SE M I N A R S I N P E R I N A T O L O G Y 39 (2015) 171–187

Available online at www.sciencedirect.com

www.elsevier.com/locate/semperi

Current status of newborn screening

worldwide: 2015
Bradford L. Therrell, PhDa,b,n, Carmencita David Padilla, MD, MAHPSc,d,
J. Gerard Loeber, PhDe, Issam Kneisser, PhDf, Amal Saadallah, PhDg,
Gustavo J.C. Borrajo, PhDh, and John Adams, BAi
a
National Newborn Screening and Genetics Resource Center (NNSGRC), Austin, TX
b
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, TX
c
College of Medicine, University of the Philippines Manila, Manila, Philippines
d
Newborn Screening Reference Center, National Institutes of Health (Philippines), Manila, Ermita, Philippines
e
International Society for Neonatal Screening, Bilthoven, Netherlands
f
Newborn Screening Unit, Medical Genetic Unit, Faculty of Medicine, Saint Joseph University, Beirut, Lebanon
g
Newborn Screening and Biochemical Genetics Laboratory, King Faisal Specialist Hospital and Research Center,
Riyadh, Saudi Arabia
h
Programa de Detección de Errores Congénitos, Fundación Bioquímica Argentina, La Plata, Argentina
i
Canadian Organization for Rare Disorders, Toronto, Ontario, Canada

article info abstra ct

Keywords: Newborn screening describes various tests that can occur during the first few hours or days
Newborn screening of a newborn’s life and have the potential for preventing severe health problems, including
Inborn errors of metabolism death. Newborn screening has evolved from a simple blood or urine screening test to a
International screening more comprehensive and complex screening system capable of detecting over 50 different
Rare disease screening conditions. While a number of papers have described various newborn screening activities
around the world, including a series of papers in 2007, a comprehensive review of ongoing
activities since that time has not been published. In this report, we divide the world into 5
regions (North America, Europe, Middle East and North Africa, Latin America, and Asia
Pacific), assessing the current NBS situation in each region and reviewing activities that
have taken place in recent years. We have also provided an extensive reference listing and
summary of NBS and health data in tabular form.
& 2015 Elsevier Inc. All rights reserved.

Introduction of a newborn’s life and which, when properly timed and

performed, have the potential for preventing severe health
The general term “newborn screening” is used to describe problems, including death. Newborn screening has evolved
various tests that can occur during the first few hours or days from a relatively simple blood or urine screening test,

All authors have seen and approved the submission of the manuscript and are willing to take responsibility for the entire manuscript.
B.L.T. developed the manuscript and assimilated data from the U.S. with input from C.D.P. (Asia Pacific), G.L. (Europe), I.K. and A.S.
(Middle East North Africa), G.J.B. (Latin America), and J.A. (Canada). All authors assert no conflict of interest.
n
Corresponding author at: National Newborn Screening and Genetics Resource Center (NNSGRC), 3907 Galacia Dr, Austin, TX 78759.
E-mail address: therrell@uthscsa.edu (B.L. Therrell).

http://dx.doi.org/10.1053/j.semperi.2015.03.002
0146-0005/& 2015 Elsevier Inc. All rights reserved.
172 SE M I N A R S I N P E R I N A T O L O G Y
originally used for detecting a single congenital condition, to
a more comprehensive and complex screening system that
can detect over 50 different conditions.1 While typically using
blood taken from a heelstick, more recent newborn screening
expansion has included bedside testing to detect conditions
such as hearing loss and cardiac disease. The latter 2
conditions are now included in the U.S. federally recom-
mended uniform screening panel (RUSP)2 and are included in
some programs in other parts of the world. This report
focuses on newborn bloodspot screening (NBS) commonly
used to identify inborn errors of metabolism or other inher-
ited disorders and updates screening reports that were
published in 2007, outlining NBS activities in various parts
of the world.3–9 More detailed information on hearing screen-
ing can be found in an earlier issue of this Journal,10 and
information on CCHD can be found elsewhere in the current
issue.11
NBS typically uses blood taken from a heelstick, absorbed
onto special collection paper (similar consistency to filter
paper), and transported to a special screening laboratory.12
While hospital laboratories may be qualified to perform NBS
testing in some settings, the screening laboratory is usually a
specialized laboratory because of the micro-techniques used,
the cost savings from centralizing the laboratory services,
and improvements in quality realized when testing large
quantities of specimens for relatively rare conditions. In the
U.S., it is most often a special public health laboratory. In
some settings, it may be part of a larger clinical genetics
laboratory, and in others, particularly in developing coun-
tries, it may be in a research setting.
In order to assess NBS activities globally, we have divided
the world into 5 regions: North America, Europe, Asia Pacific,
Middle East and North Africa (MENA), and Latin America.
Obviously missing is Sub-Saharan Africa for which little
information is currently available, and limited congenital
hypothyroidism (CH) and sickle cell NBS activities are
ongoing.13–15 A review of the literature and personal contacts
working in Africa revealed documentation of various begin-
ning newborn screening activities in Ghana,16,17 Nigeria,18
Tanzania,19 Angola,20 Ethiopia,21 Democratic Republic of
Congo,22 and South Africa.23,24 For the remainder of the
world, we have drawn on our extensive NBS experience and
contacts with NBS program managers within our respective
regions to solicit recent updates in order to comprehensively
describe ongoing regional NBS activities.
North America
For purposes of this report, North America is comprised of the
51 U.S. programs (50 states and the District of Columbia) and
15 Canadian programs (10 provinces and 3 territories with 1
territory, Nunavut, divided into 3 regions). Because of similar
language and culture, Mexico, while a part of North America,
is included in the discussion of Latin American programs.
Although screening exists in some U.S. territories, little effort
has been made to collect systematic data on these programs,
and they are not included in the discussion here. It suffices to
say that the programs in Puerto Rico, Virgin Islands, and
Guam are the most advanced U.S. territorial programs. A
39 (2015) 171–187
recent report summarizes the challenges faced by NBS
expansion in the territories, with particular emphasis on
the Virgin Islands and Puerto Rico.25 While nationally man-
aged NBS programs do not exist in either the U.S. or Canada,
the state, provincial, and territorial NBS programs have long
histories and well established infrastructures similar to
national programs in other countries.
Building on federally supported efforts to develop a
national newborn screening plan (blueprint) by the American
Academy of Pediatrics,26 the U.S. Congress passed legislation
supporting national screening efforts, which was signed into
law in 200827 and recently reauthorized.28 In addition to
funding for various newborn screening activities, the Secre-
tary of Health and Human Services’ Advisory Committee on
Heritable Disorders in Newborns and Children (SACHDNC)
was created. This committee has provided national NBS
leadership through its carefully considered recommendations
to the Secretary.29 In addition to approving recommendations
for a nationally Recommended Uniform Screening Panel
(RUSP) from the American College of Medical Genetics,30 the
SACHDNC has implemented, and periodically refined and
updated, an evidence-based protocol for reviewing and rec-
ommending other conditions for inclusion on the RUSP.31
Since adoption of the initial 29 core conditions and 25
recommended secondary targets, 4 additional core conditions
have been recommended [severe combined immunodefi-
ciency disease (SCID), critical congenital heart disease
(CCHD), Pompe disease, and Mucopolysaccharidosis type I
(MPS I)] along with 1 secondary target, T-cell lymphocyte
deficiencies. As of March 2, 2015, all except MPS-I have now
been accepted for recommendation by the Secretary increas-
ing the RUSP to 32 conditions. Several other conditions have
been nominated for inclusion on the RUSP but have not yet
met the criteria for inclusion, including early infantile Krabbe
disease and Hemoglobin H disease, among others.32
Table 1 presents a tabular overview of screening activities
in the U.S. Compared to the previous version of this table
published in 2007,3 there are several noteworthy observa-
tions. In general, the number of required screening condi-
tions has increased as state funding has permitted, following
the recommendations of the SACHDNC. Most notable has
been the addition of tandem mass spectrometry (MS/MS) to
expand screening for metabolic conditions, screening for
SCID, and CCHD screening. Expanded metabolic screening
with MS/MS is now included in every state screening program
and SCID, added to the RUSP in 2010, is now implemented in
over 30 states.33 The results of SCID screening in Wisconsin
(the first state to require NBS for SCID), California, New York
and an 11-state consortium have been published.34–37
All but 4 state programs are at least partially fee based, and
the average initial NBS screening fee has increased from
about $45 in 2007 to about $76 in 2015. Despite a SACHDNC
recommendation that states should consider linking birth
certificates to NBS screening, the Secretary of Health and
Human Services did not approve the recommendation and
many state programs are still unable to accurately determine
screening coverage (most “assume” at least 98% coverage).38
While almost all states require point-of-care screening for
hearing loss and CCHD, both included on the RUSP, many
programs have elected to monitor hospital CCHD activities
 S E M I N A R S I N P E R I N A T O L O G Y 39 (2015) 171–187 173

