Adolescents on psychotropic treatment displayed longer corrected QT intervals than unmedicated controls when they rose rapidly from the supine position.

AIM: Psychotropic medication can contribute to arrhythmia and identifying individuals at risk is crucial. This Swedish study compared the corrected QT (QTc) intervals of adolescents on psychotropic medication with unmedicated controls, when supine and after rising rapidly. METHODS: The study was carried out at Östersund County Hospital in March 2022 and February to March 2023. It comprised 16 cases, aged 10-17 years and 28 controls. QTc intervals were measured with electrocardiography and calculated using Bazett's and Fridericia's formulas. Univariate and multiple linear regressions were used to assess differences in QTc intervals between the cases and controls and across sex, age and body mass index. RESULTS: The mean QTc interval when supine, calculated with Bazett's formula, was longer for the adolescents on psychotropic medication than the controls (p = 0.046). The same was true for the mean QTc interval after rising rapidly from the supine position, calculated with both Bazett's formula (p = 0.009) and Fridericia's formula (p = 0.007). Mean QTc intervals varied by sex and age groups. Psychotropic medication prolonged QTc intervals, particularly in girls. CONCLUSION: Longer QTc intervals were found in adolescents on psychotropic medication, particularly after rising rapidly from the supine position.

Outpatient prescription of pulmonary vasodilator therapy to preterm children with bronchopulmonary dysplasia.

AIM: The use of pulmonary vasodilator therapy in children born preterm is largely unknown. Our aim was to map prescription patterns in children with bronchopulmonary dysplasia in Sweden. METHODS: This was a descriptive national registry-based study of children <7 years who had been prescribed a pulmonary vasodilator during 2007-2017, were born preterm and classified as having bronchopulmonary dysplasia. Information on prescriptions, patient characteristics and comorbidities were retrieved from the Swedish Prescribed Drug Register and linked to other national registers. RESULTS: The study included 74 children, 54 (73%) born at 22-27 weeks' gestation and 20 (27%) at 28-36 weeks. Single therapy was most common, n = 64 (86.5%), and sildenafil was prescribed most frequently, n = 69 (93%). Bosentan, iloprost, macitentan and/or treprostinil were used mainly for combination therapies, n = 10 (13.5%). Patent ductus arteriosus or atrial septal defect were present in 29 (39%) and 25 (34%) children, respectively, and 20 (69%) versus 3 (12%) underwent closure. Cardiac catheterisation was performed in 19 (26%) patients. Median duration of therapy was 4.6 (1.9-6.8, 95% CI) months. Mortality was 9%. CONCLUSION: Preterm children with bronchopulmonary dysplasia were prescribed pulmonary vasodilators, often without prior catheterisation. Sildenafil was most commonly used. Diagnostic tools, effects, and drug safety need further evaluation.

QTc interval-dependent body posture in pediatrics.

BACKGROUND: Syncope is a common and often benign disorder presenting at the pediatric emergency department. Long-QT syndrome may be presented with syncope, ventricular arrhythmias or sudden death and is vital to exclude as an underlying cause in children presented with syncope. Few studies have assessed QTc in relation to body posture in children. In this study, we assessed the QTc interval while laying down and during active standing in children with known long-QT syndrome compared to healthy controls. METHODS: Children aged 1-18 years with long-QT syndrome (N = 17) matched to two healthy controls (N = 34) were included in this case-control study. The ECG standing was performed immediately after the ECG in the supine position. The QTc interval and QTc-difference by changing the body position were calculated. RESULTS: All children with long-QT syndrome were treated with propranolol. QTc was prolonged among long-QT syndrome children while lying down and when standing up, compared to controls. A prolongation of QTc appeared when standing up for both cases and controls. There was no significant difference in QTc increase between the groups. A QTc over 440 ms was observed among four cases lying down and in eight cases while standing, but not in any of the controls. The standing test with a cut-off of 440 ms showed a sensitivity of 47% and a specificity of 100% for case-status in our study. CONCLUSION: QTc measured on ECG when rapidly rising up is prolonged in both healthy and LQTS children. More importantly, it prolongs more in children with LQTS and increases in pathological levels.

