Part IV: DEVELOPING, IMPLEMENTING, AND EVALUATING POPULATION INTERVENTIONS Chapter 22

 

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• Chapter 18
  Genetics and Prevention Effectiveness
• Chapter 22
  Newborn Screening for Sickle Cell Disease: Public Health Impact and Evaluation
• Chapter 23
  Public Health Strategies to Prevent the Complications of Hemochromatosis

Newborn Screening for Sickle Cell Disease: Public Health Impact and Evaluation

Richard S. Olney

Division of Birth Defects and Pediatric Genetics, National Center for Environmental Health, Centers for Disease Control and Prevention, 4770 Buford Highway, MS F45, Atlanta, GA 30341-3717

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Establishment | Target | Public Health | Evaluation | Importance | Remarks | Tables | References

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INTRODUCTION

The most common abnormal hemoglobin detected by newborn screening programs in the United States is S or sickle hemoglobin, the defining characteristic for sickle cell disease. Hemoglobin S is produced by a mutated gene coding for one of the blood proteins. Homozygous sickle cell (hemoglobin SS) disease results when the sickle gene mutation is inherited from each parent. Sickle cell disease also occurs when the sickle mutation is inherited from one parent, and one of several other mutations is inherited from the other parent: the most common resulting conditions are sickle cell-hemoglobin C disease and the sickle beta-thalassemia syndromes. Childhood manifestations of these conditions may include susceptibility to serious infections, life-threatening splenic sequestration and severe anemia, stroke, episodes of severe pain, or events of respiratory compromise known as the acute chest syndrome. Newborn screening allows for enrollment in comprehensive specialty care programs, early institution of prophylactic therapies, and parental education to recognize these serious complications.

Many details about basic scientific, clinical, and general preventive aspects of sickle cell disease are beyond the scope of this chapter, but several review articles pertinent to these topics have been published recently (1-7). Three recent sickle cell or newborn screening textbooks include chapters on newborn hemoglobinopathy screening with details about laboratory aspects and programmatic issues, and a supplemental issue of Pediatrics published in 1989 was devoted to individual states’ experiences with hemoglobinopathy screening and other perspectives (8-11). This chapter provides a broad overview of public health aspects of newborn hemoglobinopathy screening in the United States, with special emphasis on epidemiologic efforts to evaluate pediatric outcomes after newborn screening.

ESTABLISHMENT OF NEWBORN SCREENING PROGRAMS

Research programs directed at screening large numbers of cord blood specimens for hemoglobinopathies were done in the 1960s, but local pilot programs with clinical follow-up were not initiated by hematologists until the early 1970s, and the first statewide newborn screening program was not implemented until 1975 (Table 1) (12-14). In 1972, the 92nd Congress of the United States passed the National Sickle Cell Anemia Control Act. This law called for grant support for screening programs, “first to those persons who are entering their child-producing years, and secondly to children under the age of 7” (15). After passage of this and other legislation at the federal and state level, many state health departments received funding and mandates to expand their newborn screening programs to include hemoglobinopathies. However, widespread acceptance and implementation of newborn hemoglobinopathy screening were hampered by several factors. Doubts about one of these issues, the effectiveness of early treatment, were greatly relieved after the results of a randomized trial published in 1986 showed the efficacy of daily oral penicillin prophylaxis in preventing infection among young children with sickle cell disease (16,17).

The results of prophylactic penicillin trials in the U.S. and Jamaica led to scientific consensus about the need for screening and subsequently widespread adoption of newborn hemoglobinopathy screening programs. Details of these events provide an unusual example of the results of well-designed epidemiologic studies driving newborn screening policy; newborn screening for other conditions in the U.S. has not often been preceded by such rigorous studies of efficacy and safety (18).