Table 1 – Program demographics and screened conditions in the U.S. newborn screening programs.
174 SE M I N A R S I N P E R I N A T O L O G Y
rather than to develop a comprehensive CCHD screening
system that includes centralized monitoring of case detec-
tion, follow-up, and tracking—different from the approach
taken with hearing screening.10,11
Beginning with the requirement for Krabbe screening in
New York in 2006,39 interest in NBS for lysosomal storage
disorders (LSDs) has steadily increased, laboratory quality
control materials have been developed,40 and legislation
requiring screening for selected LSDs has been enacted in
several states. Increasingly, interest has focused on NBS for
Pompe disease since it has now been recommended by the
SACHDNC. Potential screening algorithms for the LSDs are
discussed elsewhere in this issue,41 and pilot data from
Missouri has been published.42
Although X-linked adrenoleukodystrophy (X-ALD) is not yet
a part of the RUSP, a screening test has been developed and
NSB for X-ALD is now required in New York Connecticut, and
California, a pilot already having been completed in New
York.43–45 Laboratory quality control X-ALD NBS materials are
under development.46 Research is also ongoing to develop
laboratory methods and assess public perceptions for other
conditions including Fragile-X,47,48 spinal muscular atrophy
(SMA),49,50 Wilson’s disease,51 and guanidinoacetate methyl-
transferase (GAMT) deficiency.52
With increasing interest in NBS, and the possibility of
extracting DNA from residual dried blood spot (DBS) speci-
mens, has come an increasing awareness of privacy issues,
particularly since NBS in the U.S. is legally required and
consent is usually not included as part of U.S. screening
protocols. The residual DBS specimens that remain after
initial screening tests have been completed and reported,
present storage and usage challenges. Approximately half of
U.S. NBS programs discard residual specimens by 2 years and
the rest retain them for more than 18 years.53 Legal questions
concerning NBS specimen storage and use have led to law-
suits in Texas and Minnesota resulting in significant policy
changes in both states,54 and another lawsuit now exists in
Indiana. To help address this issue, the concerns of selected
state NBS advisory committees have been assessed, and the
SACHDNC has considered the issue and made general rec-
ommendations.55,56 As in other countries, researchers in both
the U.S. and Canada have investigated parental attitudes and
public perceptions concerning potential uses of residual NBS
specimens in an effort to inform NBS programs and address
any issues revealed.57,58 In Michigan, a model NBS biobank
has been developed,59 and a Newborn Screening Transla-
tional Research Network (NBSTRN) has been funded by the
National Institutes of Health as one way of providing
researchers with improved knowledge and access to NBS
specimens in participating state NBS programs.60
In Canada, the federal government has no formal role in
newborn screening. Healthcare (and NBS) is the responsibility
of the 10 provinces and 3 territories, with the notable
exception of specific populations of aboriginals, inmates of
federal prisons, military and newly arrived immigrants and
refugees. These specific populations together make a group
larger than most provinces. In the absence of pan-Canadian
development and coordination of newborn screening policies
and practices, individual provinces have their own advisory
and decision-making processes, with varying degrees of
39 (2015) 171–187
public transparency. A recent reorganization of territorial
governments across the northern tier of Canada has also
had implications for NBS. In particular, the establishment of
the territory of Nunavut means that NBS specimens are sent
to 3 different provincial NBS labs based on historic patterns of
medical services delivery.
Since 2010, when the Canadian College of Medical Geneti-
cists took a position supporting NBS for cystic fibrosis (CF),61
most NBS programs have included it on their screening
panels. However, only 3 conditions currently are included
on the screening panels in all Canadian NBS programs,
phenylketonuria (PKU), CH, and medium chain acyl-CoA
dehydrogenase deficiency (MCADD). The number of condi-
tions routinely screened varies from 5 to over 30 across
programs (Table 2). There appears to be a new focus on
newborn screening collaboration and quality improvements
through recurring national conferences. An attempt to create
national consensus-building took place at a conference in
2007 funded by the province of Ontario, and a fresh effort
took place in 2014 as a parallel meeting of the annual
symposium of the Garrod Association (made up of the treat-
ment centers for inborn errors of metabolism).
In 2013, Ontario became the first Canadian province to
screen for SCID.62 A pilot for GAMT screening is ongoing in
British Columbia.63 In addition to bloodspot screening, a urine
screening program exists in Quebec offering expanded meta-
bolic screening and considering screening for LSDs.64,65 As in
the U.S., there has also been significant interest in the use of
residual NBS specimens for research in Canada. A number of
studies have been reported addressing concerns of parents,
the public, and professionals. With technology moving
towards less expensive high-throughput genomic testing,
the possibilities of genomic NBS are being discussed, and
the ethical, legal, and social implications debated.66–68 In both
Canada and the U.S., there is increasing emphasis on the
speed with which NBS specimens reach the testing laboratory
and have testing results available.
Europe
Europe is considered to consist of 48 jurisdictions situated
east of the Atlantic, north of or in the Mediterranean Sea and
west of the Ural Mountains, but including the whole of
Russia. The total population in 2012 was over 833 million
with annual births of more than 9.5 million (Table 3). As in
many parts of the world, NBS in Europe began in the mid-
1960s, developing from West to East, with the latest program
being initiated in Bosnia–Herzegovina in 2000.69 Four of the 48
jurisdictions are so small that screening is performed in a
larger neighboring country (Liechtenstein, Andorra, San Mar-
ino, and Monaco).
Several reports have been published about the progress of
NBS over time,4,70–73 including a recent summary of activities
in Southeastern Europe.74 The data in Table 3 were recently
collected by surveying European NBS experts and update
similar data reported in 2012.71 Currently, all European
jurisdictions have NBS for CH except Moldova, in which
screening for CH previously occurred from 1989 to 1993.
Screening for CH is planned to restart in Moldova in a few
 S E M I N A R S I N P E R I N A T O L O G Y 39 (2015) 171–187 175

Table 2 – Program demographics and screened conditions in Canadian newborn screening Programs 2014.

years.74 All jurisdictions except Macedonia [formerly called
the Former Yugoslavian Republic of Macedonia (FYROM)],
Malta and Montenegro, have screening for PKU. While PKU
screening in Finland previously targeted newborns of Swed-
ish origin, universal NBS for PKU began on January 1, 2015.
Since screening in Finland previously utilized cord blood, the
switch to DBS has allowed inclusion of glutaric aciduria type
1 (GA1), MCADD, long-chain hydroxyl acyl-CoA dehydrogen-
ase deficiency (LCHADD), and congenital adrenal hyperplasia
(CAH). Malta remains as the only country in which cord blood
is used for screening, but a switch to DBS is under discussion.
Albania is the only European country without a screening
program; however, discussions to implement it have started
recently.
NBS in European countries is heterogeneous with no con-
sensus as to what should or should not be included in NBS.75
Each jurisdiction is governed independently and makes its
own decisions concerning conditions that should be included
in NBS. Unlike the U.S. where public opinions can influence
NBS policies, there is little public knowledge concerning
healthcare organization in neighboring countries. As a con-
sequence, advocacy efforts concerning health policies across
borders are limited.
There are currently no policy recommendations or direct NBS
oversight at the European level. However, in recent years,
European best practice guidelines for cystic fibrosis NBS have
been published76 along with treatment guidelines following NBS
for both cystic fibrosis (CF) and CH.77–79 To add complexity, in
some countries, e.g., Belgium, Italy, Spain, and the UK, policy
making is decentralized to regions or provinces that function
more or less autonomously. The result is less than 100%
screening coverage for certain conditions in these countries.
176 SE M I N A R S I N P E R I N A T O L O G Y 39 (2015) 171–187

