Kuwait has established a national newborn screening program that screens all newborns for 22 disorders using tandem mass spectrometry and other methods. The program started in 2005 screening high-risk newborns for 2 disorders and expanded over time, becoming a universal screening program in 2014 that screens over 60,000 newborns annually across both governmental and private hospitals. The screening helps detect treatable genetic disorders early to improve newborn health outcomes and reduce disability and disease burden. Challenges in implementing the program were addressed through strategic planning, leadership, education, and integrating screening into the public health system to ensure sustainability.

1. Kuwait’s National Newborn Screening Program
General -Report
Author message
I would like to clarify through my message the importance of the National Program of Newborn
screening at the health and community level in order to preserve the health of future generations
and to promote our society in all fields. As usually said “the healthy mind in the healthy body”,
More over all babies have equal right to live healthy lives. As I always said. The investment
screening will certainly be rewarded many times over in terms of money spent over the care of
handicapped children, improved of life, and reducing the high burden of genetic disease. In these
papers let me review the importance of newborn screening and diseases detected through our
National Program and the number of cases Which have been discovered since it officially started
in 2014 as well as I will compare us with the other Gulf countries and worldwide situation to know
where we are?
Introduction:
The WHO defines newborn screening as a
public health program, aimed at an early
identification of conditions, for which early
and timely interventions can lead to the
elimination or reduction of associated
mortality, morbidity, and disabilities. The
diseases included in a screening program do
not manifest at birth and have a window period
of a few days to months. This gives an
opportunity to detect the condition by
performing a screening test, which if positive
need to be confirmed by a diagnostic test, and
to initiate treatment at the pre-clinical stage
thereby achieving the best possible outcome.1
The history of newborn screening dates back to
1959 when Dr Robert Guthrie developed a test
to detect high phenylalanine levels by
microbiological bacterial inhibition test on the
dry blood spot (DBS) sample collected on a
filter paper (Guthrie card) to diagnose
phenylketonuria in the newborn babies.2
Guthrie test became a routine in USA in 1962.
The approach was so successful that in 1975,
Dussault introduced screening for congenital
hypothyroidism.3 Subsequently, more
diseases like congenital adrenal hyperplasia,
galactosemia, biotinidase deficiency, G6PD
deficiency, and cystic fibrosis were included in
the screening program. The real breakthrough
in the screening for inborn errors of
metabolism came in 1990 when a new
technique of Tandem Mass Spectrometry
(TMS) was introduced by Millington.3
The TMS could identify about 30 different
metabolic diseases belonging to
aminoacidopathies, urea cycle disorders,
organic acidemia, and fatty acid oxidation
disorders by analyzing amino acids and
acylcarnitine levels on DBS sample. The
technique was subsequently automated and a
computer program was added to flag only
abnormal values.4
Selection of diseases in the screening panel
should be based on the priorities of the
individual country. In this regard, the Wilson
and criteria can serve as a useful guide.
Basically, consideration should be given to
disease prevalence and the cost vs. benefit of
screening and treatment. a program is proposed
incorporating common diseases that can be
treated by simple and cost effective means.5
Tandem mass spectrometry (MS/MS), has
gotten increased attention since it was first
added to the newborn screening programs. The
technology of MS/MS consist of two mass
spectrometers coupled, result is displayed by
computer as a mass spectrum profile. MS/MS
can screen for disorders of amino acids,
organic acid metabolism, and fatty acid
oxidation and other conditions. A few drops or
even one drop of blood is enough for MS/MS,
moreover” DELFIA” Which is fluresent
immune assay also used for other disorders as

2. Kuwait’s National Newborn Screening Program
General -Report
Biotinidase deficiency, Congenital
Hypothyroidism (CH), and Congenital
Adrenal Hyperplasia (CAH), Galactosemia. 6
False positive results and relatively poor
positive predictive values for some MS/MS
tests have led to the development of second-
tier tests that require separate testing protocols.
7
Otherwise DNA-based techniques have also
been introduced to newborn screening
programs in recent years. Next Generation
Sequencing NGS have proved a more accurate
tool for newborn screening programs, however
they also can add to the cost of screening.
