Search Results (26)

Part of the vision of the ISNS is ‘to enhance the quality of neonatal screening and medical services through dissemination of information, guidelines and best practices.’ Although newborn screening encompasses testing in the newborn period for critical congenital heart disease, hearing impairment, birth defects, and congenital biochemical disorders (usually on bloodspots), this guideline is specifically about bloodspot screening. The ISNS has provided neonatal screening guidelines for many years and here presents the renewed 2025 General Guidelines for Neonatal Bloodspot Screening. They are intended to provide a framework for screening programs to develop specific policies around all aspects of the newborn screening system, offering the basic set of items for consideration. These guidelines provide trusted anchors to build, expand, or maintain robustly organized neonatal or newborn screening (NBS) programs and a checklist to evaluate and improve the essential elements of those programs. For starting or developing programs, it is a set of elements for which provisions need to be in place and a checklist of items that the screening program should at a minimum have provisions for. The publication of these guidelines is meant as a starting point for interactive discussion, to further improve this document and expand where necessary. Full article

This study aimed to report the progress and results of the newborn screening program for congenital heart disease (CHD) in south Shanghai between 2019 and 2023, and to evaluate the accuracy of the dual-index method (pulse oximetry (POX) plus cardiac murmur auscultation) in clinical practice. Between 2019 and 2023, a total of 198,606 (99.89%) newborns were screened for CHD, of whom 3299 (1.66%) tested positive, 3043 (92.24%) underwent echocardiography for CHD diagnosis and 1109 were diagnosed with CHD in a timely manner. Among 195,307 infants with negative screening results using the dual-index method, 139 (0.07%) were later diagnosed with CHD, and none of these infants died. More than half of these false-negative infants (59.39%) were identified due to the detection of a heart murmur during routine physical examinations within six months after birth. Compared to POX testing alone, the dual-index method significantly improved the sensitivity of screening for CHD, and kept high specificity in clinical practice. This study demonstrated that newborn screening for CHD has been well conducted in Shanghai, and the dual-index method had high accuracy and reliability for neonatal CHD screening in clinical practice. Full article

Background: This study aimed to enhance the scope of neonatal congenital heart disease (CHD) screening by evaluating the effectiveness of training personnel in CHD screening using the “dual-index” method, combining pulse oximetry with cardiac murmur auscultation. Methods: From 2019 to 2022, a total of 2374 screening personnel from the Xinjiang, Yunnan, Hainan, Fujian, and Anhui provinces underwent training in neonatal CHD screening using the “dual-index” method, which involves pulse oximetry and cardiac murmur auscultation. Pre- and post-training assessments were conducted using a neonatal CHD screening knowledge questionnaire, distributed through the Questionnaire Star platform, to evaluate the impact of the training. The annual neonatal CHD screening rates were consistently recorded in these five provinces during the same period to assess the increase in screening coverage. Results: After the training, the screening personnel exhibited a significantly improved understanding of the neonatal CHD screening method (p < 0.001). Additionally, the professional background (t = −8.007, p < 0.001) and years of experience (t = 2.839, p = 0.005) of the screening personnel were identified as independent factors influencing their screening knowledge. During the same period, there was consistent linear growth in the screening coverage rate for neonatal CHD across the five provinces (χ² = 121065.416, p < 0.001). Conclusion: Standardized training in the “dual-index” method, incorporating pulse oximetry and cardiac murmur auscultation, for screening personnel significantly enhances their screening knowledge, thereby playing a critical role in expanding the coverage of neonatal CHD screening. Full article

