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 Table of Contents  
Year : 2021  |  Volume : 1  |  Issue : 2  |  Page : 120-123

False negative critical congenital heart disease screening result arising from a complex cardiac disease with duct dependent systemic circulation

1 Department of Pediatric Cardiology, Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center, Bahrain Defense Forces Hospital, Riffa, Bahrain
2 Department of Pediatric Intensive Care Unit, King Hamad University Hospital, Al Sayh, Bahrain
3 Department of Pediatric Cardiology, Mohammed Bin Khalifa Bin Sulman Al-Khalifa Cardiac Center, Bahrain Defense Forces Hospital, Riffa; Department of Pediatrics, Royal College of Surgeons of Ireland, Medical University of Bahrain, Busaiteen, Bahrain

Date of Submission05-Mar-2021
Date of Decision01-May-2021
Date of Acceptance02-May-2021
Date of Web Publication31-May-2021

Correspondence Address:
Dr. Abhinav Agarwal
Department of Pediatric Cardiology, Mohammed Bin Khalifa Bin Salman Al-Khalifa Cardiac Center, Bahrain Defense Force Hospital, P. O. Box 28743, Riffa
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ipcares.ipcares_80_21

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Background: Critical congenital heart disease (CCHD) encompasses congenital structural heart defects that cause significant morbidity and mortality in the first few weeks of life unless treated and/or require surgery or catheter intervention within the 1st year of life. Since these deteriorate acutely due to their cardiac condition, they may be misdiagnosed as septicemia or perinatal asphyxia, especially in resource-poor settings. The American Academy of Pediatrics recommends universal screening with pulse oximetry after 24 h of life by a simple screening protocol. Although specificity is high, CCHD may be missed. We present a case who screened negative became symptomatic on day 10 of life and was finally diagnosed with a CCHD. Clinical Description: A full-term baby with uneventful postnatal course and negative CCHD screening was discharged on day 2 of life. He returned on day 10 with cardiogenic shock. Echocardiography confirmed interrupted aortic arch with large ventricular septal defect (VSD), moderate-sized atrial septal defect (ASD), and a small, restrictive patent ductus arteriosus (PDA). The initial false-negative result was attributed to the presence of large VSD that leads to equalization of preductal and postductal oxygen saturations. Management: The baby was stabilized with prostaglandin infusion and ventilatory support. He underwent staged repair with end-to-end anastomosis of interrupted segment and PDA ligation in the first sitting. The postoperative course was uneventful, and the patient was discharged home at day 25 of life. He is planned for VSD and ASD repair in follow-up. Conclusion: Complex heart diseases may behave unusually due to complicated inter-related hemodynamics arising from the various lesions. Primary health-care personnel should recognize the limitations of CCHD screening protocol and learn to counsel parents accordingly.

Keywords: Critical congenital heart disease screening, duct-dependent systemic circulation, pulse oximetry

How to cite this article:
Agarwal A, Loni R, Al Amer SR, Arulselvam V, Kalis NN. False negative critical congenital heart disease screening result arising from a complex cardiac disease with duct dependent systemic circulation. Indian Pediatr Case Rep 2021;1:120-3

How to cite this URL:
Agarwal A, Loni R, Al Amer SR, Arulselvam V, Kalis NN. False negative critical congenital heart disease screening result arising from a complex cardiac disease with duct dependent systemic circulation. Indian Pediatr Case Rep [serial online] 2021 [cited 2021 Sep 21];1:120-3. Available from: http://www.ipcares.org/text.asp?2021/1/2/120/317371

Congenital heart disease (CHD) is the most common defect identified at birth, with a reported incidence of 7–8/1000 live births.[1],[2] Critical CHD (CCHD) encompasses congenital structural heart defects that cause significant morbidity and mortality in the first few weeks of life unless treated and/or require surgery or catheter intervention within the 1st year of life.[3] The incidence of CCHD is reportedly 2–3/1000 live births[1] and causes 30%–50% mortality due to birth defects. Clinically, these present as hypoxemia in the early neonatal period. Causes of CCHD are usually patent ductus arteriosus (PDA) dependent structural anomalies which present with cardiovascular collapse, acidosis, and death within the first few days of life, parallel to the closure of the PDA. Mortality is preventable if timely identification is made, and reconstructive surgery is undertaken.

The American Academy of Pediatrics has recommended universal screening of newborns by pulse oximetry to rule out CCHD at 24 h of life or as late as possible if the discharge is before 24 h.[4] Oxygen saturation in the right upper limb and lower limb is measured simultaneously. A baby passes the screen (negative screen) if the oxygen saturation measurement is ≥95% in the right hand or foot with an absolute difference ≤3% between the right hand and foot. The screen is considered failed (positive screen) if any oxygen saturation measurement is <90%. If the oxygen saturation is between 90% and 95%, or if absolute difference is >3%, the measurement is repeated after an hour. The baby fails if the same findings are present on three serial measurements, each separated by 1 h. This protocol is simple, cost-effective and can be performed by any trained health-care worker.[5] It is possible for a child who has passed the screen to still have a CCHD and also for a baby who has failed the screen to not have a CCHD. We report a case of a baby in whom a CCHD was missed, despite performing a pulse oximetry test, and explain the underlying pathophysiological reasons for this.

