J. Perinat. Med.

2017; aop

Şahin Hamilçıkan and Emrah Can*

Critical congenital heart disease screening

with a pulse oximetry in neonates
DOI 10.1515/jpm-2017-0006
Received January 6, 2017. Accepted May 31, 2017.
Introduction
Abstract Congenital heart disease (CHD) is the most common con-
genital anomaly in newborns, with a birth prevalence of
Objective: To compare the results of pulse oximetry
nearly 1% [1–3]. However, in up to 30% of infants with
screening for critical congenital heart disease (CCHD) in
critical congenital heart disease (CCHD), this might not be
newborn infants performed at <24 h and >24 h following.
apparent within the first days of life [4, 5] from traditional,
Method: Measurements were taken for each group at <24 h
routine examinations. Infants with CCHD, according to
and >24  h following birth. Echocardiography was per-
the World Health Organization (WHO), are not necessarily
formed if the SpO2 readings remained abnormal results.
diagnosed in birth hospitalizations and have a risk of mor-
Results: A total of 4518 newborns were included in this
tality as high as 30% of the time [6–8]. Newborn screening
prospective descriptive study. Of these, 2484 (60.3%) were
for CCHD by pulse oximetry provides a timely identifica-
delivered vaginally and 1685 (39.7%) by cesarean section.
tion of infants with CCHD before discharge from hospital
Median time points of the screening were 25.4 (25.3–
following birth, minimizing the morbidity and mortality
25.5) vs. 17.3 (12.2–22.4) hours after birth. In 4109 infants
related to delayed diagnosis. The common cardiac causes
screened 24  h after birth, the mean pre- and postductal
of hypoxemia that can be identified through newborn
oxygen saturations (SpO2) were 96.5 ± 1.99 and 97.7 ± 1.98,
pulse oximetry screening include infection, respiratory
while 127 infants screened within 24 h of mean preductal
distress syndrome (RDS), persistent pulmonary hyper-
and postductal SpO2 were 91.33 ± 2.64 and 94.0 ± 4.44. No
tension of neonate (PPHN), meconium aspiration, pneu-
CCHD was detected during the study period. Pulse oxi-
monia, and abnormalities [9, 10]. The advantages of
metry screening was false positive for CCHD in 9 of 4109
screening in reducing mortality and morbidity related to
infants (0.02%); of these, six infants were referred to pedi-
delayed diagnosis should be weighed against the draw-
atric cardiology and three cases were diagnosed as other
back of false positives. Universal newborn screening for
significant, non-cardiac pathology. There were two cases
CCHD is supported by the American Academy of Pediat-
with AVSD (atrioventricular septal defect, three cases with
rics (AAP) and the American Heart Association (AHA) [11,
ventricular septal defect (VSD), and one case with patent
12]. Screening programs are in place in some European
ductus arteriosus (PDA).
countries and some other countries [13–16]. Screening
Conclusions: Saturation values are different between
should be performed within the first 24 h of life or as early
<24-h and >24-h neonates in pulse oximetry screening.
as possible before discharge [17–20].
The screening in this study identified infants with other
The aim of the study was to compare the results of
important pathologies, this forms an added value as an
pulse oximetry screening for CCHD in newborn infants
assessment tool for newborn infants.
performed aged <24 h and >24 h.
Keywords: Congenital heart disease; neonate; pulse
oximeter.
Methods
Study design

*Corresponding author: Emrah Can, MD, Assoc. Prof., Pediatrics and
Neonatology, Department of Neotanal Intensive Care Unit, Bagcılar
Training and Research, Hospital, Istanbul, Turkey,
Tel.: +90 212 440 00 00, Fax: +90 212 440 40 40,
E-mail: canemrahcan@yahoo.com
Şahin Hamilçıkan: Department of Neotanal Intensive Care Unit,
Bagcılar Training and Research, Istanbul, Turkey
A total of 4335 participants were included in this prospective descrip-
tive study carried out in Bagcılar Training and Research Hospital
Neonatal Intensive Care Unit between October 1, 2015 and October 31,
2016. The hospital is a third-level neonatal center with almost 5000
newborns delivered each year. Neonates born by spontaneous vagi-
nal delivery or cesarean section between gestational weeks 34 and
42, according to ultrasonographic investigations and new Ballard