Table 3 – Program demographics and screened conditions in European newborn screening programs.
 S E M I N A R S I N P E R I N A T O L O G Y
Since healthcare funding in Europe is typically organized
within a national health service or a statutory health insur-
ance (social security), parents do not usually have to pay a fee
for NBS services. This often results in complex government
financial decisions when expansion to include new condi-
tions is considered. While each is different, public healthcare
systems have defined mechanisms to assess and appraise
payment for NBS and most allow for diverse stakeholder
participation when considering technology effectiveness, dis-
ease severity, and treatment availability.80 Hearing screening
and CCHD screening are usually organized and financed
separately from NBS.81
As in other countries, there has been continuing interest in
the storage and use of residual NBS.82,83 Researchers have
examined various specimen stability issues.84,85 There has
also been considerable discussion about privacy and con-
sent.86,87 While there is experimentation and discussion
aimed at expanding current NBS panels to include one or
more LSDs, expansion is unlikely to happen on a large
scale.88–90 On the other hand, several jurisdictions are
expanding their NBS panel to include SCID.90–94
Over time, the European Union (EU), presently consisting of
28 countries, has established several treaties on topics to be
governed or overseen by the European Commission (EU’s
Executive Body). Healthcare has not been included because
the member states considered it to be their own responsi-
bility (principle of subsidiarity). It was, therefore, surprising
when the European Commission issued a recommendation
on collaboration in rare diseases (prevalence of less than
1:2000) in November 200895; included was development of an
inventory of NBS programs within the member states, which
was subsequently subsidized as a project by the European
Agency for Health and Consumers. The project group decided
that the inventory should include EU-candidate and potential
EU-candidate member countries along with European Free
Trade Association member countries. All countries west of
Russia were surveyed, and the results have been pub-
lished.72,73 Additionally, recommendations for European pol-
icy makers were also developed and published.74 Following
discussion, the European Union Committee of Experts on
Rare Diseases (EUCERD) chose to continue the original EU
policy of subsidiarity, i.e., healthcare is a matter for individual
member states.
Middle East and North Africa
The MENA region consists of 21 countries with a population
of about 440 million with 11 million annual births. There is
significant diversity between countries in population size, per
capita income, health systems, insurance coverage, and new-
born screening implementation.96 Because there are high
rates of consanguinity and first cousin marriages, genetic
disorders are relatively common. In the past decade, a
reducing (improving) infant mortality rate (IMR) has led to
growing recognition of the value of NBS, and there have been
a number of collaborations and educational efforts aimed at
its introduction and expansion in the MENA.97–99
When we reported in 2007,8 only 4 countries in the MENA
region had ongoing NBS programs, and this led participants
39 (2015) 171–187 177
at the first MENA Regional NBS Conference to create the
Marrakech Declaration.100 This declaration committed all
countries in the region to establish a NBS infrastructure and
to implement screening for at least 1 condition. To assess
progress over time, we have reviewed the current literature
and made personal contacts with MENA NBS program man-
agers and members of and Middle East Metabolic Group
(MEMG).101
Table 4 summarizes MENA data and provides an overview
of current NBS activities. Because of its global appeal as a
condition of sufficient prevalence with cost effective and
efficacious treatment, CH has usually been the first condition
emphasized in MENA NBS programs. Thus, much of the NBS
effort within the region has focused on continued assessment
of CH screening protocols and treatment outcomes.102–104
Because hemoglobinopathies (Hbs) and metabolic conditions
are also prevalent, and in order to influence policy makers,
studies within the region have often focused on the inciden-
ces of various metabolic conditions105–108 and Hbs109,110
(although in the case of Hbs, there is competing emphasis
on prevention strategies). Several NBS cost-effectiveness
studies have also been completed in various countries.111–
113
In addition to popular interest in adding MS/MS capabil-
ities to expand metabolic screening capabilities, studies have
also addressed the potential impact of adding other condi-
tions to screening panels, including glucose-6-phosphate
dehydrogenase (G6PD) deficiency, galactosemia (GAL), CAH,
and CF.
Successful screening experiences across the region have
provided a basis for considering internal expansion and
for encouraging screening activities in neighboring juris-
dictions.114,115 Likewise, successful screening models in
Lebanon and Qatar have demonstrated the feasibility of
using screening laboratories in other countries to provide
NBS services.116,117 National NBS programs with extensive
screening coverage are now present in Bahrain, Egypt,
Iran, Israel, Kuwait, Oman, Qatar, State of Palestine, Saudi
Arabia, and the United Arab Emirates. Pilot screening pro-
grams exist in Libya, Morocco (beginning in 2015), Syria,
Yemen, and Algeria. Pilot screening projects have been
completed in Jordan, Lebanon, and Tunisia, with expansion
to national implementation currently ongoing. Israel is con-
sidering the possibility of implementing NBS for SCID.118
Although technically part of the region, little is known about
screening activities in Sudan and Somalia.119 Noteworthy is
the fact that an increased incidence of biotinidase deficiency
has been observed in Somali immigrants in Minnesota,
USA.120
Latin America
Latin America consists of 20 countries as noted in our 2007
report.7 The combined population is now approximately 600
million, with annual births of 11 million. As with other
regions, there is diversity of geography, demographics, eth-
nicity, economies, and social and health systems, including
newborn screening. Language is perhaps the most important
shared characteristics since all countries except Brazil and
Haiti, are Spanish speaking. Recent NBS changes in Latin
178 SE M I N A R S I N P E R I N A T O L O G Y
Table 4 – Program demographics and newborn screening experiences in the Middle East and North Africa.
America are reviewed in this section, with the caveat that
point-of-care newborn screening for hearing loss is also
expanding across the region.121 It is important to recognize
that in some countries like Chile, Brazil, Mexico, Argentina,
Colombia, and Venezuela, NBS activities extend beyond those
established by a national or regional NBS program. Screening
for other diseases, especially those detected by MS/MS, is
often available in the private sector. A tabular summary of
regional activities is given in Table 5.
NBS programs in countries that have been functioning for
20–30 years (Cuba, Costa Rica, Uruguay, and Chile) have
continued expanding their coverage, and now all 4 reach
more than 99% of newborns. While programs in Cuba and
Chile have not changed their screening panels since 2007,
Chile is working to pilot expanded NBS to include 25 con-
ditions in 2015, and researchers in Cuba have reported on
several new screening techniques for both traditional (PKU,
GAL, and CAH)122–124 and future screening (Gaucher and MPS I
heterozygotes).125,126 Currently, NBS in Cuba is decentralized
through more than 175 laboratories. In Costa Rica, CF was
added to the screening panel in 2009, building on the pilot
program previously reported.127 By contrast, NBS in Uruguay
experienced the most important changes in the screening
panel, adding PKU and CAH in 2007, and CF in 2010; each with
official directives from the Ministry of Health that also
included MCAD.128,129 A tandem mass spectrometer was
purchased in 2008 followed by pilot testing and implementa-
tion of expanded metabolic screening.130,131 Thus, Uruguay is
the second Latin American country (together with Costa Rica)
to implement such expanded NBS. In 2013 BIO and Hbs were
added.
The NBS programs in Brazil, Mexico, and Argentina have
also increased their screening panels significantly, in turn
39 (2015) 171–187
requiring improvements in all other aspects of the screening
system (i.e., education, follow-up, and management). In
Brazil, which implemented nationwide NBS in 2001, there
has been continued evaluation and refinement of screening
for PKU, CH, CF, and Hb. There are now 30 Reference Centers
distributed throughout the country, and coverage in 2013 was
83%.132 During the last 2 years, the Ministry of Health has
been reformulating the National NBS Program to include CAH
and BIO, building on pilots already completed,133–135 with
anticipated coverage of almost 3 million newborns annually.
These activities are supported by 2 decrees passed in 2012,
which mandate their inclusion. Additionally, expanded
screening for metabolic diseases using MS/MS was imple-
mented in 2010 for the Federal District and recently as a pilot
for Minas Gerais.
In Mexico, there has been a significant increase in newborn
coverage through the activities of different subsystems of the
complex healthcare system.129 Most important is the fact that
the Secretary of Health and the Mexican Institute of Social
Security together screen more than 70% of all newborns.
Current screening coverage for the country exceeds 80% of
newborns (tested for CH, PKU, GAL, CAH, and BIO). In some
states (Tabasco, Yucatan, and Chiapas), as part of the system