  Clinical Description Top

A full-term male infant was born to a second-degree consanguineous, booked, and immunized primigravida mother with birth weight of 3.5 kg by a spontaneous vaginal delivery. Apgar score was normal. The antenatal period had been uneventful. At birth, the vital parameters were normal. The physical examination was unremarkable, with no cyanosis, or external congenital anomalies. The baby was shifted to the mother and breastfeeding initiated. The CCHD screening protocol was performed at 24 h of life. The baby passed as the oxygen saturation levels were >95% in both the right upper and lower limbs. Urine and meconium were passed normally. The baby was discharged at 48 h of life after undergoing a routine physical evaluation.

On day 10 of life, the baby presented to emergency with a history of poor feeding, lethargy, and abnormal breathing for 12 h. Before that, the baby had been well and on exclusive breastfeeds. There was no history of fever, vomiting, or diarrhea. The baby was in shock with respiratory distress (respiratory rate = 70–75 breaths/min) but normothermic and euglycemic. The arterial blood gas analysis revealed severe metabolic acidosis (pH 6.9) with HCO3 – 12 mmol/L, Base excess - “-23 mmol/L”, and lactate – 18 mmol/L. Shock was managed as per protocol until perfusion stabilized with epinephrine infusion. Mechanical ventilation was started. After stabilization, clinical examination revealed absent lower limb pulses and differential blood pressure (BP) in all four limbs with a clinical gradient of 40 mmHg between the upper and lower limbs (right upper limb – 110/77 mmHg, left upper limb – 98/60 mm Hg, left lower limb – 70/65 mmHg, and right lower limb – 72/64 mmHg). The apex beat was in the left 5th intercostal space, 0.5 cm lateral to the midclavicular line. The rest of the cardiovascular and respiratory examination was normal. There was no hepatomegaly. The chest radiograph showed cardiomegaly with pulmonary plethora. Electrocardiogram was unremarkable apart from sinus tachycardia (180/min). Complete blood counts were within normal limits. Biomarkers of acute infection (C-reactive protein and procalcitonin) were negative. Liver function and kidney function tests were normal.

The clinical phenotype of cardiogenic shock with differential BP in the manifesting in the 2nd week of life was suggestive of a CCHD with involvement of the duct-dependent systemic circulation. Echocardiography clinched the final diagnosis; an interrupted aortic arch (IAA) with a tiny PDA that was supplying the descending aorta, transverse arch hypoplasia, large ventricular septal defect (VSD), moderate atrial septal defect (ASD), dilated right ventricle, and biventricular dysfunction [Figure 1]a.
Figure 1: (a) Two-dimensional echocardiography with color Doppler showed interrupted aortic arch with segment after interruption supplied by flow from a tiny patent ductus arteriosus; (b) 12 h after starting prostaglandin echocardiography showed large patent ductus arteriosus continuing as descending aorta; (c) reconstructed aortic arch after surgical correction. (AAo: Ascending aorta, DAo: Descending aorta, IAA: Interrupted aortic arch, PDA: Patent ductus arteriosus)

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Management and outcome

Prostaglandin infusion (0.05 mcg/kg/min) was started immediately that resulted in improvement in lower limb perfusion and BP. A continuous PDA murmur now became audible in the left 2nd intercostal space. Repeat echocardiography after 12 h showed increase in the size of the PDA and improved biventricular systolic function [Figure 1]b. Computerized tomography angiography confirmed echo findings and displayed crisscross origin of the pulmonary arteries. The brachiocephalic artery, left common carotid artery, and left subclavian artery emerged in the proximal part of the aortic arch before interruption [Figure 2]a and [Figure 2]b. Over the next few days, the baby was weaned off ventilatory and inotropic support. On the 20th day of life, he underwent an end-to-end anastomosis of the IAA along with PDA ligation [Figure 3]a and [Figure 3]b. The postoperative course was uneventful, and the baby was discharged within a week. The echocardiogram showed a good-sized reconstructed arch with unobstructed blood flow and no residual PDA [Figure 1]c. The VSD and ASD repair has been planned in the follow-up within the next few months.
Figure 2: (a) Two-dimensional computerized tomographic aortogram (sagittal view) showing interrupted aortic arch; (b) three-dimensional volume-rendered image (anterior view) showing interrupted aortic arch and patent ductus arteriosus continuing as descending aorta. (* - location of aortic arch interruption, DAo: Descending aorta, MPA: Main pulmonary artery, PDA: Patent ductus arteriosus)

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Figure 3: (a) Left thoracotomy preoperative image showing thread-like interrupted segment and large patent ductus arteriosus continuing as descending aorta (b) Left thoracotomy postoperative image showing good-sized reconstructed aortic arch with neck vessels (DAo: Descending aorta, IAA: Interrupted aortic arch, PDA: Patent ductus arteriosus)

