency]] * [[Congenital hypothyroidism]] (CH) > 1 in 5,000 * [[Biotinidase deficiency]] (BIOT) > 1 in 75,000 * [[Congenital adrenal hyperplasia]] (CAH) > 1 in 25,000 * [[Classical galactosemia]] (GALT) > 1 in 50,000 ===Newborn screening by other methods than blood testing=== * [[deafness|Congenital deafness]] (HEAR) > 1 in 5,000 ==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== * [[Inborn error of metabolism]] * [[Genetic disorder]] ==References== {{reflist}} ==External links== * [http://genes-r-us.uthscsa.edu/ U.S. National Newborn Screening and Genetics Resource Center] * [http://www.aboutnewbornscreening.com/ About Newborn Screening] * [http://www.perkinelmergenetics.com/ PerkinElmer® Genetics, Inc.] (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.) * [http://www.huntershope.org/pdf/wsj_nbs_article.pdf Waldholz, Michael, "A Drop of Blood Saves One Baby; Another Falls Ill," ''Wall Street Journal'', 17 June 2001, p. A1 (52k PDF)] * [http://www.oaanews.org/pdf/Zachary-handout-Advocacy.pdf March of Dimes, The Difference is Black and Wyvill, 2004] * [http://www.savebabies.org Save Babies Through Screening Foundation] * [http://www.oaanews.org Organic Acidemia Association] * [http://www.dhss.delaware.gov/dhss/dph/chca/dphnsp1.html $Millions saved nationally by newborn screening per Delaware DPH] * [http://www.childrenshospital.org/newenglandconsortium/ The New England Consortium of Metabolic Programs] [[Category:Pediatrics]] [[Category:Inborn errors of metabolism|*]] [[Category:Epidemiology]] [[Category:Rare diseases]] [[nl:Hielprik]] [[de:Neugeborenenscreening]]