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American Journal of Medical Genetics Part C (Seminars in Medical Genetics) 148C:15–22 (2008)
A R T I C L E
Communication of Positive Newborn ScreeningResults for Sickle Cell Disease and Sickle CellTrait: Variation Across StatesPATRICIA L. KAVANAGH,* C. JASON WANG, BRADFORD L. THERRELL, PHILIPPA G. SPRINZ,AND HOWARD BAUCHNER
In the US, all states and the District of Columbia have universal newborn screening (NBS) programs for sickle celldisease (SCD), which also identify sickle cell trait (trait). In this project, we surveyed follow-up coordinators,including one in the District of Columbia and two in Georgia, about protocols for stakeholder notification for SCDand trait. The primary outcomes were total number and type of stakeholder informed of a positive screen. Wereceived 52 completed surveys (100% response). Primary care providers (PCPs) (100%), hematologists (81%),hospitals (73%), and families (40%) were the most commonly notified stakeholders of positive SCD screens, whilePCPs (88%), hospitals (63%), and families (37%) were most commonly notified for trait. On average, 3.4stakeholders were notified for a positive screening for SCD, compared to 2.4 stakeholders for sickle cell trait(P< 0.001). In multivariate analyses for SCD, we found a 2.9% increase in stakeholders notified for eachadditional year of universal screening mandated in a state (95% CI: 1.4–4.4%). For trait, we found an 8.5%increase in stakeholders notified for each additional follow-up staff (95% CI: 1.3–15.7%), and a 1.3% increasefor each additional percent of black births in the state (95% CI: 0.1–2.5%). Wide variation exists in stakeholdernotification by NBS programs of positive screenings for SCD and trait. This variation may alter the effectiveness ofNBS programs by location of birth. � 2008 Wiley-Liss, Inc.
KEY WORDS: newborn screening; sickle cell disease; sickle cell trait; child
How to cite this article: Kavanagh PL, Wang CJ, Therrell BL, Sprinz PG, Bauchner H. 2008. Communicationof positive newborn screening results for sickle cell disease and sickle cell trait: Variation across states.
Am J Med Genet Part C Semin Med Genet 148C:15–22.
INTRODUCTION
The year 2007 marks the 20th anniver-
sary of the National Institutes of Health
(NIH) Consensus Conference on new-
born screening (NBS) for sickle cell
disease (SCD) and other hemoglobino-
pathies, which recommended universal
screening for all newborns in the US for
both SCD and sickle cell trait [National
Institutes of Health, 1987]. Early iden-
tification of children with SCD provides
the opportunity for timely initiation of
penicillin prophylaxis and parental edu-
cation, and has been shown to decrease
Patricia L. Kavanagh, M.D., is a General Pediatrics Fellow at Boston University School of Medicine/Boston Medical Center, with an interest in clinicalresearch in sickle cell disease. Her projects include the development of an electronic health record and a sickle cell self-management plan for pediatricsickle cell disease patients, and the utilization of transcranial Doppler screening tests to identify children with sickle cell disease at higher risk of stroke.
C. Jason Wang, M.D., Ph.D., is an Assistant Professor of Pediatrics and Maternal & Child Health at Boston University Schools of Medicine and PublicHealth and Boston Medical Center. He is also an adjunct Natural Scientist at the RAND Corporation. His research interests focus on assessing andimproving the quality of care for vulnerable pediatric populations, including very-low-birth-weight infants, children with sickle cell disease, andchildren with autism.
Bradford L. Therrell, Ph.D., is a Research Professor in the Department of Pediatrics at the University of Texas Health Science Center at San Antonioand is the Director of the National Newborn Screening and Genetics Resource Center in Austin, appointed in 1999. Prior to that, he was the DivisionDirector for the Chemical Services Division at the Texas Department of Health for 28 years, with oversight responsibility for the largest newbornscreening laboratory in the world. He helped establish the International Society for Neonatal Screening and served terms as Secretary and as President.In 2000, he was awarded the prestigious Guthrie Award by the Society for his international newborn screening activities.
Philippa G. Sprinz, M.D., is the Division Director of Pediatric, Hematology/Oncology at Boston Medical Center, and Assistant Professor of Pediatricsat Boston University School of Medicine. She is also actively involved in the New England Pediatric Sickle Cell Consortium, a co-operative grouprepresenting physicians and other providers across 10 institutions, representing 1,100 children with sickle cell disease.
