be symptomatic shortly after birth, they also may not present until after the patient is discharged from the hospital The delay in diagnosis may increase mortality In response, many of the states in the United States have implemented pulse oximetry screening for critical congenital heart disease This is performed at least 24 hours after birth or as delayed as possible if early discharge is planned The screening uses pulse oximetry to measure oxygen saturation in the right upper (preductal) and one lower extremity (postductal) The screening is considered positive if either oxygen saturation is less than 90% or if both the preductal and postductal saturations are less than 95% on three repeated occasions separated by 1 hour, or if there is a difference of 3% between the upper and lower extremity saturation.30 If the screening is positive, an echocardiogram is to be obtained Implementing pulse oximetry screening has been shown to have resulted in a significant decrease in mortality related to critical congenital heart disease.31 A large-scale study using a universal screening strategy for ascertainment has yet to be performed Investigators from Japan performed a more focused screening of newborns with echocardiography aimed at determining the prevalence and natural history of muscular ventricular septal defects, a lesion known to inflate estimates of prevalence.32 They screened 1028 newborns without evident chromosomal abnormalities and who had been delivered at term gestation, and identified 21 newborns with muscular ventricular septal defects, 3 with coarctation of the aorta, and 1 with a double-outlet right ventricle This gave a prevalence of 24.3 cases per 1000 live births The 95% confidence limits were wide, ranging from 15.8 to 35.7, indicating poor reliability Only 60% of the ventricular septal defects were associated with a cardiac murmur, and followup showed that 75% had closed spontaneously by the age of 12 months, with the majority closing before 6 months This has implications for strategies of ascertainment that rely on clinical presentation for identification If diagnostic confirmation is delayed, many defects will have closed spontaneously and escape verification Because many studies examined the prevalence of congenital heart disease from different populations and eras, systematic reviews might yield important insights and perhaps more reliable and generalizable estimates Two teams of reviewers have examined multiple studies of prevalence with an aim of comparing, and potentially pooling, the estimates The investigators from the Baltimore-Washington Infant Study compared the prevalence at live birth noted from their initial 2 years of their study, 1981 and 1982, to that of eight previously published and widely cited reports.33 The prevalence from the Baltimore-Washington Infant Study for that period was 3.7 cases for each 1000 live births, with all cases being confirmed by autopsy, surgery, cardiac catheterization, or echocardiography The New England Regional Infant Cardiac Program verified cases by autopsy, surgery, or cardiac catheterization, with a prevalence of 2.03.34 When cases verified only by echocardiography were excluded from the estimate of prevalence made from the Baltimore-Washington Infant Study, which lowered the estimate to 2.38, the results of the two studies were more similar The remaining seven studies included cases for which a clinical diagnosis without verification had been made, varying from three-tenths to half of included cases, with estimates ranging from 5.51 to 8.56.26,35–41 If cases that were diagnosed by clinical means only were excluded from these estimates, the prevalence then ranged from 3.75 to 4.30, which is comparable to the estimate reported by the investigators conducting the Baltimore-Washington Infant Study A more recent review provided an analysis of a larger number of studies, with an aim at determining the sources of variability in estimates of prevalence noted between studies.42 This analysis was based on review of 62 studies reported after 1955 Wide discrepancies were found in reported estimates of prevalence, ranging from 4 to 50 per 1000 live births (Fig 13.2) Estimates were stable over time, at between approximately 4 and 8 per 1000 live births, until 1985 The advent of the widespread use of echocardiography at this point resulted in estimates becoming more diverse, and the reported estimates increased and began to exceed 10 per 1000 live births (Fig 13.3) The increases in the prevalence estimates likely reflected an overall increase in ascertained cases, but this was more marked for trivial or mild lesions, particularly ventricular septal defects, with the estimated prevalence of lesions producing cyanotic disease remaining relatively stable (Fig 13.4) The median prevalence of congenital heart disease was 7.7, with an interquartile range from 6.0 to 10.6, excluding nonstenotic aortic valves with two leaflets, silent arterial ducts, and isolated partially anomalous pulmonary venous connections The median prevalence of bifoliate aortic valves was 9.2, with an interquartile range from 5.3 to 13.8 Inclusion of cases with such bifoliate aortic valves would greatly inflate estimates of prevalence The median prevalence of congenitally malformed hearts producing cyanosis was 1.08, with an interquartile range of 1.27 to 1.53 In Table 13.9, the prevalence of specific lesions per 1 million live births is shown FIG 13.2 Histogram of the prevalence of congenital cardiac defects per 1000 live birth as noted in 62 reports (From Hoffman JI, Kaplan S The incidence of congenital heart disease J Am Coll Cardiol 2002;39:1890– 1900.) FIG 13.3 Changes in the reported prevalence of congenital heart disease from multiple reports over time, and the influence of the proportion of ascertained cases that were ventricular septal defects Each circle represents the value derived from each report The horizontal lines are drawn arbitrarily at a prevalence of 10 per 1000 live births and 40% of all congenital heart disease, and the vertical lines are drawn arbitrarily at 1985 and 40%, respectively An increasing proportion of the high prevalence estimates are beyond 1985 and for series that have more than 40% ventricular septal defects CHD, Congenital heart disease; VSD, ventricular septal defect (From Hoffman JI, Kaplan S The incidence of congenital