Newborn screen is a public health program for screening infants soon after birth for a list of treatable conditions, but not clinically proven in the newborn period. Some conditions included in the new screening program can only be detected after permanent damage has been done; in some cases sudden death is the first manifestation of an illness. The screening program is often run by a state or national government agency with the aim of screening all babies born in the jurisdiction. The number of screened diseases is determined by each jurisdiction, and can vary greatly. The most recent screening test is performed by measuring the metabolites and enzyme activity across the blood samples collected on special filter paper. Many areas begin to screen babies for hearing loss using automatic auditory brainstem responses and congenital heart defects using pulse oximeter. Infants who perform positive tests undergo further testing to determine whether they are actually affected by the disease or if the test results are false positives. Follow-up testing is usually coordinated between geneticist and pediatrician or primary care physician.
Newborn screening was first introduced as a public health program in the United States in the early 1960s, and has been extended to countries around the world, with different test menus in each country. Both prenatal examination (prenatal screening) and newborn screening (screening immediately after birth) have improved health care. The first disorder detected by the newborn screening program is phenylketonuria, a metabolic condition in which the inability to lower essential phenylalanine of amino acids can lead to mental retardation that can not be repaired unless detected early. With early detection and food management, the negative effects of this disease can be eliminated largely. Robert Guthrie developed a simple method of using a bacterial inhibition test that can detect the levels of phenylalanine in the blood shortly after the baby is born. Guthrie also pioneered the collection of blood on easily filterable paper filters, recognizing the need for a simple system if screening would be done on a large scale. New screening around the world is still done using similar filter papers.
Video Newborn screening
Targeted interruption
Newborn screening is intended as a public health program to identify infants with treatable conditions before they come clinically, or suffer permanent damage. Phenylketonuria (PKU) is the first disorder targeted for newborn screening, conducted in a small number of hospitals and is rapidly expanding across the United States and around the world. After the success of newborn screening for PKU (39 infants identified and treated in the first two years of screening, with no false-negative results), Guthrie and others looked for other, identifiable and treatable disorders in infants, eventually developing inhibition of test bacteria to identify galactosemia classic and maple syrup urine disease.
Newborn screening has evolved since the introduction of PKU testing in the 1960s, but can vary greatly between countries. In 2011, the United States filtered 54 conditions, Germany for 12, Britain for 2 (PKU and medium chain dehydrogenase acyl-CoA deficiency (MCADD)), while France and Hong Kong filtered only for one condition (PKU and congenital hypothyroidism, respectively). Conditions included in newborn screening programs worldwide vary widely, based on legal requirements for screening programs, the prevalence of certain diseases in a population, political pressure, and resource availability for testing and follow-up of identified patients.
Amino acid disorders
Newborn screening originates with amino acid disorder, phenylketonuria (PKU), which can be easily treated with dietary modification, but causes severe mental retardation if not identified and treated early. Robert Guthrie introduced a newborn screening test for PKU in the early 1960s. With the knowledge that PKU can be detected before symptoms are proven, and treatment begins, screening is rapidly adopted worldwide. Austria began screening for PKU in 1966 and Britain in 1968.
Fatty acid oxidation disorder
With the advent of tandem mass spectrometry as a screening tool, some fatty acid oxidation disorders are targeted for inclusion in a newborn screening program. Acid-CoA dehydrogenase intermediate chain deficiency (MCADD), which has been implicated in some cases of sudden infant death syndrome is one of the first conditions targeted for inclusion. MCADD was the first condition that was added when the UK expanded their screening program from PKU alone. Population-based studies in Germany, the United States and Australia place the combined incidence of fatty acid oxidation disorders at 1: 9300 among Caucasians. The United States filters out all known fatty acid oxidation disorders, either as primary or secondary targets, while other countries filter some of this.
The introduction of screening for fatty acid oxidation disorders has been shown to reduce the morbidity and mortality associated with the condition, particularly MCADD. A study in Australia found a 74% reduction in severe metabolic or fatigue decompensation episodes among individuals identified with newborn screening had MCADD compared to those presented clinically prior to screening. Studies in the Netherlands and the United Kingdom found improved outcomes at lower costs when the baby was identified before being presented clinically.
