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- Title
Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis.
- Authors
Clausen, Henning; Friberg, Elin; Lannering, Katarina; Koivu, Aki; Sairanen, Mikko; Mellander, Mats; Liuba, Petru
- Abstract
Key Points: Question: Can 2 circulating blood biomarkers—amino-terminal prohormone of brain natriuretic peptide (NT-proBNP) and interleukin 1 receptor-like 1 (IL-1 RL1)—be quantified in newborns using minimal amounts of dried blood spot (DBS) samples with reliable results for the early detection of congenital heart disease (CHD) serious enough to require cardiac surgery during infancy? Findings: In this diagnostic study of 313 newborns from Sweden, NT-proBNP and IL-1 RL1 were analyzed using 3 μL of DBS and discriminated controls from CHD cases well, including asymptomatic cases not identified by fetal ultrasound, postnatal clinical examination, or pulse oximetry. Meaning: These results suggest that novel diagnostic DBS tests performed well in comparison with existing screening methods for CHD, warranting prospective evaluation to improve early diagnosis of even asymptomatic cases. This diagnostic study of individuals in Sweden born between 2005 and 2023 assesses the performance of blood biomarker testing for early detection of high-risk congenital heart disease. Importance: Congenital heart disease (CHD) is the most common human organ malformation, affecting approximately 1 of 125 newborns globally. Objectives: Assessing the performance of 2 diagnostic tests using minimal amounts of dried blood spots (DBS) to identify high-risk CHD compared with controls in a Swedish cohort of neonates. Design, Setting, and Participants: This diagnostic study took place in Sweden between 2019 and 2023 and enrolled full-term babies born between 2005 and 2023. All cases were identified through centralized pediatric cardiothoracic surgical services in Lund and Gothenburg, Sweden. Controls were followed up for 1 year to ensure no late presentations of high-risk CHD occurred. Cases were verified through surgical records and echocardiography. Exposure: High-risk CHD, defined as cases requiring cardiac surgical management during infancy due to evolving signs of heart failure or types in which the postnatal circulation depends on patency of the arterial duct. Using 3-μL DBS samples, automated quantitative tests for NT-proBNP and interleukin 1 receptor-like 1 (IL-1 RL1; formerly known as soluble ST2) were compared against established CHD screening methods. Main Outcomes and Measures: Performance of DBS tests to detect high-risk CHD using receiver operating characteristic curves; Bland-Altman and Pearson correlation analyses to compare IL-1 RL1 DBS with plasma blood levels. Results: A total of 313 newborns were included (mean [SD] gestational age, 39.4 [1.3] weeks; 181 [57.8%] male). Mean (SD) birthweight was 3495 (483) grams. Analyzed DBS samples included 217 CHD cases and 96 controls. Among the CHD cases, 188 participants (89.3%) were high-risk types, of which 73 (38.8%) were suspected prenatally. Of the 188 high-risk cases, 94 (50.0%) passed pulse oximetry screening and 36 (19.1%) were initially discharged after birth without diagnoses. Combining NT-proBNP and IL-1 RL1 tests performed well in comparison with existing screening methods and enabled additional identification of asymptomatic babies with receiver operating characteristic area under the curve 0.95 (95% CI, 0.93-0.98). Conclusions and relevance: In this diagnostic study, NT-proBNP and IL-1 RL1 DBS assays identified high-risk CHD in a timely manner, including in asymptomatic newborns, and improved overall screening performance in this cohort from Sweden. Prospective evaluation of this novel approach is warranted.
- Subjects
SWEDEN; CONGENITAL heart disease diagnosis; NEWBORN screening; CONGENITAL heart disease; RISK assessment; PEARSON correlation (Statistics); BLOOD chemical analysis; RECEIVER operating characteristic curves; RESEARCH funding; PUERPERIUM; PATENT ductus arteriosus; LOGISTIC regression analysis; HEART failure; DESCRIPTIVE statistics; MEDICAL records; ACQUISITION of data; GESTATIONAL age; BIRTH weight; CONFIDENCE intervals; DATA analysis software; BIOMARKERS; ECHOCARDIOGRAPHY; INTERLEUKIN-1; SENSITIVITY &; specificity (Statistics); DISEASE risk factors
- Publication
JAMA Network Open, 2024, Vol 7, Issue 6, pe2418097
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.18097