issues for consideration

Newborn screening has stimulated much controversy. Although newborn screening is performed on babies, the implications of a positive diagnosis from such screening can last a lifetime. Nurses perform newborn screening on nearly every baby born in the U.S. � at adds up to 4 million heel-stick blood samples every year in this country. It’s estimated that one of every 800 of these babies will screen positive for a serious disorder.

Update on Expanded Newborn

Screeningi s s u e s f o r

c o n s i d e r at i o n

Emily Drake, RN, PhDMary E. Gibson, RN, PhD

In total, newborn screening will correctly detect approximately 5,000 babies with severe disorders in the U.S. each year (Centers for Disease Control and Prevention [CDC], 2008). This article reviews where we have been and where we are now, and offers some insight into where we are headed with newborn screen-ing. We also discuss some of the ethical, social and economic dilemmas associated with this expanded screening.

BackgroundEvery day babies are routinely screened for a variety of dis-eases via dried blood spots collected on a filter paper 24 to 72 hours after birth. With tandem mass spectrometry those blood spots are now tested for multiple conditions from that single sample. This year, almost all states will require expand-ed screening for at least 21 diseases, and some states screen for

even more. The newest recommendations suggest expanded screening for 54 conditions (American College of Medical Genetics [ACMG], 2006; The President’s Council on Bioeth-ics, 2008). This screening is important because even though newborns may appear healthy, they may actually have serious, sometimes fatal disorders.

Screening is just a first step. Infants who screen positive for one of these conditions will require additional testing to con-firm the diagnosis. Those who initially screen positive may or may not become symptomatic and can often reflect false posi-tives (see Box 1). By some estimates there may be more than 10,000 false-positive newborn screenings per year in the U.S. (Gurian, Kinnamon, Henry, & Waisbren, 2006). The benefit of detecting rare but potentially debilitating or fatal diseases is that they can often be prevented or ameliorated by treatment, thus saving lives and preventing lifelong disability. But the authority that mandates the screening should provide prompt diagnosis and ongoing treatment for the conditions identified. Herein lies one concern about the new required screenings (The Presi-dent’s Council on Bioethics, 2008).

origins of newBorn screeningPhenylketonuria (PKU) was the single target of the earliest newborn screening, which began in 1961 (Tarini, 2007). This genetic disease, affecting 1 in 25,000 infants, eventually causes mental retardation due to the buildup of excess phenylalanine in a baby’s system that cannot be normally metabolized (Tarini). Dr. Robert Guthrie developed the technique of dropping blood from a newborn’s heel stick onto blotter paper that we still use today. The dried blood was tested for phenylalanine with bacte-rial inhibition assay. Despite the benefits of early detection of PKU, this simple test sparked controversy back in the 1960s, and was not initially supported by the American Medical Asso-ciation (AMA) or the American Academy of Pediatrics (AAP), because knowledge of the accuracy and reliability of the test and of the natural history and treatment of PKU was incom-plete (Tarini). Furthermore, following detection of PKU, treat-ment and necessary long term follow-up was not universally available, even after many states instituted mandatory screen-ing. This left some children diagnosed with the condition, but without resources for ongoing medical care.

Despite controversy, by the 1980s most states mandated PKU and additional newborn screening for diseases and condi-tions such as galactosemia; hemoglobinopathies, such as sickle cell anemia; metabolic abnormalities, such as maple syrup urine disease (MSUD); homocystinuria; and endocrine disor-ders, such as congenital hypothyroidism. Cystic fibrosis screen-ing was later added to routine newborn screening. These same blood samples were also sometimes used for infectious disease surveillance or research.

introduction of tandem mass spectrometryIn the 1990s, a newer testing platform became available, which could detect multiple metabolic conditions from one sample. Ear-lier tests identified disorders one by one through specific testing, which required more blood for each test added. Once introduced, tandem mass spectrometry (MS/MS) could screen for about four times the number of disorders for only a small incremental ad-ditional cost per baby (ACMG, 2006; Tarini, 2007). So while the initial investment in equipment for the states was substantial, the technology significantly increased the number of conditions that could be screened for and the efficiency of screening.

Tandem mass spectrometry (MS/MS) identifies markers for diseases, called analytes, not the diseases themselves. So, having a marker present could mean more than one thing, and further testing can narrow down just what that analyte might signify. This technology allows a total panel of screening tests to be performed at once—primarily detecting inborn errors of metabolism (fatty acid, amino acid and organic acid disorders), along with existing tests for endocrine, hemoglobinopathies

200 © 2010, AWHONN http://nwh.awhonn.org

Emily Drake, RN, PhD, and Mary E. Gibson, RN, PhD, are assistant professors at the University of Virginia School of Nursing in Charlottes-ville, VA. Address correspondence to: [email protected].

DOI: 10.1111/j.1751-486X.2010.01541.x

• The results of newborn screening can have a lifetime impact.

• Nurses play a key role in conducting screening and educating parents about it.

• The use of DNA testing will bring even greater changes to how newborn screening is done.

Bottom Line

June July 2010 Nursing for Women’s Health 201

and other disorders (McCabe & McCabe, 2008). In 2006, new recommendations from the ACMG recommended testing for a total of 54 disorders, 29 of which are core and 25 are secondary targets (ACMG, 2006) that can help clarify information on the core conditions (see Boxes 2 and 3). The 29 core tests meet the criteria established by most authorities for an effective screen-ing test, whereas the 25 secondary targets would not meet eligi-bility requirements for individual testing, but are recommended by the ACMG and AAP (among others) to improve differential diagnosis for the core conditions. At the same time, these sec-

ondary tests can identify conditions that in some cases are not well understood and do not have any known treatment.