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  Discussion Top

Screening for CCHD means early detection and planned elective surgical management. A combination of antenatal ultrasound with postnatal physical examination misses CCHD in one-third babies.[6] Prenatal detection rates are lower in low- and middle-income countries due to limited resources and as many mothers do not receive proper antenatal care.[7] CCHD screening with pulse oximetry can prevent this common cause of neonatal mortality.[4]

The sensitivity of CCHD screening is 77%, while the specificity is 98%.[5],[8],[9] These values can increase further if pulse oximetry is combined with an antenatal ultrasound and a postnatal physical examination.[8] There are many case reports describing false-positive results, but few reporting false-negative ones.[5],[7],[10] This is probably because false-positive cases get evaluated during hospital stay, whereas false-negative screens get discharged. They may go unreported due to acute deterioration and expiry at home, or being mis-diagnosed as septicemia, especially in low- and middle-income countries where access to echocardiography and pediatric cardiology facilities is limited.

CCHD screening works on the principle of identifying systemic desaturation or differential saturation in upper and lower limbs. Once detected, a detailed evaluation by pediatric cardiologists and cardiac-directed investigations are warranted. Hoffman described anomalies that are missed by pulse oximetry; very small right to left shunt, CCHD with relatively high cardiac output and high mixed venous saturation, and those without systemic desaturation.[10]

Although this infant had an IAA with duct-dependent systemic circulation, no upper and lower limb discrepancy in oxygen saturation was found. The baby escaped detection by the CCHD screening and customary neonatal examination before discharge, probably due to the following reasons: first, the large size and nonrestrictive nature of the VSD resulted in mixing of oxygenated and deoxygenated blood and thus increased the oxygen saturation of right ventricular blood that was being pumped into the descending aorta through the ductus arteriosus. The upper limbs received blood from left ventricle through the ascending aorta and the lower limbs received mixed blood through the PDA. This probably resulted in equalization of upper and lower limb oxygen saturation. Second, the large PDA resulted in the equal upper and lower limb BP. Third, a cardiac murmur was not heard due to the combination of a large VSD and large PDA.

IAA is one of the main CCHDs for which CCHD screening was devised. A difference in upper and lower limb saturation is the clinical alert for suspecting its presence. It is important to emphasize that complex CHDs although described individually in literature are in actuality a constellation of separate independent lesions that may not fit into the predefined expected clinical repertoire. A clinician who practices universal CCHD screening must be cognizant of its intrinsic limitations and be able to counsel parents regarding the screening results accordingly.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the legal guardian has given his consent for images and other clinical information to be reported in the journal. The guardian understands that names and initials will not be published and due efforts will be made to conceal patient identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Hoffman JI. Natural history of congenital heart disease. Problems in its assessment with special reference to ventricular septal defects. Circulation 1968;37:97-125.  Back to cited text no. 1
Agarwal A, Al Amer SR, Kalis NN. Epidemiology of congenital heart disease in the Kingdom of Bahrain. Bahrain Med Bull 2020;42:192-5.  Back to cited text no. 2
Frank LH, Bradshaw E, Beekman R, et al. Critical congenital heart disease screening using pulse oximetry. J Pediatr 2013;162:445-53.  Back to cited text no. 3
Mahle WT, Martin GR, Beekman RH 3rd, et al. Endorsement of Health and Human Services recommendation for pulse oximetry screening for critical congenital heart disease. Pediatrics 2012;129:190-2.  Back to cited text no. 4
Almawazini AM, Hanafi HK, Madkhali HA, Majrashi NB. Effectiveness of the critical congenital heart disease screening program for early diagnosis of cardiac abnormalities in newborn infants. Saudi Med J 2017;38:1019-24.  Back to cited text no. 5
Ewer AK. Pulse oximetry screening for critical congenitalheart defects: A life-saving test for all newborn babies. Int J Neonatal Screen 2019;5:14.  Back to cited text no. 6
Van Naarden Braun K, Grazel R, Koppel R, et al. Evaluation of critical congenital heart defects screening using pulse oximetry in the neonatal intensive care unit. J Perinatol 2017;37:1117-23.  Back to cited text no. 7
Ewer AK. Review of pulse oximetry screening for critical congenital heart defects in newborn infants. Curr Opin Cardiol 2013;28:92-6.  Back to cited text no. 8
de-Wahl Granelli A, Wennergren M, Sandberg K, Mellander M, Bejlum C, Inganäs L, et al. Impact ofpulse oximetry screening on the detection of duct dependentcongenital heart disease: A Swedish prospective screening studyin 39,821 newborns. BMJ 2009;338:a3037.  Back to cited text no. 9
Hoffman JI. False negative diagnoses of critical congenital heart disease with screening neonatal pulse oximetry. J Neonatal Perinatal Med 2020;13:5-9.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3]


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