Moreover, DNA based method can be used as
confirmatory or 2nd
tier test to the other
advanced technology like MS/MS, DELFIA,
and HPLC recommended for use by the
American Newborn screening programs expert
group. 7
Current Status of Screening in the Asia Pacific
and the Middle East/North Africa regions.
NBS has become a program of increasing
importance allocated for health within the AP
and MENA regions and to highlight some of
the obvious challenges in implementing
sustainable NBS. In recent years, Many NBS
conferences have been conducted in the AP
and MENA regions to initiate a dialog
concerning experiences and needs. These
conferences also provided an opportunity to
develop a communications network within the
2 regions as a source of support and
information sharing. Summaries of the
meetings are available online
(http://www.newbornscreening-mena.org/index.html ;
http://isns.napoleon.ch/upload/dokumente/mea%20nbs
%20publication.pdf&http://www.newbornscreening.ph
Two MENA regional meetings have been held;
the first in Marrakech, Morocco (2006), and
the second in Cairo, Egypt (2008).
At MENA conference, participants from
MENA countries developed the so-called
“Marrakech Declaration,” which states that,
“Newborn screening is an important tool in the
prevention of disease and disability in our
children and thus should be a key part of a
comprehensive public health system in all of
our countries.” Conference participants
recommended that “all countries in the region
should screen for at least one condition and
develop a national model program that takes
into account all aspects for post-testing care.”8
Also in the AP conference, participants
developed a “Cebu Declaration”with similar
language regarding future planning. 9
In the MENA region, cultural factors have led
to larger numbers of consanguineous
marriages with a consequent corresponding
increased expression of recessive and
potentially deleterious conditions in
newborns.10
Current Status of Screening in the Gulf region,
Qatar has already been running a full newborn
screening program since 2004 in collaboration
with the University Children Hospital of
Heidelberg, Germany. Until recently lab work
established in Qatar, Saudi Arabia started
national screening for CH since 1991. The
program expanded in 2007 to include 23 other
diseases tested as a nationwide screening
program. United Arab Emirates start in 1995
with PKU screening and was began in 1998 to
screen for CH and in 2002, for Sickle Cell
Disease (SCD). UAE has also expanded its
screening program in 2010. In Oman screening
for hypothyroidism has taken place since 2004
until they establish national program in 2012.
In Kuwait the program was started in 2005
with two disorders for the critical newborns
then increased to five disorders in 2012 until
recently officially started in 2014 to cover
100% of newborns with the national expand
program include panel of 22 disorders. The
investment screening will certainly be
rewarded many times over in terms of money
spent over the care of handicapped children,
improved of life, and reducing the high burden
of genetic disease. The Ministry of Health
perform free NNS for all newborns inside
Kuwait and offer proper treatment and follow-
up of positive cases.11

3. Kuwait’s National Newborn Screening Program
General -Report
History of newborn screening in Kuwait, it
starts in 2005 with two disorders screen for
high risk neonate and upgraded gradually until
officially submitted in October 2014 as expand
program screen for 22disorders for all
newborns in governmental hospital then
private hospital joined to the program from
April 2015, Successful NBS historically has
developed from the efforts of an interested
individual or group of individuals concerned
with improving the life of newborns and their
families. Sometimes, these efforts have taken
years to develop programs have been initiated
as government services, and intersect with
government public health activities. More over
the Kuwaiti population was lucky for
availability of required balance of economics,
politics, government health priorities,
personnel, and other resources. Success in
developing and institutionalizing NBS
typically has resulted from the continued
efforts of dedicated leaders willing to gain
proficiency in NBS medical and laboratory
science to overcome political, cultural, and
Year NO.samples
received
Disorders included
2005 3029
Phenylketonuria
Congenital hypothyroidism
2006 2547
2007 2438
2008 4714
2009 15287
2010 17692
2011 25228
2012 29779 Phenylketonuria
Congenital hypothyroidism
Congenital adrenal
hyperplasia
Classic galactsemia
Biotindase deficiency
2013 29517
2014 31987
Expand program of 22
disorders started in October
2014
2015 52789
2016 57951
2017 59655
2018 55210
economic challenges. Collectively, great effort
was spent in work with many individuals and
groups that are working to initiate and improve
NBS in Kuwait.
