Development and construct validation of a parent-proxy quality of life instrument in children with bronchopulmonary dysplasia aged 4-8 years old

PURPOSE: Children with bronchopulmonary dysplasia often develop complications that affect them well into adult life. Very little is known about how this affects their quality of life, since no sensitive instrument is available to measure health-related quality of life in this population. In this study, a Dutch parent-proxy instrument was developed for this purpose. METHODS: A list of items was generated after literature search and interviews with both parents of patients and clinical experts. Clinically relevant items were selected with the clinical impact method and item analysis. Results of clinical tests to measure complications in children with bronchopulmonary dysplasia were correlated with these items to select the items that show construct validity. Cronbach's alpha was calculated to estimate internal consistency of the items in the final questionnaire. RESULTS: In total, 92 children and their parents and 7 clinicians participated. Of 130 identified items, 47 showed clinical relevance. Spirometry, the Child Behavior Checklist, mean arterial pressure, and body mass index were used to determine construct validity of 33 items. These items were structured within five domains: pulmonary complaints, school functioning, growth and nutrition, exercise and locomotion, emotional functioning and health care concerns. The questionnaire showed excellent internal consistency with Cronbach's alpha of 0.919. CONCLUSION: This study developed a disease-specific parent-proxy instrument to measure health-related quality of life in children with bronchopulmonary dysplasia aged 4-8 years old, the BPD-QoL. All included items show construct validity and internal consistency reliability. Future research should focus on further validation and analysis of responsiveness and reliability

A homozygous variant in growth and differentiation factor 2(GDF2)may cause lymphatic dysplasia with hydrothorax and nonimmune hydrops fetalis

The etiology of nonimmune hydrops fetalis is extensive and includes genetic disorders. We describe a term-born female neonate with late onset extensive nonimmune hydrops, that is, polyhydramnios, edema, and congenital bilateral chylothorax. This newborn was successfully treated with repetitive thoracocentesis, total parenteral feeding, octreotide intravenously and finally surgical pleurodesis and corticosteroids. A genetic cause seemed plausible as the maternal history revealed a fatal nonimmune hydrops fetalis. A homozygous truncating variant inGDF2(c.451C>T, p.(Arg151*)) was detected with exome sequencing. Genetic analysis of tissue obtained from the deceased fetal sibling revealed the same homozygous variant. The parents and two healthy siblings were heterozygous for theGDF2variant. Skin and lung biopsies in the index patient, as well as the revised lung biopsy of the deceased fetal sibling, showed lymphatic dysplasia and lymphangiectasia. To the best of our knowledge, this is the first report of an association between a homozygous variant inGDF2with lymphatic dysplasia, hydrothorax and nonimmune hydrops fetalis

Tiotropium add-on therapy is safe and reduces seasonal worsening in paediatric asthma patients

There remains an unmet need for effective, well-tolerated therapeutic options in paediatric patients with not fully controlled asthma, for whom safety is of paramount importance. Data were pooled from five randomised, double-blind, placebo-controlled studies evaluating tiotropium 5 or 2.5 mu g versus placebo add-on therapy in patients with symptomatic asthma aged 1-17 years. Analysis included adverse events (AEs) and serious AEs (SAEs) reported throughout and for 30 days following treatment. Of 1691 patients treated, 1119 received tiotropium. Reporting of AEs was low and comparable across all groups: tiotropium 5 mu g (51%), tiotropium 2.5 mu g (51%) and placebo (54%). Reporting of drug-related AEs, those leading to discontinuation and SAEs was also low and balanced between treatment groups, irrespective of age, disease severity or sex. The number of AEs related to asthma symptoms and exacerbations was lower with tiotropium (5 mu g) than with placebo, particularly during the seasonal peaks of these AEs. This comprehensive analysis of a large safety database allowed subgroup analyses that are often impractical with individual trials and provides further support for the safety of once-daily tiotropium Respimat add-on therapy in paediatric patients with symptomatic asthma

Supplemental oxygen strategies in infants with bronchopulmonary dysplasia after the neonatal intensive care unit period:study protocol for a randomised controlled trial (SOS BPD study)