In these studies, penicillin was prescribed for daily oral use in the U.S. and monthly home intramuscular injections in Jamaica (17,19). All but one of the treated children in both countries were younger than 36 months of age at study entry, but only some were identified at birth by newborn screening. In the U.S., 105 children with hemoglobin SS were randomized to receive penicillin, and there were 143 Jamaican children in the penicillin group. Among Jamaican children younger than age 36 months, no pneumococci were isolated from the blood or spinal fluid of these children while they were receiving penicillin, whereas two pneumococcal organisms were isolated in the group not treated with penicillin; no deaths occurred in either group among children younger than age 36 months (the age when penicillin prophylaxis was terminated). In the U.S., the rate of pneumococcal septicemia or meningitis was 1.9% among the children treated with penicillin compared with 7.9% in the control group, and there were no deaths in the penicillin group compared with three in the control group.

The Jamaican results were not statistically significant, and few deaths occurred even among children in the control groups of the two studies. However, the paucity of serious pneumococcal infections in children treated with penicillin was compelling. In 1987, after publication of the U.S. study, two federal agencies, the National Institutes of Health and the Health Resources and Services Administration, sponsored a Consensus Development Conference on Newborn Screening for Sickle Cell Disease and Other Hemoglobinopathies. Published recommendations from this conference cited the U.S. trial and called for universal hemoglobinopathy screening of newborns in most states, and a similar recommendation was made in 1993 by an expert panel convened by the federal Agency for Health Care Policy and Research (AHCPR) (20,21). Statewide newborn screening programs covering the majority of children born in the United States began after the 1987 Consensus Conference (Table 1). In 1993, of approximately 4 million newborns in the United States, more than 3.6 million were screened for hemoglobinopathies (Table 1) (14). In 1996, recognizing that a few state health departments (e.g., in the Rocky Mountains) had chosen not to develop any hemoglobinopathy screening program, the American Academy of Pediatrics recommended that pediatric practitioners in these areas screen “at-risk” newborns (22,23).

TARGETED VERSUS UNIVERSAL SCREENING

Definition of the screened population has been a controversial topic in hemoglobinopathy screening. The practice of selecting certain infants for hemoglobinopathy testing on the basis of race and ethnicity is commonly known as targeted screening. As noted above, the American Academy of Pediatrics has recommended targeted screening of certain infants younger than 2 months of age when newborn screening was not done through a state program: “in addition to African-Americans, Hispanics from Panama, South America, and the Caribbean and those whose ancestors are from the Mediterranean, India, or the Near East.” (22) Until 1998, targeted screening was done statewide in Georgia among a larger group of infants of specified heritages: African, Arabian, Central American, Greek, Maltese, Hispanic, Indian, Portuguese, Puerto Rican, Sardinian, Sicilian, South American, and Southern Asian (24). Georgia investigators compared the number of black newborns screened for hemoglobinopathies between 1981 and 1985 with black natality figures for the same period and estimated that approximately 20% of black newborns were not screened (24). This figure has been widely quoted to illustrate the deficiencies of a targeted approach. Results of a study of universal screening in the multiethnic California population also indicated that an approach of targeting certain groups in that state would have missed at least 10% of those whose sickle cell disease was actually diagnosed at birth (25). Critics of the targeted approach have also raised the issue of the cost of determining race and ethnicity in the newborn nursery (26).

The costs of various screening approaches are logical issues for public policy discussion since newborn screening has been in the province of U.S. public health departments. Although all cost-effectiveness investigators have conceded the value of newborn screening in certain populations, they differ as to whether universal screening in certain areas of the United States is a rational policy (26-29). Some investigators analyzing cost-effectiveness data have discussed the financial advantages of using multistate laboratory consortiums and suggested that this approach would justify universal screening (29). Multistate consortiums have actually been used in a few geographic areas, and virtually all state health departments with hemoglobinopathy screening programs (including Georgia) have now adopted the universal approach.

PUBLIC HEALTH IMPORTANCE OF HEMOGLOBINOPATHY SCREENING

Any screening program should be justified not only by demonstrated efficacy of early treatment, as was demonstrated by the penicillin trials for sickle cell disease, but also first by the public health importance and prevalence of the screened condition and second by the broad effectiveness of these interventions in large populations (actual outcomes) (30,31). Population-based outcome studies are a major focus of the rest of this chapter, but the prevalence issue must first be addressed by examining well-established population-based data.