The following table show how the Challenges
were met in Kuwait to establish the national
program, many challenges for Implementing
Newborn Screening which identified in a
Developing Country, NBS systems have
identified the following 10 challenges to
successfully implementing sustainable NBS.12
Challen
ges
How to overcome
1 Planning Basic knowledge was collected and
vision, creating a national strategy and
pilot studies, and full implementation,
ie, starting the program, validating the
value of NBS, and creating a plan for
program development, implementation,
and sustainability.
2 Leadersh
ip
Identifying official committee as key
group(s) to develop and expand the plan
3 Medical
support
Fostering medical and scientific
knowledge development through on site
education lectures
4 Technica
l support
Create manual include protocols
providing for proper specimen
collection and transport procedures,
parent education, quality laboratory
testing (including screening and
confirmation), and screening follow-
up/tracking (including clinical
confirmation).
5 Logistica
l support
Establish of newborn screening office
co-ordinators to followup mechanisms
for blood collection and follow-up
personnel, transporting specimens to
testing laboratory, providing for
screening laboratory operations
(equipment, supplies, and maintenance),
maintaining appropriate records, and
timely reporting of screening results.
6 Educatio
n
Developing appropriate education and
public relations materials for education
and support, ie, educating consumers,
healthcare providers, and policy makers
clearly discussed in the manual
Link
(https://www.slideshare.net/NewbornSc
reeningKW/nbs-manual-2862015)
7 Protocol
/policy
develop
ment
Also manual include appropriate
screening procedures and policies that
adequately address all NBS system
components
8 Administ
ration
Managing the overall screening system,
including obtaining and documenting
physician and patient compliance, ie,
screening, short-term follow- up, and
health outcomes (long-term follow-up).

4. Kuwait’s National Newborn Screening Program
General -Report
9 Evaluati
on
Developing a comprehensive quality
assurance program that monitors critical
indicators for success, ie, external
laboratory proficiency testing supplied
by CDC
10 Sustaina
bility
Through integration into the public
health system with a plan for financial
sustainability and service offered to all
newborns free of charge
Kuwait national newborn
screening program:
Kuwait is a country in Western Asia. Situated
in the northern edge of Eastern Arabia at the
tip of the Persian Gulf, it shares borders with
Iraq and Saudi Arabia. Kuwait has a
population of 4.5 million people and newborn
about 60,000 per year. The expand national
newborn screening of Kuwait’ panel of 22
disorders cover 100% of newborns inside
Kuwait, collected from four governmental
hospitals and 13 private hospitals which
officially started at October 2014 with the four
governmental hospitals and private hospitals
joined at April 2015. 13
The medical framework for any medical
program is a comprehensive system of
education, screening, follow-up, diagnosis,
treatment/management, and evaluation that
must be institutionalized and sustained within
public health systems often challenged by
economic, political, and cultural
considerations. There are challenges in
implementing and expanding newborn
screening that can be grouped into the
following categories: (1) planning, (2)
leadership, (3) medical support, (4) technical
support, (5) logistical support, (6) education,
(7) protocol and policy development, (8)
administration, (9) evaluation, and (10)
sustainability. Kuwait’s national newborn
screening committee review some of the
experiences to overcoming implementation
challenges in Kuwait newborn screening
programs, through many efforts to encourage
increased newborn screening by support
networking and information exchange to cover
100% of newborns in Kuwait and make the
service free of charge for all newborns.
There are four governmental hospitals in
Kuwait have obstetric department associated
with the Ministry of Health hospitals (Al-
Adan, Al-Farwanyia, Al-Jahra, Maternity
hospitals). Other hospitals like Kuwait Oil
Center Hospital (KOC) also has obstetric
department, more over there are 12 private
hospitals share in the national newborn
screening as listed:
Alsalam
Hospital
RoyalHayat
Hospital
Darelshifa
Hospital
Alseif
Hospital
Almowasat
Hospital
Alorf
Hospital
Alrashid
Hospital
London
Hospital
Alia Hospital
Sidra
Hospital
Alhady
Hospital
Tiba
Hospital

5. Kuwait’s National Newborn Screening Program
General -Report
About ethical issues all samples were collected
mandatory without parental consent. But they
have the right to refuse, there are previously
made refused form and this form present in the
manual, otherwise the newborns whose mother
not have civil identification or stay temporary
as visitors not included in the program.