The recent screening program has also expanded the available information base on some rare conditions. Before being included in the new screening, short-acting short-chain dehydrogenase acids (SCADD) are considered life-threatening. Most of the patients identified through newborn screening due to lack of this enzyme showed no symptoms, as far as SCDD was omitted from screening panels in a number of areas. Without a patient cohort identified by newborn screening, this clinical phenotype is unlikely to be identified.
Endocrinopathy
The most common disorders of the endocrine system are congenital hypothyroidism (CH) and congenital adrenal hyperplasia (CAH). Tests for both disorders can be performed using blood samples collected on a newborn standard screening card. Screening for CH is performed by measuring thyroxine (T4), thyrotropin (TSH) or a combination of both analytes. Increased 17? -hydroxyprogesterone (17? -OHP) is the main marker used when screening for CAH, most often performed using enzyme-linked immunosorbant assays, with many programs using a second tandem spectrometry test to reduce the number of false-positive results. Careful analysis of screening results for CAH can also identify cases of congenital adrenal hypoplasia, which appear with very low 17-OHP levels.
CH was added to many newborn screening programs in the 1970s, often as a second condition including after PKU. The most common cause of CH is thyroid gland dysgenesis After years of newborn screening, worldwide CH events have been estimated at 1: 3600 births, with no obvious improvement in certain ethnic groups. Recent data from certain areas showed an increase, with New York reporting incidents 1: 1700. The reasons for the increase in apparent incidence were investigated, but no explanation was found.
Classic CAH, a disorder targeted by the newborn screening program, is caused by a deficiency of the 21-hydroxylase steroid enzyme, and comes in two forms - simple virilization and salt-containing forms. CAH incidents can vary widely between populations. The highest reported incident rate was between Yupic Eskimo Alaska (1: 280) and on the French RÃÆ'Â Â © Ã… union island (1: 2100).
Hemoglobinopathies
Any condition that produces abnormal hemoglobin production is included in the broad category of hemoglobinopathies. Worldwide, it is estimated that 7% of the population can carry hemoglobinopathy with clinical significance. The most famous condition in this group is sickle cell disease. Recent baby screening for a large number of hemoglobinopathies is done by detecting abnormal patterns using isoelectric focusing, which can detect various types of abnormal hemoglobin. In the United States, newborn screening for sickle cell disease was recommended for all infants in 1987, but it was not implemented in all 50 states until 2006.
Early identification of individuals with sickle cell disease and other hemoglobinopathies allows treatment to begin in a timely manner. Penicillin has been used in children with sickle cell disease, and blood transfusion is used for patients identified with severe thalassemia.
Organic acidids
Most jurisdictions do not initiate screening for any of the organic acids before tandem mass spectrometry significantly extends the list of disorders detected by newborn screening. Quebec has been in a voluntary second-level screening program since 1971 using a urine sample collected at three weeks of age to screen out a list of expanded organic acids using thin-layer chromatography. Newborn screening using tandem mass spectrometry can detect some organic acids, including propionic acidemia, methylmalonic acidemia and isoyclic acid.
Cystic fibrosis
Cystic fibrosis (CF) was first added to a newborn screening program in New Zealand and the Australian territory in 1981, by measuring the immunoreactive tripsinogen (IRT) in place of dry blood. Once the CFTR genes have been identified, Australia introduces a two-tiered testing program to reduce the number of false positives. Samples with elevated IRT values ​​were then analyzed by molecular method to identify the presence of the disease that caused the mutation before it was reported back to the parents and the health care provider. CF is included in the core panel of recommended conditions for inclusion in all 50 states, Texas was the last country to implement their screening program for CF in 2010. Alberta was the first Canadian province to carry out CF screening in 2007. Quebec, New Brunswick, Nova Scotia, Newfoundland and Prince Edward Island excluded CFs in their screening programs. The UK and many EU countries also filter CFs. Switzerland is one of the newest countries to add CFs to their newborn screening menu, doing so in January 2011.
urea cycle breakdown
Disturbances of distal urea cycles, such as citrullinemia, argininosuccinic aciduria and argininemia are included in newborn screening programs in many jurisdictions that use tandem mass spectrometry to identify major amino acids. Proximal urea cure defects, such as ornithine transcarbamylase deficiency and carbamoyl phosphate synthetase deficiencies, are not included in the new screening panels because they are not reliably detected using current technology, and also because highly affected babies will appear with clinical symptoms before newborn screening results available. Some areas claim screening for HHH syndrome (hyperammonemia, hyperornithinemia, homocitrullinuria) based on the detection of elevated ornithine levels in the spot of dry blood screening for newborns, but other sources have shown that affected individuals have no high ornithine at birth.