Rates of sickle cell disease by race and ethnicity are often cited in discussions about the population to be screened. Table 2 shows abbreviated results of a meta-analysis of newborn screening and other data published by the AHCPR Sickle Cell Disease Guideline Panel in 1993. Although sickle cell disease is most prevalent among African-Americans, in certain states Hispanic infants constitute a substantial percentage of those identified by newborn screening, and other races are also affected. In California, in the early to mid-1990s approximately 45% of newborns were classified as Hispanic, 35% white (not Hispanic), 10% Asian, and 7% black, and the rate of sickle cell disease at birth in the entire population was 1 per every 4,417 births (6% of infants with sickle cell disease were reportedly Hispanic and not black) (32). This figure is similar to the rate of congenital hypothyroidism, the most prevalent condition of U.S. newborn screening programs (23). In states such as New York and those in the Southeast U.S. with a higher percentage of black births, the rate of sickle cell disease in the entire birth population would be even higher than the California figures. With these rates of sickle cell disease, at birth more than 2000 infants are identified annually with sickle cell disease in the U.S., and at least 50,000 Americans are estimated to be currently affected (14,20,33). Worldwide, birth prevalence figures have been calculated from trait frequencies in different continents since newborn screening is not widely done; an estimated 120,000 to 250,000 affected infants are born annually across the globe (7,34).

Other hemoglobinopathies found particularly among people of Asian and Mediterranean descent, such as beta thalassemia major, are also detected by hemoglobinopathy screening. Identification and counseling of families with sickle cell and other hemoglobinopathy traits is a natural by-product of these newborn screening programs. Some public health advocates point to counseling of carriers as a positive benefit; as an example of this “benefit beyond the target,” these authors discuss the opportunity trait counseling provides for offering prenatal diagnosis in subsequent pregnancies (35). Parents with sickle cell disease who were unaware of their diagnosis have also been identified when their newborns were screened. In contrast, other authors have presented arguments against carrier identification and counseling by state-sponsored newborn screening programs, citing a number of issues: ethical concerns about government involvement in this issue, insurance and employment discrimination as a consequence of carrier identification, and the potential for the vulnerable child syndrome scenario in affected families (28). Nevertheless, national newborn screening guidelines, put forth by the U.S. Council of Regional Networks for Genetic Services, strongly advocate resource allocation for carrier counseling (with particular reference to hemoglobinopathy screening) (36).

EVALUATION OF OUTCOMES AFTER NEWBORN SCREENING

As noted above, while the efficacy of prophylactic penicillin was demonstrated by randomized trials, the true measure of effectiveness of the combination of newborn screening and early preventive measures is actual outcomes in large populations. The distinction between efficacy and effectiveness is that efficacy is often a research demonstration of a therapy under ideal conditions, whereas the effectiveness of a prevention strategy should be measured in community settings (37). Stated another way, in the public health arena, research must be translated into practice, and newborn screening follow-up studies are necessary to fully evaluate these programs– a key step in applying genetic technology to disease prevention (30).

Mortality Studies

One traditional epidemiologic approach to population-based studies is to use large, public, electronic databases. The major strengths of this approach are that it is truly population-based, often has sufficient power to answer epidemiologic questions because large numbers of records may be analyzed, and does not usually suffer from questions of representativeness or selection bias since the entire U.S. or other population can be analyzed. Disadvantages of using large databases to measure clinical outcomes include systematic problems with coding that may be magnified if the study period is long or if the study area is large; inadequate sensitivity caused by missing data, since such databases are usually not exclusively designed to examine specific diseases; and inability to analyze health outcomes associated with risk factors other than those provided by the basic demographic information (e.g., race, sex, age) contained in many such databases.

