Objective. To determine the sensitivity, specificity, predictive value, and accuracy of a program of pulse oximetry screening of asymptomatic newborns for critical congenital cardiovascular malformation (CCVM).
Methods. Pulse oximetry was performed on asymptomatic newborns in the well-infant nurseries of 2 hospitals. Cardiac ultrasound was performed on infants with positive screens (saturation ≤95% at >24 hours). Data regarding true and false positives as well as negatives were collected and analyzed.
Results. Oximetry was performed on 11 281 asymptomatic newborns, and 3 cases of CCVM were detected (total anomalous pulmonary venous return ×2, truncus arteriosus). During the study interval, there were 9 live births of infants with CCVM from a group of 15 fetuses with CCVM detected by fetal echocardiography. Six infants with CCVM were symptomatic before screening. There was 1 false-positive screen. Two infants with negative screens were readmitted (coarctation, hypoplastic left pulmonary artery with aorto-pulmonary collaterals). Other cardiac diagnoses in the database search were nonurgent, including cases of patent foramen ovale, peripheral pulmonic stenosis, and ventricular septal defect. The prevalence of critical CCVM among all live births was 1 in 564 and among the screened population was 1 in 2256 (sensitivity: 60%; specificity: 99.95%; positive predictive value: 75%; negative predictive value: 99.98%; accuracy: 99.97%).
Conclusions. This screening test is simple, noninvasive, and inexpensive and can be administered in conjunction with state-mandated screening. The false-negative screen patients had lesions not amenable to detection by oximetry. The sensitivity, specificity, and predictive value in this population are satisfactory, indicating that screening should be applied to larger populations, particularly where lower rates of fetal detection result in increased CCVM prevalence in asymptomatic newborns.
Congenital cardiovascular malformations (CCVMs) are relatively common with a prevalence of 5 to 10 in every 1000 live births.1 In New York State, approximately 25% of malformations are CCVMs.2 With improvements in diagnosis and treatment, the outlook for newborns with CCVMs has changed considerably, but these malformations still contribute to significant morbidity and mortality in this age group. Children with CCVM are at approximately 12 times higher risk of mortality in the first year of life.3 Several life-threatening CCVMs are not recognized with screening level II obstetrical ultrasound4,5 or clinically apparent in the early newborn period. Routine neonatal examination fails to detect >50% of infants with CCVM.6 One in 10 infants with CCVM who died in the first year did not have a diagnosis made of the malformation before death, and of those who died in the first week, 25% did not have the diagnosis identified before death.7 With the average length of stay of asymptomatic newborns reduced to 48 hours, many of these infants will already be at home at the time of onset of clinical signs.
Newborn screening is an essential, preventive public health program. For nearly 40 years, newborn screening programs have provided an important public health service by identifying newborns with congenital conditions that could be managed effectively with intervention early in life.8 Screening programs have been developed for metabolic, hematologic, and endocrine disorders and more recently for hearing loss.9 The effectiveness of a screening program is dependent on 1) prevalence of the disorder of interest, 2) simple and reliable methods, 3) available treatment, and 4) favorable cost/benefit ratio.10 On the basis of these criteria, CCVM represents a newborn condition that would be ideally suited to a screening program if simple and reliable methods were available.
The 4-chamber view screening performed by obstetricians does allow for prenatal detection of many, although not all, affected fetuses.4,5 The costs associated with routine fetal echocardiography would make it impractical as a screening modality. At present, the only method available for screening large numbers of asymptomatic newborns for CCVM is the discharge physical examination, which has been shown to be ineffective.11,12 Pulse oximetry has been suggested as a method to screen newborns in the early neonatal period to detect these lesions and initiate therapy before they become life-threatening. Byrne et al13 reported the detection of desaturation secondary to hypoplastic left heart syndrome, coarctation, and tetralogy of Fallot in a group of asymptomatic newborns through the use of simultaneous upper and lower extremity pulse oximetry. Kao et al14 reported similar findings but cautioned that pulse oximetry may be inadequate as a screen for coarctation and aortic stenosis (Table 1). In view of the results of these preliminary studies, we were interested in extending the work of Byrne et al and Kao et al to determine the sensitivity, specificity, predictive value, and accuracy of a program of pulse oximetry screening of asymptomatic newborns for critical CCVM.