Newborn screening is mandatory in all states. However, the disorders tested for vary by state. Almost all states test for at least 21 diseases, and some states, such as North Carolina, California, Wisconsin, and Massachusetts, require more tests (National Newborn Screening and Genetics Resource Center, 2010). Likewise, in Canada the number and requirements for screening tests vary by province (Canadian Organization for Rare Disorders, 2008).

identification of conditions By tandem mass spectrometryMany current tests screen for conditions that are serious but treatable, whereas others screen for untreatable conditions. One of the more recently added tests screens for primary carnitine de-

ficiency, a genetic fatty acid oxygenation disorder that can cause serious brain, heart and liver problems. This condition occurs in 1 in every 100,000 births. Diagnosis may not only detect the con-dition in the newborn, but may also identify carrier status or dis-ease in the mother and siblings. This condition can be treated by avoiding fasting and adding carnitine dietary supplements. Thus, this screening may help prevent morbidity or mortality in the in-fant as well as in family members (McCabe & McCabe, 2008).

Many of these rare conditions are treatable with special di-ets or hormone supplements. For example, isovaleric acidemia

(IVA), an organic acid disorder, can cause mental or physical disability or even death, but can be prevented by starting a modified diet free of protein containing leucine (National Li-brary of Medicine, 2009). Thus, this newborn screening and early intervention can truly save lives.

But screening may not save lives in all cases (den Boer et al., 2002). For example, babies with long-chain hydroxyachyl-CoA dehydrogenase deficiency (LCHAD) are at risk for serious heart problems, breathing difficulties, coma and sudden death. Some will die in infancy, perhaps even before screening results are in, but the screening data can provide parents with factual information, which could help them to process the loss and to plan for next pregnancy. Acute fatty liver disease in pregnancy may be associated with LCHAD in the fetus (Bellig, 2004).

Additional optional screening is available for some ex-tremely rare genetic conditions, such as Fabry disease, Gaucher disease, Krabbe disease, Niemann-Pick disease and Pompe

Box 1 Definition of Screening Terms

term definition

Screening test Test designed to distinguish in a population those who have a disease and those who do not. The validity and reliability of the tests vary.

Diagnosis Confirmed existence of a disease or condition.

Presymptomatic Testing for a disease prior to the appearance of any symptoms (e.g., Huntington’s screening Disease).

Susceptibility Genetic testing for predisposition to disease that may or may not actually occur testing (e.g., genetic predisposition to Type I diabetes).

Sources: Gordis (2009); Stanhope and Lancaster (2008)

Although newborn screening is performed on babies, the implications of a positive diagnosis

from such screening can last a lifetime

202 Nursing for Women’s Health Volume 14 Issue 3

Box 2 Core Conditions Recommended for Newborn Screening

PhenylketonuriaType: AA

CitrullinemiaType: AA

Argininosuccinic acidemiaType: AA

Tyrosinemia type IType: AA

sequelae name of of untreated available condition incidence disease treatment


Isovaleric academia Type: OA

Glutaric acidemia type IType: OA

3-Hydroxy-3-methyl-glutaryl-CoA lyase deficiencyType: OA

Multiple carboxylase deficiencyType: OA

Methylmalonic acidemia (mutase deficiency) Type: OA

3-Methylcrotonyl-CoA carboxylase deficiencyType: OA

Methylmalonic acidemia (Cbl A,B) Type: OA

Propionic acidemia Type: OA

β-ketothiolase deficiency Type: OA

Homocystinuria (caused by cystathionine β-synthase)Type: AA

Maple syrup diseaseType: AA

<1/100,000

> 1/75,000

<1/100,000

<1/100,000

> 1/75,000

> 1/75,000

<1/100,000

> 1/75,000

<1/100,000

<1/100,000

<1/100,000

1/25,000

<1/100,000

<1/100,000

<1/100,000

• Organic acid disorders: Toxic encephalopathy, vomit-ing, poor feeding, neurologic symptoms (seizures/decreased tone, lethargy, coma), hypogly-cemia

• Adolescent forms: Decreased intellectual function, focal neuro signs, keto-acidosis.

• Greater incidence of infection, pancreatitis, or renal failure, liver damage

• Involvement of the eye, skeletal system, vascular system, and CNS

• Maple syrup odor seizures, coma and death

• Permanent intellectual disability• Seizures, delayed development,

behavioral problems, and psy-chiatric disorders

• Type 1 – buildup of ammonia lethargy, feeding problems, vomiting, seizures, loss of con-sciousness

• Type 2 – confusion, restless-ness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma

• Usually presents early in NBN life – (lethargic) or unwilling to eat, and have poorly controlled breathing rate or body tempera-ture; seizures or unusual body movements, increased blood ammonia, coma, developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.

• Type 1 (severe) – first months of life: failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Can lead to liver and kidney fail-ure, problems affecting the nerv-ous system, and an increased risk of liver cancer; rickets.

• Type 2 – early childhood: affects eyes, skin, and mental devel-opment; photophobia & optic symptoms; lesions palms/soles; 50% have intellectual disability

• Type 3 – intellectual disability, seizures; intermittent ataxia

• Dietary treatment to restore biochemical and physiologic homeostasis.