of the Secretary of Health, there is additional screening for CF,
Hb, and MS/MS detectable metabolic conditions. All condi-
tions screened are included as part of the Mexican Official
Rule for the Prevention and Control of Congenital Defects in
force since 2012.136
In Argentina, regional NBS programs ongoing in the Prov-
ince of Buenos Aires,137 Mendoza and the Autonomous City of
Buenos Aires (ACBA) since the mid-1990s, became consoli-
dated. In 2006, the National Ministry of Health implemented
its Strengthening Program whose activities include distributing
 S E M I N A R S I N P E R I N A T O L O G Y
Table 5 – Program demographics and screened conditions in Latin American screening programs.
NBS reagents to provinces without organized screening, thus
determining the existence of 20 regional NBS programs. At the
same time, new national legislation in 2007 expanded manda-
tory screening to PKU, CH, CF, GAL, CAH, BIO, hearing loss, and
retinopathy of prematurity. A 2008 provincial law (Province of
Buenos Aires) also required screening for maple syrup urine
disease (MSUD). Additionally, the ACBA NBS program imple-
mented MCAD screening by MS/MS at the beginning of 2014.
Currently, the NBS coverage in Argentina is approximately 90%.
In Colombia and Venezuela, emphasis has been on screen-
ing coverage and projects for the coming years. Presently,
screening for CH is the only systematically required condition
in Colombia. Screening is decentralized and coordinated by
the National Institute of Health. Screening procedures have
been recently included in the Public Health Surveillance Protocol
for Congenital Defects138 and screening coverage exceeds 80%.
In 2014, the Ministry of Health enacted the Guideline for
Newborn Assistance which recommends NBS for PKU, CAH,
and GAL and acknowledges the recent implementation of
39 (2015) 171–187 179
some private NBS programs by health insurance companies.
Additionally, at the beginning of 2014, a pilot program by MS/
MS was implemented in 7 departments (provinces), being
centralized in the National Institute of Health. The national
NBS program in Venezuela was implemented in 1999 and is
coordinated by the National Institute of Hygiene. Screening is
regional and includes both PKU and CH. Coverage has grown
until it now covers approximately 70% of newborns. There are
pilot screening projects for Hb, GAL, and BIO, and the Ministry
of Health is planning to add CAH, GAL, and BIO to the
National NBS Network in 2015. In Venezuela, there is limited
metabolic screening with MS/MS by request.
Screening programs in Paraguay, Panama, and Nicaragua are
relatively recent. In 2003, the Paraguay Ministry of Health and
Social Welfare created the National Program for the Prevention of
Cystic Fibrosis and Mental Retardation caused by CH and PKU.
Screening for CH began in 2004, for PKU in 2007, and later for
CF.129 Total coverage exceeded 60% in 2013, except for CF which
was 24%; however, for newborns born in public institutions
180 SE M I N A R S I N P E R I N A T O L O G Y
coverage was 94% and 31%, respectively. Currently, the national
program is focused on increasing the coverage for CF and
planning expansion to include piloting CAH, GAL, and MS/MS
in 2015. In Panama, the national NBS program for CH and G6PD
deficiency began in 2007, expanding to include GAL and PKU in
2008, and CAH and Hb more recently.129 Screening occurs in 11
regional NBS centers of the Ministry of Health, and there is an
independent program implemented by the social insurance.
Together, the 2 programs cover more than 75 % of newborns.
Legislation was critical to NBS success in both Paraguay and
Panama. In Nicaragua, a regional NBS program was started at
the National Autonomous University of Nicaragua—Leon in
2005. Initially it targeted newborns in the Northwest region,
extending its scope to the rest of country’s departments later.139
Screening is exclusively for CH using cord blood, and the
coverage exceeds 86%.
Ecuador, Peru, and Bolivia have shown the most important
advances in recent years. The national NBS program in
Ecuador began in December of 2011, and included PKU, CH,
CAH, and GAL, with current coverage of approximately 90% of
newborns. The Universal NBS Program in Peru was created by
law in 2012 with PKU, CH, CAH, GAL, CF, and hearing loss as
the conditions included in the initial phase. NBS activities are
carried out mainly by the Maternal Perinatal National Insti-
tute and ESSALUD, organizations belonging to the public and
the private sector, respectively. Despite a law, coverage in
Peru is only about 20% and screening for some conditions like
CF have not yet been implemented. In Bolivia, a 2006
Ministerial Decision declared NBS to be mandatory for CH,
but until now a national program has still not been imple-
mented. Similar to Peru, Bolivia has 2 main initiatives: one in
Santa Cruz in the public sector and the other in La Paz in a
private hospital with departmental (provincial) coverage of
70%. Three additional public programs have recently been
implemented in Chuquisaca, Cochabamba, and Tarija, so that
total coverage from all programs is about 20%.
NBS in other countries in the region have not exhibited
significant changes. A national NBS program was started in
Guatemala in 2003, building on pilot CH NBS activities initiated
with funding from the International Atomic Energy Agency in
the mid-1990s; however its scope is limited only to newborns
born in 2 hospitals in Guatemala City. Diseases screened include
CH, PKU and CAH covering approximately 1% of newborns. In
the Dominican Republic, there are only minimal NBS activities
carried out on request in the private sector. Other metabolic
diseases are screened by sending samples to private laboratories
in USA. At present, specialists are working on a project to
include screening for CH, PKU, Hb and G6PD in 2015. In El
Salvador, a regional NBS program began in 2008 for newborns
born exclusively in the metropolitan and paracentral regions of
the country, but this program was discontinued by lack of
funding. In Honduras, several different projects aimed at imple-
menting NBS have been attempted since 2007, but none have
been sustained. In Haiti, there are no known NBS activities.
Asia Pacific
The Asia Pacific region extends from New Zealand on the
south to Mongolia on the north, and reaches to Pakistan in
39 (2015) 171–187
the east (see map in 2007 report).6 Of the 138 million babies
born in the world, almost half (67 million) are born in the Asia
Pacific region. Countries in the region vary widely in size,
economic development, and geography. There are many
different languages, cultural sensitivities, and religions, each
creating its own challenges in implementing NBS. In some
areas, the number of births outside of hospitals approaches
80%, and literacy is very low. Despite these challenges, NBS
continues to grow throughout the region.
Almost 80% of the births in the Asia Pacific region occur in 5
countries—China, Indonesia, Bangladesh, India, and Paki-
stan. The IMR has been found to be a good predictor of when
competing health issues acknowledge the need for NBS, and
all countries with an IMR lower than of 7 per 1000 live births
have been able to reach NBS coverage of more than 90%.140
The number of conditions screened varies widely across the
region. Several recent reports review NBS expansion activities
across the region.141–149
At the time or our 2007 report,6 only Australia, New
Zealand, and Taiwan included expanded metabolic screening
with MS/MS in their screening panels.6 Since that time, other
countries in the Asia Pacific region have expanded to include
not only additional metabolic screening, but also a number of
other conditions not in their panels at that time. The
Japanese Ministry of Health and Welfare decided to expand
publicly funded NBS to include inborn errors of amino acid,
organic acid, and fatty acid metabolism in 2012,150 but in
most other Asian countries, patients must pay for this addi-
tional (optional) testing. There has also been increasing
interest in NBS for LSDs, and significant progress with Pompe
disease screening has been reported in Taiwan,151–153
Japan,154 and Korea.155 Additional pilot studies in the region
for other LSDs (Niemann-Pick A/B, Krabbe, Gaucher, Fabry,
and Hurler syndrome) have been reported.156–159 Other con-
ditions for which there have been ongoing NBS pilot studies
include citrin deficiency,160 SCID,161 Fragile-X syndrome,162 X-
ALD,44 and Wilson’s disease.163
Currently, Taiwan is the only country in the region that
includes both Pompe disease and SCID in the national panel
of conditions. The screening coverage rate is reported to be
approximately 95% for Pompe disease and 85–88% for SCID.
There have been several pilot programs including Fabry
(2006–2014), Gaucher (since 2011), MPS I (since 2008), aromatic
amino acid decarboxylase deficiency (AADC deficiency) (since
2013), and newborn screening (since 2014). Preliminary inci-
dences were at least 1:875 in males (Fabry), 1:101,134
(Gaucher), 2:35,285 (MPS I), 3:53,807 AADC deficiency, and
1:12,000 (SMA). (Chien YH., 2015, personal communication).
Pilot NBS project for LSDs, Fragile-X syndrome, and SCID is
also ongoing in Australia,164 and there is continuing interest
in public perceptions, privacy, and consent issues.165 Federal
government oversight of NBS has recently surfaced as an
issue166 in Australia (programs are currently state responsi-
bilities).6 A working party has been tasked with developing a
policy for harmonization of NBS across Australia and a
mechanism for adding and removing conditions from screen-
ing panels. A final submission is due at the end of 2016.(Wiley
V., 2015, personal communication)
India has the most births of any country in the world, yet
NBS is still not a healthcare priority.167 While the percentage
 S E M I N A R S I N P E R I N A T O L O G Y 39 (2015) 171–187 181