Lysosomal storage disorder
Lysosomes storage disorders are not included in high-frequency newborn screening programs. As a group, they are heterogeneous, with screening only viable for a fraction of the approximately 40 identified disorders. The arguments for their inclusion in new infant screening programs center around the benefits of early treatment (when treatment is available), avoiding diagnostic travelers for families and providing information for family planning for couples with affected children. Opposing arguments including this disorder, as a group or individually focus on the difficulty of identifying reliable individuals who will be affected by severe forms of disturbance, relatively unproven nature of treatment methods, and high/high risk associated with some treatment options.
New York State started a pilot study to screen Krabbe's disease in 2006, largely due to the efforts of Jim Kelly, whose son, Hunter, had the disease. A pilot pilot program for four lysosomous storage diseases (Gaucher's disease, Pompe's disease, Fabry's disease and Niemann-Pick's disease was performed using an anonymized dry blood stain completed in Austria in 2010. Their data show an increased incidence of what is expected in the population. , as well as a number of forms of the disease that appear more slowly, which is usually not the target for newborn screening programs.
Hearing loss
Undiagnosed hearing loss in children can have serious effects on many areas of development, including language, social interactions, emotions, cognitive abilities, academic performance and job skills, combinations that can have a negative impact on quality of life. The serious impact of late diagnosis, combined with high incidence (estimated 1 - 3 per 1000 live births, and as high as 4% for patients with neonatal intensive care units) has been a driving force behind screening programs designed to identify infants with hearing impairment as early as possible. Initial identification allows patients and their families to access the resources needed to help them grow.
A new hearing test is performed by the bed using temporarily induced autoimoustic emissions, automatic auditory brainstem responses or a combination of both techniques. The auditory examination program has found preliminary testing for a fee between $ 10.20 and $ 23.37 per baby, depending on the technology used. Since this is just a screening test, false-positive results will occur. The auditory program review found a varying initial reference rate (positive screen results) from 0.6% to 16.7%. The highest incidence of overall hearing detection was 0.517%. A large number of positive screen babies are lost to follow-up, before diagnosis can be confirmed or ruled out in all screening programs.
Congenital heart defects
The pulse oximeter has recently been added as a bedside screening test for a critical congenital heart defect.
Severe immunodeficiency deficiency
Severe combined immunodeficiency (SCID) caused by T-cell deficiency is a disorder that has recently been added to newborn screening programs in some areas of the United States. Wisconsin was the first state to add SCID to their mandatory screening panels in 2008, and it was recommended to be included in the panels of all states in 2010. The identification of infants with SCID was done by detecting a circle of excision of T-cell receptors (TRECs) polymerase chain reaction time (qPCR). TREC decreases in infants affected by SCID.
SCID has not been added to newborn screening on a wide scale for several reasons. This requires technology that is not currently used in most newborn screening laboratories, since PCR is not used for other tests included in screening programs. Follow-up and treatment of affected infants also require skilled immunologists, who may not be available in all areas. Treatment for SCID is a stem cell transplant, which can not be done in all centers.
Other conditions
Duchenne muscular dystrophy (DMD) is an X-linked disorder caused by the production of damaged dystrophin. Many jurisdictions around the world have been screened, or attempted to screen for DMD using elevated levels of creatine kinase as measured in dry blood spots. Since universal newborn screening for DMD has not been performed, affected individuals often have significant delays in diagnosis. As treatment options for DMDs become more and more effective, interest in adding newborn screening tests increases. On various occasions since 1978, DMDs have been included (often as pilot studies in a small proportion of the population) in newborn screening programs in Edinburgh, Germany, Canada, France, Wales, Cyprus, Belgium and the United States. In 2012, Belgium is the only country that continues to filter out DMDs using creatin kinase levels.