Howard Bauchner, M.D., is a Professor of Pediatrics and Public Health, and Director of the Division of General Pediatrics at Boston University Schoolof Medicine/Boston Medical Center. His career has been committed to patient-oriented research, and has focused on the role of parents in healthpromotion and treatment of children. He has published more than 125 peer-reviewed articles, commentaries, and editorials. He is Editor-in-Chief ofArchives of Disease in Childhood.
Grant sponsor: NIH T32; Grant number: HP1001414; Grant sponsor: Maternal and Child Health Bureau, HRSA; Grant number: 6 U32 MC00148-08-02.
*Correspondence to: Patricia L. Kavanagh, M.D., Division of General Pediatrics, Boston University School of Medicine/Boston Medical Center, 91 E.Concord Street, MAT-4, Boston, MA 02118. E-mail: [email protected]
DOI 10.1002/ajmg.c.30160
� 2008 Wiley-Liss, Inc.
the morbidity [Bardakdijian-Michau
et al., 2002] and mortality of SCD in
young children [Gaston et al., 1986; Lee
et al., 1995], making NBS for this
condition particularly important. Cur-
rent screening procedures also identify
sickle cell trait. At the time of the NIH
consensus conference, only 10 states
mandated universal screening for SCD
and sickle cell trait. As of 2006, all 50
states and the District of Columbia have
universal programs in place [Therrell
et al., 2006].
Currently, the NBS system is
decentralized in the US, with each state
responsible for its own program. For
SCD and sickle cell trait, some states
have well-developed follow-up pro-
grams in which nurses or program
specialists contact families of infantswith
positive NBS results and, as necessary,
arrange confirmatory testing and fol-
low-up with specialists and genetic
counselors [Shafer et al., 1996]. Other
Currently, the NBS system is
decentralized in the US, with
each state responsible for
its own program. For SCD and
sickle cell trait, some states have
well-developed follow-up
programs in which nurses or
program specialists contact
families of infants with positive
NBS results and, as necessary,
arrange confirmatory testing
and follow-up with specialists
and genetic counselors.
states rely on the primary care provider
(PCP) to arrange for confirmatory test-
ing, provide education to parents and
referral to specialists.
The purpose of this study was to
describe the reporting procedures for
SCD and sickle cell trait that currently
exist in NBS programs. Although many
programs screen for other hemoglobi-
nopathies, we decided to focus on SCD
and trait for this study. In particular,
we determined which stakeholders
(e.g., PCPs, hematologists, families,
etc.) are informed of a positive screening
test for these conditions, how they are
informed, and how the receipt of this
information is confirmed. Our hypoth-
esiswas that wide variation existed across
states in the notification of key stake-
holders for both SCD and sickle cell
trait.
METHODS
We surveyed follow-up coordinators for
NBS programs in all 50 states and the
District of Columbia, as listed on the
National Newborn Screening and
Genetic Resource Center’s website
[National Newborn Screening and
Genetics Resource Center, 2007]. In
Georgia, there were two NBS programs
with separate organizational structures
and personnel, therefore, a total of 52
coordinators were surveyed over a 1-
month period in 2007. A letter describ-
ing the study was sent to each coordina-
tor by email, with the survey included as
an attachment. A reminder email was
sent 1 week later to non-respondents. A
phone call was then placed during
the following week to those who had
not responded to the two electronic
requests. This study was considered
exempt for review by the Institutional
Review Board of Boston University
Medical Campus and Boston Medical
Center.
Survey Instrument
We developed a brief survey instrument
to determine the follow-up protocols
used by NBS programs for SCD and
sickle cell trait, and the staff available to
perform these tasks (see Appendix I).We
assumed that a laboratory report was
generated for all positive newborn
screening tests for SCD and trait, which
was then provided to the NBS program
as well as the submitter of the specimen
(e.g., hospital). Therefore, we asked
respondents to describe the actions taken
by their program, including those duties
performed by the state laboratory or
contracted external agencies (e.g., Ore-
gon PublicHealth Laboratory), to notify
various stakeholders when a positive
screening result occurred. The instru-
ment was field-tested with two follow-
up coordinators, and minor modifica-
tions were made prior to finalization of
the survey instrument.