(1) Background: Sudden Infant Death Syndrome (SIDS) represents sudden and unexplained deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for a prolonged QTc interval, a marker for Long QT Syndrome (LQTS), should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiograms (ECGs) could identify congenital heart defects (CHDs) early, especially those not detected at birth. Infants with prolonged QTc intervals typically undergo genetic analysis for Long QT Syndrome. (2) Methods: The study involved infants aged 20–40 days, born with no apparent clinical signs of heart disease, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHDs identified immediately after birth, as well as infants who had previously had an ECG or echocardiogram for other medical reasons, were excluded from the study. We used statistical software (SPSS version 22.0) to analyze the data. (3) Results: Of the 42,200 infants involved, 2245 were enrolled, with 39.9% being males. Following this initial screening, 164 children (37.8% males) with prolonged QTc intervals underwent further evaluation. Out of these 164 children, 27 children were confirmed to have LQTS. However, only 18 children were finally investigated for genetic mutations, and mutations were identified in 11 tests. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Treatment options included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%. (4) Conclusions: This screening approach has demonstrated effectiveness in the early identification of LQTS and other cardiac rhythm anomalies, with additional identification of mutations and/or prolonged QTc intervals in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening. Full article

Background: Congenital anomalies, representing structural or functional abnormalities present at birth, pose a substantial global health challenge, affecting 8 million newborns annually. With 3.3 million succumbing before age five and 3.2 million facing physical or mental disability, their diverse causes necessitate comprehensive understanding for effective healthcare planning. This study explores the prevalence of congenital anomalies among newborns in the Abha Maternity and Children Hospital (MCH) in Abha, Kingdom of Saudi Arabia. Methodology: A descriptive cross-sectional record-based study was conducted on newborns born between 2018 and 2022. Data were gathered in 4 months from September to December 2023. Purposive sampling was employed to select the case records of newborns with congenital anomalies after careful screening and considering inclusion and exclusion criteria. Data was acquired through a self-designed study tool, and the data were entered into Google Forms. Results: Congenital anomalies’ five-year prevalence was 3.21%, and one year, in 2022, the prevalence was 4.02%. Female neonates exhibited higher anomalies (59.3%), and preterm births accounted for 39.6%, emphasizing their vulnerability. The findings indicate that consanguineous marriages are linked to 63.3% of anomalies, notably neural tube defects (25%) and congenital heart diseases (19.7%). Anomalies are not significantly associated with consanguinity or birth order, but maternal age, education, employment, and antenatal maternal medical issues are associated considerably. Conclusions: These study insights contribute to health planners planning targeted interventions and awareness programs that are crucial to mitigate risks associated with preterm births and consanguineous marriages. The promotion of 100% antenatal screening and prophylactic medication for high-risk women and couples is necessary to prevent inherited deformities. In future the Ministry of Health must plan large-group prospective research to better understand the associated risk factors that will help public health initiatives minimize congenital-associated neonatal mortality and improve pregnancy outcomes. Full article

Background: Newborns with a critical congenital heart disease left undiagnosed and untreated have a substantial risk for serious complications and subsequent failure to thrive. Prenatal ultrasound screening is not widely available, nor is postnatal echocardiography. Physical examination is the standard for postnatal screening. Pulse oximetry has been proposed in numerous studies as an alternative screening method. This systematic review and meta-analysis aims to determine the diagnostic accuracies of both screening methods separately and combined. Methods: A systematic literature search of the Embase, PubMed, and Global Health databases up to 30 November 2023 was conducted with the following keywords: critical congenital heart disease, physical examination, clinical scores, pulse oximetry, and echocardiography. The search included all studies conducted in the newborn period using both physical examination and pulse oximetry as screening methods and excluded newborns admitted to the intensive care unit. All studies were assessed for risk of bias and applicability concerns using the QUADAS-2 score. The review adhered to the PRISMA 2020 statement guideline. Results: Out of 2711 articles, 20 articles were selected as eligible for meta-analysis. Cumulatively, the sample included 872,549 screened newborns. The pooled sensitivity of the physical examination screening method was found to be 0.69 (0.66–0.73 (95% CI)) and specificity was found to be 0.98 (0.98–0.98). For the pulse oximetry screening method, the pooled sensitivity and specificity yielded 0.78 (0.75–0.82) and 0.99 (0.99–0.99), respectively. The combined method of screening yielded improved diagnostic characteristics at a sensitivity and specificity of 0.93 (0.91–0.95) and 0.98 (0.98–0.98, respectively. Conclusions: The evidence indicates that combining both physical examination and pulse oximetry to screen for critical congenital heart disease exceeds the accuracy of either separate method. The main limitation is that solely newborns with suspected critical congenital heart disease were subjected to the reference standard. We recommend adapting both methods to screen for critical congenital heart diseases, especially in settings lacking standard fetal ultrasound screening. To increase the sensitivity further, we recommend increasing the screening time window and employing the peripheral perfusion index. Full article