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2      Hamilçıkan and Can, Congenital heart disease early screening with pulse oxymetry

scoring, were included in the study. The hospital has a 24/7 echo-
cardiography service with a pediatric cardiologist on call. All term
and late preterm infants (gestational age >34 weeks) who were not
admitted to the neonatal intensive care unit and were not monitored
by a pulse oximeter (PO) were eligible for this study. Parents were
informed of the PO screening prenatally and written informed con-
sent was obtained prior to performing the screening. Our hospital
full-term discharge policy is a minimum of 24 h for normal vaginal
delivery and 48–72 h for cesarean-section delivery. Early discharge is
defined as <24 h.
Measurements
Parents were informed about re-screening on a control day
within 24–48 h. If the neonate was to be discharged <24 h, screen-
ing for CCHD was performed in the pre-discharge period. CCHD was
identified as having hypoplastic left heart syndrome, pulmonary
atresia with intact ventricular septum, simple transposition of the
great arteries, interruption of the aortic arch, total anomalous pul-
monary venous return, or bicuspid atresia, as well as any infants
dying or requiring medical intervention within the first 28 days of life
as a result of coarctation of the aorta, aortic valve stenosis, pulmo-
nary stenosis, Tetralogy of Fallot (TOF), double outlet right ventricle,
Epstein anomaly, or pulmonary atresia with ventricular septal defect.
The study was approved by the local hospital medical Ethics Com-
mittee.

PO measurements were obtained by the same nurse for each group,

<24 h and >24 h, with the sensor placed on the right hand/wrist and
either foot in a non-specified order. All screenings were performed
using a Masimo Radical-7 (Masimo Corp, Irvine, CA, USA) handheld
pulse oximeter with reusable sensors and disposable adhesive sen-
sor wraps.
The PO screening protocol used followed the AAP (2012): posi-
tive after one quality signal in a pre- or postductal SpO2 reading
of <90% [11]. The screening was also considered positive after two
repeated measurements, with a 1-h interval between them, of either
<95% for both limbs or with an absolute difference of >3% between
the pre- and postductal readings. Measurements were not performed
when the infant was crying or moving because both can reduce the
quality of the signal and the accuracy of the test. When SpO2 read-
ings in the first measurement were normal, the pre- and postductal
SpO2  measurements were not repeated. Infants with positive PO
screening were referred to the pediatric cardiology department for
physical examination and echocardiography.
Echocardiography was performed if the SpO2 readings remained
abnormal and no other cause of hypoxemia was found or if the exam-
ination revealed cardiovascular symptoms. No neonate with hypox-
emia was discharged from the hospital before excluding potentially
life-threatening conditions. Infants with positive screening results
should undergo evaluation to identify the cause of hypoxemia. Any
determination of CCHD as the cause should include high-quality
echocardiography with interpretation by a clinician with expertise in
the diagnosis of CHD. Infants with negative screening results who are
clinically well and who show no signs of possible CHD do not require
additional evaluation.
Statistical analysis
Statistical analysis was performed using the NCSS (Number Cruncher
Statistical System), 2007. A t-test and was used to calculate the differ-
ences between the two parameters in the groups; for comparison of
the data, an unpaired t-test and the Mann-Whitney U-test were con-
ducted. P < 0.05 was accepted as significant.
Results
A total of 4518 newborns were included in this prospec-
tive descriptive study; parents of 226 infants (5%) were not
approached for consent and 56 (0.1%) were approached
but refused the PO screening. Of the remaining partici-
pants, vaginal delivery accounted for 2552 (60.3%) and
cesarean section 1684 (39.7%). Data are provided for
gender, gestational week, birth weight, birth-weight loss,
Apgar scores (1st and 5th min), and preductal and post-
ductal SpO2 screening results in Table 1. Study participant
delivery characteristics are presented in Table  2. Paren-
tal consent was obtained for 4109 infants; screening was
performed in 4109/4335 infants (94.7%) overall and for
127/4335 (2.9%) of the infants, screening was performed

Table 1: Fetal characteristics in neonates.

