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Am Fam Physician. 2008;77(9):1300-1302

This statement summarizes the U.S. Preventive Services Task Force (USPSTF) recommendations on screening for sickle cell disease in newborns and the supporting scientific evidence; it also updates the 1996 recommendations contained in the Guide to Clinical Preventive Services, 2nd ed.1 See Table 1 for a description of the USPSTF grades and Table 2 for a description of USPSTF classification of levels of certainty regarding net benefit. The complete information on which this statement is based, including evidence tables and references, is included in the evidence synthesis2 on this topic, available on the USPSTF Web site at http://www.uspreventiveservicestaskforce.org. For a clinical summary of this recommendation statement, see Table 3, or go to http://www.ahrq.gov/clinic/uspstf07/sicklecell/sicklesum.htm. The recommendation is also posted on the Web site of the National Guideline Clearinghouse at http://www.guideline.gov.

The USPSTF makes recommendations about preventive care services for patients without recognized signs or symptoms of the target condition. It bases its recommendations on a systematic review of the evidence of the benefits and harms and an assessment of the net benefit of the service.

The USPSTF recognizes that clinical or policy decisions involve more considerations than this body of evidence alone. Physicians and policy makers should understand the evidence but individualize decision making to the specific patient or situation.

GradeGrade definitionSuggestions for practice
AThe USPSTF recommends the service. There is high certainty that the net benefit is substantial.Offer/provide this service.
BThe USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.Offer/provide this service.
CThe USPSTF recommends against routinely providing the service. There may be considerations that support providing the service in an individual patient. There is moderate or high certainty that the net benefit is small.Offer/provide this service only if there are other considerations in support of offering/providing the service in an individual patient.
DThe USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits.Discourage the use of this service.
IThe USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of the service. Evidence is lacking, of poor quality or conflicting, and the balance of benefits and harms cannot be determined.Read “Clinical Considerations” section of USPSTF Recommendation Statement. If offered, patients should understand the uncertainty about the balance of benefits and harms.

Summary of Recommendations and Evidence

The USPSTF recommends screening for sickle cell disease in newborns. A recommendation.

Rationale

Importance. Sickle cell anemia (hemoglobin SS) affects one in 375 African American newborns born in the United States and smaller proportions of children in other ethnic groups. Without prompt diagnosis and the initiation of prophylactic antibiotics and pneumococcal conjugate vaccination by two months of age, children with sickle cell anemia are vulnerable to life-threatening pneumococcal infections. 1

Level of CertaintyDescription
HighThe available evidence usually includes consistent results from well-designed, well-conducted studies in representative primary care populations. These studies assess the effects of the preventive service on health outcomes. This conclusion is therefore unlikely to be strongly affected by the results of future studies
ModerateThe available evidence is sufficient to determine the effects of the preventive service on health outcomes, but confidence in the estimate is constrained by factors such as:
  • the number, size, or quality of individual studies

  • inconsistency of findings across individual studies

  • limited generalizability of findings to routine primary care practice

  • lack of coherence in the chain of evidence

As more information becomes available, the magnitude or direction of the observed effect could change, and this change may be large enough to alter the conclusion
LowThe available evidence is insufficient to assess effects on health outcomes. Evidence is insufficient because of:
  • the limited number or size of studies

  • important flaws in study design or methods

  • inconsistency of findings across individual studies

  • gaps in the chain of evidence

  • findings not generalizable to routine primary care practice

  • a lack of information on important health outcomes

More information may allow an estimation of effects on health outcomes

Detection. In the United States, most state-based screening programs utilize thin-layer isoelectric focusing (IEF) or high performance liquid chromatography (HPLC) techniques performed on capillary blood collected from a heel stick and absorbed onto filter paper. The sensitivity and specificity of each of these tests approach 100 percent. 3

Benefits of detection and early intervention. There is good evidence that early detection of sickle cell anemia followed by prophylactic oral penicillin substantially reduces the risk of serious infections during the first few years of life. Additional benefits result from pneumococcal conjugate vaccination and parental education about early warning signs of infection. Finally, detection of sickle cell disease permits counseling for family members about disease management and future reproductive decisions.