Improved infrastructure and support needed for paediatric clinical trials in Sweden.

AIM: There is a lack of authorised medicines for paediatric patients and improved drug development is necessary. The aim of this study was to evaluate the need for infrastructure and support for paediatric clinical trials in Sweden. METHODS: A web-based survey was sent to doctors and nurses involved in the care of neonates, children and adolescents assessing the current situation and future needs for paediatric clinical trials in Sweden. Questions regarding premises, competence, organisation, support for paediatric clinical trials and Good Clinical Practice Training were addressed. RESULTS: In total, 137 individuals responded to the survey (109 doctors and 28 nurses). Overall, 61% of the respondents had previous experience of paediatric clinical trials. Some respondents had access to trial units, but only 34% had used the trial unit for support. Half of the responders were interested in recurrent paediatric Good Clinical Practice training. Doctors responded that clinical work often had to be prioritised and emphasised the need for research time. CONCLUSION: This study clearly shows the commitment for clinical trials among doctors and nurses involved in paediatric care in Sweden, but also that administrative, logistic and economic support in a sustainable setting and an expanded national collaboration are needed.

Risk factors for adverse events within one year after atrial septal closure in children: a retrospective follow-up study.

INTRODUCTION: Secundum atrial septal defect is one of the most common congenital heart defects. Previous paediatric studies have mainly addressed echocardiographic and few clinical factors among children associated with adverse events. The aim of this study was to identify neonatal and other clinical risk factors associated with adverse events up to one year after closure of atrial septal defect. METHODS: This retrospective case-control study includes children born in Sweden between 2000 and 2014 that were treated surgically or percutaneously for an atrial septal defect. Conditional logistic regression was used to evaluate the association between major and minor adverse events and potential risk factors, adjusting for confounding factors including prematurity, neonatal sepsis, neonatal general ventilatory support, symptomatic atrial septal defects, and pulmonary hypertension. RESULTS: Overall, 396 children with 400 atrial septal defect closures were included. The median body weight at closure was 14.5 (3.5-110) kg, and the median age was 3.0 (0.1-17.8) years. Overall, 110 minor adverse events and 68 major events were recorded in 87 and 49 children, respectively. Only symptomatic atrial septal defects were associated with both minor (odds ratio (OR) = 2.18, confidence interval (CI) 95% 1.05-8.06) and major (OR = 2.80 CI 95% 1.23-6.37) adverse events. CONCLUSION: There was no association between the investigated neonatal comorbidities and major or minor events after atrial septal defect closure. Patients with symptomatic atrial septal defects had a two to four times increased risk of having a major event, suggesting careful management and follow-up of these children prior to and after closure.

Inhaled corticosteroids in children with persistent asthma: effects of different drugs and delivery devices on growth.