The Recommended Uniform Screening Panel (RUSP) is the list of conditions recommended by the US Secretary of Health and Human Services for inclusion in state newborn screening (NBS). During 2010–2022, seven conditions were added to the RUSP: severe combined immunodeficiency (SCID) (2010), critical congenital heart disease (CCHD) (2011), glycogen storage disease, type II (Pompe) (2015), mucopolysaccharidosis, type I (MPS I) (2016), X-linked adrenoleukodystrophy (X-ALD) (2016), spinal muscular atrophy (SMA) (2018), and mucopolysaccharidosis, type II (MPS II) (2022). The adoption of SCID and CCHD newborn screening by programs in all 50 states and three territories (Washington, D.C.; Guam; and Puerto Rico) took 8.6 and 6.8 years, respectively. As of December 2022, 37 programs screen for Pompe, 34 for MPS I, 32 for X-ALD, and 48 for SMA. The pace of implementation based on the average additional number of NBS programs per year was most rapid for SMA (11.3), followed by CCHD (7.8), SCID (6.2), MPS I (5.4), Pompe (4.9), and X-ALD (4.7). Full article

Interruption of the aortic arch (IAA) is a rare but life-threatening congenital heart defect if not corrected in the neonatal period. IAA type B is highly correlated with 22q11.2 deletion syndrome (22q11.2DS); approximately 50% of patients with IAA type B also have 22q11.2DS (Peyvandi et al.; Goldmuntz et al.). Early identification and repair of IAA can prevent severe morbidity and death. However, IAA is challenging to identify prenatally, or even in the neonatal period. In this study, we examined infants with IAA, diagnosed during pregnancy and prior to discharge (PPTD) from the birth hospital vs. those diagnosed following discharge (FD) from the newborn nursery. Our goals were to determine: (1) if early diagnosis improved outcomes; and (2) if patients with IAA and without 22q11.2DS had similar outcomes. In total, 135 patients with a diagnosis of 22q11.2DS and IAA were ascertained through the 22q and You Center at the Children’s Hospital of Philadelphia (CHOP). The examined outcomes included: timing of diagnosis; age at diagnosis (days); hospital length of stay (LOS); duration of intensive care unit (ICU) stay; mechanical ventilation (days); duration of inotrope administration (days); year of surgical intervention; birth hospital trauma level; and overall morbidity. These outcomes were then compared with 40 CHOP patients with IAA but without 22q11.2DS. The results revealed that the PPTD neonates had fewer days of intubation, inotrope administration, and hospital LOS when compared to the FD group. The outcomes between deleted and non-deleted individuals with IAA differed significantly, in terms of the LOS (40 vs. 39 days) and time in ICU (28 vs. 24 days), respectively. These results support the early detection of 22q11.2DS via prenatal screening/diagnostics/newborn screening, as IAA can evade routine prenatal ultrasound and postnatal pulse oximetry. However, as previously reported in patients with 22q11.2DS and congenital heart disease (CHD), patients with 22q11.2DS tend to fare poorer compared to non-deleted neonates with IAA. Full article