• Metabolic formulas (appropri-ate to disorder)

• Adequate calories

• Adjunctive compounds to dispose of toxic metabolites

• Organ replacement specific to area of damage

• Vitamin B6 or methionine- restricted diet

• Protein-restricted diet

• Betaine treatment

• Folate and vitamin B12 supplementation

• Dietary leucine restriction

• High-calorie, branched-chain amino-acid-free formulas

• Frequent monitoring

• Restriction of dietary phenylalanine

• Supplementation with BH4

• Lipid and protein-rich low-carbohydrate diet

• Avoid high-carbohydrate meals and alcohol

• Limit protein

• Avoid fasting

• Treatment with nitisinone and a low-tyrosine diet

Abbreviations: OA = disorders of organic acid metabolism FAO = disorders of fatty acid metabolism AA = disorders of amino acid metabolism CoA = coenzyme A.


Box 2 Core Conditions Recommended for Newborn Screening

PhenylketonuriaType: AA

CitrullinemiaType: AA

Argininosuccinic acidemiaType: AA

Tyrosinemia type IType: AA



Isovaleric academia Type: OA

Glutaric acidemia type IType: OA

3-Hydroxy-3-methyl-glutaryl-CoA lyase deficiencyType: OA

Multiple carboxylase deficiencyType: OA

Methylmalonic acidemia (mutase deficiency) Type: OA

3-Methylcrotonyl-CoA carboxylase deficiencyType: OA

Methylmalonic acidemia (Cbl A,B) Type: OA

Propionic acidemia Type: OA

β-ketothiolase deficiency Type: OA

Homocystinuria (caused by cystathionine β-synthase)Type: AA

Maple syrup diseaseType: AA

<1/100,000

> 1/75,000

<1/100,000

<1/100,000

> 1/75,000

> 1/75,000

<1/100,000

> 1/75,000

<1/100,000

<1/100,000

<1/100,000

1/25,000

<1/100,000

<1/100,000

<1/100,000

• Organic acid disorders: Toxic encephalopathy, vomit-ing, poor feeding, neurologic symptoms (seizures/decreased tone, lethargy, coma), hypogly-cemia

• Adolescent forms: Decreased intellectual function, focal neuro signs, keto-acidosis.

• Greater incidence of infection, pancreatitis, or renal failure, liver damage

• Involvement of the eye, skeletal system, vascular system, and CNS

• Maple syrup odor seizures, coma and death

• Permanent intellectual disability• Seizures, delayed development,

behavioral problems, and psy-chiatric disorders

• Type 1 – buildup of ammonia lethargy, feeding problems, vomiting, seizures, loss of con-sciousness

• Type 2 – confusion, restless-ness, memory loss, abnormal behaviors (such as aggression, irritability, and hyperactivity), seizures, and coma

• Usually presents early in NBN life – (lethargic) or unwilling to eat, and have poorly controlled breathing rate or body tempera-ture; seizures or unusual body movements, increased blood ammonia, coma, developmental delay and intellectual disability. Progressive liver damage, skin lesions, and brittle hair may also be seen.

• Type 1 (severe) – first months of life: failure to thrive, diarrhea, vomiting, jaundice, cabbage-like odor, and increased tendency to bleed (particularly nosebleeds). Can lead to liver and kidney fail-ure, problems affecting the nerv-ous system, and an increased risk of liver cancer; rickets.

• Type 2 – early childhood: affects eyes, skin, and mental devel-opment; photophobia & optic symptoms; lesions palms/soles; 50% have intellectual disability

• Type 3 – intellectual disability, seizures; intermittent ataxia

• Dietary treatment to restore biochemical and physiologic homeostasis.

• Metabolic formulas (appropri-ate to disorder)

• Adequate calories

• Adjunctive compounds to dispose of toxic metabolites

• Organ replacement specific to area of damage

• Vitamin B6 or methionine- restricted diet

• Protein-restricted diet

• Betaine treatment

• Folate and vitamin B12 supplementation

• Dietary leucine restriction

• High-calorie, branched-chain amino-acid-free formulas

• Frequent monitoring

• Restriction of dietary phenylalanine

• Supplementation with BH4

• Lipid and protein-rich low-carbohydrate diet

• Avoid high-carbohydrate meals and alcohol

• Limit protein

• Avoid fasting

• Treatment with nitisinone and a low-tyrosine diet

Abbreviations: OA = disorders of organic acid metabolism FAO = disorders of fatty acid metabolism AA = disorders of amino acid metabolism CoA = coenzyme A.


Box 2 Core Conditions Recommended for Newborn Screening (cont.)


Sickle cell anemia (Hb SS disease) HbType: H

Hb S/β-thalassemiaType: H

Hb S/C diseaseType: H

Congenital hypothyroidismType: Other

Biotinidase deficiencyType: Other

Congenital adrenal hyperplasia (21-hydroxy-lase deficiency)Type: Other

> 1/5000

> 1/50,000

< 1/25,000

> 1/5,000

> 1/75,000

> 1/25,000

• Anemia, sickle cell crisis, organ damage, pulmonary hyperten-sion, heart failure.