BACKGROUND: Inhaled corticosteroids (ICS) are the most effective treatment for children with persistent asthma. Although treatment with ICS is generally considered to be safe in children, the potential adverse effects of these drugs on growth remains a matter of concern for parents and physicians. OBJECTIVES: To assess the impact of different inhaled corticosteroid drugs and delivery devices on the linear growth of children with persistent asthma. SEARCH METHODS: We searched the Cochrane Airways Trials Register, which is derived from systematic searches of bibliographic databases including CENTRAL, MEDLINE, Embase, CINAHL, AMED and PsycINFO. We handsearched respiratory journals and meeting abstracts. We also conducted a search of ClinicalTrials.gov and manufacturers' clinical trial databases, or contacted the manufacturer, to search for potential relevant unpublished studies. The literature search was initially conducted in September 2014, and updated in November 2015, September 2018, and April 2019. SELECTION CRITERIA: We selected parallel-group randomized controlled trials of at least three months' duration. To be included, trials had to compare linear growth between different inhaled corticosteroid molecules at equivalent doses, delivered by the same type of device, or between different devices used to deliver the same inhaled corticosteroid molecule at the same dose, in children up to 18 years of age with persistent asthma. DATA COLLECTION AND ANALYSIS: At least two review authors independently selected studies and assessed risk of bias in included studies. The data were extracted by one author and checked by another. The primary outcome was linear growth velocity. We conducted meta-analyses using Review Manager 5.3 software. We used mean differences (MDs) and 95% confidence intervals (CIs ) as the metrics for treatment effects, and the random-effects model for meta-analyses. We did not perform planned subgroup analyses due to there being too few included trials. MAIN RESULTS: We included six randomized trials involving 1199 children aged from 4 to 12 years (per-protocol population: 1008), with mild-to-moderate persistent asthma. Two trials were from single hospitals, and the remaining four trials were multicentre studies. The duration of trials varied from six to 20 months.One trial with 23 participants compared fluticasone with beclomethasone, and showed that fluticasone given at an equivalent dose was associated with a significant greater linear growth velocity (MD 0.81 cm/year, 95% CI 0.46 to 1.16, low certainty evidence). Three trials compared fluticasone with budesonide. Fluticasone given at an equivalent dose had a less suppressive effect than budesonide on growth, as measured by change in height over a period from 20 weeks to 12 months (MD 0.97 cm, 95% CI 0.62 to 1.32; 2 trials, 359 participants; moderate certainty evidence). However, we observed no significant difference in linear growth velocity between fluticasone and budesonide at equivalent doses (MD 0.39 cm/year, 95% CI -0.94 to 1.73; 2 trials, 236 participants; very low certainty evidence).Two trials compared inhalation devices. One trial with 212 participants revealed a comparable linear growth velocity between beclomethasone administered via hydrofluoroalkane-metered dose inhaler (HFA-MDI) and beclomethasone administered via chlorofluorocarbon-metered dose inhaler (CFC-MDI) at an equivalent dose (MD -0.44 cm/year, 95% CI -1.00 to 0.12; low certainty evidence). Another trial with 229 participants showed a small but statistically significant greater increase in height over a period of six months in favour of budesonide via Easyhaler, compared to budesonide given at the same dose via Turbuhaler (MD 0.37 cm, 95% CI 0.12 to 0.62; low certainty evidence). AUTHORS' CONCLUSIONS: This review suggests that the drug molecule and delivery device may impact the effect size of ICS on growth in children with persistent asthma. Fluticasone at an equivalent dose seems to inhibit growth less than beclomethasone and budesonide. Easyhaler is likely to have less adverse effect on growth than Turbuhaler when used for delivery of budesonide. However, the evidence from this systematic review of head-to-head trials is not certain enough to inform the selection of inhaled corticosteroid or inhalation device for the treatment of children with persistent asthma. Further studies are needed, and pragmatic trials and real-life observational studies seem more attractive and feasible.

Increased risk of pulmonary hypertension following premature birth.

BACKGROUND: Pulmonary hypertension (PAH) among children and adults has been linked to premature birth, even after adjustments for known risk factors such as congenital heart disease and chronic lung disease. The aim of this population-based registry study was to assess the risk of PAH following exposure to premature birth and other factors in the decades when modern neonatal care was introduced and survival rates increased. METHODS: Data on pulmonary hypertension and perinatal factors were retrieved from population-based governmental and national quality registers. Cases were adults and children over five years of age with pulmonary hypertension born from 1973 to 2010 and individually matched to six controls by birth year and delivery hospital. Conditional multiple logistic regression was performed to assess the risk of pulmonary hypertension following premature birth and to adjust for known confounding factors for the total study population and for time of birth, grouped into five-year intervals. RESULTS: In total, 128 cases and 768 controls were included in the study group. Preterm birth was over three times more common among cases (21%) than among controls (6%). The overall adjusted risk of pulmonary hypertension was associated with premature birth, OR = 4.48 (95% CI; 2.10-9.53). Maternal hypertension, several neonatal risk factors and female gender were independently associated with PAH when potential confounders were taken into account. For each five-year period, the risk of PAH following premature birth increased several times for children born in the 2000s and later, OR = 17.08 (95% CI 5.60-52.14). CONCLUSIONS: Preterm birth, along with other factors, significantly contributes to PAH. PAH following premature birth has increased over the last few decades. Our study indicates that new, yet unknown factors may play a role in the risk of preterm-born infants developing PAH later in life.