Early prenatal screening with an ultrasound (US) can significantly lower newborn mortality caused by congenital heart diseases (CHDs). However, the need for expertise in fetal cardiologists and the high volume of screening cases limit the practically achievable detection rates. Hence, automated prenatal screening to support clinicians is desirable. This paper presents and analyses potential deep learning (DL) techniques to diagnose CHDs in fetal USs. Four convolutional neural network architectures were compared to select the best classifier with satisfactory results. Hence, dense convolutional network (DenseNet) 201 architecture was selected for the classification of seven CHDs, such as ventricular septal defect, atrial septal defect, atrioventricular septal defect, Ebstein’s anomaly, tetralogy of Fallot, transposition of great arteries, hypoplastic left heart syndrome, and a normal control. The sensitivity, specificity, and accuracy of the DenseNet201 model were 100%, 100%, and 100%, respectively, for the intra-patient scenario and 99%, 97%, and 98%, respectively, for the inter-patient scenario. We used the intra-patient DL prediction model to validate our proposed model against the prediction results of three expert fetal cardiologists. The proposed model produces a satisfactory result, which means that our model can support expert fetal cardiologists to interpret the decision to improve CHD diagnostics. This work represents a step toward the goal of assisting front-line sonographers with CHD diagnoses at the population level. Full article

Background: Congenital heart disease/defect (CHD) is one of the most common congenital disabilities. Early diagnosis of CHD can improve the prognosis of newborns with CHD. The aim of this study was to evaluate the relationship between the factors and the onset of fetal congenital heart disease by measuring fetal umbilical artery (UA) Doppler index, maternal HCY, and Cys C levels during pregnancy. Methods: This retrospective study analyzed 202 fetuses with CHD, including 77 cases (39.1%) of simple CHD and 120 cases (60.9%) of complex CHD. Singleton pregnant women who were examined at the same time and whose malformation screening did not suggest any structural abnormalities in the fetus were assigned to the control group (n = 400). The UA Doppler index, plasma HCY, and Cys C levels were compared among the pregnant women across the three groups, and logistic regression analysis was performed on statistically significant markers. The ROC of UA S/D, PI, RI, HCY, and Cys C were plotted, and the area under the ROC (AUC) was calculated. Results: The UA S/D, PI, and RI in the complex CHD group were significantly higher than those in the control group (p < 0.05). The levels of HCY and Cys C in the CHD group were significantly higher than those in the control group (p < 0.05). HCY and S/D revealed a positive correlation (r = 0.157), and the difference was statistically significant (p < 0.001). Cys C and S/D were positively correlated (r = 0.131), and the difference was statistically significant (p < 0.05). The levels of UA Doppler indices, maternal plasma HCY, and Cys C were elevated in fetuses with CHD. The AUC of the combined test of the UA index, HCY, and Cys C was higher than that of each individual test. Conclusions: Elevated levels of the UA doppler indices, HCY, and Cys C during pregnancy are positively associated with the development of congenital heart disease in offspring. The combination of HCY and Cys C was the most efficient test for the diagnosis of CHD. We are the first to report that plasma Cys C levels of women pregnant with fetuses with CHD were higher than those of women pregnant with normal fetuses. Full article

22q11.2 deletion syndrome is a phenotypic spectrum that encompasses DiGeorge syndrome (OMIM: 188400) and velocardiofacial syndrome (OMIM: 192430). It is caused by a 1.5–3.0 Mb hemizygous deletion of locus 22q11.2, which leads to characteristic facies, conotruncal cardiovascular malformations, velopharyngeal insufficiency, T-lymphocyte dysfunction due to thymic aplasia, and parathyroid hypoplasia, and, less frequently, neurological manifestations such as delayed psychomotor development or schizophrenia. This study aimed to describe a screening method for the diagnosis of 22q11.2 deletion syndrome in patients with Conotruncal Congenital Heart Disease (CCHD), using qPCR to detect the copy number of the TBX1 gene in a single DNA sample. A total of 23 patients were included; 21 with a biallelic prediction of the TBX1 copy number gene and 2 with a monoallelic prediction who were suspected to be positive and subjected to MLPA confirmation. One patient (4.34%) with truncus arteriosus CCHD was confirmed to have 22q11.2 deletion syndrome. We propose this approach as a possible newborn screening method for 22q11.2 deletion syndrome in CCHD patients. Full article