Table 6 – Program demographics and screened conditions in Asia Pacific newborn screening programs.

coverage from NBS has increased over years, it is still not
quantifiable. Some state programs are now beginning, and a
number of provincial pilots are ongoing, including some
efforts in the private sector. Initiatives include BIO, CAH,
CH, Fragile-X, G6PD, GAL, and MS/MS. (Kabra M., 2015,
personal communication). The situation has recently been
reviewed by Verma et al.168 with suggestions to the govern-
ment for screening implementation. As a first step, the
authors suggest convening a central advisory committee to
plan for program development. Three conditions are
recommended for immediate introduction in urban hospitals
(CH, CAH, and G6PD deficiency), while the recommendation
for rural areas is only for CH, especially in the sub Himalayan
areas. Screening with MS/MS is suggested once there is a firm
infrastructure in place. The challenges noted and their
potential solution are similar to those experienced in most
developing programs, only they encompass a much larger
screening population.169,170
Among the countries that lack total NBS coverage, the
obstacles are usually the same: poor economies, insufficient
182 SE M I N A R S I N P E R I N A T O L O G Y
health education, lack of government support, early hospital
discharge, and large numbers of out-of-hospital births. Cer-
tain items have been identified as essential to success for
sustainable programs: (1) government prioritization, (2) full or
partial government financing, (3) public education and
acceptance, (4) health practitioner cooperation/involvement,
and (5) government participation in program institutionaliza-
tion.169,170 Despite more than a decade of pilot testing, some
countries in the region with large numbers of births, i.e.,
Bangladesh, Indonesia, Pakistan, and India, continue to
struggle in securing government support.
In order to provide information sharing and ongoing educa-
tional support, a network of developing programs has existed
for several years.170 This network continues with program
reviews and goal setting as a major agenda item. A summary
of regional activities is given in Table 6. Noteworthy is the
success at screening implementation in China, which now
reaches over 85% of all Chinese newborns. NBS in the
Philippines continues as a model for developing programs
with 65% coverage, recent addition of regional comprehen-
sive follow-up/treatment centers to its infrastructure, and
implementation of expanded screening, including MS/MS
screening and screening for Hbs, CF, and BIO. Based on
preliminary clinical estimates, NBS for Hbs in the Philippines
should identify larger numbers of thalassemia patients than
seen in any other thalassemia NBS program.
Summary comments
While CH remains the most significant condition included in
NBS programs worldwide due to its relatively high incidence
(particularly in iodine deficient areas), readily available low-
cost treatment and successful treatment results, screening
for various other conditions is also of high importance. Each
condition included in NBS must be carefully evaluated on the
basis of medical and scientific evidence surrounding the
natural history of the condition and the local ability to
decrease morbidity and mortality through screening. Care
must be taken in implementing new programs not to make
the same mistakes made by others. Carefully planned pilot
testing should always include a thorough analysis of public
health impact and cost effectiveness with an eye to the
future. As an example, while it is true that cord blood
screening can be effective as a screening mechanism for
some conditions like CH and G6PD, it is equally true that cord
blood specimens cannot be reliably used for metabolic
screening. So, while cord blood may be appealing for pro-
grams beginning to screen for CH or G6PD, blood spot screen-
ing is the better choice because of its increased flexibility and
the high likelihood of expansion to metabolic testing at some
future time.
Developing programs must continually take advantage of
progress already made by others. This report has identified
various regional training and support activities that have
assisted in the development of new programs and the refine-
ment of already established programs. In an effort to encour-
age worldwide harmonization and to provide guidance in
establishing the most effective and efficient protocols, the
Clinical and Laboratory Standards Institute has refocused its
39 (2015) 171–187
efforts on international NBS consensus standards and guide-
lines. At least 6 such documents currently exist and more are
planned.171–176 The International Society for Neonatal Screen-
ing (ISNS) also provides support for improving NBS worldwide
through its collaboration with organizations like CLSI, CDC,
and others and by providing expert advice and information to
developing programs. Regional ISNS meetings provide addi-
tional opportunities for collaborations. NBS programs should
take advantage of these and other international efforts to
improve screening quality.177
This report emphasizes the complexity of NBS and the
continuing need for system-wide evaluation and improve-
ment. It also provides information about global NBS activities
and points to the importance of transparency and knowledge
in achieving public support worldwide. Through shared
commitment and information, we will continue to expand
NBS opportunities and, as a consequence, health and life
outcomes.54,69,154
Acknowledgments
The authors gratefully acknowledge the cooperation of col-
leagues in each region in providing information about their
screening activities. Many who contributed have not been
acknowledged through documented personal communica-
tions, but their responsiveness to our requests will not go
unnoticed.
re fe r en ces
1. Therrell BL Jr. Newborn dried bloodspot screening. In: Dris-
coll CJ, McPherson B, et al., eds. Newborn Screening Systems—
The Complete Perspective. San Diego: Plural Publishing, Inc;
2010. 133–156.
2. 〈www.hrsa.gov/advisorycommittees/mchbadvisory/heritable
disorders/recommendedpanel/index.html〉; Accessed 10.01.
15.
3. Therrell BL, Adams J. Newborn screening in North America. J
Inherit Metab Dis. 2007;30:447–465.
4. Loeber JG. Neonatal screening in Europe: the situation in
2004. J Inherit Metab Dis. 2007;30(4):430–438.
5. Bodamer OA, Hoffman GF, Lindner M. Expanded newborn
screening in Europe 2007. J Inherit Metab Dis. 2007;30(4):
439–444.
6. Padilla CD, Therrell BL. Newborn screening in the Asia Pacific
region. J Inherit Metab Dis. 2007;30(4):490–506.
7. Borrajo GJ. Newborn screening in Latin America at the
beginning of the 21st century. J Inherit Metab Dis. 2007;30(4):
466–481.
8. Saadallah AA, Rashed MS. Newborn screening: experiences
in the Middle East and North Africa. J Inherit Metab Dis.
2007;30(4):482–489.
9. Lindner M, Abdoh G, Fang-Hoffman J, et al. Implementation
of extended neonatal screening and a metabolic unit in the
State of Qatar: developing and optimizing strategies in
cooperation with the Neonatal Screening Center in Heidel-
berg. J Inherit Metab Dis. 2007;30(4):522–529.
10. White KR, Forsman I, Eichwald J, Munoz K. The evolution of
early hearing detection and intervention programs in the
United States. Semin Perinatol. 2010;34(2):170–179.
 S E M I N A R S I N P E R I N A T O L O G Y
11. Olney RS, Ailes EC, Sontag MK. Detection of critical congen-
ital heart defects: review of contributions from prenatal and
newborn screening. Semin Perinatol. 2015;39(4) [this issue].
12. Hannon WH, De Jesús V, Ballance LO, et al. Blood collection on
Filter Paper for Newborn Screening Programs—Approved Standard
—Sixth Edition. Wayne, PA: Clinical Laboratory Standards
Institute; 2013;2013 [CLSI document NBS01-A6].
13. Adeniran KA, Limbe M. Review article on congenital hypo-
thyroidism and newborn screening program in Africa; the
present situation and the way forward. J Thyroid Disord Ther.
2012. http://omicsgroup.org/journals/2167-7948/2167-7948-1-
102.php?aid=4617.
14. Tshilolo L, Kafando E, Sawadogo M, et al. Neonatal screening
and clinical care programmes for sickle cell disorders in sub-
Saharan Africa: lessons from pilot studies. Public Health.
2008;122(9):933–941.
15. Mutesa L, Boemer F, Ngendahayo L, et al. Neonatal screening
for sickle cell disease in Central Africa: a study of 1825
newborns with a new enzyme-linked immunosorbent assay
test. J Med Screen. 2007;14(3):113–116.
16. Ohene-Frempong K, Oduro J, Tetteh H, Nkrumah F. Screen-
ing newborns for sickle cell disease in Ghana. Pediatrics.
2008;121:S120–S121.
17. Treadwell MJ, Anie KA, Grant AM, Ofori-Acquah SF, Ohene-
Frempong KJ. Using formative research to develop a coun-
selor training program for newborn screening in Ghana.
Genet Couns. 2015;24(2):267–277.
18. Adeniran KA, Okolo AA, Onyiriuka AN. Thyroid profile of
term appropriate for gestational age neonates in Nigeria: a
forerunner to screening for congenital hypothyroidism.
J Trop Pediatr. 2010;56(5):329–332.
19. Makani J, Soka D, Rwezaula S, et al. Health policy for sickle cell
disease in Africa: experience from Tanzania on interventions
to reduce under-five mortality. Trop Med Int Health. 2015;20(2):
184–187.
20. McGann PT, Ferris MG, Ramamurthy U, et al. A prospective
newborn screening and treatment program for sickle cell
anemia in Luanda, Angola. Am J Hematol. 2013;88(12):984–989.
21. Feleke Y, Enquoselassie F, Deneke F, et al. Neonatal con-
genital hypothyroidism screening in Addis Ababa, Ethiopia.
East Afr Med J. 2000;77(7):377–381.