Adverse events within 1 year after surgical and percutaneous closure of atrial septal defects in preterm children.

INTRODUCTION: Atrial septal defect is the third most common CHD. A hemodynamically significant atrial septal defect causes volume overload of the right side of the heart. Preterm children may suffer from both pulmonary and cardiac comorbidities, including altered myocardial function. The aim of this study was to compare the rate of adverse events following atrial septal defect closure in preterm- and term-born children. METHOD: We performed a retrospective cohort study including children born in Sweden, who had a surgical or percutaneous atrial septal defect closure at the children's hospitals in Lund and Stockholm, between 2000 and 2014, assessing time to the first event within 1 month or 1 year. We analysed differences in the number of and the time to events between the preterm and term cohort using the Kaplan-Meier survival curve, a generalised model applying zero-inflated Poisson distribution and Gary-Anderson's method. RESULTS: Overall, 413 children were included in the study. Of these, 93 (22.5%) were born prematurely. The total number of adverse events was 178 (110 minor and 68 major). There was no difference between the cohorts in the number of events, whether within 1 month or within a year, between major (p = 0.69) and minor (p = 0.84) events or frequencies of multiple events (p = 0.92). CONCLUSION: Despite earlier procedural age, larger atrial septal defects, and higher comorbidity than term children, preterm children appear to have comparable risk for complications during the first year after surgical or percutaneous closure.

National cohort study showed that infants with Down's syndrome faced a high risk of hospitalisation for the respiratory syncytial virus.

AIM: The respiratory syncytial virus (RSV) is a leading cause of hospitalisation in infants. We investigated this risk in children with Down's syndrome under two years of age, adjusted for other known risk factors. METHODS: This national, retrospective 1:2 matched cohort study comprised all Swedish children born with Down's from 2006 to 2011, who were each randomly matched to two controls without Down's. Data on RSV hospitalisation and risk factors for RSV were obtained from national registers. The risk of RSV hospitalisation was assessed using multivariable Cox regression with pairwise stratification. RESULTS: The study comprised 814 children with Down's and 1628 controls. We found that 82 children with Down's (10.1%) and 22 controls (1.4%) were hospitalised for RSV. The hazard ratio for children with Down's was 4.00 (95% confidence interval 1.58-10.13) for up to one year of age and 6.60 (95% CI: 2.83-15.38) for up to two years of age, adjusted for other risk factors. During the second year of life, RSV hospitalisation continued for children with Down's, while it was minimal for the controls. CONCLUSION: Children with Down's faced a high risk of RSV hospitalisation, which continued beyond the first year of age.

Early Complications After Percutaneous Closure of Atrial Septal Defect in Infants with Procedural Weight Less than 15 kg.

Atrial septal defect (ASD) is the most common congenital cardiac lesion accounting for 10-15% of all cardiac malformations. In the majority of cases, the secundum type of the ASD is closed percutaneously in the catheterization laboratory. Although transcatheter closure of ASD is considered safe and effective in pediatric patients, there are limited data regarding the efficacy and safety of device ASD closure in smaller infants. The aim of this study was to determine risk of complications within 72 h following device closure of ASD in children of body weight <15 kg compared to larger children. Overall 252 children who underwent transcatheter closure of ASD at Children's Heart Centre in Lund, Sweden, between 1998 and 2015 were included. Data regarding demographics, comorbidity and complications occurring during and after device procedure until discharge were retrieved from the hospital's databases. Echocardiographic data were obtained from the digital and videotape recordings. Nearly half of the study cohort (n = 112; 44%) had a procedural weight <15 (median 11.3) kg with a median procedural age of 2.02 years. Among this study group, 22 (9%) children had post-procedural in-hospital complications, of which 16 (7%) were considered as major and six (2%) considered as minor. No deaths occurred. There was no significant difference in of the occurrence of major or minor complications between the two groups (p = 0.32). Larger ASD was more often associated with minor complications, OR 1.37 (95% CI 0.99-1.89), which most often consisted of transient arrhythmias during or after the procedure. Percutaneous ASD device closure can be performed safely in low-weight infants with a risk of post-procedural in-hospital complications comparable to larger/older children. Nevertheless, careful considerations of the indications to device closure is needed, particularly in children with larger ASD, as recommended by the current international guidelines for ASD closure.