For both SCD and sickle cell trait,
the questionnaire focused on: (1) who
was informed of a positive screening
result (i.e., primary care physician/other
provider, hematology consultant, public
health nurse, family, hospital or other
submitter, community-based sickle cell
organization, or other); (2) how they
were informed (i.e., phone, letter,
certified letter, fax, email, or other);
and (3) how notification was ensured
(i.e., no protocol, phone log, electronic
log, certified letter receipt, return fax,
return email, or other).
Responses to the above items were
carefully reviewed in order to develop a
consistent and accurate picture of activ-
ities performed by the follow-up pro-
gram or the program’s designee. In cases
where one stakeholder was responsible
for informing another, the first stake-
holder would be marked as ‘‘Yes,’’ but
the second stakeholderwould bemarked
as ‘‘No,’’ since the follow-up program
did not routinely inform this second
party directly. For example, if PCPswere
contacted by the follow-up program
with positive NBS results and were then
responsible for informing the family, the
PCP was coded as ‘‘Yes,’’ and the family
was coded as ‘‘No.’’ Less than 1% of
responses were re-coded using this
scheme.
In addition, we developed a proto-
col for missing stakeholder data (3.7%, or
26/728) by consulting the comments
sections of the survey for additional
information. If no information was
available, we treated the missing data as
‘‘No.’’ If additional information was
available and it fulfilled our stringent
criteria for a positive response, we
re-coded the response as ‘‘Yes.’’
Outcome Variables
The primary outcome measure of this
study was the total number of stake-
holders informed of a positive screening
16 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ARTICLE
result. Separate analyses were done for
SCD and sickle cell trait.
Independent Variables
To assess possible factors that may
influence the number of stakeholders
informed, we identified five key varia-
bles from the literature and from inves-
tigators’ experience to include as
predictors in our models: follow-up
program staffing, total number of black
births per state, ratio of black births to
total births per state, number of years of
mandated universal screening for SCD
per program, and presence of compre-
hensive sickle cell center within a state.
We considered the use of positive screens
as an independent variable. However,
the most recent data on positive screens
for SCD and sickle cell trait was available
from 2001 [National Newborn Screen-
ing and Genetics Resource Center,
2001], and seven states (13% of total
programs surveyed) did not mandate
universal screening at that time, limiting
the utility of using positive screens as a
proxy of the affected population.
Staffing levels. Survey respondentswere
asked to list the number of staff that
performed follow-up duties, including
those who provided cross-coverage for
vacation, illness, etc., for both SCD and
sickle cell trait.
Number and ratio of black births. We
used 2004 vital statistics data from the
National Center for Health Statistics to
estimate the total number of black births
and the ratio of black births to total births
in each state [Martin et al., 2006].
Although SCD and sickle cell trait affect
many ethnicities and racial groups with
ancestry from equatorial andMediterra-
nean regions (e.g., Central and South
America, Greece, etc.), we were limited
by the availability of reliable vital sta-
tistics data for these populations in the
US; therefore, we used black births as a
proxy for the affected population. In
addition, since the black population is
disproportionately affected in the US,
we hypothesized that states with larger
black populations would be pressured by
various stakeholders to devote more
resources to screening and follow-up
programs.
Number of years of universal screening. Data
from the National Newborn Screening
Information System provided the year
each state instituted mandated universal
screening for SCD and trait [National
Newborn Screening and Genetics
Resource Center, 2007].
Presence of comprehensive sickle cell centers.
We identified the states that currently
have one of the ten comprehensive
sickle cell centers (CSCC) funded by
the National Heart, Lung, and Blood
Institute.
Statistical Analyses
Responses were tabulated in an Excel
database (Microsoft Office, Redmond,
WA), and analyzed using Stata Version
9 (StataCorp, College Station, TX).
Descriptive statistics were performed
for which stakeholders were informed,
and the modalities used to convey and
ensure receipt of this information. In
addition, we examined bivariate associ-
ations between the number of stake-
holders notified (outcome) and the
independent variables listed above using
linear regression analyses, performed
separately for SCD and sickle cell trait.
We performed a logarithmic transfor-
mation on our outcome variable (i.e.,
total number of stakeholders informed)
for SCD and sickle cell trait, which
allowed us to interpret the results of the
linear regression as a percentage change.