As treatment improves, newborn screening becomes a possible distraction that may benefit from early intervention, but nothing is available before. Adrenoleukodystrophy (ALD), a peroxisomal disease that has variable clinical presentation is one of the disorders that has been the target for those seeking to identify patients early on. ALD can be present in several different forms, some of which are absent until adulthood, making it a difficult choice for countries to add to screening programs. The most successful treatment option is stem cell transplantation, a procedure that carries significant risks.
Eye and vision screening that can be done within a few months of life includes: strabismus screening using Hirschberg test (or more recently using binocular retinal birpalal imaging for higher precision), and retinoblastoma screening using red reflexes. Further eye examination may be necessary in some cases.
Maps Newborn screening
Disease qualification
The newborn screening program initially used screening criteria determined by JMG Wilson and F. Jungner in 1968. Although not specifically about the newborn population screening program, their publications, the principles and practice of screening for the disease proposed ten criteria that the screening program must meet before being used as a public health measure. New screening programs are conducted in each jurisdiction, with additions and deletions from the panel usually reviewed by an expert panel. Four criteria of dependable publications when making decisions for a newborn screening program are:
- has an acceptable treatment protocol in place that alters results for patients diagnosed early with disease
- understanding of the natural history of this condition
- an understanding of who will be treated as a patient
- reliable NBS screening test for affected and unaffected and publicly acceptable patients
When diagnostic techniques have evolved, the debate has arisen like how the screening program has to adapt. Tandem mass spectrometry has greatly expanded the potential number of diseases that can be detected, even without satisfying all the other criteria used to make screening decisions. Duchenne muscular dystrophy is a disease that has been added to screening programs in several jurisdictions around the world, despite the lack of evidence whether early detection improves clinical outcomes for patients.
Technique
Sampling
A recent baby screening test is most often performed from whole blood samples collected on specially designed filter paper. Filter paper is often attached to forms that contain necessary information about babies and parents. This includes the date and time of birth, date and time of sample collection, infant weight and gestational age. The form will also have information about whether the baby has undergone a blood transfusion and additional nutrients that the baby may have received (total parenteral nutrition). Most newborn screening cards also include contact information for infant doctors in cases where further examination or treatment is required. The Canadian province of Quebec performs a newborn screening of blood samples collected as in most other jurisdictions, and also runs a voluntary urine screening program in which parents collect samples at 21 days of age and submit them to the provincial laboratory for additional panel conditions.
New baby screening samples were collected from infants between 24 hours and 7 days after birth, with the requirement that infants have been fed at least once. Samples can be collected in hospitals, or by midwives. If samples are collected from infants younger than 24 hours, the laboratory will often request a repeating specimen taken after 24 hours. Samples are sent daily to the laboratory responsible for testing. In the United States and Canada, newborn screening is mandatory, with the option for parents to opt out of screening in writing if they wish. In most of Europe, baby screening is done with the consent of the parents. Screening supporters are required to claim that this test is in the best interest of the child, and that parents should not be able to opt out on their behalf. In areas that support informed consent for this procedure, they report no increased cost, no decrease in the number of children screened and no cases of illness included in non-screening children.
Laboratory testing
As the newborn screening program tests for a number of different conditions, a number of different laboratory methods are used, as well as bedside testing for hearing loss using potential hearing loss and congenital heart defects using pulse oximeter. Newborn screening begins by using a simple bacterial inhibitory test to screen out a single disorder, beginning with phenylketonuria in the early 1960s. With this testing methodology, newborn screening requires one test to detect one condition. As mass spectrometry becomes more widely available, this technology allows the rapid determination of a number of acylcarnitines and amino acids from a single point of dry blood. This increases the number of conditions that can be detected by newborn screening. Enzyme tests are used for screening galactosemia and biotinidase deficiency. Immunoassays measure thyroid hormone for the diagnosis of congenital hypothyroidism and 17? -hydroxyprogesterone for the diagnosis of congenital adrenal hyperplasia. Molecular techniques are used for the diagnosis of severe combined cystic fibrosis and combined immunodeficiency.
