essential, and the parent must be able to contact the provider when the infant is ill.

Appropriate medical followup must include regular visits to assess the child's medical status, administration of age-appropriate immunizations— including pneumococcal, conjugated Haemophilus influenzae, and hepatitis B vaccines and provision of other infant-specific health care services. The importance of nutrition and well-child care should be stressed. The provider should assess the family's need for supportive social services, including those related to transportation, financial aid, and mental health, and make appropriate referrals when indicated. The provider also should provide anticipatory guidance related to psychosocial issues relevant to sickle cell disease.

Education and Genetic Counseling

Education services should be offered to all parents of infants who are identified with a hemoglobin abnormality. These services should be nondirective and conducted in an environment conducive to the free exchange of information. Parents should be offered the opportunity to be tested if desired. The education curriculum should define clearly differences between disease and trait conditions and provide information to parents on the risks of having future children with disease. Educators should be sensitive to parental anxieties and be willing to schedule additional sessions as needed. The education component adds substantial cost to the screening program, particularly in those areas where large numbers of African-American individuals reside, as 8 percent of this ethnic group can be anticipated to have sickle cell trait. “Single gene” educators -specifically trained, properly supervised, and monitored can be used to meet this need.

Decision-making counseling should be offered to all parents of infants who are affected with disease and to those parents at risk for having other children infected with disease. This counseling should be provided by persons specially trained for this task, including physicians, genetic counselors, nurses, and medical social workers.

Conclusion

Overriding these recommendations is the basic tenet that a newborn sickle cell screening program must include several components that are operative and fully integrated if the program is to succeed in reducing morbidity and mortality from sickle cell disease. These components include an administrative component, a laboratory component, a medical followup component, and an education/counseling component.

Several different models have been used successfully in the United States to establish and monitor newborn hemoglobinopathy screening programs. In most instances, the State department of health is the agency

responsible for the overall conduct of all components of the screening program. Usually that State department of health collaborates with a coordinating or advisory group within the screening jurisdiction.

Laboratory testing may be performed by a State laboratory or contracted to a laboratory based in a medical center, hospital, or other facility. Several strategies have been used to provide education and genetic counseling services. These include the use of State-employed genetic counselors or contracting with counselors who are based either in hospitals or community agencies. Several different approaches have been taken to the medical followup component. Some States provide no support, others provide funding for total care, and still others fund only consultative visits or prophylactic penicillin therapy.

For the screening program to be successful in documenting its ability to meet stated goals, each component must report to the program's administrative group, and the administrative component must have the authority and resources to correct identified deficiencies.

Overview

Introduction

Neonatal screening and comprehensive health care can significantly reduce morbidity and mortality in infants with sickle cell disease. In addition to saving lives and reducing morbidity, neonatal sickle cell disease screening has other benefits, including the identification of individuals with sickle cell trait and other hemoglobin disorders, as well as couples at risk for having a child with a hemoglobin disease.

This guideline makes specific recommendations about the population to be screened for sickle cell disease, the laboratory methods currently acceptable for screening and diagnosis, the care of infants with sickle cell disease, and the provision of educational and decision-making counseling services to parents of affected infants and those whose infants have sickle cell trait.

What is sickle cell disease?

The term sickle cell disease refers to a group of genetic disorders characterized by the presence of sickle hemoglobin (Hb S), anemia, and acute and chronic tissue injury secondary to blockage of blood flow by abnormally shaped red cells. Normal hemoglobin, hemoglobin A (Hb A), is composed of two alpha (a) globin chains and two beta (B) globin chains. In Hb S, the a chain is the same as in Hb A, but the ẞ globin chain differs from the normal by the substitution of valine for glutamic acid at the sixth position (B). The most common type of sickle cell disease is sickle cell anemia in which the affected individual is homozygous for the ẞs gene. Other common forms of sickle cell disease include the inheritance of the ẞs gene and a gene for ẞ-thalassemia (Hb S Bthalassemia) or another abnormal ẞ globin gene. Examples of these latter conditions include Hb SC disease (Hb S and Hb C), Hb S OArab (HbS and Hb OArab) and Hb SD (Hb S and Hb D), and Hb SE (Hb S and Hb E) disease.

The hallmark features of sickle cell disease are chronic hemolytic anemia and both acute and chronic tissue injury. The amino acid substitution in the ẞ globin of Hb S results in polymerization of the Hb S molecules within the red cell upon deoxygenation. This polymerization of Hb S produces a change in the red cell shape from a biconcave disc to a crescent or sickle shape. Upon reoxygenation, the red cell initially resumes a normal configuration, but after repeated cycles of "sickling and unsickling," the erythrocyte is damaged permanently and hemolyzes. This hemolysis is responsible for the anemia in sickle cell disease.

The tissue injury is secondary to the obstruction of blood flow produced by the abnormally shaped red cells. All tissues within the body

are at risk for damage as a consequence of the vascular obstruction produced by the sickled red cells. The more common complications include painful episodes involving soft tissues and bones, acute chest syndrome, priapism, cerebral vascular accidents, and both splenic and renal dysfunction. In sickle cell anemia, the splenic dysfunction develops during infancy and predisposes the infant to overwhelming infection from encapsulated bacteria, particularly members of the Streptococcus pneumoniae and Haemophilus influenzae species.

Who is affected by sickle cell disease?

Sickle cell disease is estimated to affect more than 50,000 Americans and has been identified in persons from several different racial backgrounds. The estimated prevalence of the common sickle cell disease variants in African-American live births is approximately 1 in 375 for sickle cell anemia, 1 in 835 for Hb SC disease, and 1 in 1,667 for the sickle B-thalassemia disorders. While sickle cell disease is most commonly found in persons of African ancestry, it also affects persons of

Mediterranean, Caribbean, South and Central American, Arabian, and East Indian ancestry.

What is sickle cell trait?

In sickle cell trait, the individual has inherited both a normal ẞ globin gene and a ẞs globin gene. Individuals with sickle cell trait produce both normal hemoglobin (Hb A) and Hb S and have a predominance of Hb A. Red cells from persons with sickle cell trait do not sickle except under adverse circumstances. Persons with sickle cell trait have normal hemoglobin concentrations and normal red cell morphology.

Approximately 8 percent of the African-American population in the United States has sickle cell trait. The prevalence of sickle cell trait is lower in other racial and ethnic groups.

Background

The passage of the National Sickle Cell Anemia Control Act in 1972 authorized funding for research, testing, and education related to sickle cell anemia. Funds appropriated within the budget of the National Heart, Lung, and Blood Institute, National Institutes of Health, established several federally funded sickle cell screening programs, as did monies from the Bureau of Maternal and Child Health, Health Resources and Services Administration. These early programs focused on detecting persons with sickle cell trait so that they could be educated about the trait and its genetic implications. Education and genetic counseling for persons with sickle cell trait were important components of these early programs.