Using this method, we also built multi-
variate linear regression models to
further explore associations between
our independent variables and the total
number of stakeholders notified, for
both SCD and sickle cell trait. For
bivariate and multivariate analyses, per-
centage change and 95% confidence
intervals (CI) were reported, with sig-
nificance defined as P< 0.05.
RESULTS
We received 52 completed surveys
(100% response) from follow-up pro-
grams in all 50 states, including two from
Georgia and one from the District of
Columbia. Table I provides the list of
stakeholders notified of positive screen-
ing tests for SCD and sickle cell trait, by
program. PCPs (100%), hematologists
(81%), hospitals/agencies submitting the
samples (73%), and families (40%) were
the most common stakeholders notified
of a positive screen for SCD, while PCPs
(88%), hospitals (63%), and families
(37%) were most commonly notified
for sickle cell trait (see Fig. 1). For SCD,
19% of programs informed five or more
stakeholders, 60% informed three to
four stakeholders, and 21% of programs
informed one to two stakeholders of
positive results (see Fig. 2). For sickle cell
trait, 4% of programs informed five or
more stakeholders, 42% informed three
to four stakeholders, 50% informed one
to two stakeholders, and 4% of programs
did not inform any stakeholders of
positive results. In three states, families
were the only stakeholder notified by the
follow-up program for a positive sickle
cell trait screening result. On average,
3.4 stakeholders were notified for a
positive screening for SCD, compared
to 2.4 for sickle cell trait (P< 0.001).
This difference is due primarily to
hematologists, who were usually noti-
fied of positive screening results for SCD
(81%), but not sickle cell trait (13%).
On average, 3.4 stakeholders
were notified for a positive
screening for SCD, compared to
2.4 for sickle cell trait
(P< 0.001). This difference is
due primarily to hematologists,
who were usually notified of
positive screening results
for SCD (81%), but not sickle
cell trait (13%).
In addition, we examined the
number of modalities used to notify
key stakeholders of positive screening
results. Phone (31%), letter (27%), and
ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c 17
TABLE I. Stakeholders Informed by NBS Programs
State Sickle cell disease Sickle cell trait
Alabama PCP, Heme, Hospital, Sickle cell org PCP, Public health nurse, Sickle cell org
Alaska PCPa, Hemea, Hospitalb PCPa, Hospitalb
Arkansas PCP, Heme, Hospital PCP, Family, Hospital
Arizona PCP, Heme, Family, Sickle cell org PCP, Family, Sickle cell org
California PCP, Heme, Family, Hospital PCP, Family, Hospital
Colorado PCP, Heme, Family PCP
Connecticut PCP, Heme, Family PCP, Family, Hospital, Sickle cell org
Delaware PCP, Heme, Family, Hospital, Child Development
Watch (with permission)
PCP, Family, Hospital
District of Columbia PCP, Heme, Family, Hospital, Sickle cell org PCP, Heme, Family, Hospital, Sickle cell org
Florida PCP, Heme, Family, Hospital Family
Georgia (MCG) PCP, Public Health Nurse
Georgia (Grady) PCP, Public Health Nurse
Hawaii PCPa, Hemea, Public health RNa, Familya, Hospitalb,
Hawaii Community Genetics
PCPa, Hospitalb
Idaho PCPa, Hemea, Hospitalb PCPa, Hospitalb
Illinois PCP, Sickle cell org PCP, Sickle cell org
Indiana PCP, Heme, Family, Hospital, Sickle cell org PCP, Sickle cell org
Iowa PCP, Heme, Hospital PCP, Heme, Hospital
Kansas PCP, Family PCP
Louisiana PCP, Heme, Family, Hospital, Sickle cell org Family
Kentucky PCP, Heme, Hospital PCP, Hospital
Maine PCP, Heme, Hospital PCP, Heme, Hospital
Maryland PCP, Heme, Family, Hospitalb PCPb, Hospitalb
Massachusetts PCP, Heme, Hospital PCP, Family, Hospital
Michigan PCP, Heme, Family, Hospital, Sickle cell org PCP, Family, Hospital, Sickle cell org
Minnesota PCP, Heme, Hospital PCP, Hospital
Mississippi PCP, Heme, Public health RN, Family, Hospitalb PCP, Public health RN, Family, Hospitalb