Harms of detection and early treatment. Incidental detection of sickle cell carrier status and hemoglobin disorders of questionable clinical significance has the potential to cause psychosocial harms, which may include exposure of nonpaternity, stigma and discrimination, negative impact on self-esteem, and anxiety about future health.

USPSTF assessment. The USPSTF concludes that there is high certainty that the net benefit of screening for sickle cell disease in newborns is substantial.

Clinical Considerations

Patient Population. This recommendation applies to all newborns.

Screening Tests. Screening for sickle cell disease in newborns is mandated in all 50 states and the District of Columbia. Most states use either thin-layer IEF or HPLC as the initial screening test. Both methods have extremely high sensitivity and specificity for sickle cell anemia. Specimens must be drawn before any blood transfusion because of the potential for a false-negative result caused by the transfusion. Extremely premature infants may have false-positive results when adult hemoglobin is undetectable.4

Timing of Screening. All newborns should undergo testing regardless of birth setting. In general, birth attendants should make arrangements for samples to be obtained, and the first physician to see the child at an office visit should verify screening results. Confirmatory testing should occur no later than two months of age.

Treatment. Children with sickle cell anemia should begin prophylactic penicillin by two months of age and receive pneumococcal immunizations at recommended intervals.

PopulationAll newborns
RecommendationScreen for sickle cell disease
Grade: A
Screening TestsScreening for sickle cell disease in newborns is mandated in all 50 states and the District of Columbia In most states, one of these tests is used for the initial screening:
  • thin-layer isoelectric focusing (IEF)

  • high-performance liquid chromatography (HPLC)

Both IEF and HPLC have extremely high sensitivity and specificity for sickle cell anemia
Timing of ScreeningAll newborns should undergo screening regardless of birth setting; birth attendants should make arrangements for samples to be obtained; the first physician to see the infant at an office visit should verify screening results; confirmatory testing should occur no later than two months of age
TreatmentInfants with sickle cell anemia should receive:
  • prophylactic penicillin starting by age two months

  • pneumococcal immunizations at recommended intervals

Other relevant recommendations from the USPSTFAdditional USPSTF recommendations regarding screening tests for newborns can be accessed at http://www.ahrq.gov/clinic/cps3dix.htm#pediatric
These recommendations and related evidence are available at http://www.uspreventiveservicestaskforce.org/recommendations.htm

Other Considerations

Research Needs and Gaps. Screening tests will identify approximately 50 sickle cell carriers for every infant diagnosed with sickle cell disease. Research is needed to determine the psychosocial effects of communicating newborn carrier status information, and to identify the types of counseling practices most likely to benefit families and minimize harmful effects. Research is also needed on alternative methods of screening capable of identifying only clinically significant hemoglobinopathies.

Discussion

After reviewing the evidence in 1996, the USPSTF recommended screening for sickle cell disease in newborns.1 In 2007, the USPSTF performed a brief literature review and determined that the benefits of screening continue to be well established. This update included a search for new and substantial evidence on the benefits and harms of screening.2 The USPSTF found no new substantial evidence on the benefits and harms of screening for sickle cell disease in newborns and therefore reaffirms its recommendation that all newborns be screened for sickle cell disease. The 1996 recommendation statement and supporting materials, and the 2007 summary of the updated literature search, can be found at http://www.uspreventiveservicestaskforce.org/recommendations.htm.

Recommendations from Other Groups

The American Academy of Family Physicians,5 the American Academy of Pediatrics,6 and the American College of Medical Genetics7 strongly recommend universal newborn screening for sickle cell disease.

This series is coordinated by Joanna Drowos, DO, contributing editor.

A collection of USPSTF recommendation statements published in AFP is available at https://www.aafp.org/afp/uspstf.

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