Laboratory methods
Kuwait’s expand newborn screening panel
include 22 disorders through biomarkers
which measured in dried blood spot samples
collected 48–72 hours after birth by the heel-
prick method. using standard Whatman 903™
Specimen Collection cards. All guidelines for
collection, transport, and processing of
samples were followed. And for premature
another two samples collected after two weeks
and after one month further more for any
samples collected before 24 hours another
sample recollected within one week. The
samples were analyzed using tandem mass
spectrometry (LC-MS/MS) with electrospray
ionization and the DELFIA® time-resolved
fluorescence (TRF) intensity technology. All
the assays were validated and well controlled.
Proficiency testing samples from the Centers
of Disease Control and Prevention (CDC) were
run along with the neonatal samples. The cut-
off values used for various parameters were
validated and found to be acceptable.14
The cut-off values for our tests were calculated
from our results for tandem biomarker as mean
+5SD and for Biotindase , GALT , T.GAL
,TSH ,17OHP adapted from the kit inserts;
operation manuals of the analyzers;
PerkinElmer with modification in TSH cutoff
to be age related cutoff and modification in
17OHP to be age and weight depending cutoff
,for all biotindase ,GALT,T.GAL,TSH,17OHP
we use 50 % of cutoff as borderline ,the yellow
region before the real red region to avoid false
negative results from the effect of cutoff , in
the future this yellow region can be decrease
after many years of experience with real cases
Biomarkers List of disorders related
Phenyl alanine
Phenyl
alanine/tyrosine
Ratio
 Phenylketonuria (PKU)
Citrulline  Citrullinemia
 Argininosuccinic aciduria
Valine
leucine/isoleucine
 MSUD
Tyrosine
&Succinylacetone as
2nd
tier test
 Tyrosinemia I, II, III
Methionine  Homocystinuria
(Cystathionine synthase def.)
C3
C3/C2
 Propionic acidemia
 Methyl malonic acidemia
C5 , C5/C2 , C5/C3  Isovaleric acidemia
C8 , C8/C2 , C8/C10
, C10:1
 Medium chain Acyl-CoA
dehydrogenase deficiency
(MCAD deficiency)
C14:1 , C14 ,
C14:1/C2 ,
C14:1/C16 , C14:2
 Very long-chain Acyl-CoA
dehydrogenase deficiency
C16OH , C18OH  Long-chain hydroxyacyl-CoA
dehydrogenase deficiency
 Beta Ketothiolase deficiency
(Mitochondral Acetoacetyl
CoA Thiolase def)
C5DC  Glutric aciduria I
C5OH,C5OH/C3  3-Hydroxy-3-methylglutaryl-
CoA lyase def. (3HMG)
 Trifunctional protein
deficiency (TFP)
 Multiple CoA Carboxylase
def. (MCD)
 3-Methylcrotonyl-CoA
Carboxylase def. (3MCC)
17-hydroxy
progesterone (17-
OH-P)
 Congenital adrenal
hyperplasia
Thyroid stimulating
hormone (hTSH)
 Congenital hypothyroidism
Galactose-1-
phosphate uridyl
transferase (GALT)
Total Galactosemia
 Classic galactosemia
Biotinidase enzyme  Biotindase deficiency
Quality Control
Internal quality control tests were run with
each batch of tests. The results were evaluated
for acceptable criteria. Also The laboratory
participates in the Newborn Screening Quality
Assurance Program (NSQAP) run by the
Centers of Disease Control and Prevention
(CDC), USA.