Report results
The goal is to report the results in a short time. If the screen is normal, paper reports are sent to the hospital that it sends and parents rarely hear about it. If abnormalities are detected, the agent's employee, usually the nurse, starts trying to contact the doctor, the hospital, and/or the nursery by telephone. They are persistent until they can arrange an infant's evaluation by a suitable specialist (depending on the illness). The specialist will attempt to confirm the diagnosis by repeating the test by different methods or laboratories, or by performing other tests that corroborate or disprove. Confirmation tests vary depending on the positive result on the home screen. Confirmation tests may include specific analytical tests to confirm any detectable elevation, functional studies to determine enzyme activity, and genetic testing to identify disease-causing mutations. In some cases, a positive new screen can also trigger tests on other family members, such as siblings who are not undergoing newborn examinations for the same condition or the baby's mother, as some maternal conditions can be identified through results on a newborn screen. Depending on the likelihood of diagnosis and the risk of delay, specialists will begin treatment and provide information to the family. Program performance is reviewed regularly and strenuous efforts are made to maintain a system that captures every infant with this diagnosis. Guidelines for screening and follow-up newborns have been published by the American Academy of Pediatrics and the American College of Medical Genetics.
Lab performance
Newborn screening programs participate in quality control programs like in other laboratories, with some notable exceptions. Much of the success of the newborn screening program depends on the filter paper used for sample collection. Initial studies using the Robert Guthrie test for PKU reported a high false-positive rate associated with a poorly selected filter paper type. The source of this variation has been eliminated in most newborn screening programs through standardized filter paper sources approved for use in newborn screening programs. In most areas, newborn screening cards (containing demographic information and filter papers attached to blood collection) are provided by testing organizations to remove variations from these sources.
History
Robert Guthrie was given a great deal of credit for pioneering the earliest screening for phenylketonuria in the late 1960s using blood samples obtained by stabbing the heel of a newborn on the second day of life on filter paper. Congenital hypothyroidism was the second most commonly added disease in the 1970s. Guthrie and colleagues also developed a bacterial inhibition test to detect classic maple syrup and classic galactosemia. The development of tandem mass spectrometry screening in the early 1990s led to a major expansion of potential congenital metabolic diseases that could be identified by patterns of amino acid characteristics and acylcarnitines.
In the United States, the American College of Medical Genetics recommends a uniform disease panel that all babies born in every state must have. They also developed a evidence-based review process for the addition of future conditions. Implementation of this panel across the United States means all babies born will be screened for a number of similar conditions. Prior to this, babies born in different countries had received different screening rates. On April 24, 2008, President George W. Bush signed the Newborn Screening Act Saving the Life Story of 2007. This action was put in place to raise awareness among parents, health professionals, and communities on testing newborns to identify specific disorders. It also seeks to improve, expand, and improve current state-of-the-art screening programs.
Society and culture
Controversy
Recent screening tests have been the subject of political controversy in the last decade. In 2003, two California babies, Zachary Wyvill and Zachary Black, both born with Glutaric acidemia type I. Wyvill-born hospitals were only tested for four diseases mandated by state law, while Black was born in a participating hospital in an expanded test. pilot program. Black disease treated with diet and vitamins; Wyvill disease is undetectable for more than six months, and during that time damage due to enzyme deficiency becomes irreversible. Lobbyists birth defects are pushing for a broader and more universal standard for newborn testing citing this as an example of how much impact testing can have.
Performing MS/MS screening checks often require substantial forward expenditure. When countries choose to run their own programs, the initial cost of equipment, training, and new staff can be significant. In addition, MS/MS only provides screening results and not the result of confirmation. The same should be done further by higher technology or procedures such as GC/MS, Enzyme Assays or DNA Test. This basically adds to the cost burden and makes the doctor lose valuable time. To avoid at least some of the upfront costs, some countries such as Mississippi have opted for contracts with private labs for expanded screening. Others have chosen to form a Regional Partnership that shares costs and resources.
