Blood Samples

• To obtain reliable results, blood samples for sickle cell screening must be collected prior to transfusion.

• Blood samples collected from the infant by heel stick onto filter paper are preferred for sickle cell screening because shipment to the laboratory is easy. This collection method is currently employed for other screening programs including those for phenylketonuria, hypothyroidism, and galactosemia.

• Liquid blood samples, obtained from the umbilical cord or directly from the infant, are acceptable alternatives but are more expensive and difficult to transport to the screening laboratory.

Testing Methods

• Hemoglobin electrophoresis, isoelectric focusing, and high performance liquid chromatography are all proven, reliable, and accurate methods for defining an infant's hemoglobin phenotype.

• Globin DNA analysis is an additional testing method, though this method requires considerable expertise and is costlier than the more established methods.

• The methods chosen for screening newborns should have high rates of sensitivity and specificity for identification of newborns with sickle cell disease and other clinically important hemoglobinopathies.

Note: Neither the sodium metabisulfite sickle cell preparation nor solubility tests employing a concentrated phosphate buffer and sodium dithionate should be used for newborn screening or confirmation of Hb S in early infancy.

Responsibilities of Health Care Providers

• Assignment of definitive diagnosis is the responsibility of the infant's physician. Physicians unfamiliar with diagnostic criteria should seek consultation from hematologists knowledgeable about sickle cell disease, thalassemia, and other hemoglobinopathies.

• When a newborn tests positively for sickle cell disease or other hemoglobinopathy, health care providers should immediately contact the parents to inform them of the need for the infant's immediate evaluation and retesting.

• Since newborn screening does not establish a definitive diagnosis, a second sample must be collected from the infant. In addition to defining the hemoglobin phenotype, the second specimen should be used to determine a complete blood count with red cell indices and assessment of red cell morphology.

• Characterization of the hemoglobin phenotype of the parents can be extremely helpful. The clinician must be aware that testing of the parents may disclose nonpaternity.

• DNA analysis of the infant's beta globin gene complex also may be used to establish a definitive diagnosis.

• Physicians and other health care providers must be aware that any sign of illness in an infant with sickle cell disease is a potential medical emergency. Complications of sickle cell disease include, but are not limited to sepsis, acute chest syndrome, splenic sequestration crisis, aplastic crisis, stroke and hand-and-foot syndrome, and painful episodes.

• The physician or other health care provider is responsible for providing or arranging for appropriate education and genetic counseling for the parents.

Prophylactic Penicillin

• Infants with documented or suspected sickle cell anemia or Hb S beta^o-thalassemia should be started on twice-daily oral prophylactic penicillin as soon as possible, but no later than 2 months of age.

• In those instances where the definitive diagnosis cannot be determined, an infant with the FS phenotype should be maintained on prophylactic penicillin until the definitive diagnosis is established.

• Prophylactic penicillin should be continued until at least 5 years of age.

Well-Baby Care

• Infants with sickle cell disease should receive standard well baby care. In addition to immunizations against polio, diphtheria, tetanus, measles, mumps, and rubella, children with sickle cell disease should be immunized against Haemophilus influenzae beginning at age 2 months and should receive polyvalent pneumococcal vaccine at age 2 years. Infants also should be immunized against hepatitis B virus.

• Diet should be monitored to ensure that the child with sickle cell disease is receiving all necessary nutrients and adequate calories. Multivitamins during the first 2 years of life may be appropriate.

Parental Instruction

• Health care providers must stress to parents the importance of twice-daily doses of prophylactic penicillin as an effective measure to reduce both morbidity and mortality from pneumococcal infections in infants with sickle cell anemia and Hb S beta^o-thalassemia.

• Parents of infants with sickle cell disease should be instructed in all aspects of routine child care and should be able to determine accurately the infant's temperature. They must be able to recognize complications of sickle cell disease, including the signs and symptoms of fever, pallor, and respiratory distress. Parents should be instructed on palpation of the infant's spleen and be taught to recognize splenic enlargement.

• The parents must understand the importance of prompt assessment of the infant by a physician knowledgeable about sickle cell disease when there is fever, pallor, unexplained irritability, diarrhea, vomiting, or other signs of illness.

Access to Care

• Acutely ill infants with sickle cell disease should have access to tertiary care facilities that are staffed by pediatricians and pediatric surgeons knowledgeable about sickle cell disease.

• These facilities should include a sophisticated blood bank and clinical laboratories, as well as modern imaging equipment.

Principles

• A neonatal sickle cell screening program not only identifies infants with sickle cell disease, but also opens a "genetic window," which can result in the detection of other family members with sickle cell trait, sickle cell disease, or other hemoglobin diseases and heterozygotes for hemoglobin variants.

• Screening programs have an obligation to inform parents regarding their infant's result and to offer related education and counseling.

• Screening provides an invaluable opportunity to educate and counsel families.

Education

• Sickle cell education should include an explanation of the differences between the disease and the trait, prevalence of sickle cell trait and anemia in the U.S. population, the health status of persons with sickle cell trait, and the risks of having a child with sickle cell disease for persons with the trait.

• Information should be presented clearly using interactive techniques, appropriate graphics, and plain language. Easily understandable literature should be given to the parents to take home at the end of the education session.

• Parents should be offered the opportunity to be tested if they so desire. All adults testing positive for either Hb S, beta^o-thalassemia trait, or a variant hemoglobin and those who have partners with either of these conditions also should be offered decision-making counseling.

• At a minimum, sickle cell educators should have a high school diploma and a certificate of competency in sickle cell education. The certifying process should be approved by the administrative component of the screening program and include successful completion of an examination that assesses knowledge of the material.