• Microcytic hypochromic ane-mia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A anemia, hepato splenomegaly, failure to thrive

• Chronic anemia; abnormal hemoglobin (one gene for HgS and one gene for HgC; similar to sickle cell but milder. Can cause gross hematuria, reti-nal hemorrhages, and aseptic necrosis of the femoral head

• Intellectual disability and ab-normal growth; early diagnosis (1st month) permits treatment

• Severe – often have seizures, weak muscle tone (hypotonia), breathing problems, and delayed development. If left untreated, the disorder can lead to hearing loss, eye abnormalities and loss of vision, problems with move-ment and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection

• Partial (milder) – hypotonia, skin rashes, and hair loss

• Virilization type – buildup of androgens → masculinization of female external genitalia (nor-mal internal female organs)

• Salt loss type – decreased aldos-terone secretion → inability of kidneys to reabsorb sodium;

• Blood transfusions, fluids, pain management, other treatments

• Major – regular transfusions to correct the anemia, suppress erythropoiesis and inhibit increased gastrointestinal absorption of iron

• Intermediate – symptomatic, splenectomy and folic acid supplementation

• Hydration, transfusions

• Throxine, if very early detec-tion, can reverse damage

• Treatment with biotin (Note: optic atrophy, hearing loss, or developmental delay may not be reversible)

• Hormone/glucocorticoid replacement therapy

• Feminizing genitoplasty

• Prenatal dexamethazone treatment

• Mineralocorticoid replacement Sources: American Academy of Pediatrics Newborn Screening Authoring Committee (2008); ACMG (2006); March of Dimes (2009); National Library of Medicine (2010)


(cont.)

Classical galactosemiaType: Other

Cystic fibrosis (CF)Type: Other

Hearing lossType: Other


> 1/50,000

> 1/5,000

> 1/5,000

poor feeding, weight loss, failure to thrive, vomiting, dehydration, hypotension, hyponatremia, and hyperkalemic metabolic acidosis progressing to adrenal crisis

• Non-classic type – s and sx of adrogen excess after birth (may not be detected through NBN screening)

• Type 1 (classic) – Early feeding difficulties, lethargy, a failure to thrive, jaundice, liver damage, and bleeding

• Type 2 – (milder) cataracts, de-layed growth and development, intellectual disability, liver & kidney disease

• Meconium ileus; progressive damage to the respiratory system and chronic digestive system problems; infertility; CF-related diabetes

• Auditory deprivation in first 2 years can result in poor reading and communication /speech

• Lactose-free diet

• Treating or preventing pulmo-nary complications may include oral, inhaled or IV antibiotics, bronchodilators, anti-inflam-matory agents, mucolytic agents and chest physiotherapy

• Nutritional therapy may include special formulas for infants to enhance weight gain through improved intestinal absorption

• Oral pancreatic enzyme replace-ment

• Educational strategies

• Cochlear implantation, hearing augmentation, and follow-up by audiologist, otolaryngologist, pediatrician, geneticist and deaf education specialist


Box 2 Core Conditions Recommended for Newborn Screening (cont.)


Sickle cell anemia (Hb SS disease) HbType: H

Hb S/β-thalassemiaType: H

Hb S/C diseaseType: H

Congenital hypothyroidismType: Other

Biotinidase deficiencyType: Other


> 1/5000

> 1/50,000

< 1/25,000

> 1/5,000

> 1/75,000

> 1/25,000

• Anemia, sickle cell crisis, organ damage, pulmonary hyperten-sion, heart failure.

• Microcytic hypochromic ane-mia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of hemoglobin A anemia, hepato splenomegaly, failure to thrive

• Chronic anemia; abnormal hemoglobin (one gene for HgS and one gene for HgC; similar to sickle cell but milder. Can cause gross hematuria, reti-nal hemorrhages, and aseptic necrosis of the femoral head

• Intellectual disability and ab-normal growth; early diagnosis (1st month) permits treatment

• Severe – often have seizures, weak muscle tone (hypotonia), breathing problems, and delayed development. If left untreated, the disorder can lead to hearing loss, eye abnormalities and loss of vision, problems with move-ment and balance (ataxia), skin rashes, hair loss (alopecia), and a fungal infection

• Partial (milder) – hypotonia, skin rashes, and hair loss

• Virilization type – buildup of androgens → masculinization of female external genitalia (nor-mal internal female organs)

• Salt loss type – decreased aldos-terone secretion → inability of kidneys to reabsorb sodium;

• Blood transfusions, fluids, pain management, other treatments

• Major – regular transfusions to correct the anemia, suppress erythropoiesis and inhibit increased gastrointestinal absorption of iron

• Intermediate – symptomatic, splenectomy and folic acid supplementation

• Hydration, transfusions

• Throxine, if very early detec-tion, can reverse damage

• Treatment with biotin (Note: optic atrophy, hearing loss, or developmental delay may not be reversible)

• Hormone/glucocorticoid replacement therapy

• Feminizing genitoplasty

• Prenatal dexamethazone treatment

• Mineralocorticoid replacement Sources: American Academy of Pediatrics Newborn Screening Authoring Committee (2008); ACMG (2006); March of Dimes (2009); National Library of Medicine (2010)


(cont.)

