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These chapters were published with modifications by Oxford University Press (2000) |
Genetics and Public Health in the 21st Century |
Contents I Part I I Part II I Part III I Part IV I Part V I Part VI
Part IV
DEVELOPING, IMPLEMENTING, AND EVALUATING POPULATION INTERVENTIONS
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
Establishment I Target I Public Health I Evaluation I Importance I Remarks I Tables I References
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,
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. 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)
Source: Council
of Regional Networks for Genetic Services (14) *Targeted
screening in 1993
**1992: 70,245 hemoglobin results reported, 70,902 total births (33)
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*
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Address correspondence to Dr Khoury at
Office of Genomics and Disease Prevention
Centers for Disease Control and Prevention
4770 Buford Hwy, Mail Stop K28
Atlanta, Georgia 30341