• The educator's skills should be evaluated periodically, and their sickle cell knowledge base should be updated annually.

Decision-Making Counseling

• Decision-making counseling should provide objective information about sickle cell disease and trait to individuals who are at risk of having a child with sickle cell disease. It should include specific information on the natural history of the type of sickle cell disease that may affect the individual's offspring and the resources that may be required to care for the child. This empowers the prospective parents to make informed decisions.

• Decision-making counseling must always be objective and should not offer specific recommendations. The counseling atmosphere must be private and conducive to a free exchange of information.

• Counseling should be done by professionals with backgrounds and training in guidance and counseling, such as physicians, clinical geneticists, genetic associates, medical social workers, and nurses.

• Quality assurance is an essential component of a genetic counseling program.

Universal screening

1. The panel concluded that universal newborn screening should be conducted to detect sickle cell disease. This conclusion is based both on considerations of practicality and cost-effectiveness. Screening for hemoglobinopathies should be conducted in parallel with other conditions routinely screened for in newborns.

Performed in laboratories meeting appropriate standards

2. The panel concluded that sickle cell screening should be performed only in laboratories that meet appropriate standards of performance and reporting. Quality assurance activities and appropriate reporting practices are discussed in Chapter 2.

The panel concluded that any of three methods are acceptable for sickle cell screening: (1) hemoglobin electrophoresis, (2) isoelectric focusing, and (3) high performance liquid chromatography. All are considered reliable and accurate. Metabisulfite sickle cell preparations and solubility testing, however, are not acceptable screening methods for newborns and should not be used to confirm the presence of hemoglobin S in newborns and infants.

Blood samples for testing may be submitted as anticoagulated blood from the umbilical cord or as dried blood spots collected onto filter paper. Each method has advantages and disadvantages. Filter paper samples are more easily integrated into existing newborn screening programs.

Abnormality detected?

3-4. The common types of sickle-cell abnormalities are discussed in Chapters 1 and 2.

Parents of sickle cell trait infants should be offered education and counseling. Couples at risk for having an infant with sickle cell disease should be offered decision-making counseling.

Other disease?

Parents of infants with other diseases or heterozygote conditions should be offered education and counseling. Couples at risk for having a child with disease should be offered decisionmaking counseling.

5. The presence of another abnormal hemoglobin may warrant referral for medical care. Parents of children with trait should receive counseling. These issues are discussed in Chapters 1, 2, and 4.

Appropriate reporting

6. Reporting of preliminary screening results is discussed in Chapters 2 and 3.

Initiation of comprehensive care including penicillin prophylaxis and immunization

7. Children with sickle cell disease identified on screening examination should be referred to a comprehensive care program without delay. Because confirmatory testing may not be complete for several weeks or months, it is important not to delay the basic elements of care, as described in nodes 9-12.

The panel concluded that prophylaxis against pneumococcal infection is warranted in all children with sickle cell anemia and sickle beta^o-thalassemia. Administration of twice-daily oral penicillin has been demonstrated to reduce morbidity and mortality in these children. Children with sickle cell anemia also are at high risk for pneumococcal and Haemophilus influenzae infections. Immunization is extremely important (Chapter 3) and should be initiated by 2 months of age.

Confirmatory testing positive?

8. All positive screening tests for sickle cell disease require a second blood sample to confirm the initial hemoglobin phenotype. A definitive diagnosis should be established by the infant's physician.

Counseling and education of parents

9. Parents of infants with sickle cell disease must be counseled concerning the implications of their child's condition. Specifically, parents should be informed about the need for close vigilance with respect to the development of signs and symptoms that could indicate a serious medical problem. Any of the following warrant immediate medical consultation: (1) fever, (2) symptoms of respiratory tract infection, (3) increasing pallor, (4) increasing spleen size or abdominal distension, (5) weakness or numbness of an extremity, and (6) painful swelling of hands and feet. Information also should be provided concerning diet and adequate hydration. Parents should be trained in home management skills and should receive genetic counseling (Chapters 3 and 4).

Health maintenance and compliance

10. The schedule of health maintenance visits need not differ from that used for a well child. Strenuous efforts must be made by the health care provider to ensure compliance with penicillin prophylaxis (Chapter 3).

Parent presents child for emergency care?

11. Parents should be encouraged to seek immediate medical attention whenever the warning signs described in node 12 are noted.

Patient febrile?

12. Fever over 101 degrees F (38.5 degrees C) requires immediate medical evaluation. The parent also should be told that changes in behavior (unusual somnolence or irritability) or alimentation (refusing feeding, vomiting or diarrhea) are other possible early signs of significant illness.

Consider sepsis

13. It is critical that all health care providers who care for patients with sickle cell disease be knowledgeable about the significance of fever in these children. The importance of evaluating febrile sickle cell children promptly and administering broad spectrum antibiotics are emphasized. Management of febrile children with sickle cell disease is discussed in Chapter 3.

Pallor, lethargy, and abdominal symptoms?

14-15. Acute anemia emergencies are common in children with sickle cell disease, particularly acute splenic sequestration and aplastic crises. Diagnosis and management of these conditions are discussed in Chapter 3.

Limping, paresis, or other symptoms compatible with stroke?

16-17. Although relatively infrequent, both parents and providers must be alert for the possibility of a stroke. Any loss of consciousness or weakness of an extremity should be evaluated promptly.

Painful swelling of hands and feet?

18-19. The most frequent early complication of sickle cell disease is the hand-and-foot syndrome, or dactylitis (Chapter 3).

Note: All chapter references are to the complete Clinical Practice Guideline, Sickle Cell Disease: Screening, Diagnosis, Management, and Counseling in Newborns and Infants.