22. Tshilolo L, Aissi LM, Lukusa D, et al. Neonatal screening for
sickle cell anaemia in the Democratic Republic of the Congo:
experience from a pioneer project on 31,204 newborns. J Clin
Pathol. 2009;62(1):35–38.
23. Lebea PJ, Pretorius PJ. Newborn screening for classic galac-
tosemia and primary congenital hypothyroidism in the
Nkangala district of the Mpumalanga province of South
Africa. S Afr J Child Health. 2008;2(1):19–22.
24. Malan L, Reinecke CJ. Towards a newborn screening system
for South Africa: the need for a systems approach. Proceed-
ings of the 12th Annual CPTS Working Conference; 2006:62-78.
25. Morales A, Wierenga A, Cuthbert C, et al. Expanded newborn
screening in Puerto Rico and the US Virgin Islands: educa-
tion and barriers assessment. Genet Med. 2009;11(3):169–175.
26. Newborn Screening Task Force, American Academy of
Pediatrics. Serving the family from birth to the medical
home. Newborn screening: a blueprint for the future. Pedia-
trics. 2000;106(suppl):S383–S427.
27. Public Law 110-204. Newborn screening saves lives Act of
2008. 〈https://www.govtrack.us/congress/bills/110/s1858/text〉;
Accessed 26.12.14.
28. Public Law 113-240. Newborn screening saves lives reautho-
rization Act of 2014. 〈https://www.govtrack.us/congress/
bills/113/hr1281/text〉; Accessed 26.12.14.
29. 〈www.hrsa.gov/advisorycommittees/mchbadvisory/herita
bledisorders/index.html〉; Accessed 26.12.14.
39 (2015) 171–187 183
30. American College of Medical Genetics, Newborn Screening
Expert Group. Newborn screening: toward a uniform
screening panel and system. Genet Med. 2006;8(suppl 1):
1S–252S.
31. Kemper AR, Green NS, Calonge N, et al. Decision-making
process for conditions nominated to the recommended uni-
form screening panel: statement of the US Department of
Health and Human Services Secretary’s Advisory Committee
on Heritable Disorders in Newborns and Children. Genet Med.
2014;16(2):183–187.
32. 〈www.hrsa.gov/advisorycommittees/mchbadvisory/herita
bledisorders/nominatecondition/workgroup.html〉; Acces-
sed 26.12.14.
33. Kwan A, Puck J. History and current status of newborn
screening for severe combined immunodeficiency. Semin
Perinatol. 2015;39(4).
34. Verbsky JW, Baker MW, Grossman WJ, et al. Newborn
screening for severe combined immunodeficiency; the Wis-
consin experience (2008–2011). J Clin Immunol. 2012;32(1):
82–88.
35. Kwan A, Church JA, Cowan MJ, et al. Newborn screening for
severe combined immunodeficiency and T-cell lymphopenia
in California: results of the first 2 years. J Allergy Clin Immunol.
2013;132(1):140–150.
36. Vogel BH, Bonagura V, Weinberg GA, et al. Newborn screen-
ing for SCID in New York State: experience from the first two
years. J Clin Immunol. 2014;34(3):289–303.
37. Kwan A, Abraham RS, Currier R, et al. Newborn screening for
severe combined immunodeficiency in 11 screening pro-
grams in the United States. J Am Med Assoc. 2014;312
(7):729–73820. 2014;312(7):729–738.
38. Therrell BL Jr, Colleen WU, Secretary of Health and Human
Services Advisory Committee on Heritable Disorders in
Newborns and Children, et al. Including the initial newborn
screening bloodspot collection device serial number on birth
certificates: basis and recommendations from the Secretary
of Health and Human Services’ Advisory Committee on
Heritable Disorders in Newborns and Children (SACHDNC).
Genet Med. 2013;15(3):229–233.
39. Duffner PK, Caggana M, Orsini JJ, et al. Newborn screening
for Krabbe disease: the New York State model. Pediatr Neurol.
2009;40(4):245–252 [discussion 253–255].
40. De Jesús VR, Zhou H, Vogt RF. Dried blood spot
quality control materials for newborn screening to detect
lysosomal storage disorders. Clin Chem. 2013;59(8):1275–1276.
41. Matern D, Gavrilov D, Oglesbee D, et al. Newborn
screening for lysosomal storage diseases. Semin Perinatol.
2015;39(4).
42. Hopkins PV, Campbell C, Klug T, et al. Lysosomal storage
disorder screening implementation: findings from the first
six months of full population pilot testing in Missouri.
J Pediatr. 2015;166(1):172–177.
43. Hubbard WC, Moser AB, Liu AC, et al. Newborn screening for
X-linked adrenoleukodystrophy (X-ALD): validation of a
combined liquid chromatography–tandem mass spectro-
metric (LC–MS/MS) method. Mol Genet Metab. 2009;97(3):
212–220.
44. Theda C, Gibbons K, Defor TE, et al. Newborn screening for
X-linked adrenoleukodystrophy: further evidence high
throughput screening is feasible. Mol Genet Metab. 2014;111
(1):55–57.
45. Turgeon CT, Moser AB, Mørkrid L, et al. Streamlined deter-
mination of lysophosphatidylcholines in dried blood spots
for newborn screening of X-linked adrenoleukodystrophy.
Mol Genet Metab. 2015;114(1):46–50.
46. Haynes CA, De Jesús VR. The stability of hexacosanoyl
lysophosphatidylcholine in dried-blood spot quality control
184 SE M I N A R S I N P E R I N A T O L O G Y
materials for X-linked adrenoleukodystrophy newborn
screening. Clin Biochem. 2015;48(1–2):8–10.
47. Sorensen PL, Gane LW, Yarborough M, Hagerman RJ, Tas-
sone F. Newborn screening and cascade testing for FMR1
mutations. Am J Med Genet A. 2013;161A(1):59–69.
48. Taylor JL, Lee FK, Yazdanpanah GK, et al. Newborn bloodspot
screening test using multiplexed real-time PCR to simulta-
neously screen for spinal muscular atrophy and severe
combined immunodeficiency. Clin Chem. 2015;61(2):412–419.
49. Dobrowolski SF, Pham HT, Downes FP, et al. Newborn
screening for spinal muscular atrophy by calibrated short-
amplicon melt profiling. Clin Chem. 2012;58(6):1033–1039.
50. Pyatt RE, Mihal DC, Prior TW. Assessment of liquid
microbead arrays for the screening of newborns for spinal
muscular atrophy. Clin Chem. 2007;53(11):1879–1885.
51. Hahn SH. Population screening for Wilson’s disease. Ann N Y
Acad Sci. 2014;1315:64–69.
52. Pasquali M, Schwarz E, Jensen M, et al. Feasibility of newborn
screening for guanidinoacetate methyltransferase (GAMT)
deficiency. J Inherit Metab Dis. 2014;37(2):231–236.
53. Therrell BL Jr, Hannon WH. Newborn dried blood spot
screening: residual specimen storage issues. Pediatrics.
2012;129(2):365–366.
54. Caggana M, Jones EA, Shahied SI, et al. Newborn screening:
from Guthrie to whole genome sequencing. Public Health Rep.
2013;128(suppl 2):S14–S19.
55. Rothwell EW, Anderson RA, Burbank MJ, et al. Concerns of
newborn blood screening advisory committee members
regarding storage and use of residual newborn screening
blood spots. Am J Public Health. 2011;101(11):2111–2116.
56. Therrell BL Jr, Hannon WH, Bailey DB Jr, et al. Committee
Report: considerations and recommendations for national
guidance regarding the retention and use of residual dried
blood spot specimens after newborn screening. Genet Med.
2011;13(7):621–624.
57. Botkin JR, Rothwell E, Anderson R, et al. Public attitudes
regarding the use of residual newborn screening specimens
for research. Pediatrics. 2012;129(2):231–238.
58. Bombard Y, Miller FA, Hayeems RZ, et al. Citizens’ values
regarding research with stored samples from newborn
screening in Canada. Pediatrics. 2012;129(2):239–247.
59. Langbo C, Bach J, Kleyn M, Downes FP. From newborn screening
to population health research: implementation of the Michigan
BioTrust for health. Public Health Rep. 2013;128(5):377–384.
60. Botkin JR, Lewis MH, Watson MS, et al. Parental permission
for pilot newborn screening research: guidelines from the
NBSTRN. Pediatrics. 2014;133(2):e410–e417.
61. 〈ccmg-ccgm.org/index.php/publications/practice-guidelines-
position-statements-and-reports.html〉; Accessed 09.01.15.
62. Cross C. Ontario newborns now screened for SCID. CMAJ.
2013;185(13):E616.
63. Mercimek-Mahmutoglu S, Sinclair G, van Dooren SJ, et al.
Guanidinoacetate methyltransferase deficiency: first steps to
newborn screening for a treatable neurometabolic disease.
Mol Genet Metab. 2012;107(3):433–437.
64. Auray-Blais C, Cyr D, Drouin R. Quebec neonatal mass
urinary screening programme: from micromolecules to mac-
romolecules. J Inherit Metab Dis. 2007;30:515–521.
65. Auray-Blais C, Maranda B, Lavoie P. High-throughput tan-
dem mass spectrometry multiplex analysis for newborn
urinary screening of creatine synthesis and transport dis-
orders, Triple H syndrome and OTC deficiency. Clin Chim
Acta. 2014;25(436):249–255.
66. Khoo SK, Dykema K, Vadlapatla NM, et al. Acquiring
genome-wide gene expression profiles in Guthrie card blood
spots using microarrays. Pathol Int. 2011;61(1):1–6.
39 (2015) 171–187
67. Bombard Y, Miller FA, Hayeems RZ, et al. Public views on
participating in newborn screening using genome sequenc-
ing. Eur J Hum Genet. 2014;22(11):1248–1254.
68. Knoppers BM, Sénécal K, Borry P, Avard D. Whole-genome
sequencing in newborn screening programs. Sci Transl Med.
2014;6(229):229cm2.
69. Tahirovic H, Toromanovic A. Neonatal screening for con-
genital hypothyroidism in the Federation of Bosnia and
Herzegovina: eight years’ experience. Eur J Pediatr. 2009;168
(5):629–631.
70. Tezel B, Dilli D, Bolat H, et al. The development and
organization of newborn screening programs in Turkey.
J Clin Lab Anal. 2014;28(1):63–69.
71. Loeber JG, Burgard P, Cornel MC, et al. Newborn screening
programmes in Europe; arguments and efforts regarding
harmonization. Part 1. From blood spot to screening result.
J Inher Metab Dis. 2012;35:603–611.
72. Burgard P, Rupp K, Lindner M, et al. Newborn screening
programmes in Europe; arguments and efforts regarding
harmonization. Part 2—From screening laboratory results
to treatment, follow-up and quality assurance. J Inherit Metab
Dis. 2012;35:613–625.
73. Cornel MC, Rigter T, Weinreich SS, et al. Expert Opinion
document Newborn screening in Europe. A framework to