>24 h (n: 4109) Mean ± SD <24 h (n: 127) Mean ± SD P-value

Gestational week 38.56 ± 1.26 37.0 ± 1.58 0.001

Birth weight (g) 3201.88 ± 494.82 3142 ± 698.06 0.18
Height (cm) 49.19 ± 2.89 48.4 ± 2.50 0.002
Head circumference (cm) 34.68 ± 1.60 34.70 ± 1.75 0.89
Apgar score
 1 min 9.56 ± 1.17 9.36 ± 1.08 0.05
 5 min 9.78 ± 0.71 9.68 ± 0.51 0.11
Median screening time (min–max) 25.4 (25.3–25.5) 17.3 (12.2–22.4)
Preductal SpO2 97.55 ± 1.99 91.33 ± 2.64 0.0001
Postductal SpO2 98.79 ± 1.98 94.0 ± 4.44 0.0001

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 Hamilçıkan and Can, Congenital heart disease early screening with pulse oxymetry      3

Table 2: Delivery characteristics. results (repeated tests). No CCHD was detected during the
study period. The false positive (FP) prevalence was 0.9%
  >24 h  <24 h in the first 24 h after birth. After referral, important non-
(n: 4109), % (n: 127), %
critical cardiac and other non-cardiac pathologies were
Maternal age (mean ± SDa)   28.2 ± 3.1  27.5 ± 2.64 found in 66% of the FP screenings. There were no false
Gender negative screenings or true positive screenings during the
 Male   2112 (51.40)  75 (59.0)
study period. No deaths occurred in the cohort of screened
 Female   1997 (48.60)  52 (40.9)
Delivery mode infants. No CCHD was detected, nor were there any cases
 Vaginally   2484 (61.00)  68 (53.5) missed by PO screening. PO screening was total FP ratio
 Cesarean   1625 (39.00)  59 (46.4) for CCHD in 9/4236 infants (0.002). Of these, six infants
Breech delivery   45 (1.00)  0 were referred to pediatric cardiology and three cases were
Vacuum extraction   5 (0.10)  0
diagnosed with other significant, non-cardiac pathol-
Pregnancy
 Singleton   4087 (99.40)  127 (100)
ogy [infection/sepsis, transient tachypnea in newborns
 Twins   22 (0.60)  0 (TTN)]. In nine infants, physical examination was normal;
Active resuscitation   224 (5.40)  0 repeated PO after referral to pediatric cardiology showed
Gestational diabetes mellitus   133 (3.2)  5 (3.9) normal results. Echocardiography determined noncriti-
Preeclampsia   287 (6.9)  6 (4.7) cal defects in six neonates, and there were two cases with
Meconium stain amniotic fluid  128 (3.1)  2 (1.5)
AVSD, three cases with VSD, and one case with PDA.
Admission to the NICUb   487 (11.80)  0

SD = Standard deviation; bNICU = neonatal intensive care unit.

a

<24 h (Figure 1). Median screening times were 25.4 (25.3–

Discussion
25.5) vs. 17.3 (12.2–22.4) hours after birth. In 4109 infants
Following the recommendations of the AAP, increased
screened >24 h, the mean pre- and postductal SpO2 were
numbers of pulse oximetry screenings of newborn infants
96.5 ± 1.99 and 97.7 ± 1.98. Otherwise, 127 infants screened
for CCHD have been reported globally [13, 14]. In these
<24 h showed preductal and postductal SpO2 of 91.33 ± 2.64
studies, the sensitivity of pulse oximetry has been reported
and 94.0 ± 4.44. These results are of the combined all tests
as 76.5% (95% CI 67.7–83.5); specificity is 99.9 (95% CI
99.7–99.9) [21]. There have been different time presenta-
tion varieties with underlying lesion and a dependence on
4518 Neonate original cohort
the presence of PDA reported, as well as defects in related
PDA clinically manifesting after the closure of PDA. One
282 Neonates were excluded
observational study of 3603 infants with CCHD born
226 Not approached for consent
through the United States Birth Defect Registry, found that
56 were refused
25% of neonates were not diagnosed during hospitaliza-
4236 Neonates were performed by tion, a ratio that is particularly problematic for diseases
pulse oxymetry screening
that need to be diagnosed early in newborns [22].
The results of pulse oximetry screening can be inad-
4109 Neonates were screened 127 Neonates were screened equate in cases of early birth, but it is still considered
>24 h <24 h
that early testing provides more reliable results, espe-
cially when fetal adaptation to neonatal life is achieved
[11]. However, since fetal adaptation varies from infant to
4106 Neonates were passed 121 Neonates were passed
3 Neonates were failed 6 neonates were failed infant, very early screening is not recommended as there
is a possibility that SpO2 may not yet have reached >95%
because of varied post-birth adaptation [11]. In the present
study, 127 neonates were evaluated by pulse oximetry
2 AVSD
1 ASD <24 h and 6 failed the test. Thanks to this early test, TTN
1 VSD
1 VSD
2 TTN
in two patients and early neonatal sepsis in one patient
1 PDA
1 Sepsis was diagnosed as needing intensive-care follow-up. Of the
4109 babies who were scanned on time, only three neo-
Figure 1: Study participant selection analysis. nates did not pass the test. Noncritical cardiac pathologies