One of the most easily quantifiable outcomes available in the U.S. is mortality, since the National Center for Health Statistics compiles death certificates from each state in the Multiple Cause Mortality Files. Investigators have analyzed sickle cell-coded death certificates to examine age-specific death rates, temporal trends, and geographic variation in recent U.S. mortality (38-41). A problem with examining temporal trends in rates of sickle cell disease relates to the coding scheme for these records: from 1968 until 1979, the International Classification of Diseases lumped sickle cell trait with sickle disease, and even after 1978 the coding system lumped sickle-beta thalassemia syndromes with thalassemia major rather than with the category for hemoglobin SS disease and sickle cell-hemoglobin C disease. As a result, some investigators have excluded pre-1979 records or children with sickle-beta thalassemia syndromes from their analyses, making the results of various death certificate studies not completely comparable with each other or with results from published cohort studies. Nevertheless, the results of these studies have consistently demonstrated a decline in mortality among children with sickle cell disease in recent years.

The study by Davis et al. provided the most published details of pediatric mortality trends based on death certificates (38). Mortality rates during the years from 1968 through 1992 declined in three different pediatric age groups (infants were excluded from the analysis), although the steepest declines occurred among young children born before 1980, when most newborn screening programs had not been established (Table 1). In a separate analysis of the same data, these investigators also concluded that individual states had statistically significant differences in pediatric mortality rates and identified a handful of states with particularly high or low mortality rates relative to the entire U.S. (39). However, in that analysis, Davis et al. did not attempt to isolate any influence that newborn screening may have had on mortality rates by, for example, analyzing data before and after statewide screening programs started or comparing mortality rates in states with targeted screening versus those in states with universal screening during certain time periods.

Results of clinic-based cohort studies have also provided data addressing mortality after newborn screening. Two studies warrant special discussion because of their size and ongoing influence on screening policy: the U.S. Cooperative Study of Sickle Cell Disease (CSSCD) and a large Jamaican cohort study. The prophylactic penicillin studies discussed above both included children from these studies, but published mortality and morbidity data include data from a much larger pool of children followed in the same centers. The comprehensive care provided by these specialty centers, generally large academic hospitals, represent the “gold standard” of prophylactic and acute medical care for children with sickle cell disease.

Enrollment of children in the CSSCD began in 1979, and Leikin et al. first published mortality data in 1989 (42). The CSSCD was not purely a follow-up study of a cohort of children identified as newborns: of 2824 children who enrolled in the study, only 640 entered the study before 6 months of age. Among this group of children identified in early infancy, those with hemoglobin SS disease had a mortality rate before age 3 years ranging from 5.08 deaths per 100 person-years among those entering in 1980 to 0.69 deaths/100 person-years among those entering in 1983. The overall rates of mortality during the entire study period (1979-1987) were 0.81 deaths per 100 person-years for infants and 1.66 per 100 person-years for children age 1-3 years. In an updated report on the cohort of infants from the CSSCD, Gill et al. calculated a rate of 1.1 deaths per 100 person-years with a mean follow-up period of 4.2 years, with the highest rate among children between 6 months and 3 years of age (43). Davis et al. also estimated person-year mortality rates in their study of national death certificates and found rates comparable with those of the CSSCD for children in three different age groups (38).

In their discussion of the mortality data, Leikin et al. point out the difficulty of comparing the CSSCD with earlier studies with different methodologies, but nevertheless cite higher rates of person-year mortality among children born before the CSSCD and attribute improvements to the increased use of antibiotics for febrile episodes. In contrast, Davis et al. suggest that improved survival from 1968 through 1992 was due to multiple factors, including the establishment of newborn screening programs, more comprehensive medical care, widespread acceptance of penicillin prophylaxis, and new vaccinations.