start the debate on neonatal screening policies in the EU. Eur
J Hum Genet. 2014;22:12–17.
74. Groselj U, Tansek MZ, Smon A, et al. Newborn screening in
southeastern Europe. Mol Genet Metab. 2014;113(1–2):42–45.
75. Holmes D. Europe plays catch-up on neonatal screening as
US skips ahead. Nat Med. 2012;18(11):1596.
76. Castellani C, Southern KW, Brownlee K, et al. European best
practice guidelines for cystic fibrosis neonatal screening.
J Cyst Fibros. 2009;8(3):153–173.
77. Sermet-Gaudelus SJ, Mayell KW, et al. Guidelines on the
early management of infants diagnosed with cystic fibrosis
following newborn screening. J Cyst Fibros. 2010;9:323–329.
78. Mayell SJ, Munck A, Craig JV, et al. A European consensus for
the evaluation and management of infants with an equivo-
cal diagnosis following newborn screening for cystic fibrosis.
J Cyst Fibros. 2009;8(1):71–78.
79. Léger J, Olivieri A, Donaldson M, et al. European Society for
Paediatric Endocrinology consensus guidelines on screening,
diagnosis, and management of congenital hypothyroidism.
J Clin Endocrinol Metab. 2014;99(2):363–384.
80. Fischer KE, Rogowski WH. Funding decisions for newborn
screening: a comparative review of 22 decision processes in
Europe. Int J Environ Res Public Health. 2014;11(5):5403–5430.
81. Hom LA, Martin GR. U.S. international efforts on critical
congenital heart disease screening: can we have a
uniform recommendation for Europe? Early Hum Dev. 2014;
90(suppl 2):S11–S14.
82. Petrini C, Olivieri A, Corbetta C, et al. Common criteria
among States for storage and use of dried blood spot speci-
mens after newborn screening. Ann Ist Super Sanita. 2012;48
(2):119–121.
83. Douglas CM, van El CG, Faulkner A, Cornel MC. Governing
biological material at the intersection of care and research:
the use of dried blood spots for biobanking. Croat Med J.
2012;53(4):390–397.
84. Gauffin F, Nordgren A, Barbany G, Gustafsson B, Karlsson H.
Quantitation of RNA decay in dried blood spots during 20
years of storage. Clin Chem Lab Med. 2009;47(12):1467–1469.
85. Hollegaard MV, Grove J, Thorsen P, Norgaard-Pedersen B,
Hougaard DM. High-throughput genotyping on archived
dried blood spot samples. Genet Test Mol Biomarkers.
2009;13:173–179.
 S E M I N A R S I N P E R I N A T O L O G Y
86. Nicholls SG, Southern KW. Informed choice for newborn
blood spot screening in the United Kingdom: a survey of
parental perceptions. Pediatrics. 2012;130(6):e1527–e1533. 106.
87. Allen J, McCarthy P, Dempsey EM, Hourihane JO. Guthrie
cards in Republic of Ireland. Irish public would prefer
legislation to protect Guthrie card archive rather than 107.
destroy it. Br Med J. 2013;347:f5232.
88. Mechtler TP, Stary S, Metz TF, et al. Neonatal screening for
lysosomal storage disorders: feasibility and incidence from a 108.
nationwide study in Austria. Lancet. 2012;379(9813):335–341.
89. Paciotti S, Persichetti E, Pagliardini S, et al. First pilot new-
born screening for four lysosomal storage diseases in an
Italian region: identification and analysis of a putative 109.
causative mutation in the GBA gene. Clin Chim Acta.
2012;413(23–24):1827–1831.
90. Rigter T, Weinreich SS, van El CG, et al. Severely impaired 110.
health status at diagnosis of Pompe disease: a cross-
sectional analysis to explore the potential utility of neonatal
screening. Mol Genet Metab. 2012;107(3):448–455. 111.
91. Audrain M, Thomas C, Mirallie S, et al. Evaluation of the
T-cell receptor excision circle assay performances for severe
combined immunodeficiency neonatal screening on Guthrie
cards in a French single centre study. Clin Immunol. 2014;150 112.
(2):137–139.
92. Adams SP, Rashid S, Premachandra T, et al. Screening of
neonatal UK dried blood spots using a duplex TREC screen-
ing assay. J Clin Immunol. 2014;34(3):323–330. 113.
93. Olbrich P, de Felipe B, Delgado-Pecellin C, et al. A first pilot
study on the neonatal screening of primary immunodefi-
ciencies in Spain: TRECS and KRECS identify severe T- and B- 114.
cell lymphopenia. An Pediatr (Barc). 2014;81(5):310–317 [article
in Spanish].
94. la Marca G, Giocaliere E, Malvagia S, et al. The inclusion of
ADA-SCID in expanded newborn screening by tandem mass 115.
spectrometry. J Pharm Biomed Anal. 2014;88:201–206.
95. Tauriscio D, Trama A, Stefanov R. Tackling rare diseases at
European level: why do we need a harmonized framework? 116.
Folia Med (Plovdiv). 2007;49(1–2):59–67.
96. Shawky RM. Newborn screening in the Middle East and
North Africa—challenges and recommendations. Hamdan
Med J. 2012;5(3):191–192. 117.
97. Krotoski D, Namaste S, Raouf RK, et al. Conference report:
second conference of the Middle East and North Africa
newborn screening initiative: partnerships for sustainable
newborn screening infrastructure and research opportuni-
ties. Genet Med. 2009;11:663–668. 118.
98. Solanki KK. Training programmes for developing countries.
J Inherit Metab Dis. 2007;30:596–599.
99. Fukushi M. An international training and support pro- 119.
gramme for the establishment of neonatal screening in
developing countries. J Inherit Metab Dis. 2007;30(4):593–595.
100. 〈links.lww.com/GIM/A81〉; Accessed 04.01.15.
101. 〈www.evaluategroup.com/Universal/View.aspx?type=Story 120.
&id=139887〉; Accessed 04.01.15.
102. Al-Alwani I, AlRowaeah A, Bawazeer M. Diagnosed congen-
ital hypothyroidism with missing follow-up: is it time for a
national registry? Ann Saudi Med. 2012;32(6):652–655. 121.
103. Shamshiri AR, Yarahmadi S, Forouzanfar MH, et al. Evalua-
tion of current Guthrie TSH cut-off point in Iran congenital
hypothyroidism screening program: a cost-effectiveness 122.
analysis. Arch Iran Med. 2012;15(3):136–141.
104. Golbahar J, Al-Khayyat H, Hassan B, et al. Neonatal screen-
ing for congenital hypothyroidism: a retrospective hospital 123.
based study from Bahrain. J Pediatr Endocrinol Metab. 2010;23
(1–2):39–44.
105. Golbahar J, Al-Jishi EA, Altayab DD, et al. Selective newborn 124.
screening of inborn errors of amino acids, organic acids and
39 (2015) 171–187 185
fatty acids metabolism in the Kingdom of Bahrain. Mol Genet
Metab. 2013;110(1–2):98–101.
Al Riyami S, Al Maney M, Joshi SN, Bayoumi R. Detection of
inborn errors of metabolism using tandem mass spectrometry
among high-risk Omani patients. Oman Med J. 2012;27(6):482–485.
Al Obaidy H. Patterns of inborn errors of metabolism: a 12
year single-center hospital-based study in Libya. Qatar Med J.
2013;2013(2):57–65.
Abdel-Hamid M, Tisocki K, Sharaf L, Ramadan D. Develop-
ment, validation and application of tandem mass spectrom-
etry for screening of inborn metabolic disorders in Kuwaiti
infants. Med Princ Pract. 2007;16(3):215–221.
El-Hazmi MA, Al-Hazmi AM, Warsy AS. Sickle cell disease in
Middle East Arab countries. Indian J Med Res. 2011;134(5):
597–610.
Alkindi S, Al Zadjali S, Al Madhani A, et al. Forecasting
hemoglobinopathy burden through neonatal screening in
Omani neonates. Hemoglobin. 2010;34(2):135–144.
Hatam N, Shirvani S, Javanbakht M, Askarian M, Rastegar M.
Cost-utility analysis of neonatal screening program, Shiraz
University of Medical Sciences, Shiraz, Iran, 2010. Iran
J Pediatr. 2013;23(5):493–500.
Sladkevicius E, Pollitt RJ, Mgadmi A, Guest JF. Cost effective-
ness of establishing a neonatal screening programme for
phenylketonuria in Libya. Appl Health Econ Health Policy. 2010;
8(6):407–420.
Khneisser I, Adib SM, Loiselet J, Megarbane A. Cost-benefit
analysis of G6PD screening in Lebanese newborn males. J
Med Liban. 2007;55(3):129–132.
Al Hosani H, Salah M, Osman HM, et al. Expanding the
comprehensive national neonatal screening programme in
the United Arab Emirates from 1995 to 2011. East Mediterr
Health J. 2014;20(1):17–23.
Al Arrayed S, Al Hajeri A. Newborn Screening Services
in Bahrain between 1985 and 2010. Adv Hematol. 2012;2012:
903219.
Khneisser I, Adib SM, Megarbane A, Lukacs Z. International
cooperation in the expansion of a newborn screening
programme in Lebanon: a possible model for other pro-
grammes. J Inherit Metab Dis. 2008;31(suppl 2):S441–S446.
Lindner M, Abdoh G, Fang-Hoffmann J, et al. Implementa-
tion of extended neonatal screening and a metabolic unit in
the State of Qatar: developing and optimizing strategies in
cooperation with the Neonatal Screening Center in Heidel-
berg. J Inherit Metab Dis. 2007;30(4):522–529.
Somech R, Lev A, Simon AJ, et al. Newborn screening for
severe T and B cell immunodeficiency in Israel: a pilot study.
Isr Med Assoc J. 2013;15(8):404–409.
Babiker AMI, Al Jurayyan NA, Mohamed SH, Abdullah MA.
Overview of diagnosis, management and outcome of con-
genital hypothyroidism: a call for a national screening
programme in Sudan. Sudanese J Pediatr. 2012;12(2):7–16.
Sarafoglou K, Bentler K, Gaviglio A, et al. High incidence of
profound biotinidase deficiency detected in newborn screen-
ing blood spots in the Somalian population in Minnesota.
J Inherit Metab Dis. 2009;32(suppl 1):S169–S173.
Gerner de Garcia B, Gaffney C, Chacon S, Gaffney M. Over-
view of newborn hearing screening activities in Latin Amer-
ica. Rev Panam Salud Publica. 2011;29(3):145–152.
Frómeta A, Reyes EC, Castells E, et al. Quantitative ultra-
microtest for newborn screening of galactosemia in Cuba.
J Perinat Med. 2011;39(1):77–81.
González EC, Frómeta A, del Río L, et al. Cuban neonatal
screening of phenylketonuria using an ultramicro-
fluorometric test. Clin Chim Acta. 2009;402(1–2):129–132.
González EC, Marrero N, Pérez PL, et al. An enzyme immuno-
assay for determining 17alpha-hydroxyprogesterone in
186 SE M I N A R S I N P E R I N A T O L O G Y
dried blood spots on filter paper using an ultramicroanalyt-
ical system. Clin Chim Acta. 2008;394(1–2):63–66.