But for many states, filtering is an integrated part of the health department that can not or will not be easily replaced. Thus early expenditures can be difficult for countries with tight budgets to justify. The cost of screening has also increased in recent years as health care costs are rising and more and more countries are adding MS/MS screening to their programs. (See Sum Reporting Charges Charged for Newborn Baby Screening, 2001-2005) The dollars spent on these programs can reduce the resources available to potentially life-saving programs. It has been suggested that one disorder, Short Chain Acyl-coenzyme A Dehydrogenase Deficiency, or SCAD, is omitted from the screening program, due to "false associations between SCAD and symptoms, but recent research suggests that expanded screening is cost effective". ACMG Report page 94-95 and articles published in Pediatrics '. Advocates quickly demonstrated such research while trying to convince state legislatures to expand screening mandates.
The new expanded screening is also challenged by some healthcare providers, who fear that effective follow-up and treatment may be unavailable, that a false-positive screening test can cause hazards, and informed consent issues. A recent study by the Genetic Alliance and partners shows that communication between healthcare providers and parents can be key in minimizing potential harm when a false-positive test occurs. The results of the study also reveal that parents find newborn screening as a useful and necessary tool to prevent treatable diseases. To address false positives, researchers from the University of Maryland, Baltimore and the Genetic Alliance set up checklists to help healthcare providers communicate with parents about the screen's positive results.
Controversy has also erupted in some countries over the collection and storage of blood or DNA samples by government agencies during the routine of a newborn blood test. It was revealed that in Texas the country has collected and stored blood and DNA samples on millions of newborns without the knowledge or consent of parents. These samples are then used by the state for genetic experiments and to prepare a database for cataloging all samples/newborns. Samples obtained without parental consent were destroyed.
Bioethics
When additional tests are discussed for adding panels, problems arise. Many questions if expanded testing is still below the requirements needed to justify additional tests. Many new diseases are tested rarely and have no known treatment, while some diseases need not be treated until later in life. This raises more problems, such as: if there is no treatment available for the disease, should we test it at all? And if we do, what do we say to the families of those who have children who suffer from one of the untreatable diseases? Studies show that the more rare the disease is and the more diseases it tests, the more likely it will be to produce false-positive. This is a problem because the new period of birth is an important time for parents to bond with children, and it has been noted that ten percent of parents whose children are diagnosed with false positives are still worried that their child is vulnerable and/or sickly though not, potentially prevent the formation of parent-child bonding as it should be. As a result, some parents may start choosing not to check their newborns. Many parents also worry about what happens with their baby's blood sample after being filtered. Initial samples were taken to test preventable diseases, but with advances in genome sequencing technology, many samples were stored for DNA identification and research, increasing the likelihood that more children will be selected from newborn examinations of parents looking at stored samples. as a form of research conducted on their child.
References
External links
- US. New Screening and Genetics Resource Center
- List of current test by country
- The History of Newborn Screening - Flash Cast by Harvey Levy, MD: In this 40 minute talk and slide presentation, is offered here in ten short video sections, Dr. Levy includes a history of newborn screening, beginning with the origin of the concept of innate metabolic error in the early 1900s, which includes the development of Dr. Robert Guthrie for newborn screening for PKU, and move through current screening methods and public health approaches.
- Examination Information Born & amp; Homepage Resources from the Save Babies Through Screening Foundation, a grassroots advocacy group solely aimed at expanding, and raising awareness of, Newborn Examinations.
- About the New Born Examination
- Baily, M.A. and Murray, T.H. (2009). Ethics and Genetic Screenings Just Born . Johns Hopkins University Press. ISBN 978-0-8018-9151-9
- PerkinElmer Genetics, Inc. (A commercial company that pioneered multiple screening procedures and offered direct parental testing.A excellent link collection to other sites about metabolic diseases and screening.)
- Waldholz, Michael, "A Blood Sow Saves a Baby, Others Sick," Wall Street Journal , June 17, 2001, p. A1 (52k PDF)
- [3]
- Novogenia DNA Plus Genetic Testing can save newborns
- New Born Screening Program for Mumbai, Navi-Mumbai, and Thane
- Non-Invasive Baby Screening in India
- Baby's First Test (The educational website produced by the non-profit Genetic Alliance.)
- [4] Henry Morgan Anderson obituary
- [5] The adventures of Henry, LLC publish
Source of the article : Wikipedia
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