The Jamaican study provides another perspective on the effect of newborn screening and early intervention on sickle cell-related mortality rates (44). Children with hemoglobin SS disease were identified after 100,000 consecutive deliveries from 1973 through 1981 at the main hospital in Kingston. The mortality rates among children born later in the study period were significantly lower than those among children born earlier, in particular mortality rates from pneumococcal infections and splenic sequestration. Jamaican investigators attributed these changes partly to improved pneumococcal prophylaxis and parental education programs to recognize splenic sequestration. In a separate Jamaican study of splenic sequestration, investigators analyzed morbidity from these events among children identified by newborn screening before and after an education program about splenic palpation was instituted (45). They found that the rate of sequestration increased but that the fatality rate from this event fell, suggesting that increased early detection by parents after education led to a decline in mortality rates. The Jamaican studies provide direct evidence that recent reductions in pediatric mortality rates are not due solely to newborn screening per se, since the trends were seen among children who were all identified as having sickle cell disease at birth. However, early diagnosis provided the opportunity to institute public health programs that would not have affected survival so dramatically if not directed toward infants and their parents.

In the United States, investigators have also studied outcomes in cohorts of children identified with sickle cell disease shortly after birth. In Northern California, newborn screening was done in a limited number of hospitals between 1975 and 1985, which allowed investigators to study two cohorts of children followed at a comprehensive sickle cell center: a group diagnosed shortly after birth and a group diagnosed at a mean age of 21 months (46). The overall mortality rate in the newborn screening group after approximately 7 years of follow-up was 1.8%, compared with 8% in the group diagnosed later and followed for a mean of approximately 9 years. As in Jamaica, parents of infants screened at birth were offered an extensive education program, although most of the children were born before the widespread use of prophylactic penicillin and some new vaccinations. The authors of this study noted that life-threatening events did not occur less frequently in the group screened at birth but suggested that early recognition of these complications by parents and tertiary care providers resulted in improved survival rates.

Several state newborn screening programs have also been conducting follow-up studies to evaluate outcomes among children they have identified with sickle cell disease. Some of the states with large and well-established newborn screening programs actively involved with such studies include California, Georgia, Illinois, Louisiana, Maryland, Mississippi, New Jersey, New York, and Texas. Types of follow-up efforts include periodic or one-time physician surveys, parent interviews, medical record abstraction, and analysis of vital records. Some states such as California, Illinois, and New York have collaborated and pooled their data for publication of large outcome studies (47). These collaborative efforts have been particularly useful for mortality studies in this era of markedly improved survival.

In California, Illinois, and New York, investigators used identifying variables from state sickle cell databases for children born 1990 through 1994 and compared these with state death certificate files. Some additional follow-up information was available through physician surveys and reports from public health nurses about details of deaths. During the 5-year period, 2487 children with sickle cell disease were identified by the three newborn screening programs. Among the children with hemoglobin SS disease with follow-up information through age 3 years, 1.0% died of sickle cell-related causes. This mortality rate was equivalent to 0.35 per 100 person-years, less than the lowest mortality rate in the 1989 report of the Cooperative Study of Sickle Cell Disease discussed above. Similarly low mortality rates have been reported by other state newborn screening programs in recent years (47).

Morbidity Studies

The low mortality rates of the 1990s, which now approach expected infant mortality rates for the general population, have focused public health efforts on reducing other serious complications of sickle cell disease following newborn screening. Improved preventive strategies such as pneumococcal vaccines for infants may also reduce the burden of sickle cell-related hospitalizations in the future, as may new therapeutic strategies such as outpatient treatment of febrile children with sickle cell disease and outpatient transfusion therapy (6,48). Morbidity in the early childhood years (the immediate focus of newborn screening programs) focuses on the effects of the disease on three organs: the brain, spleen, and lungs, including infections that involve these organs (1). As with mortality data, epidemiologic studies of these complications include large studies of state or national databases, clinically based cohort studies, and population-based follow-up studies (43,47,49-51).