6. Kuwait’s National Newborn Screening Program
General -Report
Analyte Our
cutoff
Unit Method
VAL 180 µM/L TM MS/MS
LEU 254 µM/L TM MS/MS
PHE 123 µM/L TM MS/MS
PHE/TYR 2.2 µM/L TM MS/MS
CIT 43 µM/L TM MS/MS
TYR 265 µM/L TM MS/MS
MET 44 µM/L TM MS/MS
C3 6.4 µM/L TM MS/MS
C3/C2 0.28 µM/L TM MS/MS
C5 0.73 µM/L TM MS/MS
C5/C2 0.04 µM/L TM MS/MS
C5/C3 0.44 µM/L TM MS/MS
C5OH 1 µM/L TM MS/MS
C5OH/C3 0.53 µM/L TM MS/MS
C5DC 0.52 µM/L TM MS/MS
C8 0.13 µM/L TM MS/MS
C8/C2 0.01 µM/L TM MS/MS
C8/C10 2.01 µM/L TM MS/MS
C14 0.47 µM/L TM MS/MS
C5:1 0.02 µM/L TM MS/MS
C10:1 0.11 µM/L TM MS/MS
C14:1 0.29 µM/L TM MS/MS
C14:1/C2 0.03 µM/L TM MS/MS
C14:1/C16 0.22 µM/L TM MS/MS
C16OH 0.07 µM/L TM MS/MS
C18OH 0.06 µM/L TM MS/MS
17OHP 30 nM/L DELFIA
TSH 15 µU/ml DELFIA
GALT 3.5 U/g/Hg DELFIA
TGAL 15 Mg/dl DELFIA
BIOTINDASE 60 U DELFIA
Results
Currently, the Kuwait’s National Newborn
Screening Program includes the following 22
disorders: congenital hypothyroidism;
galactosemia; congenital adrenal hyperplasia;
BIOT; and 18 amino acids, organic acid, and
fatty acid disorders. analyzing the data of NNS
from January 2015 to December 2018; the
results showed that the detection rate of
screened disorders was 1:1,504 for congenital
hypothyroidism; 1: 18,800 for galactosemia; 1:
2,718 for (amino acid, organic acid, and fatty
acid disorders); 1: 11,873 for classical
congenital adrenal hyperplasia; 1: 22,560 for
profound BIOT. The following table show
detail:
Differentiation of samples received after
expand the program from 2015-2018 shown in
this table
Year No of
received
samples
No of
samples
positive
in screen
False
positive
Confirmed
positive
2015 52789 1595 1477 118
2016 57951 986 874 112
2017 59655 1098 984 114
2018 55210 931 796 135
The following table show distribution of
samples according to the site of collection from
annual statistic in 2018 (note that Royal Hayat
Hospital not included in the list as it recently
joined the program in May 2019)

7. Kuwait’s National Newborn Screening Program
General -Report
Hospital Percentage
maternity 22.7 %
jahra 10.4 %
farwanyia 14.7 %
adan 12.6 %
alsalam 5.4 %
alseif 3.3 %
darelshifa 10.8 %
aliaa 0.8 %
alorf 4.5 %
alhady 4.6 %
sidra 3.5 %
almowasat 3.2 %
alrashid 0.9 %
london 1.1 %
KOC 0.7 %
tiba 1.0 %
The following diagram show increase in No. of samples
received in newborn screening lab from 2005 to 2018
Discussion
In this report, we have shown the incidence of
all 22 disorders screened by the NBS Program
in Kuwait is nearly 1:835 (without calculation
of partial deficiency of biotindase enzyme) and
this detection rate consider as one of the
highest incidences reported in the worldwide.
Our data were comparable with the data
reported by other countries of Gulf
Cooperation Council like Saudi Arabian, Qatar
and United Arab Emirates which were reported
as 1:1043, 1:1327 and 1:1047 correspondingly.
Such findings are explained by high rates of
consanguineous marriages in Kuwait’s
population especially first cousin marriages.15
Note that premarital screening program
include haemoglobinopathies and G6PD, so
it’s not included in the newborn screening
program to avoid double cost from double
screen to same disorders as carrier already
informed and take all education information
and counseling about the future risk ,otherwise
this statistic may slightly different than the
reality and this could be explained by the
following: (a) missing confirmation of a
relevant number of true abnormal cases due to
failure in claiming a second recall samples; (b)
some hospitals performs the confirmatory
testing onsite without reporting abnormal
results to the NBS Program; (c) baby may be
died before confirmation.
An effective prevention strategy is needed to
eradicate the great financial burden required by
governments for the managements of these
disorders. A great example of successful
prevention program is premarital screening
program however marriage cancellation for at
risk couples cannot prove 100 %.
Summarization
The components of the newborn screening
involve proper handling and safe
3029 2547 2438
4714
15287
17692
25228
29779 29517
31987
52789
57951 59655
55210
0
10000
20000
30000
40000
50000
60000
70000
2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018

8. Kuwait’s National Newborn Screening Program
General -Report
transportation of the samples from the
referring hospital to the designated laboratory,
proper documentation of the demographic data
from the referring hospital where the newborn
was delivered (private &governmental), The
proper communication channel between the
laboratory and the referring doctor when there
is an abnormal result identified or suspected.