Oximetric screening for critical CCVM was performed by obtaining a single determination of postductal saturation on all asymptomatic newborns (n = 11 281) in the well-infant nurseries of 2 participating hospitals during the study interval. All newborns in the nursery at the time of New York State metabolic screening (hospital A) or all newborns who were being discharged from the well-infant nursery (hospital B) and did not manifest cyanosis, tachypnea (respiratory rate: >60/min), grunting, flaring, retraction, murmur, active precordium, or diminished pulses underwent oximetric screening. Any infant who did manifest any of these clinical findings was transferred to the neonatal intensive care unit for customary evaluation and was not included in the analysis. To ensure universal screening, the timing of the oximetry determination was linked to the state-mandated metabolic screening (>24 hours of age) at hospital A (n = 8642 [76%]). At hospital B (n = 2639 [24%]), screening was performed immediately before discharge as part of the list of discharge procedures (average length of stay for vaginal delivery: 56.9 hours; for cesarean section: 103.2 hours). Critical CCVM was defined as a lesion that would likely require surgical correction during the first month of life. All newborns found to have a postductal saturation ≤95% underwent additional evaluation by echocardiography. Data were collected from May 1998 to November 1999.
The number of true and false positives and the predictive value positive of the screening test were determined from data collected at the study sites. However, determining the false negatives and the sensitivity and specificity required follow-up for children who were readmitted for delayed diagnoses of CCVM. The New York State Congenital Malformations Registry (CMR) was used to ascertain these cases.
The CMR is a statewide birth defects registry. State law mandates reporting by hospitals and physicians of a child who receives a diagnosis of a birth defect before 2 years of age. CMR reports include the narrative description of the defect, and trained registry staff do the coding. The CMR monitors reporting and compares with hospital discharge data to ensure completeness of reporting. Malformation registration using capture-recapture analysis has been estimated to be 87% complete.15 We also supplemented our case finding using hospital discharge data and death certificates.
All CCVM cases in the CMR were matched to the birth file to determine the hospital of birth and to generate a list of children who were born at the participating institutions. This resulted in a list of children who passed the screening test but were later found to have CCVM (false-negative rate). From this the sensitivity and specificity were determined. The medical records of CCVM cases that screened negative were reviewed to determine the accuracy of the diagnosis.
Determination of oxygen saturation by pulse oximetry was the standard of care for all pediatric inpatients at our institution. Pulse oximetry was already in routine use in the well-infant nursery for symptomatic infants. The use of pulse oximetry as a routine vital sign was extended to the standard care of all infants in the nursery regardless of their symptoms. Therefore, informed consent was not requested. The New York State Department of Health Institutional Review Board approved the review of patients’ medical records by the CMR, and confidentiality of patient’s medical records was ensured.
Oximetric screening was performed on 11 281 asymptomatic newborns during the study interval: 8642 at hospital A and 2639 at hospital B (Table 2). Three cases of CCVM were detected, including 2 patients with total anomalous pulmonary venous return (oxygen saturation by pulse oximeter: 92%, 88%) and 1 patient with truncus arteriosus (oxygen saturation by pulse oximeter: 86%; Table 3). Therefore, 1 in 3760 asymptomatic newborns was found to have a CCVM by oximetric screening before discharge. There was no accrued cost as reusable oximeter probes were used with oximeters already in place in the nurseries. There was 1 false-positive screen. An asymptomatic infant underwent echocardiography for postductal desaturation and was found to have a structurally normal heart with persistent right to left ductal shunting as a result of delayed transition from the fetal to the neonatal circulation. Two screened infants were readmitted (coarctation, hypoplastic left pulmonary artery with aorto-pulmonary collaterals). Other cardiac diagnoses in the database search were nonurgent, including cases of patent foramen ovale, peripheral pulmonic stenosis, and ventricular septal defect. The prevalence of all cases of critical CCVM in the total population was 1 in 564, whereas in the screened population it was 1 in 2256. Analysis of the screening test’s performance revealed sensitivity of 60%, specificity of 99.95%, positive predictive value of 75%, negative predictive value of 99.98%, and accuracy of 99.97%.
At hospital A, echocardiography was performed on 798 fetuses with expected dates of confinement occurring during the study interval, yielding a diagnosis of CCVM in 15 fetuses with 9 of these being delivered (Tables 2 and 3). Echocardiography performed on 108 fetuses at hospital B detected no major lesions (Table 2). Six infants became symptomatic before screening, and 3 infants who were readmitted from home were born at other hospitals where screening was not performed (Table 3).
The discharge physical examination has been shown to be an inadequate screen for CCVM.6,11,12 An asymptomatic newborn may appear pink despite having clinically significant desaturation. With the incidence of critical CCVM being approximately 2.7 per 1000 live births,16 we anticipated a higher yield of CCVM case detection by oximetric screening of asymptomatic newborns. The detection rate at hospital B of 1 in 1320 is close to the predicted incidence of 2.7 in 1000 and is comparable to the incidence of congenital hypothyroidism. Despite the large number of prenatally detected lesions, a detection rate by screening of 1 in 3760 for the 2 sites combined is far greater than the rates for most conditions included in the New York State screening program (Table 4).