Introduction Supplemental oxygen is the most important treatment for preterm born infants with established bronchopulmonary dysplasia (BPD). However, it is unknown what oxygen saturation levels are optimal to improve outcomes in infants with established BPD from 36 weeks postmenstrual age (PMA) onwards. The aim of this study is to compare the use of a higher oxygen saturation limit (≥95%) to a lower oxygen saturation limit (≥90%) after 36 weeks PMA in infants diagnosed with moderate or severe BPD. Methods and analysis This non-blinded, multicentre, randomised controlled trial will recruit 198 preterm born infants with moderate or severe BPD between 36 and 38 weeks PMA. Infants will be randomised to either a lower oxygen saturation limit of 95% or to a lower limit of 90%; supplemental oxygen and/or respiratory support will be weaned based on the assigned lower oxygen saturation limit. Adherence to the oxygen saturation limit will be assessed by extracting oxygen saturation profiles from pulse oximeters regularly, until respiratory support is stopped. The primary outcome is the weight SD score at 6 months of corrected age. Secondary outcomes include anthropometrics collected at 6 and 12 months of corrected age, rehospitalisations, respiratory complaints, infant stress, parental quality of life and cost-effectiveness. Ethics and dissemination Ethical approval for the trial was obtained from the Medical Ethics Review Committee of the Erasmus University Medical Centre, Rotterdam, the Netherlands (MEC-2018-1515). Local approval for conducting the trial in the participating hospitals has been or will be obtained from the local institutional review boards. Informed consent will be obtained from the parents or legal guardians of all study participants

Expiratory airflow in late adolescence and early adulthood in individuals born very preterm or with very low birthweight compared with controls born at term or with normal birthweight : a meta-analysis of individual participant data

Background Maximal expiratory airflow peaks early in the third decade of life, then gradually declines with age. The pattern of airflow through adulthood for individuals born very preterm (at 2499 g) or at term. Methods We did a meta-analysis of individual participant data from cohort studies, mostly from the pre-surfactant era. Studies were identified through the Adults born Preterm International Collaboration and by searching PubMed and Embase (search date May 25, 2016). Studies were eligible if they reported on expiratory flow rates beyond 16 years of age in individuals born very preterm or with very low birthweight, as well as controls born at term or with normal birthweight. Studies with highly selected cohorts (eg, only participants with bronchopulmonary dysplasia) or in which few participants were born very preterm or with very low birthweight were excluded. De-identified individual participant data from each cohort were provided by the holders of the original data to a central site, where all the data were pooled into one data file. Any data inconsistencies were resolved by discussion with the individual sites concerned. Individual participant data on expiratory flow variables (FEV1, forced vital capacity [FVC], FEV1/FVC ratio, and forced expiratory flow at 25-75% of FVC [FEF25-75%]) were converted to Z scores and analysed with use of generalised linear mixed models in a one-step approach. Findings Of the 381 studies identified, 11 studies, comprising a total of 935 participants born very preterm or with very low birthweight and 722 controls, were eligible and included in the analysis. Mean age at testing was 21 years (SD 3.4; range 16-33). Mean Z scores were close to zero (as expected) in the control group, but were reduced in the very preterm or very low birthweight group for FEV1 (-0.06 [SD 1.03] vs -0.81 [1.33], mean difference -0.78 [95% CI -0.96 to -0.61], p Interpretation Individuals born very preterm or with very low birthweight are at risk of not reaching their full airway growth potential in adolescence and early adulthood, suggesting an increased risk of chronic obstructive pulmonary disease in later adulthood. Copyright (C) 2019 Elsevier Ltd. All rights reserved.Peer reviewe

Respiratory Health in Adolescents Born Moderately-Late Preterm in a Community-Based Cohort