Classical galactosemiaType: Other

Cystic fibrosis (CF)Type: Other

Hearing lossType: Other


> 1/50,000

> 1/5,000

> 1/5,000

poor feeding, weight loss, failure to thrive, vomiting, dehydration, hypotension, hyponatremia, and hyperkalemic metabolic acidosis progressing to adrenal crisis

• Non-classic type – s and sx of adrogen excess after birth (may not be detected through NBN screening)

• Type 1 (classic) – Early feeding difficulties, lethargy, a failure to thrive, jaundice, liver damage, and bleeding

• Type 2 – (milder) cataracts, de-layed growth and development, intellectual disability, liver & kidney disease

• Meconium ileus; progressive damage to the respiratory system and chronic digestive system problems; infertility; CF-related diabetes

• Auditory deprivation in first 2 years can result in poor reading and communication /speech

• Lactose-free diet

• Treating or preventing pulmo-nary complications may include oral, inhaled or IV antibiotics, bronchodilators, anti-inflam-matory agents, mucolytic agents and chest physiotherapy

• Nutritional therapy may include special formulas for infants to enhance weight gain through improved intestinal absorption

• Oral pancreatic enzyme replace-ment

• Educational strategies

• Cochlear implantation, hearing augmentation, and follow-up by audiologist, otolaryngologist, pediatrician, geneticist and deaf education specialist


Inconsistency in ScreeningA real-life story of two babies published in the Wall Street Jour-nal (Waldholz, 2004) illustrates the need for consistency and standardization for screening (Association of Public Health Laboratories, 2008). These babies are Zachary W. and Zach-ary B., both born with glutaric acidemia type I. Z.W.’s birth hospital only tested for the four diseases mandated by state law, whereas Z.B.’s birth hospital, 60 miles away, performed expanded testing. Z.B.’s disease is currently treated with diet and vitamins, while Z.W.’s disease went undetected for more than 6 months and during that time the neurologic damage from enzyme deficiency became irreversible. This sad exam-ple clearly emphasizes the need to establish national standards for all hospitals so that every baby can have the best chance to survive and thrive.

disease. These tests are largely excluded from routine screen-ing because of their rare and fatal nature. While there is some therapy for these conditions, there is no cure and some of these therapies can cost tens of thousands of dollars per year. There-fore, they are not among the recommended tests. Commercial availability of these tests does allow parents to purchase screen-ing for these rare conditions, if desired.

principles of screening Implicit in the drive to increase the number of conditions screened for and foundational to screening up to now is the assumption that those conditions have the following: a known natural history, a viable treatment and a treatment that is available to all identified cases. Prior to the present expanded screening initiative, these were criteria agreed upon by the Institute of Medicine (IOM), AAP, the National Institutes of Health (NIH) Task Force on Genetic Testing and the Ameri-can Society of Human Genetics (The President’s Council on Bioethics, 2008).

Currently we are screening for both treatable and untreat-able diseases. Experts at the National Institute of Child Health and Human Development (NICHD) would argue that the abil-ity to screen for untreatable conditions for research purposes is important in order to learn more about the disease and develop new treatments and therapies (Alexander & van Dyck, 2006).

Until recently, principles of screening were based on the 1968 World Health Organization (WHO) report (Wilson & Jungner, 1968) on population screening, which provided a foundational guide and ethical criteria for all types of health screening (some-times called the Wilson-Jungner criteria) (Box 4). Newer policy tools became available from the ACMG in 2006 (Box 5). From an initial 84 conditions, the ACMG and a panel of experts used these criteria to identify and rank the 29 primary conditions recommended for mandatory newborn screening along with 25 secondary conditions for screening. Despite following clear principles and guidelines, different groups continue to identify problematic ethical issues (Kerruish & Robertson, 2005). Nurs-es can help by being aware of some of the issues associated with the screening and follow-up process.

screening issues in newBornsCost of Screening and Follow-Up TestingThe cost of screening may seem reasonable—about $10 to $140 per newborn for 29 tests, and this is usually covered by the state health departments or by health insurance (Johnson, Lloyd-Puryear, Mann, Ramos, & Therrell, 2006). Tech-savvy parents can order a full panel of tests online for a moderate fee; how-ever, involvement of a health care provider for specimen collec-tion and interpretation is recommended. Follow-up testing and treatment, if needed, will add additional costs.

Box 3 Secondary Conditions for Newborn Screening

Methylmalonic acidemia (Cbl C,D)

Malonic acidemia

Isobutyryl-CoA dehydrogenase deficiency

2-Methyl 3-hydroxy butyric aciduria

2-Methylbutyryl-CoA dehydrogenase deficiency

3-Methylglutaconic aciduria

Short-chain acyl-CoA dehydrogenase deficiency

Glutaric acidemia type II

Medium/short-chain L-3-hydroxy acyl-CoA dehydrogenase deficiency

Medium-chain ketoacyl-CoA thiolase deficiency

Carnitine palmitoyltransferase II deficiency

Carnitine: acylcarnitine translocase deficiency

Carnitine palmitoyltransferase I deficiency (liver)

Dienoyl-CoA reductase deficiency

Benign hyperphenylalaninemia

Tyrosinemia type II

Defects of biopterin cofactor biosynthesis

Argininemia

Tyrosinemia type III

Defects of biopterin cofactor regeneration

Hypermethioninemia


genetic disease. To help prevent this, health care providers must be very clear and careful in their communication with parents about the screening results. Referrals for additional emotional support may be necessary even when communicating what we may consider “good news.”

Access to TreatmentConsistency in testing, reporting and standardization of support programs following newborn screening should be the founda-tion of care, and equal access should be a fundamental value that drives that support system. Considerable inconsistencies still exist in the provision of support services depending on state mandates, funding, geography and economic status of the family. Access, therefore, is not equitable. So even if identification of dis-ease is successful, later consistent follow-up and treatment is not guaranteed to everyone with positive screening. The Association of Women’s Health, Obstetric and Neonatal Nurses (AWHONN) and the AAP have advocated for attempts at national oversight for both screening and treatment (AAP, 2008; AWHONN, 2005).

