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| 2. |
- Clausen, Henning, et al.
(författare)
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Newborn Screening for High-Risk Congenital Heart Disease by Dried Blood Spot Biomarker Analysis.
- 2024
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Ingår i: JAMA Network Open. - 2574-3805. ; 7:6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Jashari, Haki, et al.
(författare)
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Coarctation repair normalizes left ventricular function and aorto-septal angle in neonates
- 2017
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Ingår i: Congenital Heart Disease. - : Computers, Materials and Continua (Tech Science Press). - 1747-079X .- 1747-0803. ; 12:2, s. 218-225
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Patients with coarctation of the aorta (CoA) have increased left ventricular (LV) afterload that has been shown to impact the LV and ascending aortic function. We aimed to examine the effect of coarctation on LV function and aorto-septal angle (AoSA) before and after surgical repair.Methods: We retrospectively studied 21 patients with surgically repaired CoA at a median age of 9 (2-53) days at three time points: (1) just before intervention, (2) at short-term follow-up, and (3) at medium-term follow-up after intervention. AoSA was measured from the parasternal long axisview, at three time points during the cardiac cycle: (1) end diastole, (2) beginning of systole, and (3) at peak ejection in the descending aorta. In addition to conventional LV structure and function, global longitudinal strain, and strain rate were measured using STE technique and Tomtec soft-ware. Three groups of age matched healthy children served as controls at each time point.Results: AoSA was significantly wider before intervention, in particular at peak ejection in the descending aorta (1448 6 6.48 vs. 1368 6 4.18; P < .0001), and correlated with CoA pressure gradi-ent. After intervention, AoSA normalized and significantly correlated with the increase of LV cavity function and overall LV deformation parameters.Conclusions: AoSA is abnormally wide in neonates with CoA and is associated with severity ofobstruction, LV dysfunction and compromised LV global deformation.
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| 4. |
- Jashari, Haki, et al.
(författare)
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Persistent reduced myocardial deformation in neonates after CoA repair
- 2016
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Ingår i: International Journal of Cardiology. - : Elsevier. - 0167-5273 .- 1874-1754. ; 221, s. 886-891
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Surgical repair of coarctation of the aorta (CoA) is a safe procedure in children, however the condition is known for its potential recurrence and other related complications. The available evidence shows abnormal intrinsic properties of the aorta in CoA, thus suggesting additional effect, even after CoA repair, on left ventricular (LV) function. Accordingly, we sought to obtain a better understanding of LV myocardial mechanics in very early-corrected CoA using two-dimensional STE.METHODS AND RESULTS: We retrospectively studied 21 patients with corrected CoA at a median age of 9 (2-53) days at three time points: 1) just before intervention, 2) at short-term follow-up and 3) at medium-term follow-up after intervention and compared them with normal values. Speckle tracking analysis was conducted via vendor independent software, Tomtec. After intervention, LV function significantly improved (from -12.8±3.9 to -16.7±1.7; p<0.001), however normal values were not reached even at medium term follow-up (-18.3±1.7 vs. -20±1.6; p=0.002). Medium term longitudinal strain correlated with pre intervention EF (r=0.58, p=0.006). Moreover, medium term subnormal values were more frequently associated with bicuspid aortic valve (33.3% vs. 66.6%; p<0.05).CONCLUSION: LV myocardial function in neonates with CoA can be feasibly evaluated and followed up by speckle tracking echocardiography. LV subendocardial dysfunction however, remains in early infancy coarctation long after repair. Long-term follow-up through adulthood using myocardial deformation measurements should shed light on the natural history and consequences of this anomaly.
