Ó 2012 Wiley Periodicals, Inc.
Birth Defects Research (Part A) 94:965 969 (2012)
Editorial
Newborn Screening for Critical Congenital Heart
Disease: Essential Public Health Roles for Birth
Defects Monitoring Programs
Received 11 September 2012; Revised 16 October 2012; Accepted 16 October 2012
Newborn screening for critical congenital heart defects, added in September 2011 to the Recommended Uniform Screening Panel in the United States, is a new public health priority and has particular relevance for
state birth defects surveillance programs. In this commentary, we review the background to potential
involvement by birth defects programs with screening, and detail key questions that these programs can
evaluate: (1) health outcomes after newborn screening among affected children; (2) missed primary targets
of screening (i.e., affected children who were not screened or had false-negative screens); (3) burden and
screening accuracy for secondary targets; (4) the role of altitude, sociodemographic characteristics, and other
special circumstances; (5) the contribution of prenatal and clinical diagnoses before newborn screening; and
(6) costs and service utilization. To address these issues, monitoring programs will need to pay particular
attention to: (1) data sources and quality; (2) timeliness; (3) long-term follow-up for comprehensive outcomes; (4) reporting standards; and (5) state and national program coordination. Although some aspects of
involvement with these screening programs will require new partnerships and paradigm shifts in birth
defects program operations, the visibility of these screening programs among stakeholders will also provide
birth defects programs with new opportunities to demonstrate their usefulness. Birth Defects Research (Part
A) 94:965–969, 2012. Ó 2012 Wiley Periodicals, Inc.
In this special issue of Birth Defects Research (Part A), the
introduction to the 2012 National Birth Defects Prevention Network (NBDPN) surveillance report (Mai et al.,
2012) highlights newly compiled U.S. data for seven
types of critical congenital heart disease (CCHD): dextrotransposition of the great arteries, hypoplastic left heart
syndrome, pulmonary atresia (with intact ventricular septum), tetralogy of Fallot, total anomalous pulmonary venous return, tricuspid atresia, and truncus arteriosus.
Congenital heart defects in general, and newborn screening programs for CCHDs specifically, have become new
public health priorities in the United States. State programs and national birth defects systems, assuming that
they are adequately supported and enhanced, are
uniquely positioned to play a key role in the implementation and ongoing evaluation of CCHD newborn screening. In this editorial, we outline avenues for birth defects
programs to become effectively and integrally involved
with this new public health focus. We believe that the
potential benefits of such integration – in terms of
improved quality of public health services and reduced
costs – are considerable for both CCHD screening and
birth defects surveillance.
ACCELERATING HISTORICAL
DEVELOPMENTS, BRIEFLY CONSIDERED
The seven types of CCHD highlighted in this year’s
NBDPN surveillance report were considered by a U.S.
advisory committee as primary targets for pulse oximetry
screening (Kemper et al., 2011). These seven CCHDs,
which usually present in newborns with hypoxemia that
might be missed clinically but identified by pulse oximetry, were designated previously by a working group led
by the American Heart Association and the American
Academy of Pediatrics (Mahle et al., 2009). The advisory
committee’s recommendation to include this type of
The findings and conclusions in this report are those of the authors and do
not necessarily represent the official position of the Centers for Disease Control and Prevention.
*Correspondence to: Dr. Richard S. Olney, Pediatric Genetics Team, National
Center on Birth Defects and Developmental Disabilities, Centers for Disease
Control and Prevention (CDC), 1600 Clifton Road, Mailstop E-86, Atlanta, GA
30333. E-mail: rolney@cdc.gov
Published online 27 November 2012 in Wiley Online Library
(wileyonlinelibrary.com).
DOI: 10.1002/bdra.23103
Birth Defects Research (Part A): Clinical and Molecular Teratology 94:965 969 (2012)
966
OLNEY AND BOTTO
screening in the Recommended Uniform Screening Panel
was adopted by the U.S. Secretary of Health and Human
Services in September 2011, and has been further
endorsed by the American Academy of Pediatrics (Mahle
et al., 2012). For effective screening implementation, the
Health and Human Services Secretary reiterated the
need for: new research data; evaluation as implementation occurs; and cost-effectiveness analyses (http://
www.hrsa.gov/advisorycommittees/mchbadvisory/heri
tabledisorders/recommendations/correspondence/cyano
ticheartsecre09212011.pdf). Of note, several state legislatures are considering or have already passed legislative
initiatives to mandate or move toward implementation
of universal CCHD screening. Such implementation is
occurring piecemeal and concurrently in many locations
before the availability of population-based evaluation
data from vanguard states. With the accelerating pace of
discussions and implementation of CCHD screening,
birth defects programs should emerge as crucial, widely
available public health resources that can be put to work
quickly and efficiently as part of ongoing monitoring
and evaluation of screening.