Equal access to screening is only the beginning. On face value, it seems much less expensive to screen and treat in the newborn

Informed ConsentNewborn screening is considered routine care and is mandated by the states, although parents may “opt out” if they object, such as for religious reasons. This process is called informed dissent (Kerruish & Robertson, 2005). Parental informed con-sent is not required (except in a few states, such as Wyoming and Maryland). In some cases, parents may be unaware that newborn screening has been done or unaware of the purpose of the screening. When surveyed, most parents say they are in favor of newborn screening (Lloyd-Puryear et al., 2006). How-ever, as screening expands, this may no longer be the case.

follow-up process issuesFalse PositivesScreening is not without potential harms, including the risk of false positives (Gurian et al., 2006). For example, while the sen-sitivity and specificity for maple syrup urine disease (MSUD) screening is very good (sensitivity near 100 percent and spe-cificity 99.96 percent), the positive predictive value is low (1.4 percent), reflecting many false positive results (Schulze et al., 2003) (see Box 6). This means that some perfectly healthy in-fants will initially screen positive for disease and this may cause unnecessary alarm in the parents.

This initial distress, even if further testing reveals that the infant is actually healthy, may have long-term implications on parenting. False-positive screening has been associated with vulnerable child syndrome, parenting stress and increased hos-pitalization in these children (Waisbren et al., 2003). Vulner-able child syndrome refers to a healthy child who is viewed by the parents as being at greater risk of illness than what is actu-ally likely. Undue anxiety, excessive worrying and depression can develop after the child has survived what is perceived as a “near miss,” or what parents may perceive as an unexpected life-threatening event, such as a false-positive test for metabolic or

Box 4 Wilson-Jungner Criteria for Screening

Significant health problem

Accepted treatment with recognized disease

Facilities for diagnosis and treatment are available

Recognizable latent or early symptomatic stage

Natural history adequately understood

Cost of screening and treatment considered

Policy agreed upon on whom to treat

Source: Wilson and Jungner (1968).

False-positive screening has been associated with

vulnerable child syndrome, parenting stress and

increased hospitalization in these children


treatable. Another consideration is whether screening should be mandatory or voluntary or if pilot programs should offer options for screening of currently untreatable conditions.

Genomic medicine will then start from birth—pediatricians will possess an individualized health map including vulnerabil-ities and susceptibilities. Genomic medicine promises predic-tive, preventative and personalized health care. But it also raises many ethical issues.

One concern is having a permanent health record that may place a person at risk for discrimination in insurance cover-age or employment. However, recent national legislation in the form of the Genetic Information Nondiscrimination Act of 2008 prohibits insurance or employment discrimination on the basis of genetic information.

Another concern is DNA material for use in research. The use of “biobanking” (repositories of health information inter-linking human genotypes) is on the horizon. These banks will be able to identify subjects with tendencies or vulnerabilities. There is already controversy about privacy and informed consent in Texas, Michigan and Minnesota concerning newborn screening blood samples currently retained for research purposes (Hast-ings Center, 2009). However, most newborn screening banks de-identify the samples saved for these kind of population studies.

There are advocacy groups on both sides of this issue. For example, SaveBabies.org is a parent advocacy group that is pushing for more testing, while there are privacy advocacy groups (such as the Citizens Council on Health Care in Min-nesota and the Texas Civil Rights Project) that advocate for a slow down on testing and more parental options. Government agencies such as the Federal Advisory Committee on Heritable Disorders in Newborns and Children continue to discuss these issues and review additions to the screening recommendations (Baily & Murray, 2008).

implications for nursing practiceNurses play a critical role in newborn screening through care-ful collection of the samples. Nurses work closely with parents and other health care providers, providing parental education, emotional support, referral and resources. More information and education may help calm some of the current controversy.

Safety and QualityNurses must assure that universal precautions for blood and body fluids are followed, and that proper patient identification

period than to manage the catastrophic illness that can occur if not detected early. That’s in an ideal world; the problem is that cost-effectiveness only occurs if the child’s disease is adequately treated and followed up, and all compliance and access issues are addressed. Testing is only the first step—effective treatment still may not occur for many reasons. Some parents may have limited access to special formulas, or limited ability to follow compli-cated treatment protocols. State resources must be visible to par-ents and accessible. Nurses can advocate for every baby to have a “medical home” where all care is coordinated and directed. Nurses can also counsel parents about available resources.

dna testing on the horizonMicroarray DNA chips could be used for a broader range of disorders, but present both advantages and disadvantages (McCabe & McCabe, 2008). The NICHD favors moving from Tandem Mass Spectrometry (MS/MS) to DNA-based platform testing that “offer enormous opportunities to identify stagger-ing numbers of potentially pathogenic mutations in a very large number of disease-associated genes” (The President’s Council on Bioethics, 2008, p. 53). While this far exceeds current pat-terns of accepted usage of screening techniques, it’s the undeni-able direction in which we are heading.

With the rapid progress of DNA technologies, newborn screening is expected to become more sophisticated. Many more disease conditions could potentially be added to the screening panel. Complicated issues arise, however, when de-termining whether all available screening tests should be per-formed or whether tests should be limited to those that are

With the rapid progress of DNA technologies, newborn screening is expected to become more sophisticated

Box 5 American College of Medical Genetics Criteria

Incidence > 1/100,000

Significant morbidity/mortality

Successful treatment

Reasonable cost

Technology available

Source: ACMG (2006).


and labeling of the sample occur at the time of collection. As with all samples, it’s critical to adhere to the “5 Rights” of sam-ple collection: right specimen, right time, right patient, right method, and right documentation/labeling. Taking the sample too early (prior to 24 hours of life), prematurity, infections and total parenteral nutrition (TPN) feedings can all contribute to false readings. Newborn screening is usually first performed at 24 to 48 hours after birth. The screening can be repeated at up to 1 to 2 weeks of age if needed. In more than 10 states, new-born screening is routinely repeated at several weeks age (AAP Newborn Screening Authoring Committee, 2008).