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| 5. |
- Lannering, Katarina
(författare)
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Early detection of critical congenital heart defects in Sweden - with a focus on coarctation of the aorta
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: Despite the implementation of prenatal and neonatal screening, newborn infants with critical congenital heart defects (CCHD) remain at risk of being discharged undiagnosed, particularly newborns with coarcation of the aorta (CoA). Recent studies have suggested that perfusion index (PI) may potentially identify additional cases of CoA. Aims: To investigate the relative contributions of prenatal screening, pulse oximetry screening (POS) and newborn physical examination (NPE) to the early detection of CCHD with special attention to CoA. A second aim was to investigate the use of PI to improve the early detection of CoA. Methods: Retrospective population-based cohorts of isolated CoA (Paper I) and CCHD (Paper III) were studied with respect to the contribution of pre- and postnatal screening methods to early diagnosis. PI was measured prospectively in healthy newborns to determine the false positive rate (Paper II). The sensitivity of PI to detect aortic arch obstructions (AAO), such as CoA, was studied retrospectively in newborns with AAO who were routinely screened with PI (Paper IV). Results: In Paper I, three of 90 with CoA were diagnosed prenatally. Among 87 diagnosed postnatally, 4/19 (21%) born in units using POS screened positive. Forty-six (53%) were discharged undiagnosed. At readmission, 22 were in circulatory failure and one died at home. In Paper III, 264/630 (42%) with CCHD were diagnosed prenatally, 142 (23%) by POS and 86 (14%) as a result of NPE. Although prenatal detection increased significantly during the study period, 4 newborns died undiagnosed before discharge and 64 (10%) were discharged undiagnosed. Upon readmission 24 were in circulatory failure with one preoperative death. Of 184 with CoA, 55 (30%) were discharged undiagnosed. In Paper II, the false-positive rate of PI in 463 newborns was reduced to 0% by using repeated PI measurements and a threshold of <0.7% for a positive screen. In Paper IV, the sensitivity of PI to detect AAO in 38 cases could be increased from 45% to 76% by combining PI in right hand with POS and NPE. Conclusions: POS and NPE remain important for the early detection of CCHD, complementing the increasing prenatal detection. While the overall pre-discharge detection of CCHD was high, and improvements were made in the prenatal detection of CoA, this defect was still frequently not diagnosed before discharge. Adding PI to CCHD screening has the potential to further improve early detection of CoA but requires additional evaluation.
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| 6. |
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| 7. |
- Lannering, Katarina, et al.
(författare)
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Low false-positive rate of perfusion index as a screening tool for neonatal aortic coarctation
- 2021
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Ingår i: Acta Paediatrica, International Journal of Paediatrics. - : Wiley. - 0803-5253 .- 1651-2227. ; 110:6, s. 1788-1794
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica Aim: Adding perfusion index (PI) to pulse oximetry screening (POS) may increase neonatal detection of CoA (aortic coarctation). A cut-off <0.7% has been suggested but is associated with a high rate of false positives. We aimed to evaluate the specificity of PI when using repeated instead of single measurements. Methods: A pilot study was conducted in 50 neonates. PI was recorded in right hand and a foot by pulse oximeter. If PI was <0.7%, the measurement was immediately repeated up to 3 times. If all three measurements were <0.7% in hand and/or foot the screen was positive and echocardiography was performed. There were 3/50 false-positive screens. The protocol was therefore modified requiring 30min intervals between measurements. Results: An additional 463 neonates were included using the modified protocol at a median age of 18h. There were no false positives. The only neonate with CoA had a negative screen (PI hand 1.2% and foot 0.8%). The measurement required on average an extra 3min and 30s compared with POS only. Conclusion: The false-positive rate of PI was reduced by using repeated PI measurements. The sensitivity for CoA using this protocol should be evaluated in large-scale prospective studies.
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| 8. |
- Lannering, Katarina, et al.