Missouri PCP, Heme, Family, Hospital PCP, Heme, Family, Hospital
Montana PCPb PCPb
Nebraska PCP, Heme, Hospital PCP, Family, Hospital
Nevada PCPa, Hemea, Hospitala PCPa
New Hampshire PCP PCP
New Jersey PCP, Heme, Family, Hospitalb Family, Hospitalb
New Mexico PCP, Heme, Public health RN, Family, Hospital,
Sickle cell org
PCP, Public health RN, Hospital, Sickle cell org
New York PCP, Heme, Public health RN, Hospital PCP, Hospital
North Carolina PCP, Sickle cell org, Sickle cell educator PCPb, Sickle cell orgb, Sickle cell educator
North Dakota PCPa, Hemea PCPa, Hemea
Ohio PCP, Heme, Hospital PCP, Hospital, Sickle cell org
Oklahoma PCP, Heme, Hospital, Sickle cell org PCP, Family, Sickle cell org
Oregon PCP, Heme, Hospital PCP, Hospital
Pennsylvania PCP, Heme, Hospital PCPa, Hemea
Rhode Island PCP, Heme PCP
South Carolina PCP, Hospital PCP, Hospital, Sickle cell orgb
South Dakota PCPa, Hemea, Hospitalb PCPa, Hemea, Hospitalb
Tennessee PCP, Heme, Family, Hospital PCP, Family, Hospital
Texas PCP, Public health RN, Family, Hospital PCPb, Hospitalb
Utah PCP, Hospital PCP, Hospital
Vermont PCP, Heme, Family PCP, Hospital
Virginia PCP, Heme, Hospitalb, Sickle cell org PCP, Family
Washington PCP, Heme, Hospital, Sickle cell org PCP, Hospital, Sickle cell org
West Virginia PCP, Heme PCP, Family
Wisconsin PCP, Heme, Public health RN, Hospital PCP, Hospital
Wyoming PCP, Heme, Family PCP
aContracts with outside laboratory/program.bInformation provided by state laboratory only.
18 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ARTICLE
fax (24%) were most commonly used to
inform stakeholders of positive screens
for SCD, while letter (51%) and ‘‘other’’
(i.e., electronic monthly report, NBS
database, etc.) (21%) were most com-
monly used for sickle cell trait. For SCD,
PCPswere notified of positive screening
results by an average 2.4 modalities,
compared to 1.2 modalities used for
sickle cell trait (P< 0.001). For hospitals,
an average of 0.9 mechanisms were used
to communicate results for SCD com-
pared to 0.7 for sickle cell trait
(P¼ 0.002). Finally, hematologists were
notified of positive SCD tests through
1.5 notification modalities, compared to
0.3 for sickle cell trait (P< 0.001). For
the remaining stakeholders, less than one
modality was used, on average, for
notification.
Finally, we determined the number
of mechanisms used to ensure that this
information was received by stakehold-
ers. Electronic log (26%), phone log
(16%), and return fax (13%) were the
most common modalities used for SCD,
and no protocol (37%) and electronic log
(16%) were used most commonly for
sickle cell trait. For SCD, 1.4 commu-
nication mechanisms were used to
ensure information was received by
PCPs, compared to 0.5 for sickle cell
trait (P< 0.001). For hospitals, 0.4 and
0.2 modalities were used for SCD and
sickle cell trait, respectively (P¼ 0.006).
For hematologists, the mean number of
modalities used to ensure the receipt of
information was 1.1 for SCD and 0.1 for
sickle cell trait (P< 0.001). For the
remaining stakeholders, less than one
modality was used, on average, to ensure
receipt of these results.
Bivariate and Multivariate Analyses
In bivariate and multivariate analyses,
the total number of stakeholders notified
for SCD was positively associated with
the number of years of universal NBS
mandated in a state (bivariate: 2.9%
increase for each addition year the NBS
program had been in place, 95% CI:
1.6–4.2%; multivariate: 2.9% increase
for each additional year of NBS pro-
gram, 95% CI: 1.4–4.4%) (see Table II).
For sickle cell trait, both bivariate and
multivariate analyses found the total
numberof stakeholders notifiedwas posi-
tively associated with total follow-up
staffing level (bivariate: 9.0% increase for
each additional staff, 95%CI: 1.8–16.2%;
multivariate: 8.5% increase for each
additional staff, 95% CI: 1.3–15.7%).