Proper collection of newborn screening samples from heel sticks of newborn infants requires training and skill. Some samples must be repeated due to collection error. Nurses and technicians know many techniques and tricks for obtaining an adequate and reliable sample while at the same time provid-ing for patient comfort and safety. Collecting blood samples on newborns is not easy and can be painful for the infant. Warm-ing the heel, using proper positioning, selecting the proper lo-cation on the heel and using gentle, intermittent massage are all helpful in maintaining a steady flow of capillary blood. Each of the five circles on the filter paper must be completely filled in when viewed from both sides. Blood must be applied only

Box 6 Sensitivity and Specificity in Newborn Screening

example from reported rates term definition for maple syrup urine disease (msud)

Sensitivity

Specificity

Positive predictive value (PPV)

False positive

Sources: Gordis (2009); Stanhope and Lancaster (2008); Tarini (2007)

Ability of the test to identify correctly those who have the disease/condition.

Ability of the test to identify correctly those who do not have the disease/condition.

Proportion of persons with a positive test who actually have the disease (probability that an individual with a positive test has the disease)

Those identified as positive who do not actually have the disease/condition

100%

99.96%

1.4%PPV is based on 68 false positives for every true positive detected, and an estimated prevalence of one in 180,000 for MSUD

3 million newborns screened positive for MSUD in the U.S. in 2007, but only 1249 tested positive and only 18 were actually confirmed. The other 1231 were false positives. Overall it is estimated that MS/MS screening will have yielded more than 10,000 false positives/year


conclusionHistorically in health care we try to catch up ethically, socially and economically with issues identified by new knowledge and technology. One strategy is to increase the knowledge of all

to the front, filling each circle before moving to the next, and avoiding overlapping previously applied blood. After collec-tion, the sample paper must air-dry for at least 3 hours. Then the sample is sent to the lab and results are reported to the state health department and to the infant’s pediatrician who reports the results to the parents.

Quality Parent and Family EducationCommunication with parents is key. This education about new-born screening can begin in the prenatal period. After delivery, parents need to know that the screening has been done. They also need to understand the limitations of screening, especially because of the risk of false positives. It may be helpful to say to parents, “We are screening now to determine what testing your baby may need to have done later, if any.”

Emotional Support Nurses in pediatric outpatient settings also play an impor-tant role. One of the most difficult aspect of positive newborn screening results is helping families cope with the anxiety raised by results. A prolonged waiting time (days, weeks or months) for follow-up lab results can be an excruciating experience for parents (Gurian et al., 2006). It’s important to keep parents calm and informed during repeat screening. Taking time to make sure that the information about negative screening or testing results is clear and helping parents process this infor-mation may help avoid vulnerable child syndrome. They need to know their child is healthy. Parents can easily misunderstand even negative results.

If screening is positive, parents need to know their child will still need more thorough diagnostic testing and follow-up be-fore a diagnosis can be made. Providing information and sup-port is essential to ensure that all their needs and questions are answered. At first, parents may have concerns about diagnosis and treatment for their newborn, but later they may express fear and anxiety related to identifying affected siblings (or them-selves), and fear of recurrence in future pregnancies. Nurses can provide information and referrals throughout this process.

A positive screen and follow-up test can be very distress-ing. It can be hard to believe, especially when the baby other-wise appears healthy. The good news is that in many of these cases, simple diet changes can prevent serious physical or mental disability.

Nurses need to be knowledgeable about the new tests and implications and controversies. Educational resources for health care providers and parents are available through many organizations (see Get the Facts). Nurses should also be aware of their own local resources, experts and community groups. Collaborating with physicians, genetic counselors, dietitians and health departments, we can all help ensure close follow-up and supportive counseling for families.

Get the Facts

AAP

http://medicalhomeinfo.org/screening/newborn parent resources.html

ACMG

http://www.acmg.net/

ACOG

http://www.acog.org/from_home/misc/ dept_pubs.cfm

March of Dimes

http://www.marchofdimes.com/580_9611.asphttp://www.marchofdimes.com/298_834.asp

National Library of Medicine

http://newbornscreeningcodes.nlm.nih.gov/nb/sc/

National Newborn Screening and Genetics Resource Center

http://genes-r-us.uthscsa.edu/

National Newborn Screening Status Report

http://genes-r-us.uthscsa.edu/nbsdisorders.pdf

Save Babies Through Screening Foundation, Inc.

http://www.savebabies.org/http://www.savebabiescanada.org/

U.S. Department of Health and Human Services

http://www.mchb.hrsa.gov/screening/ summary.htm


health care providers regarding screening, testing and positive results for each of these diseases. Working together with or-ganizations such as AWHONN, AAP, American College of Ob-stetricians and Gynecologists (ACOG), ACMG and state health departments we can help meet this goal. Another important goal is to increase public awareness and educate families about these new screening tests.

Within our professional lifetimes, expansion of current technology to a DNA platform will include screening for con-ditions that are currently not treatable and some that may not present symptoms for decades. The ethical implications are staggering. The genetic revolution has arrived and will require maternal-child health nurses to keep current on the rapidly changing area of newborn screening. NWH

referencesAlexander, D., & van Dyck, P. C. (2006). A vision of the future of

newborn screening. Pediatrics, 117(5, Pt. 2), S350–S354.

