Of 9441 infants with nonsyndromic congenital heart defects and a 1998–2007 EDD whose mothers participated in an NBDPS interview, 3746 were included in the analysis (Figure). Of these, 1106 (29.5% [95% CI, 28.1%–31.0%]) underwent diagnosis through echocardiography more than 3days after birth (Table 2). For 6 infants (0.2% [95% CI, 0.1%–0.4%]), CCHD diagnosis occurred at autopsy more than 3 days after birth (Table 2). Late detection by CCHD type ranged from 9 of 120 infants (7.5%[95%CI, 3.5%–13.8%])with pulmonary atresia to 497 of 801 (62.0%[58.7%–65.4%])with coarctation of the aorta (Table 2). The frequency of late detection varied within CCHD types by the presence or absence of extracardiac defects and by NBDPS study site (Supplement [eFigures 1 and 2]). For 542 infants (14.5% [95% CI, 13.3%–15.6%]), the first echocardiogram documented in the abstracted medical record was prenatal. Among infants with late-detected CCHD diagnosed through echocardiography (n = 1100), the median time from birth to diagnosis was 14 (range, 4–363; interquartile range [IQR], 7–48) days (Table 2). Among the 6 infants who received the initial diagnosis at autopsy more than 3 days after birth (n = 6), the median time from birth to diagnosis was 5 (range, 4–21; IQR, 4–11) days (data not shown).

When we controlled for all demographic and clinical factors under consideration, the prevalence of late detection among infants with CCHD varied significantly by the presence of extracardiac defects, CCHD type, and NBDPS study site (Table 3). The estimated adjusted prevalence of late detection among infants with extracardiac defects was 42% less (adjusted PR, 0.58 [95% CI, 0.49–0.69]) than the adjusted prevalence in infants without extracardiac defects (Table 3). The estimated adjusted prevalence of late detection among infants with Ebstein anomaly, single ventricle, critical pulmonary stenosis, interrupted aortic arch, tetralogy of Fallot, double-outlet right ventricle, truncus arteriosus, total anomalous pulmonary venous return, and coarctation of the aorta were each significantly greater than the adjusted prevalence among infants with hypoplastic left heart syndrome (the reference group). Late detection varied significantly by NBDPS study site, with a 2-fold difference between the sites with the lowest and highest adjusted prevalence of late detection (adjusted PR, 2.09 [95% CI, 1.66–2.63]) (Table 3).

Based on data from the NBDPS, we estimated that the diagnosis of nonsyndromic CCHD occurred more than 3 days after birth in 29.5%of infants, including fewer than 1%with the initial diagnosis at autopsy. These infants, therefore, might have benefited from universal screening through pulse oximetry at their birth hospitals. Infants with extracardiac defects were significantly less likely to have late detection, and late detection varied by CCHD type and NBDPS study site.

Our study focused explicitly on the potential effect of new US recommendations for CCHD screening using multisite data and examined the diagnostic experience of infants with CCHD during the entire first year of life. Our estimate is similar to that of a retrospective study at an NBDPS contributing site— metropolitan Atlanta—that estimated that 31.3%of infants with CCHD did not receive a diagnosis on their day of birth.³¹ Other retrospective US studies with substantially lower estimated proportions of infants with late detection of CCHD (ie, 4%–7%)^32,35 examined fewer CCHD types than our study or identified late detection of CCHD only through the occurrence of death.^33,35 However, estimates from most previous studies of late CCHD detection^{28–30,32–35} (Table 1) appear to have included infants with genetic disorders, whereas our study excluded such infants. Most previous studies^29,30,32,35 used exclusively administrative coding to identify CCHD diagnoses, which might inaccurately classify heart defects or fail to capture whether a defect such as aortic stenosis or pulmonary stenosis is critical.^36,37 Previous studies of late CCHD detection also used different data sources—such as hospital admission records with or without accompanying statewide death records— to identify infants with late detection of CCHD. One previous study³⁰ ascertained infants with late detection of CCHD less than 1 month after birth. Finally, previous studies were limited to 2 hospitals,³⁴ a single metropolitan area,^31,35 or a single state.^{28–30,32,33}

