Evaluation of Circulating Cardiovascular Biomarker Levels for Early Detection of Congenital Heart Disease in Newborns in Sweden

This diagnostic study assesses the use of dried blood samples to detect prohormone brain-type natriuretic peptide for diagnosis of congenital heart disease in neonates in Sweden.
Key Points Question Could a new test that measures the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) using dried blood samples be used to identify neonates born with congenital heart disease (CHD)? Findings In this diagnostic study of 115 newborns in Sweden, a fully automated diagnostic assay for NT-proBNP quantification was developed that used 3 μL of dried blood spot samples. This new test discriminated well between newborns with CHD and control newborns. Meaning Results of this study suggest that the new NT-proBNP test warrants further evaluation in larger cohorts to assess its ability for universal detection of CHD through established newborn screening programs.
Importance Congenital heart disease (CHD) is the most common congenital malformation in humans worldwide. Circulating cardiovascular biomarkers could potentially improve the early detection of CHD, even in asymptomatic newborns. Objectives To assess the performance of a dried blood spot (DBS) test to measure the cardiovascular biomarker amino terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) levels in newborns and to compare DBS with standard EDTA analysis in control newborns during the first week of life. Design, Setting, and Participants This diagnostic study was conducted in a single regional pediatric service in southern Sweden. Healthy, term neonates born between July 1, 2018, and May 31, 2019, were prospectively enrolled and compared against retrospectively identified newborns with CHD born between September 1, 2003, and September 30, 2019. Neonates who required inpatient treatment beyond the standard postnatal care were excluded. Exposure New DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard. Main Outcomes and Measures Performance of the new test and when combined with pulse oximetry screening was measured by receiver operating characteristic curve analysis. Performance of the new test and EDTA screening was compared using Pearson linear correlation analysis. Results The DBS samples of 115 neonates (81 control newborns and 34 newborns with CHD, of whom 63 were boys [55%] and the mean [SD] gestational age was 39.6 [1.4] weeks) were analyzed. The new NT-proBNP test alone identified 71% (n = 24 of 34) of all CHD cases and 68% (n = 13 of 19) of critical CHD cases as soon as 2 days after birth. Detection of any CHD type improved to 82% (n = 28 of 34 newborns) and detection of critical CHD improved to 89% (n = 17 of 19 newborns) when combined pulse oximetry screening and NT-proBNP test results were used. Performance of the NT-proBNP test was excellent when control newborns were matched to newborns with CHD born between July 1, 2018, and May 31, 2019 (area under the curve, 0.96; SE, 0.027; 95% CI, 0.908-1.0; asymptotic P