Abstract
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. 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. 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. New DBS test for NT-proBNP quantification in newborns that used 3 μL of blood vs the current screening standard. 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. 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 < .05). This study found that NT-proBNP assay using minimal DBS samples appears to be timely and accurate in detecting CHD in newborns and to discriminate well between healthy newborns and newborns with various types of CHD. This finding warrants further studies in larger cohorts and highlights the potential of NT-proBNP to improve neonatal CHD screening.
Highlights
Congenital heart disease (CHD) affects approximately 1 in 125 newborns and is the most common congenital malformation in humans, causing substantial morbidity and mortality rates worldwide.[1,2,3] This prevalence has led to the development of highly specialized services with favorable surgical mortality outcomes, which are largely attributed to centralized pediatric cardiac centers and dedicated intensive care units.[4]To improve the early identification of CHD, maternity services have implemented prenatal ultrasonography screening programs
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
Summary
Congenital heart disease (CHD) affects approximately 1 in 125 newborns and is the most common congenital malformation in humans, causing substantial morbidity and mortality rates worldwide.[1,2,3] This prevalence has led to the development of highly specialized services with favorable surgical mortality outcomes, which are largely attributed to centralized pediatric cardiac centers and dedicated intensive care units.[4]To improve the early identification of CHD, maternity services have implemented prenatal ultrasonography screening programs. If the newborn has a positive screen result (in this study, positive is defined as a problem identified, whereas negative indicates no problem), prompt neonatal assessment and subsequent echocardiographic evaluation are paramount. In this setting, some neonates with even minor hypoxemia owing to delays in adaptation from the fetal circulation or those with primary pulmonary disease will inevitably have positive screen results. No prospective studies have been performed on the POX screening method used solely for identifying pulmonary disease.[20,21] concerns remain that POX screening is imperfect for uncovering CHD lesions involving a duct-dependent systemic circulation, the method has become a widespread tool for detecting critical CHD in many health care systems.[15,22]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