Two examples of large electronic databases amenable to sickle cell studies are the National Hospital Discharge Survey and state hospital discharge tapes. A recent publication containing data from the National Hospital Discharge Survey reported no detailed information about causes of morbidity but did provide information about the annual numbers of hospitalization, the costs of these hospitalizations, and the sources of payment including government programs (49). In this study of U.S. hospitalizations from 1989 to 1993, children less than age 20 years accounted for more than half of the estimated 75,000 annual hospitalizations for people with sickle cell disease. Results of a study of state hospital discharge data showed more than 3000 pediatric hospitalizations in California for hemoglobinopathies in 1991, with a mean charge of $7000 per hospitalization (50). The California data also contained detailed information about discharge diagnoses (not published because sickle cell was not the focus of the article), which showed that the predominant reasons for hospitalization among children less than age 3 years were bacterial infections, pulmonary infections, and other suspected infections. This type of data can be used to follow temporal trends in the types, volume, and costs of hospitalization and the age-distribution of patients hospitalized. Indeed, as part of the follow-up study in Illinois discussed above, investigators have examined state hospital discharge records.

The Cooperative Study of Sickle Cell Disease has provided volumes of epidemiological data relating to pediatric morbidity, although as with the mortality studies mentioned earlier, these investigators have not focused exclusively on outcomes after newborn screening. However, for the most part the outcomes of 703 infants who were enrolled in the study at less than 6 months of age (mean 3 months) reflect the experience of those identified through newborn screening, since most adverse events begin later in infancy (43,51). As noted above, since these children were offered the “gold standard” of medical care, their outcomes might be expected to reflect the best possible scenario, but the strength of this data is the clinical detail, specificity, and prospective nature of data collection. In general, children with sickle cell-hemoglobin C disease had fewer episodes of sepsis, splenic sequestration, stroke, and other events compared with children with hemoglobin SS disease. In children with hemoglobin SS, the peak age for bacteremia was the second 6 months of infancy; splenic sequestration occurred most frequently among 1-year-old children; and stroke did not occur among infants and occurred at the highest rate (2.1 events per 100 person-years) among 6-year-old children. There was a suggestion of a decreased rate of pneumococcal infections after 1986 when penicillin prophylaxis became routine, although the decrease was not statistically significant. An ongoing extension study should provide more information about temporal trends in the rates of these pediatric complications among children born in the 1990s with an opportunity to benefit from new vaccines and therapies and more widespread use of prophylactic penicillin.

State newborn screening programs doing follow-up studies of morbidity have focused on such endpoints as hospitalizations, emergency room visits, and developmental status. Many of these studies such as those in Georgia, Illinois, Louisiana, Maryland, Mississippi, New Jersey, and New York are ongoing, with observations currently unpublished or in abstract or health department report form (47,52-54). In Maryland, the state health department is particularly interested in preventable hospitalizations related to sickle cell disease and is attempting to correlate factors such as use of penicillin (ascertained from Medicaid claims) with these outcomes. In the California, Illinois, and New York studies, researchers have collected information such as children’s demographic characteristics, antibiotic use, immunization status, and genetic subtypes, as well as parental sickle cell knowledge, and insurance status in order to analyze the association of these variables with outcomes.

IMPORTANCE OF NEWBORN FOLLOW-UP STUDIES AND FUTURE DIRECTIONS

Data collected by evaluating the community effectiveness of trial-proven strategies such as penicillin prophylaxis have an obvious value in academic studies such as cost-effectiveness analyses. However, they also have considerable practical uses. For example, state health departments could potentially use collected data to improve procedures for enrolling children in comprehensive care if delays in initiation of prophylaxis are found in certain cities, or to target high-risk populations that continue to experience excess morbidity. There is also evidence of a need for ongoing surveillance of outcomes even when proven prevention strategies have been implemented. For example, the emergence of penicillin-resistant organisms and evident problems with children not receiving their prescribed penicillin daily have raised concerns and provided further impetus for trials of new pneumococcal vaccines for infants (55-57).