125. Campos D, Monaga M, González EC, Herrera D. Identification
of mucopolysaccharidosis I heterozygotes based on bio-
chemical characteristics of L-iduronidase from dried blood
spots. Clin Chim Acta. 2014;430:24–27.
126. Herrera D, Monaga M, Campos D, et al. Ultramicro-
fluorometric assay for the diagnosis of Gaucher disease in
dried blood spots on filter paper. J Neonatal Perinatal Med.
2013;6(1):61–67.
127. de Céspedes C, Saborío M, Trejos R, et al. Evolution and
innovations of the National Neonatal and High Risk Screen-
ing Program in Costa Rica. Rev Biol Trop. 2004;52(3):451–466.
128. Queiruga G, Queijo C, Lemes A, Machado M, Garlo P, Salud
Sistema. Nacional de Pesquisa Neonatal en Uruguay. Mem
Inst Investig Cienc. 2011;9(2):72–77.
129. Borrajo G. Panorama epidemiológico de la fenilcetonuria
(PKU) en Latinoamérica. Acta Pediatr Mex. 2012;33(6):279–287.
130. Queijo C, Machado M, Franca F, et al. Pilot Programe for
newborn screening using mass spectrometry in Uruguay.
Rev Invest Clín. 2009;61(suppl 1):90.
131. Queijo C, Lemes A, Machado M, et al. Newborn screening of
medium-chain acyl-CoA dehydrogenase deficiency in Uru-
guay. Acta Bioquím Clín Latinoam. 2011;45(1):87–93.
132. 〈www.unisert.org.br/Informativo_PNTN_8%C2%AA_ed.pdf〉;
Accessed 30.12.14.
133. Lopes ME. The successful “Guthrie test” celebrates its 10th
birthday in Brazil!. Cien Saude Colet. 2011;16(suppl 1):716–717.
134. Maciel LM, Kimura ET, Nogueira CR, et al. Congenital hypo-
thyroidism: recommendations of the Thyroid Department of
the Brazilian Society of Endocrinology and Metabolism. Arq
Bras Endocrinol Metabol. 2013;57(3):184–192.
135. Barone B, Lopes CL, Tyszler LS, et al. Evaluation of TSH cutoff
value in blood-spot samples in neonatal screening for the
diagnosis of congenital hypothyroidism in the Programa
“Primeiros Passos”—IEDE/RJ. Arq Bras Endocrinol Metabol.
2013;57(1):57–61.
136. Norma Oficial Mexicana NOM-034-SSA2-2013. Para la preven-
ción y control de los defectos al nacimiento. 〈http://www.
dof.gob.mx/nota_detalle.php?codigo=5349816&fecha=24/06/
2014〉; Accessed 30.12.14.
137. González V, Santucci Z, Pattin J, et al. Programa de pesquisa
neonatal de hipotiroidismo congénito de la Provincia de
Buenos Aires: 1.377.455 niños evaluados en diez años de
experiencia. Arch Argent Pediatr. 2007;105(5):390–397.
138. 〈www.ins.gov.co/lineas-de-accion/Subdireccion-Vigilancia/
sivigila/Protocolos%20SIVIGILA/PRO%20Defectos%20Congeni
tos.pdf〉; Accessed 30.12.14.
139. Ramírez C, Machado G, Lara M, Castellón E. Tamizaje neo-
natal para hipotiroidismo congénito en Nicaragua. Nicaragua
Pediatr. 2013;1(2):6–10.
140. Padilla CD, Therrell BL. Screening newborns in the Asia-
Pacific Region. In: Kumar D, ed, Genomics and Health in the
Developing World. Oxford: Oxford University Press; 2012.
764–781.
141. Shi XT, Cai J, Wang YY, et al. Newborn screening for inborn
errors of metabolism in mainland China: 30 years of expe-
rience. JIMD Rep. 2012;6:79–83.
142. Zhan JY, Qin YF, Zhao ZY. Neonatal screening for congenital
hypothyroidism and phenylketonuria in China. World J
Pediatr. 2009;5(2):136–139.
143. Lim JS, Tan ES, John CM, et al. Inborn Error of Metabolism (IEM)
screening in Singapore by electrospray ionization–tandem
mass spectrometry (ESI/MS/MS): an 8 year journey from pilot
to current program. Mol Genet Metab. 2014;113(1–2):53–61.
144. Padilla C. Enhancing case detection of selected inherited
disorders through expanded newborn screening in the
Philippines. Acta Med Philippina. 2012;46(4):24–29.
39 (2015) 171–187
145. Hettiarachchi M, Amarasena S. Indicators of newborn
screening for congenital hypothyroidism in Sri Lanka: pro-
gram challenges and way forward. BMC Health Serv Res.
2014;12(14):385.
146. Leong YH, Gan CY, Tan MA, Majid MI. Present status
and future concerns of expanded newborn screening in
malaysia: sustainability, challenges and perspectives.
Malays J Med Sci. 2014;21(2):63–67.
147. Yamaguchi S, Purevusren J, Kobayashi H, et al. Expanded
newborn mass screening with MS/MS and medium-chain
acyl-CoA dehydrogenase (MCAD) deficiency in Japan. J Jap
Soc Mass Screen. 2013;23:270–276.
148. Morikawa S, Nakamura A, Fujikura K, et al. Results from 28
years of newborn screening for congenital adrenal hyper-
plasia in Sapporo. Clin Pediatr Endocrinol. 2014;23(2):35–43.
149. Heather NL, Seneviratne SN, Webster D, et al. Newborn
screening for congenital adrenal hyperplasia in New Zea-
land 1994–2013. J Clin Endocrinol Metab. 2015;100(3):1002–1008.
150. Kitagawa T. Newborn screening for inborn errors of metab-
olism in Japan. A history of the development of newborn
screening. Pediatr Endocrinol Rev. 2012;10(suppl 1):8–25.
151. Chien YH, Lee NC, Chen CA, et al. Long-term prognosis of
patients with infantile-onset Pompe disease diagnosed by
newborn screening and treated since birth. J Pediatr. 2015;166
(4):985–991.
152. Yang CF, Liu HC, Hsu TR, et al. A large-scale nationwide
newborn screening program for Pompe disease in Taiwan:
towards effective diagnosis and treatment. Am J Med Genet A.
2014;164A(1):54–61.
153. Chiang SC, Hwu WL, Lee NC, Hsu LW, Chien YH. Algorithm for
Pompe disease newborn screening: results from the Taiwan
screening program. Mol Genet Metab. 2012;106(3):281–286.
154. Oda E, Tanaka T, Migita O, et al. Newborn screening for
Pompe disease in Japan. Mol Genet Metab. 2011;104
(4):560–565.
155. Han M, Jun SH, Song SH, et al. Use of tandem mass
spectrometry for newborn screening of 6 lysosomal storage
disorders in a Korean population. Korean J Lab Med. 2011;31
(4):250–256.
156. Liao HC, Chiang CC, Niu DM, et al. Detecting multiple
lysosomal storage diseases by tandem mass spectrometry–
a national newborn screening program in Taiwan. Clin Chim
Acta. 2014;431:80–86.
157. Hwu WL, Chien YH, Lee NC, Wang SF, Chiang SC, Hsu LW.
Application of mass spectrometry in newborn screening:
about both small molecular diseases and lysosomal storage
diseases. Top Curr Chem. 2014;336:177–196.
158. Lin SP, Lin HY, Wang TJ, et al. A pilot newborn screening
program for Mucopolysaccharidosis type I in Taiwan. Orpha-
net J Rare Dis. 2013;8:147.
159. Wang LY, Chen NI, Chen PW, et al. Newborn screening for
citrin deficiency and carnitine uptake defect using second-
tier molecular tests. BMC Med Genet. 2013;10(14):24.
160. Inoue T, Hattori K, Ihara K, et al. Newborn screening for
Fabry disease in Japan: prevalence and genotypes of Fabry
disease in a pilot study. J Hum Genet. 2013;58(8):548–552.
161. Morinishi Y, Imai K, Nakagawa N, et al. Identification of
severe combined immunodeficiency by T-cell receptor exci-
sion circles quantification using neonatal Guthrie cards.
J Pediatr. 2009;155(6):829–833.
162. Inaba Y, Schwartz CE, Bui QM, et al. Early detection of fragile
X syndrome: applications of a novel approach for improved
quantitative methylation analysis in venous blood and new-
born blood spots. Clin Chem. 2014;60(7):963–973.
163. Kim GH, Yang JY, Park JY, et al. Estimation of Wilson’s
disease incidence and carrier frequency in the Korean
population by screening ATP7B major mutations in newborn
filter papers using the SYBR green intercalator method based
 S E M I N A R S I N P E R I N A T O L O G Y
on the amplification refractory mutation system. Genet Test.
2008;12(3):395–399.
164. Adayev T, LaFauci G, Dobkin C, et al. Fragile X protein in
newborn dried blood spots. BMC Med Genet. 2014;15(1):119.
165. Charles T, Pitt J, Halliday J, Amor DJ. Implementation of
written consent for newborn screening in Victoria, Australia.
J Paediatr Child Health. 2014;50(5):399–404.
166. Maxwell SJ, O’Leary P. Newborn bloodspot screening: setting
the Australian national policy agenda. Med J Aust. 2014;200
(3):142–143.
167. Kapoor S, Gupta N, Kabra M. National newborn screening
program still a hype or a hope now? Indian Pediatr. 2013;50
(7):639–643.
168. Verma IC, Bijarnia-Mahay S, Jhingan G, Verma J. Newborn screen-
ing: need of the hour in India. Indian J Pediatr. 2015;82(1):61–70.
169. Therrell BL, Padilla CD Barriers to implementing sustainable
national newborn screening in developing health systems. Int J
Pediatr Adolesc Med. 2014;2(1):49-60. 〈http://www.sciencedirect.
com/science/article/pii/S2352646714000179〉; Accessed 20.04.15.
170. Padilla CD, Therrell BL Jr. Consolidating newborn screening
efforts in the Asia Pacific region: networking and shared
education. J Community Genet. 2012;3(1):35–45.
39 (2015) 171–187 187
171. CLSI. Blood Collection on Filter Paper for Newborn Screening
Programs; Approved Standard—Sixth Edition. Wayne, PA: Clin-
ical and Laboratory Standards, Institute; 2013;2013 [CLSI
document NBS01-A6].
172. CLSI. Newborn Screening Follow-up; Approved Guideline—Second
Edition. Wayne, PA: Clinical and Laboratory Standards, Insti-
tute; 2013;2013 [CLSI document NBS02-A2].
173. CLSI. Newborn Screening for Preterm, Low Birth Weight, and Sick
Newborns; Approved Guideline. Wayne, PA: Clinical and Labora-
tory Standards, Institute; 2009;2009 [CLSI document NBS03-A].
174. CLSI. Newborn Screening by Tandem Mass Spectrometry;
Approved Guideline. Wayne, PA: Clinical and Laboratory
Standards, Institute; 2010;2010 [CLSI document NBS04-A].
175. CLSI. Newborn Screening for Cystic Fibrosis; Approved Guideline.
Wayne, PA: Clinical and Laboratory Standards, Institute;
2011;2011 [CLSI document NBS05-A].
176. CLSI. Newborn Blood Spot Screening for Severe Combined
Immunodeficiency by Measurement of T-cell Receptor Excision
Circles; Approved Guideline. Wayne, PA: Clinical and
Laboratory Standards, Institute; 2013;2013 [CLSI document
NBS06-A].
177. 〈http://www.isns-neoscreening.org/〉; Accessed 14.01.15.