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4      Hamilçıkan and Can, Congenital heart disease early screening with pulse oxymetry
were excluded from echocardiography performed by the
pediatric cardiologist and neonates were monitored. When
the preductal and postductal values were compared, it was
thought that the difference could be related to early post-
natal adaptation. Further research remains to be done to
test whether the accuracy would be similar to PO screening
in other countries [21, 23–25]. In our study, false positivity
was very low in <24 h after birth. However, these positivi-
ties helped with other, non-cardiac pathology diagnoses
such as TTN, neonatal sepsis, and RDS.
Study limitations
This study has some limitations. Firstly, the study popula-
tion was relatively small; a larger study population would
provide a higher statistical power. Secondly, pulse oxi-
metry analyses were not performed at different discharge
times in this study.
Conclusion
Finally, saturation values differ between <24-h and >24-h
neonates in pulse oximetry screening. We believe that, as
the screening process in this study identified infants with
other important pathologies, this forms an added value
as an assessment tool for newborn infants; we recom-
mend that you do this scan for neonates who are <24  h
discharged for any reason, and these scan results may be
verified over a larger series.
Author’s statement
Conflict of interest: Authors state no conflict of interest.
Material and methods: Informed consent: Informed
consent has been obtained from all individuals included
in this study.  AB. Aspects of pulse oximetry screening for critical congenital
Ethical approval: The research related to human subject
use has complied with all the relevant national regula-
tions, and institutional policies, and is in accordance
with the tenets of the Helsinki Declaration, and has been
approved by the authors’ institutional review board or
equivalent committee.
References
[1] Tennant PW, Pearce MS, Bythell M, Rankin J. 20-year survival of
children born with congenital anomalies: a population-based
study. Lancet. 2010;375:649–56.
[2] Bird TM, Hobbs CA, Cleves MA, Tilford JM, Robbins JM. National
rates of birth defects among hospitalized newborns. Birth
Defects Res A Clin Mol Teratol. 2006;76:762–9.
[3] Canfield MA, Honein MA, Yuskiv N, Xing J, Mai CT, Collins JS,
et al. National estimates and race/ethnic-specific variation of
selected birth defects in the United States, 1999–2001. Birth
Defects Res A Clin Mol Teratol. 2006;76:747–56.
[4] Khoshnood B, Lelong N, Houyel L, Thieulin AC, Jouannic JM,
Magnier S, et al. Prevalence, timing of diagnosis and mortality
of newborns with congenital heart defects: a population-based
study. Heart. 2012;98:1667–73.
[5] Ailes EC, Gilboa SM, Honein MA, Oster ME. Estimated number
of infants detected and missed by critical congenital heart
defect screening. Pediatrics. 2015;135:1000–8.
[6] Kuehl KS, Loffredo CA, Ferencz C. Failure to diagnose congeni-
tal heart disease in infancy. Pediatrics. 1999;103:743–7.
[7] Eckersley L, Sadler L, Parry E, Finucane K, Gentles TL. Timing of
diagnosis affects mortality in critical congenital heart disease.
Arch Dis Child. 2016;101:516–20.
[8] Chang RK, Gurvitz M, Rodriguez S. Missed diagnosis of
critical congenital heart disease. Arch Pediatr Adolesc Med.
2008;162:969–74.
[9] Garg LF, Van Naarden BK, Knapp MM, Anderson TM, Koppel
RI, Hirsch D, et al. Results from the New Jersey statewide criti-