Comparing the data for the 2 participating institutions reveals the impact of frequently performed fetal echocardiography on the yield from screening (Table 2). Our data suggest that in a center where fetal echocardiography is readily accessible, many lesions will be diagnosed prenatally and therefore will not require screening for detection. This phenomenon has the effect of decreasing the prevalence of CCVM in the population of asymptomatic infants undergoing oximetric screening. Centers where fetal echocardiography is performed less frequently are likely to demonstrate higher yields from oximetric screening.
It is impossible to know whether the newborns with fetal echocardiographic diagnoses in our series would have been detected by screening or would have become symptomatic before screening. However, the prenatally diagnosed lesions in our series, with the possible exception of the case of coarctation, would have been amenable to oximetric detection (Tables 1 and 3). The 2 false-negative screen patients (coarctation, hypoplastic left pulmonary artery with aorto-pulmonary collaterals) had lesions that may not cause desaturation and therefore represent the limitations of screening for CCVM by oximetry (Table 1).
A total of 4 echocardiograms were performed on the basis of postductal desaturation at the time of screening of 11 281 asymptomatic infants. Three of these echocardiograms revealed major CCVM in asymptomatic infants. No unnecessary echocardiograms were performed in the context of this study. Although the fourth echocardiogram did not detect a major CCVM, the infant did have delayed transition from fetal to neonatal circulation with evidence of increased pulmonary artery pressure and right-to-left ductal shunting. This infant remained hospitalized for observation until the pulmonary hypertension resolved.
Oximetric screening for CCVM seems to satisfy the requirements for a screening test: 1) the prevalence of CCVM among asymptomatic newborns is high, particularly in areas with lower rates of fetal echocardiography, 2) the technique of oximetric screening is simple and reliable, 3) effective cardiovascular interventions are available, and 4) the cost/benefit ratio in our series was favorable. No costs were incurred for equipment, supplies, or personnel, and 3 asymptomatic newborns were prevented from going home with undiagnosed CCVM. Oximetric screening for CCVM compares favorably to other newborn screening programs already in place9 (Table 5).
The issue of whether detection of critical CCVM by oximetric screening improves the perioperative and long-term outcomes for these infants is beyond the scope of this study. However, studies have shown a favorable impact on outcome with fetal detection of hypoplastic left heart syndrome17 and transposition of the great arteries18 compared with neonatal detection. These critical lesions are detectable by oximetric screening (Table 1), and, therefore, it is likely that infants with these lesions detected by screening before discharge from the nursery would also have a better outcome than infants readmitted from home. It is important to note that 10% of the postnatally diagnosed cases in the hypoplastic left heart syndrome study were readmitted from home.17
Pulse oximetry is already in widespread use in newborn nurseries, and normative data regarding saturation during the period of neonatal cardiopulmonary adaptation has been developed.19 Oximetry screening is not intended to serve as a substitute for a careful physical examination. Our screening test, based on a single determination of postductal saturation, is noninvasive, cost-effective, and readily coordinated with state-mandated screening tests. The sensitivity, specificity, and predictive value in this population are satisfactory, indicating that screening should be applied to larger populations, particularly where lower rates of fetal detection result in increased CCVM prevalence in asymptomatic newborns. Despite its limitations, implementation of oximetry screening will increase the likelihood that newborns with clinically occult CCVM will be identified in a timely manner.
This study was supported in part by a cooperative agreement from the Centers for Disease Control and Prevention.
We acknowledge the nursing staff of the newborn nurseries at Long Island Jewish Medical Center and Good Samaritan Hospital for dedicated participation in this study. Oximeters were provided by Ohmeda Medical.
- ↵Payne RM, Johnson MC, Grant JW, Strauss AW. Toward a molecular understanding of congenital heart disease. Circulation.1995;91 :494– 504
- ↵New York State Department of Health. Congenital Malformations Registry Annual Report. Albany, NY: New York State Department of Health; 1997
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- ↵Mehl AL, Thomson V. Newborn hearing screening: the great omission. Pediatrics.1998;101(1) . Available at: www.pediatrics.org/cgi/content/full/101/1/e4
- ↵Cartlidge PH. Routine discharge examination of babies: is it necessary? Arch Dis Child.1992;67 :1421– 1422
- ↵Abu-Harb M, Wyllie J, Hey E, Richmond S, Wren C. Presentation of obstructive left heart malformations in infancy. Arch Dis Child Fetal Neonatal Ed.1994;71 :F179– F183
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- ↵Bonnet D, Coltri A, Butera G, et al. Detection of transposition of the great arteries in fetuses reduces neonatal morbidity and mortality. Circulation.1999;99 :916– 918
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