BIRTH DEFECTS PROGRAM CAPACITIES
What capacities are necessary for birth defects programs to be effectively involved in screening evaluations?
Are such capacities already present in some states? If
not, how can these capacities be achieved quickly? What
role can population-based birth defects surveillance have
in addressing gaps in knowledge that might impede fully
successful implementation of universal CCHD screening?
To begin addressing these questions, NBDPN investigators conducted surveys in 2010 and 2011, the results of
which were compiled recently (Centers for Disease
Control and Prevention, 2012). Of respondents from all
50 states and the District of Columbia, 43 reported having a
birth defects surveillance program. Among these 43 programs, the majority reported being able to collect information that could be used to evaluate outcomes of interest,
such as survival, links to support services, and even data to
assess screening accuracy. Indeed, population-based data
gathered before 2010 in state health departments already
helped to evaluate the sensitivity and specificity of pulse
oximetry screening, and provided early indications about
the potential benefits of early identification to prevent
delayed diagnoses and deaths from CCHD not recognized
in newborn nurseries (Kuehl et al., 1999; Koppel et al.,
2003; Aamir et al., 2007; Chang et al., 2008; Ng and Hokanson, 2010). Since then, more comprehensive analyses from
other countries have addressed accuracy issues (de-Wahl
Granelli et al., 2009; Riede et al., 2010; Ewer et al., 2012;
Thangaratinam et al., 2012). However, there remains a
need for ‘‘real world’’ data from widespread implementation across diverse populations. To gather such data, birth
defects monitoring programs will need to further
strengthen public health activities, even beyond those suggested in previous editorials (Correa and Kirby, 2010).
ADDRESSING THE IMPORTANT QUESTIONS
In considering the role of birth defects surveillance
programs in CCHD screening, it is helpful to return to
two key concepts. First, newborn screening is not a test,
but a comprehensive process, and this process ideally
Birth Defects Research (Part A) 94:965 969 (2012)
also involves follow-up assessment of a wide range of
outcomes (Pass et al., 2000). Birth defects programs, if
appropriately enhanced and integrated into the screening
process, are well positioned to provide much of this information efficiently. Second, screening activities are by
their nature long-term and ongoing. Thus, the related
evaluations and monitoring of outcomes need to be
ongoing and timely, and the information thus generated
needs to be fed back quickly to the screening activities
for systematic program improvement. These characteristics – ongoing, systematic, timely monitoring of birth
defects linked to public health activities – are the core
elements of birth defects surveillance (Hall et al., 2012).
Whereas one-time studies are important for generating
initial data, ongoing birth defects surveillance is and will
continue to be an indispensable component of CCHD
screening programs.
More specifically, Table 1 outlines some of the many
lingering questions related to the evidence of benefits of
CCHD screening, which can be addressed by evaluations
through birth defects surveillance programs. For example, programs could provide new and continuously
updated population-based data to quantify the burden,
outcomes, and screening accuracy of pulse oximetry for
the seven primary CCHDs and other heart defects identified through screening (defined here as cardiac ‘‘secondary targets’’). Some secondary targets have been reported
in limited numbers or not at all in pilot studies (de-Wahl
Granelli et al., 2009; Riede et al., 2010), particularly major
defects obstructing the left ventricular outflow tract, such
as critical aortic stenosis, coarctation of the aorta, and interrupted aortic arch.
Most notably, only statewide surveillance programs
would systematically ascertain primary targets that might
have been overlooked through current protocols, either
by not being screened or by passing a pulse oximetry
screen (false negatives). The frequency of missed cases
and the related determinants are of critical importance
not only in the initial implementation of screening but
also as part of continuing quality improvement of the
system, and every effort should be taken to minimize
missed cases. Such events might occur due to local complications with implementation procedures, oximetry
thresholds that might be inappropriate in special circumstances such as high altitudes, or other implementation
realities that are inevitable with any widespread pointof-care screening program. The relative impact of these
factors might vary in different areas or states; for this
reason, surveillance programs ideally would be in place
wherever screening occurs. Other data categories detailed
in Table 1 of particular interest to surveillance programs
include prenatal and clinical diagnoses before newborn
screening; outcomes after screening such as hospitalizations, surgical interventions, or deaths; and cost-effectiveness analyses.