Ability to perform confirmatory testing and
subsequent diagnosis. Moreover, Early
involvement of the attending physician for
abnormal results, proper management as time
factor is important in management outcome
and prognosis. Although, program provide
medical education for health providers,
families, parents, and patients, to ensure
appropriate genetic counseling and follow –up
treatment and management of the disorder.
Also, program continuous inspect laboratory
quality assurance through continuous periodic
inspection, laboratory standards evaluation
and quality assurance is essential tools to run
the newborn screening program without
missing any positive cases.
The situation of national newborn screening
program in Kuwait, we can say that the efforts
have been successful and we are now enjoying
the results of the good job but we cannot say
that we are at the end of the road but we are
still at the beginning and aspire to more than
that as our Kuwaiti society deserves from us
more and more efforts , we plan to increase the
number of diseases included in the program
soon and introduce the latest technology to
make Kuwait one of a pioneers in this field in
the gulf region and middle east . In general,
some factors made the newborn screening
program successful and sustainable as
government prioritization, full government
financing, public education and acceptance,
cooperation of health practitioners, and good
institutionalization of the program.
References:
1 World Health Organization, Scientific
Group on Screening for Inborn Errors
of Metabolism. WHO Technical
Report Series 1968;401:1-57.
2 Guthrie R, Susi A. A simple
Phenylalanine method for detecting
phenylketonuria in large populations
of newborn infants. Pediatrics 1963
Sep;32:338-343.
3 Millington DS, Kodo N, Norwood DL,
Roe CR. Tandem mass spectrometry: a
new method for acylcarnitine profiling
with potential for neonatal screening
for inborn errors of metabolism. J
Inherit Metab Dis 1990;13(3):321-
324.
4 Rashed MS, Rahbeeni Z, Ozand PT.
Application of electrospray tandem
mass spectrometry to neonatal
screening. Semin Perinatol 1999
Apr;23(2):183-193.
5 Wilson JM, Jungner G. 1968.
Principles and practice of screening for
diseases. (Public health papers No 34)
World Health Organization, Geneva.
6 Saadallah AA, Rashed MS. Newborn
screening: experiences in the Middle
East and North Africa. J Inherit Metab
Dis 2007 Aug;30(4):482-489.
7 Matern D, Tortorelli S, Oglesbee D,
Gavrilov D, Rinaldo P. Reduction of
the false-positive rate in newborn
screening by implementation of
MS/MS-based second-tier tests: the
Mayo Clinic experience (2004–2007).
J Inherit Metab Dis. 2007;30(4):585–
92.
8 Marrakech Declaration. Available at:
http://isns.napoleon.ch/upload/
dokumente/marrakech_declaration.pd
f. Accessed December 20, 2009
9 Cebu Declaration. Available at:
http://www.newbornscreening.ph/
images/stories/ResourcesTechnicalDo
cuments/cebu%20declaration.pdf.
Accessed December 20, 2009
10 Hamamy H, Bittles AH: Genetic
clinics in Arab communities: meeting

9. Kuwait’s National Newborn Screening Program
General -Report
individual, family and community
needs. Public Health Genomics 12: 30-
40, 2008
11 Surendra Nath Joshi, Riad Bayoumi,
Newborn Screening Program for
Oman: The Time is Here and Now :
Oman Medical Journal (2012) Vol. 27,
No. 5: 346-347
12 Padilla CD: Towards universal
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countries: obstacles and the way
forward. Ann Acad Med Singapore
37:6-9, 2008 (suppl 3)
13 "Population of Kuwait". Kuwait
Government Online. 2013. Archived
from the original on 17 January 2013.
14 Dietzen DJ, Rinaldo P, Whitley RJ,
Rhead WJ, Hannon WH, Garg UC, et
al. National Academy of Clinical
Biochemistry Laboratory Medicine
Practice Guidelines: follow-up testing
for metabolic disease identified by
expanded newborn screening using
tandem mass spectrometry; executive
summary. Clin Chem.
2009;55(9):1615–26.
15 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: 17–23.