American Academy of Pediatrics Newborn Screening Authoring Committee. (2008). Newborn screening expands: Recommenda-tions for pediatricians and medical homes—Implications for the system. Pediatrics, 121(1), 192–217.

American College of Medical Genetics. (2006). Newborn screening: Toward a uniform screening panel and system. Genetics in Medi-cine, 8(Suppl. 1), 1S–252S.

Association of Public Health Laboratories (2008). Saving babies with a drop of blood. Retrieved from http://www.aphl.org/AboutAPHL/publications/Documents/CA_newborn_success_story.pdf

Association of Women’s Health, Obstetric and Neonatal Nurs-es. (2005). National standards for newborn screening. Re-trieved from http://www.awhonn.org/awhonn/content.do;jsessionid=57B472378BCD172DB6DEAA15CE169D55?name=02_PracticeResources/2C3_Focus_NearTermInfant.htm

Baily, M., & Murray, T. (2008). Ethics, evidence, and cost in newborn screening. Hastings Center Report, 38(3), 23–31.

Bellig, L. L. (2004). Maternal acute fatty liver of pregnancy and the associated risk for long-chain 3-hydroxyacyl-coenzyme a dehy-drogenase (LCHAD) deficiency in infants. Advances in Neonatal Care, 4(1), 26–32.

Canadian Organization for Rare Disorders. (2008). National New-born Screening and Genetics Resource Center. Retrieved from http://genes-r-us.uthscsa.edu/CA_nbsdisorders.pdf

Centers for Disease Control and Prevention. (2008). Impact of ex-panded newborn screening—United States, 2006. Morbidity and Mortality Weekly Report, 57(37), 1012–1015.

den Boer, M. E., Wanders, R. J., Morris, A. A., IJlst, L., Heymans, H. S., & Wijburg, F. A. (2002). Long-chain 3-hydroxyacyl-CoA de-hydrogenase deficiency: Clinical presentation and follow-up of 50 patients. Pediatrics, 109(1), 99–104.

Gordis, L. (2009). Epidemiology. Philadelphia, PA: Saunders Elsevier.

Gurian, E. A., Kinnamon, D. D., Henry, J. J., & Waisbren, S. E. (2006). Expanded newborn screening for biochemical disorders: The ef-fect of a false-positive result. Pediatrics, 117(6), 1915–1921.

Hastings Center. (2009). Disputes over research with residual new-born screening blood specimens. Retrieved from http://www.the-hastingscenter.org/Bioethicsforum/Post.aspx?id=3826

Johnson, K., Lloyd-Puryear, M. A., Mann, M. Y., Ramos, L. R., & Therrell, B. L. (2006). Financing state newborn screening programs: Sources and uses of funds. Pediatrics, 117(5, Pt. 2), S270–S279.

Kerruish, N. J., & Robertson, S. P. (2005). Newborn screening: New developments, new dilemmas. Journal of Medical Ethics, 31(7), 393–398.

Lloyd-Puryear, M. A., Tonniges, T., van Dyck, P. C., Mann, M. Y., Brin, A., Johnson, K., et al. (2006). American academy of pediat-rics newborn screening task force recommendations: How far have we come? Pediatrics, 117(5, Pt. 2), S194–S211.

March of Dimes. (2009). Newborn screening. Retrieved from http://www.marchofdimes.com/580_9611.asp

McCabe, L. L., & McCabe, E. R. (2008). Expanded newborn screen-ing: Implications for genomic medicine. Annual Review of Medi-cine, 59, 163–175.

National Library of Medicine. (2009). Newborn screening coding and terminology guide. Retrieved from http://newbornscreeningcodes.nlm.nih.gov/nb/sc/

National Library of Medicine. (2010). Genetics home reference. Re-trieved from http://ghr.nlm.nih.gov/

National Newborn Screening and Genetics Resource Center. (2010). National newborn screening status report. Retrieved from http://genes-r-us.uthscsa.edu/nbsdisorders.pdf

The President’s Council on Bioethics. (2008). The changing moral focus of newborn screening: An ethical analysis by the President’s Council on Bioethics. Retrieved from http://www.bioethics.gov/reports/newborn_screening/index.html

Schulze, A., Lindner, M., Kohlmuller, D., Olgemoller, K., Mayatepek, E., & Hoffmann, G. F. (2003). Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: Results, outcome, and implications. Pediat-rics, 111(6, Pt. 1), 1399–1406.

Stanhope, M., & Lancaster, J. (2008). Public health nursing. St Louis, MO: Mosby Elsevier.

Tarini, B. A. (2007). The current revolution in newborn screening: New technology, old controversies. Archives of Pediatrics and Ad-olescent Medicine, 161(8), 767–772.

Waisbren, S. E., Albers, S., Amato, S., Ampola, M., Brewster, T. G., Demmer, L., et al. (2003). Effect of expanded newborn screening for biochemical genetic disorders on child outcomes and parental stress. Journal of American Medical Association, 290(19), 2564–2572.

Waldholz, M. (2004, June 17). A simple test saves one baby; another falls ill. Wall Street Journal, p. A1.

Wilson, J., & Jungner, G. (1968). Principles and practice of screening for disease. Geneva, Switzerland: World Health Organization. Re-trieved from http://whqlibdoc.who.int/php/WHO_PHP_34.pdf

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