Serious complications in male infant circumcisions in Scandinavia indicate that this always be performed as a hospital-based procedure.

AIM: More than 7000 male circumcisions are performed in Scandinavia every year. Circumcision is regulated in different ways in Sweden and Denmark and Norway. This study reviewed and described factors associated with complications of circumcision in infant boys in Scandinavia over the last two decades and discussed how these complications could be avoided. METHODS: Data on significant complications following circumcision on boys under the age of one in Scandinavia over the last 20 years were collected. Information was retrieved from testimonies of circumcisers, witnesses, medical records and verdicts. A systematic review was performed of fatal cases in the literature. RESULTS: We found that 32 cases had been reported to the health authorities in the three countries, and we identified a total of 74 complications in these cases. These included four boys with severe bleeding and circulatory shock, which ended in the death of one boy. Other less serious complications may have occurred in other boys, but not been reported. CONCLUSION: Complications following male circumcision in Scandinavia were relatively rare, but serious complications did occur. Based on the analyses of the severe cases, we argue that circumcision should only be performed at hospitals with 24-hour emergency departments.

Respiratory Tract Infection and Risk of Hospitalization in Children with Congenital Heart Defects During Season and Off-Season: A Swedish National Study.

Respiratory tract infections (RTI) are common among young children, and congenital heart defect (CHD) is a risk factor for severe illness and hospitalization. This study aims to assess the relative risk of hospitalization due to RTI in winter and summer seasons for different types of CHD. All children born in Sweden and under the age of two, in 2006-2011, were included. Heart defects were grouped according to type. Hospitalization rates for respiratory syncytial virus (RSV) infection and RTI in general were retrieved from the national inpatient registry. The relative risk of hospitalization was calculated by comparing each subgroup to other types of CHD and otherwise healthy children. The relative risk of hospitalization was increased for all CHD subgroups, and there was a greater increase in risk in summer for the most severe CHD. This included RSV infection, as well as RTI in general. The risk of hospitalization due to RTI is greater for CHD children. Prophylactic treatment with palivizumab, given to prevent severe RSV illness, is only recommended during winter. We argue that information to healthcare staff and parents should include how the risk of severe infectious respiratory tract illnesses, RSV and others, is present all year round for children with CHD.

Some neonatal risk factors for adult pulmonary arterial hypertension remain unknown.

AIM: Pulmonary hypertension has been linked to premature birth, chronic lung disease, bronchopulmonary dysplasia and congenital heart disease. This national population-based registry study assessed the risk of adult pulmonary hypertension following premature birth, adjusted for known risk factors. METHODS: We focused on adults in the Swedish Pulmonary Arterial Hypertension Registry, who were born prematurely, and controls randomly selected from the Swedish medical birth register and matched to each case by birth year and delivery hospital. Information on perinatal factors was also retrieved from the medical birth register. Conditional multiple logistic regression was used to evaluate the association between premature birth and adult pulmonary hypertension, taking into account the potential confounding factors. RESULTS: The study population comprised 427 adults born between 1973 and 1996, with 61 cases and 366 controls. Adult pulmonary hypertension was associated with premature birth, with an odds ratio of 3.08 and 95% confidence interval of 1.21-7.87. The association did not alter after adjusting for potential confounders. CONCLUSION: By adjusting for factors linked to adult pulmonary hypertension, namely congenital heart defects, pulmonary diseases and premature birth, we were able to show that other unknown factors may influence the risk for pulmonary hypertension among adults who were born premature.