IMPROVING BIRTH DEFECTS MONITORING
Table 2 highlights particular issues for birth defects
programs concerned with CCHD screening evaluations.
Briefly, there needs to be a relentless focus on quality,
including standards on the accuracy of diagnoses compiled in surveillance data (Bedard et al., 2012), timeliness
of ascertainment and reporting, and longitudinal outcomes beyond the newborn period. State-based programs
MONITORING CONGENITAL HEART DEFECTS SCREENING
967
Table 1
Critical Congenital Heart Disease Newborn Screening: Questions for Birth Defects Programs Conducting
Population-Based Surveillance
Evaluation question
Health outcomes after screening
Comment
Missed cases (rates of false
negative screens and
unscreened but affected)
Burden and accuracy for secondary
screening targets
Role of altitude, sociodemographic
characteristics, and other
special circumstances
Impact of prenatal and clinical
diagnoses before NBS
Costs and service utilization
Currently mortality is fairly easy to ascertain directly or through record linkage (e.g., vital
records, National Death Index).
Other key outcomes such as morbidity and disability need to be assessed. While historically
challenging to assess for many surveillance programs, these outcomes could be addressed by
improved integration of data sources and additional record abstraction.
Evaluating frequencies and reasons for missed cases is crucial. Surveillance programs must
have the ability to follow the cohort of all children with CCHDs longitudinally, well beyond
the newborn period.
Missed case information could be used to revise screening algorithms for improved screening
results.
Noncardiac conditions such as pulmonary defects and diseases and some cardiac ‘secondary
targets’ (heart defects that present with hypoxemia only in some instances) will be identified
by CCHD screening.
Many BD programs currently perform population-based ascertainment of many types of
congenital heart defects (beyond CCHDs), and are thus positioned to help assess the
usefulness of CCHD screening beyond the primary targets.
BD programs represent diverse geographic regions of the United States and many ascertain
cases statewide, and therefore are positioned to provide population-based data about
screening accuracy rates in a variety of geographic settings.
Modified screening algorithms for high altitudes can be evaluated by BD programs
population-wide.
Prenatal (fetal echocardiography) and pulse oximetry screening rates and outcomes can
be stratified by demographic characteristics such as rural/urban residence, race/ethnicity,
maternal age, or place of delivery.
Prenatal diagnosis is possible for many CCHDs and genetic disorders frequently associated
with CCHDs, but uptake and sensitivity vary by specific CCHD, genetic disorder, and
population.
Because screening is specifically useful for newborns with CCHDs that were not identified
by fetal echocardiography, programs need to find or improve ways to collect prenatal
diagnostic information.
Some affected newborns will present with signs and symptoms in the pre-screening
period immediately after birth or have neonatal echocardiograms before screening due
to prenatal genetic diagnoses, so ideally programs should also collect accurate information
about the timing and methods of diagnosis for these types of CCHDs.
Population-based, pre-screening diagnostic data will be important metrics for evaluating
the impact of NBS.
CEAs to date on NBS for CCHD have been conducted in specific geographic areas of the
world and specific birth cohorts, and do not completely reflect population-based
ascertainment of parameter (data) inputs.
BD programs could provide robust, up-to-date information so that new CEAs could
include population-based clinical data (e.g., prenatal diagnosis, specific treatments, medical
complications, and mortality) and health services data (e.g., location/type of birthing center,
transfers, transports, hospitalizations, and rehabilitation services).
CCHD, critical congenital heart disease; BD, birth defects; NBS, newborn screening; CEAs, cost-effective analyses.
inevitably differ as they are shaped by local regulations,
available resources, local expertise, and other factors
(Mai et al., 2007). Nevertheless, common standards and
effective coordination can and ought to emerge. A key
role can be played by organizations such as NBDPN,
which have effectively supported the development of
multistate surveillance.
An example is the aforementioned compilation of
multistate CCHD data, which required consensus coding
standards for ascertaining such data across programs.
Further multistate standardization with high-quality
surveillance procedures will allow for better sharing of
compatible data. Showing the immediate importance of
their data for a real-time program should allow birth
defects programs to increase their visibility, and perhaps
even their resources, while enhancing their value for
public health.
