Newborn Screening

Chapter 57 Newborn Screening



Louis E. Bartoshesky, MD, MPH




Speaking Intelligently


Newborn screening (NBS) is of proven public health value. Although it is true that the disorders screened for are relatively uncommon (ranging from congenital hypothyroidism occurring about 1 per 4000 live births to some of the organic acidopathies or fatty acid oxidation disorders occurring less than 1 per 100,000), when taken together the disorders are common enough that screening is clearly cost-effective. About 1 in every 600 infants has a disorder identifiable by newborn screening. Newborn blood spot screening is a program, not just a laboratory test. The mission of NBS programs is to eliminate or reduce morbidity, mortality, and disability that result from disorders in the screening panel. To accomplish this, all affected newborns must receive early confirmatory diagnosis and optimal long-term management.



Medical Knowledge and Patient Care


The components of a newborn screening program are:


1 Screening: The laboratory testing

2 Follow-up: Rapid location and referral of potentially affected infants

3 Diagnosis: Confirmation or exclusion of the presumptive diagnosis

4 Management: Planning and implementation of long-term management, ideally coordinated in the child’s medical home (see Chapter 25, The Special Needs Child)

5 Evaluation and quality assurance: Validation of testing material, assessment of efficiency of follow-up procedures, analysis of cost-benefit ratios, and assessment of benefit to patients, families, and the public

6 Education of health-care institutions and providers and the public

The NBS team includes the birth hospital where the specimen is obtained; the screening laboratory where testing is carried out; the follow-up team whose job is to communicate results and recommendations for follow-up with family, primary care provider, and referral center; the family; the public health infrastructure; specialty referral centers; and the primary care pediatrician whose job is to coordinate the often complex evaluation and follow-up of infants who test positive.1


Interpretation of an NBS result requires an understanding of population screening and appreciation of the features of a good screening test:2


• Reasonable sensitivity, specificity, and predictive value

• Reasonable prevalence rate of the disorder

• Cost-effectiveness

• Availability of an effective intervention

• Reproducible results and timely reports

• Public health and community resources to do adequate follow-up and management of detected disorders

Life-threatening disorders (e.g., congenital adrenal hyperplasia, galactosemia, maple syrup urine disease, propionic acidemia and other organic acidopathies, disorders of urea cycle) demand immediate response, and others are associated with increasing disability with delay in intervention (e.g., congenital hypothyroidism, phenylketonuria [PKU]). Some disorders do not require immediate attention (e.g., hemoglobinopathies, cystic fibrosis [CF]), but should be dealt with promptly by the NBS program and pediatrician.


Family history is important in evaluating a newborn with a suspicious newborn screening result. Previous infant deaths, relatives with metabolic, endocrinologic, and hematologic disorders are important to know about. The NBS program should know the birth weight and gestational age of babies screened. Interpretation of results on very low-birth-weight (VLBW) infants may be difficult. Amino acids may be elevated in infants receiving parenteral nutrition. VLBW infants may have low thyroxine (T4) level with normal thyroid-stimulating hormone (TSH) level. Certain acyl carnitines detected by tandem mass spectroscopy (MS-MS) may appear elevated in babies on certain antibiotics. 17-Hydroxyprogesterone (the analyte elevated in infants with 21-hydroxylase deficiency congenital adrenal hyperplasia [CAH]) levels are higher in low-birth-weight infants and sometimes in more mature babies who are stressed (e.g., neonatal sepsis).


Some disorders, particularly organic acidopathies and amino acidopathies, may be characterized by poor feeding, irritability, and/or seizures, with onset before the NBS result is available.


The NBS specimen is usually collected on day 2 to 3 of life, but the infant should be at least 24 hours old and fed at least twice at the time of specimen collection. In some situations (e.g., a sick newborn being transferred to another hospital), an earlier specimen may be obtained, but early specimens (before 24 hours) must be followed by a repeat screen at a week or so. Some states have a mandatory second screen at 2 to 4 weeks of age. Some infants with congenital hypothyroidism, a few with CAH, and some with other disorders may be missed on first screen and detected on the second. Evidence of the value of a mandatory screen is anecdotal, although a collaborative study comparing one-screen and two-screen states is under way.


States that perform a single NBS may suggest a prompt repeat screen for a suspicious but not definitively abnormal initial NBS. For example, if the cutoff or “action level” at a given newborn screening laboratory for phenylalanine (the analyte elevated in PKU) is 121 µmole/L, but the level known to be associated with PKU is >150 µmole/L, the NBS program may suggest a prompt repeat screen for babies whose initial level is >120 but <150 µmole/L.


The point of newborn screening is to identify affected infants before symptoms develop, so physical examination is usually normal in the newborn nursery. However, certain features may give clues to a disorder in the NBS. Ambiguous genitalia and/or increased pigmentation may be seen in infants with 21-hydroxylase deficiency; children with certain organic or amino acidopathies may be irritable, hypertonic, or hypotonic; infants with glutaric aciduria I may have macrocephaly; infants with galactosemia may have detectable cataracts, direct hyperbilirubinemia, and/or clinical evidence of coagulopathy; infants with disorders of urea cycle may have tachypnea and irritability associated with hyperammonemia; infants with certain organic or amino acidopathies may have a characteristic smell such as the smell of maple syrup.


Each state decides for which disorders it wishes to screen. However, recently an expert panel convened by the American College of Medical Genetics with support from the federal Genetics Branch of the Maternal and Child Health Bureau recommended a panel of 28 disorders (29 including newborn hearing screening) as the “core panel.” Another 25 or so disorders (the number may vary depending on how multiple possible hemoglobinopathies are counted) were recommended as “secondary targets” that a state may wish to include as part of its program. Some secondary targets are identified by the same analytes that identify core disorders (e.g., tyrosinemia types I, II, and III are all identified by elevated blood tyrosine level.). Recently, severe combined immunodeficiency (SCID) was approved to be included in the core panel.3,4


The 29 disorders on the core panel are:


Organic acidopathies: Isovaleric aciduria, glutaric aciduria I, 3-OH 3CH3 glutaric aciduria (HMG), multiple carboxylase deficiency, methylmalonic acidemia, 3-methylcrotonyl CoA carboxylase deficiency, cobalamine A, B disorders, propionic acidemia, β-ketothiolase deficiency.
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Related posts:

  1. The Special Needs Child
  2. Diarrhea (Case 6)
  3. Pediatric Poisonings (Case 54)
  4. Note Writing

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Jul 18, 2016 | Posted by in PEDIATRICS | Comments Off on Newborn Screening

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