(författare)
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Screening for Critical Congenital Heart Defects in Sweden
- 2023
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Ingår i: PEDIATRICS. - : American Academy of Pediatrics (AAP). - 0031-4005 .- 1098-4275. ; 152:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES Early diagnosis of critical congenital heart defects (CCHD) improves survival. We evaluated the relative contributions of prenatal ultrasound, neonatal pulse oximetry screening (POS), and neonatal physical examination (NPE) to the early detection (before discharge) of CCHD in the context of increasing prenatal detection, and POS being a national standard since 2013.METHODS Retrospective, nationwide population-based study. All full-term live-born infants with CCHD in Sweden between 2014 and 2019 were included. CCHD was defined as a congenital heart defect requiring surgery or catheter-based intervention or resulting in death within 28 days of birth.RESULTS Of 630 infants, 89% were diagnosed before discharge or death, 42% prenatally, 11% from early symptoms, 23% by POS, and 14% from NPE after a negative POS. Four (0.6%) died undiagnosed before discharge and 64/630 (10%) were discharged undiagnosed, with 24/64 being readmitted with circulatory failure and causing 1 preoperative death. Coarctation was the most prevalent CCHD (N = 184), 25% of whom were detected prenatally (12% by POS and 29% by NPE). Two died undiagnosed before discharge and 30% were discharged undiagnosed. Transposition was the second most common defect (N = 150) and 43% were detected prenatally (33% by POS, 1 by NPE) and 2 died undiagnosed before POS. None was discharged undiagnosed.CONCLUSIONS POS and NPE remain important for the early detection of CCHD complementing prenatal ultrasound screening. Nevertheless, 1 in 10 with CCHD leaves the hospital without a diagnosis, with coarctation being the predominant lesion. Future research on CCHD screening should have a particular focus on this cardiac defect.
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| 9. |
- Lannering, Katarina, et al.
(författare)
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Screening for critical congenital heart defects in sweden
- 2024
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Ingår i: Obstetrical and Gynecological Survey. - : Lippincott Williams & Wilkins. - 0029-7828 .- 1533-9866. ; 79:4, s. 185-187
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Tidskriftsartikel (refereegranskat)abstract
- (Abstracted from Pediatrics 2023;152:e2023061949 Critical congenital heart defects (CCHDs) affect between 1 and 3 of every 1000 live-born infants and require intervention in the short term after birth. Early identification of affected infants contributes to significantly to better outcomes in both the short- and long-term.
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| 10. |
- Nordenström, Kajsa, et al.
(författare)
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Low risk of necrotising enterocolitis in enterally fed neonates with critical heart disease: An observational study
- 2020
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Ingår i: Archives of Disease in Childhood: Fetal and Neonatal Edition. - : BMJ. - 1359-2998 .- 1468-2052. ; 105:6, s. 609-614
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Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to investigate the frequency of necrotising enterocolitis (NEC) in infants with critical congenital heart disease (CCHD) hypothesising that preoperative enteral feeding does not increase the risk of NEC. Background: When NEC affects term infants, underlying risk factors such as asphyxia, sepsis or CCHD are often found. Due to fear of NEC development in infants with CCHD great caution is practised in many countries to defer preoperative enteral feeding, but in Sweden this is routinely provided. Design, setting and patients: An observational study of all infants born with CCHD who were admitted to Queen Silvia Children's Hospital in Gothenburg between 2010 and 2017. The International Classification of Diseases 10th Revision diagnosis code of NEC was used to identify NEC cases in this group. Infants described as fully fed' or who were fed at least 45 mL/kg/day before cardiac surgery were identified. Main outcome measures: NEC in infants with CCHD in relation to preoperative enteral feeding. Results: There were 458 infants with CCHD admitted during the study period. 408/458 were born at term and 361/458 required prostaglandin E1 before surgery. In total, 444/458 infants (97%) were fully fed or fed at least 45 mL/kg daily before cardiac surgery. Four of 458 infants developed NEC (0.9%). All four had other risk factors for NEC. Conclusions: This study showed a low risk of NEC in term infants fed enterally before cardiac surgery. We speculate that preoperative enteral feeding of neonates with CCHD does not increase the risk of NEC development. © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
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| 11. |
- Tesan, Tajana, 1977, et al.