As state health departments have become more involved with diagnosis of genetic disease through their state laboratories, many have become obligated to adopt regulations to control the content and quantity of services provided for children they have identified after diagnosis. For example, in funding Illinois hematologists, the Department of Public Health has included provisions that require penicillin prophylaxis for young children identified by the state screening program (58). Some state health departments such as California’s are involved with certifying sickle cell counselors; this type of regulation ensures the quality of genetic education at the provider level, but the proof of the efficacy of these policies is the actual knowledge taken home by parents (59). The ongoing California and Illinois follow-up studies include a parental questionnaire that theoretically can ascertain the type and quality of services parents are receiving from regulated providers; this type of data has been difficult to collect retrospectively, and in future studies this type of data might be more easily collected through a questionnaire regularly administered as the services are provided.

Public interest in sickle cell disease has been piqued by well-publicized studies in which researchers have attempted to cure sickle cell disease through bone marrow transplantation or gene therapy (60,61). While it is safe to say that these efforts are currently in early stages and have had little public health impact to date, when they become more widespread they will lead to dilemmas such as the selection of ideal candidates and the timing for such therapy. Population-based outcome studies will provide further data with which to identify children at particularly high risk for morbidity and mortality.

CONCLUDING REMARKS

Despite controversies about cost-effectiveness and ethical quandaries of carrier identification and targeted versus universal approaches, newborn screening programs for hemoglobinopathies in the United States are firmly entrenched, at least in part because of strong epidemiological data suggesting that early identification of affected newborns is a rational policy. However, as noted above, as prevention-oriented policies are directed toward large populations and manifestations of disease complications change, ongoing data collection is needed to ensure the effectiveness of these strategies at the community level. Funding for follow-up studies is as important as funding for studies at the basic science level to understand and even cure the underlying disease. Sickle cell disease is an example of a common genetic condition for which preventive strategies have been particularly effective at reducing rates of complications, and the historical precedents of sickle cell newborn screening and treatment may serve as a public health model for other conditions considered for population screening in the future.

TABLES

Table 1. 24 selected states with newborn hemoglobinopathy screening programs, by year started and number of infants screened in 1993 (excludes states with incomplete reporting, limited screening, or no screening program)

Year Started	State	Number of Infants Screened, 1993	Total Live Births, 1993
1975	New York	282,978	283,328
1980	Georgia	83,284*	111,318
1983	Texas	319,742 (estimated)	326,267
1985	Maryland	69,293	69,494
1985	Indiana	83,387	83,622
1987	North Carolina	36,404*	101,663
1987	South Carolina	52,314	52,110
1987	Iowa	37,865	38,113
1988	Florida	193,032	193,035
1988	Louisiana	105,030**	69,474**
1988	Arkansas	33,738	33,173
1988	Minnesota	65,900	64,517
1989	Virginia	96,667	92,499
1989	Connecticut	47,496	46,756
1989	Wisconsin	68,532	68,917
1989	Illinois	190,500	187,461
1990	New Jersey	113,928	114,501
1990	Pennsylvania	155,657	161,493
1990	California	578,820	585,564
1991	Tennessee	76,988	77,534
1991	Oklahoma	50,763	45,351
1991	Mississippi	41,639	41,639
1991	Washington	72,983	77,182
1992	Kansas	45,341	35,850
	Total, 24 States	2,902,281 (estimated)	2,960,861
	U.S. Totals	3,660,355 (estimated)	4,068,211

Source: Council of Regional Networks for Genetic Services (14)

*Targeted screening in 1993 **1992: 70,245 hemoglobin results reported, 70,902 total births (33)

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Table 2. Prevalence of sickle cell disease (Hb SS, sickle cell-hemoglobin C disease and sickle beta-thalassemia syndromes) by racial or ethnic group, per 100,000 live births, United States, 1990 and unspecified years*

 

Racial or ethnic group	Mean prevalence	95 percent confidence interval
White	1.72	1.06 – 2.66
Black	289	277 – 300
Hispanic, total	5.28	2.60 – 9.61
Hispanic, Eastern States	89.8	27.0 – 190.0
Hispanic, Western States	3.14	1.19 – 6.86
Asian	7.61	1.85 – 57.20
Native American	36.20	0.04 – 182

* Abbreviated and modified from results of Bayesian meta-analysis published by Sickle Cell Disease Guideline Panel,
1993 (20)

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