In our study, the prevalence of late detection varied widely (from 7.5% to 62.0%) by CCHD type. Evidence suggests that the sensitivity of CCHD screening through pulse oximetry also may vary substantially by CCHD type—a proxy for the presence of hypoxemia. A recent meta-analysis² reported that pulse oximetry conducted at least 24 hours after birth was 78% sensitive to detect CCHD overall. However, a review of 13 screening studies⁴³ (with 258 809 infants undergoing screening, of whom 256 were ultimately diagnosed as having CCHD) from 1998 through 2009 reported sensitivities ranging from 36% (95% CI, 24%–50%) for coarctation of the aorta and interrupted aortic arch (18 of 50 infants) to 100% (95% CI, 44%–100%) for single ventricle (6 of 6 infants), double-outlet right ventricle (5 of 5 infants), and pulmonary atresia with intact septum (3 of 3 infants). Screening-detectable CCHD constitutes a heterogeneous group of rare congenital heart defects, and the numbers of infants included in these CCHD defect–specific estimates are very small. The high rate of late detection among infants with coarctation of the aorta (62.0%) in our study influenced our overall estimate of 29.5% late detection; excluding these infants would result in an overall estimate of late detection in 609 of 2945 (20.7% [95% CI, 19.2%–22.2%]). Nonhypoxemic cases of coarctation of the aorta (ie, not detectable through screening) likely contributed to our estimated prevalence of late detection for that condition. Unfortunately, we were unable to ascertain lesion severity.

Infants with extracardiac defects were less likely to have late detection of CCHD in our study. Infants with birth defects affecting multiple organ systems may receive additional medical attention prenatally or at birth, which might explain why late detection was significantly lower among such infants. The proportion of infants in our study with nonsyndromic extracardiac defects (17.0% [95% CI, 15.8%- 18.2%]) was similar to those of other population-based studies of infants and children with congenital heart defects.^44,45 However, because the NBDPS excludes infants with genetic syndromes, our study might have estimated a higher proportion of late detection than actually exists in the population. Our results also indicated that late CCHD detection varied significantly among the 9 NBDPS study sites included in this analysis. This variation may reflect, in part, nonuniformity in neonatal clinical practice, which cannot be addressed using existing birth defects surveillance data in the NBDPS. In addition, the NBDPS sites draw from different populations in terms of socioeconomic status, urbanicity, and geographic region; thus, inference about the underlying meaning of the observed study site variability would require further investigation.

We found no significant temporal trend in terms of increasing or decreasing prevalence of late CCHD detection during the study period (Table 2). Recent studies^46–49 have reported inconsistent findings about whether race/ethnicity is associated with outcomes such as mortality and hospital readmission among infants with congenital heart defects, although no significant racial/ethnic associations were observed in this analysis. We found no significant association between the timing of the first prenatal care visit and timely CCHD detection; however, this variable is a limited indicator of the experience of prenatal care.

This study has a number of limitations. The NBDPS does not explicitly seek information on the initial diagnosis of congenital heart defects, but instead a diagnosis by specific means (echocardiography, autopsy, catheterization, or surgery). Therefore, we may have overestimated the proportion of infants with late CCHD detection owing to missing information on initial diagnoses. However, echocardiography is recommended to diagnose CCHD, even if an infant receives a definitive diagnosis through other means.^3,50 Missing or erroneous examination information might vary by NBDPS site because ascertainment of follow-up records (ie, outpatient echocardiography) is not standardized. Another limitation is that we restricted our analysis to infants in the NBDPS whose mothers were interviewed. Because infants of noninterviewed mothers did not undergo classification by NBDPS clinicians, we were unable to compare the 2 groups. A related limitation is that many of the factors we assessed were based on mothers’ self-reported demographic and clinical information (ie, timing of entry into prenatal care, diabetes mellitus status, and prepregnancy body mass index).

Our study has 3 notable strengths that distinguish it from previous US studies. First, we used data compiled from multiple population-based birth defects surveillance programs that included infants with clinically validated CCHD diagnoses.⁵¹ Second, because we used abstracted medical records to identify and classify infants according to CCHD type, we likely have achieved greater clinical accuracy than previous studies that relied exclusively on administrative data to classify CCHD diagnoses. Third, we used clinical definitions of CCHD and timely detection that are directly pertinent to new US federal recommendations for universal newborn screening for CCHD through pulse oximetry.

We estimate that 29.5% of live-born infants with nonsyndromic CCHD in the NBDPS received the diagnosis more than 3 days after birth. The proportions of infants with late CCHD detection varied substantially by CCHD type, from 7.5% (pulmonary atresia) to 62.0% (coarctation of the aorta). These results suggest that many infants with CCHD might benefit from screening through pulse oximetry before birth hospital discharge. Whether such infants are detected through screening is likely to vary by a number of factors, including CCHD type and the presence of extracardiac defects. Additional population-based studies of universal screening in practice are needed.