The existing pulse oximetry monitoring protocol to detect critical congenital heart disease, is restricted to neonates 24 to 48 hours of age in well infant nursery [5]. A simple algorithm for units catering to sick newborns is challenging because of heterogeneity of underlying conditions; need of studies across a broad range of newborn delivery systems has been expressed [5]. Pulse oximetry as a screening test for congenital cyanotic heart disease has been evaluated among well neonates [2,6-10], but not in sick neonates.The present study was designed to evaluate the utility of pulse oximetry screening in detecting congenital cyanotic heart disease among sick neonates in a referral neonatal unit catering to outborn neonates.

The study was conducted in the Referral Neonatal Unit of a teaching hospital between April 2013 and January 2014. The unit caters exclusively to outborn sick neonates referred from community hospitals of Delhi and surrounding states, or to those born at home and transported to the hospital directly by the parents. All neonates admitted to the unit during the study period were eligible for inclusion. Neonates in whom stable pulse oximeter signals could not be obtained were excluded. Informed written consent was obtained from the parents of all enrolled subjects. The study was approved by the Institutional ethical committee.

All neonates at admission were clinically evaluated by a resident doctor for temperature, heart rate, respiratory rate (RR), chest retractions, central cyanosis, femoral pulses, other peripheral pulses, capillary filling time, peripheries (cool or warm) and clubbing. Presence of either tachypnea (RR >60/min), retractions, central cyanosis, poor femoral pulses, precordial pulsations, hepatomegaly or murmur was considered as positive clinical examination suggestive of congenital heart diease [11]. Pulse oximetry readings (BPL Excello oximeter with reusable Nellcor Oximax probe accuracy of + 2 %) were taken at admission from right upper limb and either foot with infant breathing room air. The recordings were noted two minutes after stable signals were obtained. Pulse oximetry was considered abnormal if oxygen saturation at room air or on oxygen therapy measured <90% or there was more than 3% difference between right hand and foot [5]. All neonates with abnormal pulse oximetry were subjected to three observations each, separated by at least 1 hour. Screen was considered positive only if the abnormality persisted till the last reading. Echocardio-graphy (Philips iE33 xMATRIX echocardiography system) was performed by a pediatric cardiologist on all neonates with a positive pulse oximetry screen (study group) and on one subsequently enrolled neonate with negative screen per neonate with positive screen (controls).

Data were analyzed using Statistical Package for Social Sciences software (version 21). Student-t test was used for continuous variables and Chi-square test was used for comparing proportions. Multivariate logistical regression (using the forward logistical regression model) was done to find predictors of cyanotic heart disease. Sensitivity, specificity, positive and negative predictive value, positive likelihood ratio and negative likelihood ratio of pulse oximetry in detecting cyanotic heart disease in sick neonates were calculated.

A total of 950 neonates admitted in referral neonatal unit during the study period were screened. Pulse oximetry was positive in 210 neonates, and in five neonates, stable pulse oximeter signals could not be obtained. Fig. 1 shows flow of the study. Out of the 210 controls, 11 neonates (3 with shock, 3 with transient tachypnea of newborn and 5 with pneumonia) had an initial saturation of <90%, but repeat readings were >90%.

Fig. 1 Flow of participants in the study.

Table I compares the baseline demographic and clinical characteristics of cases and controls. Pulse oximetry was positive in 20 out of 21 (95.2%) neonates with echocardiography proven cyanotic heart disease. This included lesions with increased pulmonary blood flow (d-transposition of great arteries, n=8), lesions with decreased pulmonary blood flow (tetrology of Fallot, n=5; double outlet right ventricle with pulmonary atresia/severe pulmonary stenosis, n=3; single ventricle with pulmonary stenosis, n=1) and lesions with pulmonary venous hypertension (obstructed total anomalous pulmonary venous connection, n=3). Pulse oximetry was negative in 1 neonate with tetralogy of Fallot with mild pulmonary stenosis and large left to right shunt.

TABLE I	Comparison of Characteristics of Cases and Controls

The sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio and odds ratio (95% CI) of pulse oximetry to detect cyanotic congenital heart disease was 95.2%, 52.4% 9.5%, 99.5%, 2.0, 0.1 and 22 (5.3, 91.4), respectively . The sensitivity of pulse oximetry to detect critical congenital heart disease (cyanotic heart disease, n=21 and critical duct dependent systemic lesion, n=1) and PPHN (n=18) was 97.5 % (39/40) with negative predictive value of 99.5% (209/210).

Table II shows pulse oximetry findings in study population. The pre-post ductal difference was >3% only in cases of cyanotic heart disease, coarctation of aorta and persistent pulmonary hypertension of newborn.

TABLE II  Pulse Oximetry Findings in Study Population

On univariate analysis significant predictors of cyanotic heart disease among sick neonates was positive pulse oximetry, male gender, history of consanguinity, history of pregnancy induced hypertension in mother, family history of congenital heart disease and smoking, and presence of tachycardia, central cyanosis, murmur or hepatomegaly. The significant predictors of cyanotic heart disease among sick neonates on multivariate analysis are outlined in Table III.

TABLE III  Predictors of Cyanotic Heart Disease in Sick Neonates

In the present study, all congenital heart diseases with different hemodynamics, except one case of tetralogy of Fallot, were detected using pulse oximetry screen. The sensitivity and negative predictive values of pulse oximetry screening to detect cyanotic heart disease and critical congenital heart disease were high. Murmur, central cyanosis, male gender, consanguinity, family history of smoking and history of pregnancy induced hypertension were significant predictors of cyanotic heart disease.

The limitations of present study include single center-based enrolment, and no a priori sample size calculation. Also, echocardiography was done only on selected controls rendering calculations of sensitivity, specificity and predictive values inaccurate.

To conclude, pulse oximetry screening is useful in detecting cyanotic heart diseases in a setting catering to sick out born neonates. Negative predictive value of pulse oximetry is high, making it useful to reliably rule out critical congenital heart disease or PPHN among sick neonates, thus avoiding need for an urgent echocardiography.