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein–protein interactions (PPIs) using our High-Precision Protein–Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities. A total of 364 genes including 73 novel interactors were differentially regulated in tissue/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. We found that 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy- and microcephaly-associated genes, with the shared genes enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways, respectively. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly, respectively. Full article

Secondary screening for missed congenital hypothyroidism (CH) has been introduced sporadically, but its necessity and optimal strategy have not been recognized. We hypothesized that a simple clinical protocol (performed by a medical group without a governmental mandate) targeting infants at high risk for missed CH can identify cases. We performed a 9-year retrospective review of 338,478 neonates within a California health plan following the introduction of thyrotropin (TSH) secondary screening for neonates at high risk for missed CH due to very-low-birthweight (VLBW), hospitalized congenital heart disease (CHD), and same-sex multiples (SSM). Screening performance by day 60 of life was 95% successful for VLBW and >50% for CHD and SSM, leading to an additional 35% CH treated cases despite re-testing only 1.7% of the cohort. Infants with VLBW or CHD were 33 times more likely (190 times more likely for CHD with Down Syndrome) to receive treatment for CH than random infants diagnosed by primary screening (p < 0.001), and 92% of these infants were not found by primary newborn screening. Currently, permanent disease has been documented in 84% of CH by primary screening compared to 27% by secondary screening (p < 0.001). This targeted secondary screening program identifies and treats additional CH cases after TSH-only newborn screening. Full article

The current diagnosis of Congenital Heart Disease (CHD) in neonates relies on echocardiography. Its limited availability requires alternative screening procedures to prioritise newborns awaiting ultrasound. The routine screening for CHD is performed using a multidimensional clinical examination including (but not limited to) auscultation and pulse oximetry. While auscultation might be subjective with some heart abnormalities not always audible it increases the ability to detect heart defects. This work aims at developing an objective clinical decision support tool based on machine learning (ML) to facilitate differentiation of sounds with signatures of Patent Ductus Arteriosus (PDA)/CHDs, in clinical settings. The heart sounds are pre-processed and segmented, followed by feature extraction. The features are fed into a boosted decision tree classifier to estimate the probability of PDA or CHDs. Several mechanisms to combine information from different auscultation points, as well as consecutive sound cycles, are presented. The system is evaluated on a large clinical dataset of heart sounds from 265 term and late-preterm newborns recorded within the first six days of life. The developed system reaches an area under the curve (AUC) of 78% at detecting CHD and 77% at detecting PDA. The obtained results for PDA detection compare favourably with the level of accuracy achieved by an experienced neonatologist when assessed on the same cohort. Full article

Newborn screening for critical congenital heart disease (CCHD) is recommended for implementation in many developed countries as the standard of care. Efforts to implement this point of care screen in developing regions face unique barriers, and present important opportunities. The First Pan-African Newborn Screening Conference, held in Rabat in June 2019, incorporated a workshop dedicated specifically to identifying and discussing CCHD screening issues in the Middle East Northern Africa (MENA) region. The issues explored may be beneficial as part of the greater discussion of CCHD screening’s growing importance in developing regions around the world. Screening experts presented education and lessons learned from previous CCHD implementations, including a hands-on technical demonstration of CCHD screening. Children’s HeartLink, The Newborn Foundation, and Children’s National Hospital each presented on their experiences working with teams and pilot projects from around the world. Experience in implementation from Children’s Hospital Marrakesh was presented and highlighted some of the unique findings, challenges, and experiences of screening in Morocco. As developing regions investigate the implementation of CCHD screening using pulse oximetry either as part of research studies, pilots, regional studies, or as part of a nationally supported program, data to inform policymakers on the benefits of screening and specific needs for infrastructure development and resources are essential. This special issue contains initial lessons learned on newborn CCHD screening from a select number of developing countries, including Saudi Arabia and Morocco and regions such as Latin America. Full article