(författare)
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A new GTF2I-BRAF fusion mediating MAPK pathway activation in pilocytic astrocytoma
- 2017
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:4
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Tidskriftsartikel (refereegranskat)abstract
- Pilocytic astrocytoma (PA) is the most common pediatric brain tumor. A recurrent feature of PA is deregulation of the mitogen activated protein kinase (MAPK) pathway most often through KIAA1549-BRAF fusion, but also by other BRAF- or RAF1-gene fusions and point mutations (e.g. BRAFV600E). These features may serve as diagnostic and prognostic markers, and also facilitate development of targeted therapy. The aims of this study were to characterize the genetic alterations underlying the development of PA in six tumor cases, and evaluate methods for fusion oncogene detection. Using a combined analysis of RNA sequencing and copy number variation data we identified a new BRAF fusion involving the 5' gene fusion partner GTF2I (7q11.23), not previously described in PA. The new GTF2I-BRAF 19-10 fusion was found in one case, while the other five cases harbored the frequent KIAA1549-BRAF 16-9 fusion gene. Similar to other BRAF fusions, the GTF2I-BRAF fusion retains an intact BRAF kinase domain while the inhibitory N-terminal domain is lost. Functional studies on GTF2I-BRAF showed elevated MAPK pathway activation compared to BRAF WT. Comparing fusion detection methods, we found Fluorescence in situ hybridization with BRAF break apart probe as the most sensitive method for detection of different BRAF rearrangements (GTF2I-BRAF and KIAA1549-BRAF). Our finding of a new BRAF fusion in PA further emphasis the important role of B-Raf in tumorigenesis of these tumor types. Moreover, the consistency and growing list of BRAF/RAF gene fusions suggests these rearrangements to be informative tumor markers in molecular diagnostics, which could guide future treatment strategies.
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| 12. |
- Tyrstrup, Mia, et al.
(författare)
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Reduction in antibiotic prescribing for respiratory tract infections in Swedish primary care- a retrospective study of electronic patient records
- 2016
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Ingår i: BMC Infectious Diseases. - : Springer Science and Business Media LLC. - 1471-2334. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Swedish studies on antibiotic use in primary care have been based on one-week registrations of infections. In order to study adherence to guidelines, analyses based on large databases that provide information on diagnosis linked prescriptions, are needed. This study describes trends in management of infections in Swedish primary care particularly with regards to antibiotic prescribing and adherence to national guidelines. Methods: A descriptive study of Sweden's largest database regarding diagnosis linked antibiotic prescription data, the Primary care Record of Infections in Sweden (PRIS), for the years 2008, 2010 and 2013. Results: Although the consultation rate for all infections remained around 30% each year, antibiotic prescribing rates decreased significantly over the years from 53.7% in 2008, to 45.5% in 2010, to 38.6% in 2013 (p = .032). The antibiotic prescribing rate for respiratory tract infections (RTIs) decreased from 40.5% in 2008 to 24.9% in 2013 while those for urinary tract infections and skin and soft tissue infections were unchanged. For most RTI diagnoses there was a decrease in prescription rate from 2008 to 2013, particularly for the age group 0-6 years. Phenoxymethylpenicillin (PcV) was the antibiotic most often prescribed, followed by tetracycline. Tonsillitis and acute otitis media were the two RTI diagnoses with the highest number of prescriptions per 1000 patient years (PY). For these diagnoses an increase in adherence to national guidelines was seen, with regards to treatment frequency, choice of antibiotics and use of rapid antigen detection test. The frequency in antibiotic prescribing varied greatly between different Primary Healthcare Centres (PHCCs). Conclusion: Falling numbers of consultations and decreased antibiotic prescription rates for RTIs have reduced the antibiotic use in Swedish primary care substantially. Overprescribing of antibiotics could still be suspected due to large variability in prescribing frequency, especially for acute bronchitis and sinusitis. Continuous evaluation of diagnosis linked prescribing data and feedback to doctors is essential in order to achieve a more prudent antibiotic use.
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