cal congenital heart defects screening program. Pediatrics.
2013;132:e314–23.
[10] Ewer AK, Middleton LJ, Furmston AT, Bhoyar A, Daniels JP,
Thangaratinam S, et al. Pulse oximetry screening for congenital
heart defects in newborn infants (PulseOx): a test accuracy
study. Lancet. 2011;378:785–94.
[11] Mahle WT, Martin GR, Beekman RH 3rd, Morrow WR, Section
on Cardiology and Cardiac Surgery Executive Committee.
Endorsement of health and human services recommendation
for pulse oximetry screening for critical congenital heart
disease. Pediatrics. 2012;129:190–2.
[12] Kemper AR, Mahle WT, Martin GR, Cooley WC, Kumar P, Morrow
WR, et al. Strategies for implementing screening for critical
congenital heart disease. Pediatrics. 2011;128:e1259–67.
[13] 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:S11–4.
[14] Narayen IC, Blom NA, Ewer AK, Vento M, Manzoni P, te Pas
heart defects: when, how and why? Arch Dis Child Fetal Neona-
tal Ed. 2016;101:F162–7.
[15] de-Wahl Granelli A, Meberg A, Ojala T, Steensberg J, Oskarsson
G, Mellander M. Nordic pulse oximetry screening–implementa-
tion status and proposal for uniform guidelines. Acta Paediatr.
2014;103:1136–42.
[16] Al Mazrouei SK, Moore J, Ahmed F, Mikula EB, Martin GR.
Regional implementation of newborn screening for critical con-
genital heart disease screening in Abu Dhabi. Pediatr Cardiol.
2013;34:1299–306.
[17] Valmari P. Should pulse oximetry be used to screen for
congenital heart disease? Arch Dis Child Fetal Neonatal Ed.
2007;92:F219.
[18] Richmond S, Reay G, Abu Harb M. Routine pulse oximetry in
the asymptomatic newborn. Arch Dis Child Fetal Neonatal Ed.
2002;87:F83–8.
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Download Date | 7/5/17 8:52 AM
 Hamilçıkan and Can, Congenital heart disease early screening with pulse oxymetry      5
[19] Koppel RI, Druschel CM, Carter T, Goldberg BE, Mehta PN,
Talwar R, et al. Effectiveness of pulse oximetry screening for
congenital heart disease in asymptomatic newborns. Pediat-
rics. 2003;111:451–5.
[20] Thangaratinam S, Daniels J, Ewer AK, Zamora J, Khan KS. Accu-
racy of pulse oximetry in screening for congenital heart disease
in asymptomatic newborns: a systematic review. Arch Dis Child
Fetal Neonatal Ed. 2007;92:F176–80.
[21] Thangaratinam S, Brown K, Zamora J, Khan KS, Ewer AK. Pulse
oximetry screening for critical congenital heart defects in
asymptomatic newborn babies: a systematic review and meta-
analysis. Lancet. 2012;379:2459–64.
[22] Peterson C, Dawson A, Grosse SD, Riehle-Colarusso T, Olney
RS, Tanner JP, et al. Hospitalizations, costs, and mortality
among infants with critical congenital heart disease: how
important is timely detection? Birth Defects Res A Clin Mol
Teratol. 2013;97:664–72.
[23] Ewer AK, Furmston AT, Middleton LJ, Deeks JJ, Daniels JP,
Pattison HM, et al. Pulse oximetry as a screening test for
congenital heart defects in newborn infants: a test accuracy
study with evaluation of acceptability and cost-effectiveness.
Health Technol Assess. 2012;16:v–xiii:1–184.
[24] de-Wahl Granelli A, Wennergren M, Sandberg K, Mellander M,
Bejlum C, Inganäs L, et al. Impact of pulse oximetry screening
on the detection of duct dependent congenital heart disease:
a Swedish prospective screening study in 39 821 newborns.
Br Med J. 2009;338:a3037.
[25] Zhao QM, Ma XJ, Ge XL, Liu F, Yan WL, Wu L, et al. Pulse oximetry
with clinical assessment to screen for congenital heart disease in
neonates in China: a prospective study. Lancet. 2014;384:747–54.
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