PERSPECTIVES ON THE ROAD AHEAD
Efforts to implement CCHD screening programs are
well underway. As is appropriate with CCHD screening,
much of the initial emphasis will be on the practicalities
of point-of-care screening: the ability to conduct accurate
and timely screening at the bedside before discharge
from the nursery. These activities will include organizing
screening, communication, and follow-up protocols; educating parents; and training providers. Because of their
ties to local stakeholders and their expertise in congenital
defects, birth defects programs can facilitate these efforts.
In addition to these important activities during implementation, birth defects surveillance programs have an
even greater role to play in ensuring the core public
health functions of assessment, such as epidemiologic
studies of CCHDs, and assurance, such as evaluations of
Birth Defects Research (Part A) 94:965 969 (2012)
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OLNEY AND BOTTO
Table 2
Program Issues for Birth Defects Monitoring Related to Critical Congenital Heart Disease Newborn Screening
Issue
Needs
Data sources and quality
Timeliness
Long-term follow-up for
comprehensive outcomes
Standardization of reporting
State and national program
coordination
To address the complexity of CCHDs, key data sources are likely to include medical
records with echocardiography results and follow-up information, from specialty
clinics and referral hospitals.
Accurate case review and classification require specialized clinical expertise.
Timely, systematic feedback is a major task for surveillance programs, because of their role in
evaluating and improving NBS services.
BD programs should consider ways to streamline notification and processing of records related
to CCHDs.
BD programs need to incorporate follow-up well beyond the neonatal period.
Enhancements in data sources, data quality, and expert review will likely be necessary to assess
many outcomes, including morbidity, disability, health service utilization, and costs.
Standardized case definitions and diagnostic codes and associated variables will allow for
appropriate comparisons within and between programs (states) and over time.
To maximize the use of data from programs with varying abilities and resources, it is important
to define sets of variables (e.g., core, expanded, and optional), with explicit definitions and
quality indicators.
In some states, there will be a need to develop closer interactions between NBS and BD programs
for comprehensive evaluations to address the points above.
Interstate data exchange agreements can be critical in some localities when birth and postnatal
referral patterns cross state lines.
Nationally, pooling of standardized data would be necessary to improve evaluations, particularly
for rarer outcomes and to assess diverse demographic issues.
Technical assistance to some BD programs would need to be expanded to include broader sets of
outcomes, cost-effectiveness analyses, and other new activities.
CCHD, critical congenital heart disease; BD, birth defects; NBS, newborn screening.
prevention effectiveness (Khoury, 1996). Specifically for
newborn screening programs, evaluation needs include
long-term follow-up activities, particularly for continuous
quality improvement (e.g., refining screening algorithms,
screening procedures, and follow-up) and new knowledge discovery (Kemper et al., 2008). To conduct these
activities well, monitoring programs will need to reach
high standards of timeliness, flexibility, quality, and
acceptability (German et al., 2001). In some cases, programs will need to shift resources and priorities. Such a
shift might be challenging in the short run, but ultimately
could provide considerable rewards: efficient integration
of public health resources (e.g., screening and surveillance) within state health departments, less additional
state burdens in implementing screening (by enhancing
existing surveillance rather than creating a new system),
and higher quality birth defects surveillance. From a
systems perspective, these integrated methods should
translate into better value (quality/cost) for the investments that CCHD screening will likely require from the
public health system, the health care sector, and medical
professionals. From a health perspective, for individuals
with CCHDs and their families, this approach should
lead to realistic but useful evaluations of this promising
new phase of newborn screening.
ACKNOWLEDGMENTS
We thank our many colleagues for their visionary
discussions, helpful comments, and practical suggestions
about the ideas in this editorial, particularly Coleen
Boyle, Cynthia Cassell, Margaret Honein, Marcia Feldkamp, Cara Mai, Cynthia Moore, and Phoebe Thorpe.
Birth Defects Research (Part A) 94:965 969 (2012)
Richard S. Olney1*
Lorenzo D. Botto2,3
1
National Center on Birth Defects and Developmental
Disabilities, Centers for Disease Control and Prevention (CDC),
Atlanta, Georgia
2
Division of Medical Genetics, Department of Pediatrics,
University of Utah Health Sciences Center, Salt Lake City, Utah
3
Utah Birth Defect Network, Utah Department of Health,
Salt Lake City, Utah
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