Evaluating national guidelines for the prophylactic treatment of respiratory syncytial virus in children with congenital heart disease.

AIM: This is the first study to evaluate compliance with the 2003 Swedish national guidelines for prophylactic treatment of respiratory syncytial virus (RSV) in children with congenital heart disease (CHD). We estimated the relative risk (RR) of children with CHD being hospitalised with a RSV infection, studied the extent to which RSV prophylactic treatment with palivizumab corresponded to the guidelines and determined the morbidity of children with CHD who developed RSV infection despite prophylaxis. METHODS: This national observational study comprised prospectively registered data on 219 children with CHD treated with palivizumab, medical records on RSV cases and information on hospitalisation rates of children with CHD and RSV infection. RESULTS: The calculated RR of children with CHD being hospitalised with RSV infection was 2.06 (95% CI 1.6-2.6; p < 0.0001) compared with children without CHD. Approximately half of the patients (49%) born before the RSV season and 25% born during the RSV season did not start treatment as recommended by the guidelines. CONCLUSION: Having CHD increased the rate and estimated RR of children being hospitalised with RSV infection. The guidelines were not followed for about half of the children born before a RSV season and a quarter of the children born during a RSV season and need updating.

Risk factors for isolated atrial septal defect secundum morbidity.

Atrial septal defect secundum is a common type of congenital heart defect and even more common among children born premature. The aim of this study was to assess premature birth as a potential associated risk factors for cardiac morbidity in children with isolated ASD II. In this retrospective national registry-based case-control study all children born in Sweden between 2010 and 2015 with an isolated ASD II diagnosis were included. Association between premature birth and cardiac morbidity in children with isolated ASD II was assessed by different outcomes-models using conditional logistic regression and adjustments were made for confounding factors. Overall, 11% of children with an isolated ASD II received treatment for heart failure. Down syndrome was the only independent risk factors for associated with cardiac morbidity in children with ASD II (OR = 2.25 (95%CI 1.25-4.07). Preterm birth in children was not associated with an increased risk of ASD II cardiac morbidity.

Insulin resistance prior to term age in very low birthweight infants: a prospective study.

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.

A longitudinal follow-up of continuous laryngoscopy during exercise test scores in athletes irrespective of laryngeal obstruction, respiratory symptoms, and intervention.

BACKGROUND: Exercise-induced laryngeal obstruction (EILO) is diagnosed by the continuous laryngoscopy during exercise (CLE) test. Whether or how much CLE test scores vary over time is unknown. This study aimed to compare CLE test scores in athletes over time, irrespective of respiratory symptoms and grade of laryngeal obstruction. METHODS: Ninety-eight athletes previously screened for EILO were invited for a follow-up CLE test irrespective of CLE scores and respiratory symptoms. Twenty-nine athletes aged 16-27 did a follow-up CLE test 3-23 months after the baseline test. Laryngeal obstruction at the glottic and supraglottic levels was graded by the observer during exercise, at baseline and follow-up, using a visual grade score (0-3 points). RESULTS: At baseline, 11 (38%) of the 29 athletes had moderate laryngeal obstruction and received advice on breathing technique; among them, 8 (73%) reported exercise-induced dyspnea during the last 12 months. At follow-up, 8 (73%) of the athletes receiving advice on breathing technique had an unchanged supraglottic score. Three (17%) of the 18 athletes with no or mild laryngeal obstruction at baseline had moderate supraglottic obstruction at follow-up, and none of the 3 reported exercise-induced dyspnea. CONCLUSIONS: In athletes with repeated testing, CLE scores remain mostly stable over 3-24 months even with advice on breathing technique to those with EILO. However, there is some intraindividual variability in CLE scores over time. TRIAL REGISTRATION: ISRCTN, ISRCTN60543467, 2020/08/23, retrospectively registered, ISRCTN - ISRCTN60543467: Investigating conditions causing breathlessness in athletes.