Potential Impact of CCHD Screening in US Infants

1. JAMA Pediatrics Journal Club Slides:Potential Impact of CCHD Screening Peterson C, Ailes E, Riehle-Colarusso T, et al. Late detection of critical congenital heart disease among US infants: estimation of the potential impact of proposed universal screening using pulse oximetry. JAMA Pediatr. Published online February 3, 2014. doi:10.1001/jamapediatrics.2013.4779.

2. Introduction • Congenital heart defects affect approximately 1% of live births in the United States; 25% are considered critical congenital heart disease (CCHD), requiring surgery or catheterization at or before age 1 year. • CCHD was added to the US Recommended Uniform Screening Panel for Newborns in 2011. • Screening performed using pulse oximetry. • Screening recommended within 24-48 hours of birth. • Study Objectives • To estimate proportion of US infants with clinically validated, nonsyndromic, screening-detectable CCHD whose condition was detected late (>3 days after birth). • To investigate clinical and demographic factors associated with late detection.

3. Methods • Study Design: National Birth Defects Prevention Study (NBDPS). • Ongoing, population-based, case-control study of >30 major birth defects. • CCHD confirmed by echocardiography, catheterization, surgery, or autopsy. • Chromosomal or single-gene disorders excluded. • Clinical data obtained from medical records. • Demographic characteristics, exposures, and medications from maternal interview. • Setting • Infants born from January 1, 1998, through December 31, 2007. • Mothers lived in sampled states (Arkansas, California, Georgia, Iowa, Massachusetts, New Jersey, New York, North Carolina, Texas, Utah) at time of delivery. • Patients • Live-born infants with nonsyndromic, clinically verified CCHD.

4. Methods From birth defects surveillance data • NBDPS study site. • Presence of extracardiac defects (ie, major defects in organ systems outside the heart). • CCHD type. • Gestational age at delivery. • Estimated date of delivery year. From NBDPS maternal interview data • First-degree family history of CHD. • Plurality. • Maternal race/ethnicity and education. • Maternal age at delivery. • Pregestational diabetes. • Prepregnancy body mass index. • Preexisting hypertension. • Fertility treatments. • Previous pregnancy losses. • Trimester of the first prenatal care visit. • Outcome: Late CCHD detection. • No evidence of diagnostic echocardiography prenatally or ≤3 days of birth. • Analysis • Assessed timing of CCHD diagnosis (prenatal, postnatal, and autopsy). • Poisson multivariable regression model with robust sandwich error variance used to examine factors associated with late detection, including:

5. Results Derivation of Study Sample of Infants With CCHD in the NBDPS, 1998-2007

6. Results

7. Results • In multivariable analysis, late detection varied significantly by the following: • CCHD type: Adjusted prevalences 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 among infants with hypoplastic left heart syndrome. • Study site: Two-fold difference between the sites with the lowest and highest adjusted prevalence of late detection (adjusted prevalence ratio = 2.09; 95% CI, 1.66-2.63). • Presence of extracardiac defects: Adjusted prevalence of late detection among infants with extracardiac defects was 42% less (adjusted prevalence ratio = 0.58; 95% CI, 0.49-0.69) than among infants without extracardiac defects. • Late detection did not vary significantly by other maternal or infant characteristics studied.

8. Comment Limitations • May have overestimated the proportion of infants with late detected CCHD, as NBDPS captures diagnosis by specific means (echocardiography, autopsy, surgery) rather than initial date of diagnosis. • Analysis limited to infants with CCHD whose mothers had participated in NBDPS. Strengths • Multisite population-based study with excellent CCHD diagnostic accuracy. • Clinical definition of CCHD and timely detection directly pertinent to new US recommendations for universal newborn screening.

9. Comment • Estimated 30% of live-born infants with nonsyndromicCCHD in the NBDPS were diagnosed >3 days after birth. • Varied substantially by CCHD type from 8% (pulmonary atresia) to 62% (coarctation of the aorta). • Many infants with CCHD might benefit from screening through pulse oximetry before birth hospital discharge. • Whether these infants are actually detected through screening is likely to vary by a number of factors, including CCHD type and the presence of extracardiacdefects. • Future studies of routine screening in practice might provide more insight into detection rates by CCHD type.

10. Contact Information • If you have questions, please contact the corresponding author: • Cora Peterson, PhD, National Center for Injury Prevention and Control, Centers for Disease Control and Prevention, Mailstop F-62, 4770 Buford Hwy, Atlanta, GA 30341 (cora.peterson@cdc.hhs.gov). Funding/Support • This study was supported by cooperative agreements under PA 96043, PA 02081, and FOA DD09-001 from the Centers for Disease Control and Prevention. Conflict of Interest Disclosures • None reported.