In addition, for sickle cell trait using
multivariate analysis, the total number of
stakeholders notified was positively
associated with the ratio of black to total
births per state (1.3% increase for each
additional percent of black births in a
state, 95% CI: 0.1–2.5%).
DISCUSSION
To our knowledge, this is the first study
that documents the variation across NBS
follow-up programs in the notification
of stakeholders for positive screening
results for SCD and sickle cell trait. For
SCD, even though 100% of the PCPs
were informed, only approximately
three-quarters of hematologists and
hospitals, and 40% of families were
informed of these results. For sickle
cell trait, the numbers are even lower
(i.e., only 88%of PCPs, 63%of hospitals,
and 37% of families were notified). In
addition,more than one-third of follow-
up programs had no protocols in place to
Figure 1. Percent of NBS follow-up programs notifying stakeholders. (P-valuesdenote differences between SCD and sickle cell trait).
Figure 2. Number of stakeholders notified by NBS follow-up programs. (P-valuesdenote differences between SCD and sickle cell trait).
For SCD, even though
100% of the PCPs were
informed, only approximately
three-quarters of hematologists
and hospitals, and
40% of families were informed
of these results. For sickle
cell trait, the numbers are even
lower (i.e., only 88%
of PCPs, 63% of hospitals,
and 37% of families
were notified).
ARTICLE AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c 19
ensure that positive results for sickle cell
trait were received. Finally, 79% of
follow-up programs informed three or
more stakeholders of positive screens for
SCD compared to 46% for sickle cell
trait, and 4% of follow-up programs did
not inform any stakeholders of sickle cell
trait screening results. These differences
in policies and procedures create the
possibility that diagnoses could be
delayed or missed, especially for sickle
cell trait.
Variation has also been noted in
other aspects of NBS programs. Stod-
dard et al. noted state-to-state variation
in the evaluation and adoption of NBS
tests [Stoddard and Farrell, 1997], a
difference that persists today [Therrell
et al., 2006]. In addition, Farrell et al.
recognized differences in the genetic
counseling and risk communication
services offered by NBS follow-up
programs [Farrell et al., 2001]. In this
study,many programs placed the respon-
sibility of counseling on the PCP.
However, the follow-up coordinators
surveyed felt that the quality of counsel-
ing provided by PCPs was lower than
that delivered by other professionals,
including subspecialty physicians, nurse
specialists, and genetic counselors [Far-
rell et al., 2001]. The effectiveness of
NBS is dependent on informing key
stakeholders, counseling of families, and
ensuring that appropriate care is pro-
vided over time. These findings, com-
bined with our study results, suggest
that the effectiveness of the NBS pro-
gram may vary according to location of
birth.
In this study, we found that all
programs notify the PCP of record for a
positive SCD screening, and 88% of
PCPs are notified for sickle cell trait.
However, Listernick et al. [1992]
described significant delays in confirma-
tory diagnosis after documentation of
telephone contact between NBS pro-
grams and the PCP; therefore, the
authors recommended direct contact
between NBS programs and parents. In
addition, a recent study by Kemper et al.
found that approximately 10% of pedia-
tricians and one-third of family physi-
cians did not feel competent discussing
SCD [Kemper et al., 2006]. These
findings highlight the need for further
training for PCPs on the interpretation
and management of positive NBS tests
for hemoglobinopathies. Organizations
such as the American Academy of
Pediatrics have recently disseminated
updated educational materials for NBS
tests [Kaye and Committee on Genetics,
2006], but additional training strategies
may be needed for PCPs.
NBS for hemoglobinopathies raises
ethical issues for the child and family.
Currently, there is no guidance available
on the best approach in disclosing to
parents the newborn carrier status iden-
tified by routine NBS for hemoglobi-
nopathies [Oliver et al., 2004]. Making
this diagnosis provides the opportunity
for genetic counseling and testing for
parents, and genetic counseling for
patients as they approach their child-
bearing years [Ross andMoon, 2000]. In
addition, sickle cell trait has been
associated with several renal pathologies
(e.g., papillary necrosis and loss of
concentrating ability) [Kiryluk et al.,
2006], and more rarely, splenic syn-
drome at high altitudes [Franklin et al.,
1999; Sheikha, 2005] and sudden death
due to physical exertion [Kark et al.,
1987; Kerle and Runkle, 1996]. How-
ever, potential risks exist for neonatal
detection of carrier status, including
misdiagnosis (if the screen is incorrect),
inadvertent exposure of non-paternity,
social stigma for patient and family, and
adverse psychological effects for the
individual and family [Laird et al.,
1996]. These issues (including providing
positive screening results, social risks
associated with diagnosis, etc.) also apply
to disclosing the results of a positiveNBS
for SCD. Currently, there is a need to
TABLE II. Bivariate and Multivariate Analyses
Bivariate analyses Multivariate analyses
Sickle cell disease total
stakeholders informed
% change (95% CI)
Sickle cell trait total
stakeholders informed
% change (95% CI)
Sickle cell disease total
stakeholders informed
% change (95% CI)
Sickle cell trait total
stakeholders informed
% change (95% CI)
Total follow-up staff per
program
1.5% (�1.4–4.4%) 9.0% (1.8–16.2%)* 1.6% (�1.2–4.3%) 8.5% (1.3–15.7%)*
Total black births per state 27.3% (�41.7–96.3%) �5.2% (�102.1–91.8%) �49.6% (�133.4–34.1%) �98.3% (�234.7–38.2%)
Ratio of black births to
total births per state
0.7% (�0.02–1.5%) 0.9% (�0.1–1.9%) 0.5% (�0.3–1.4%) 1.3% (0.1–2.5%)*
Years of universal screening
for hemoglobinopathies
2.9%a (1.6–4.2%)** 0.6% (�1.3–2.6%) 2.9% (1.4–4.4%)** 0.3% (�1.8–2.5%)
Presence of CSCC 7.8% (�20.3–35.9%) 13.7% (�21.7–49.0%) �4.1% (�34.4–26.1%) 29.7% (�10.8–70.3%)
*P< 0.05.
**P< 0.001.aThere is a 2.9% increase in the total number of stakeholders notified for each additional year of mandated universal screening for
hemoglobinopathies.
20 AMERICAN JOURNAL OF MEDICAL GENETICS PART C (SEMINARS IN MEDICAL GENETICS): DOI 10.1002/ajmg.c ARTICLE
develop resources and guidelines for
communication of carrier status, in
collaboration with parents and health
professionals.
There are several limitations of this
study. First, several follow-up NBS
programs use in-state laboratories, con-
tracted laboratories, or follow-up serv-
ices through regional centers to inform
key stakeholders of positive screens for
SCD and sickle cell trait. In these cases,
we could not verify if these services are
actually provided, or how they are
provided, since we only surveyed the
follow-up coordinators. Future studies
should contact these external entities to
fully understand the procedures used to
inform stakeholders of NBS results.
A second limitation is that we cannot
determine from our data which pro-
tocol and/or organizational structure is
best to inform stakeholders and convey
results to families, with the ultimate
goal of arranging confirmatory testing,
and referring children with SCD to
specialty services. Additional studies
are needed to evaluate which stake-
holders and which methods are most
effective in communicating results to
families and arranging follow-up care.
Additional studies are
needed to evaluate which
stakeholders and
which methods are most
effective in communicating
results to families and
arranging follow- up care.
Finally, we did not compare the com-
munication for SCD and trait with other
conditions screened in NBS programs.
However, SCD and trait are the most
common conditions detected by NBS
programs [Therrell and Hannon, 2006],
therefore, comparing follow-up proto-
cols for these conditions with those for
much rarer conditions may not be an
appropriate comparison.
In summary, we found variation
among follow-up programs in the noti-
fication of stakeholders for SCD and
sickle cell trait, which may lead to
varying levels of effectiveness among
NBS programs according to location of
birth. Additional studies are needed to
understand how the different organiza-
tional structures of follow-up programs
may impact the number of days to
confirmed diagnosis of a genetic con-
dition, the number of children receiving
specialty care (for SCD), and those lost
to follow-up. Ideally, we should develop
national guidelines for the reporting of
NBS results for SCD and sickle cell trait
and counseling of patients and their
families for these conditions.
ACKNOWLEDGMENTS
We thank Barry Zuckerman, M.D., for
his support of this work.
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APPENDIX I: SurveyInstrument
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