Objectives To determine the long-term effects of moderately-late preterm (MLP) birth on respiratory and allergic symptoms, lung function, and exercise capacity in adolescence. Study design Outcome variables in this prospective cohort were prevalence of symptoms determined by International Study of Asthma and Allergies in Childhood questionnaires, lung function, and exercise measures. Results Response rate was 47% and did not vary importantly by background characteristics. In total. 71 children (aged 13-14 years) participated in the measurements, 37 born MLP and 34 born full term. Both groups were comparable in height, weight, and exercise activities but differed in gestational age (MLP 34 +/- 1 weeks, full term 39 +/- 0.9 weeks) and birth weight (MLP 2442 +/- 539 g, full term 3693 +/- 393 g). Adolescents born MLP reported more (dry) cough (MLP 25% vs those born full term 3%, P = .016) and hay fever (MLP 34% vs those born full term 9%, P = .015). Adolescents born MLP did not report more wheeze, dyspnea, asthma, and eczema. Most lung function measurements were within the normal range for both groups, except peak expiratory flow (MLP 86% of predicted vs those born full term 93%, P = .05) and maximum expiratory flow when 75% of the forced vital capacity has been exhaled (MLP 86% predicted vs those born full term 96% predicted, P = .06). which were at the lower limit of normal. We observed no differences between the groups in exercise parameters. Conclusion Moderately late preterm birth has little effect on respiratory health in adolescence. Adolescents born MLP report few symptoms, have only slightly more lung function abnormalities than those born full term, and do not differ in the maximal exercise test and in physical activity level

Development of moderately preterm-born children

Children born 4-8 weeks prematurely have a higher risk of developmental problems than previously presumed. This is one of the findings in the Pinkeltje study, set up by UMCG paediatrician and neonatologist Jorien Kerstjens. ‘Some seven percent of all children in the Netherlands are born prematurely and the majority of them (70-85%) fall into this category,’ says Kerstjens. ‘It is a “forgotten” group. Unlike children born more than eight weeks prematurely (the “real” premature infants), paediatrics does not provide follow-up monitoring during their development.’ In view of the fact that 35% of brain development takes place in the final phase of pregnancy, Kerstjens is arguing for greater awareness of the risk of developmental problems in moderately preterm-born children. She will be awarded a PhD by the University of Groningen on 13 May 2013. Kerstjens compared the development of children born moderately prematurely with that of children born full term and very prematurely (pregnancy of less than 32 weeks). At four years of age, she found developmental problems in 8.3% of the moderately preterm-born children, which is double the percentage found in children born full term. Developmental problems were evident in 14.9% of the seriously preterm-born children. By the age of seven, the moderately preterm-born children were scoring lower than children born full term for IQ, the development of visual-spatial skills (such as doing jigsaws), attention span and selective focusing on main issues. ‘Up until now, it was generally assumed that moderately preterm-born children would develop normally, but my research shows that some of these children show clear signs of long-term developmental problems’, says Kerstjens. Exponential The more prematurely infants are born, the higher the risk of developmental problems, concludes Kerstjens. ‘We think this is because the most important part of brain development takes place in the third trimester of pregnancy. Many premature infants have also experienced other problems relating to the placenta; they are put into incubators immediately after birth, are fed differently and exposed to different stimuli than if they had been carried to full term. This causes their brains to develop differently from children born full term.’ Kerstjens would like to see more attention paid to these risks when deciding whether or not to deliver an infant before term. Factors A number of well-known factors increase the risks of premature labour and developmental problems in moderately preterm-born children. Kerstjens cites smoking during pregnancy and obesity on the part of the mother. ‘Multiple pregnancies also tend to be shorter. Fertility treatment such as IVF often leads to multiple births. Indirectly, my research seems to be advising women not to wait too long before getting pregnant,’ says Kerstjens. Social importance According to Kerstjens, we are currently putting a lot of effort into monitoring and helping children born more than eight weeks prematurely. ‘This is obviously important, but we should be doing more for the group of moderately preterm-born children too. The social importance of monitoring and helping this group should not be underestimated. It’s actually more important than helping the group of very preterm-born children.’ In absolute terms, the group of moderately preterm-born 4-year-olds with retarded development in the Netherlands is probably twice as large as the group of more seriously preterm-born 4-year-olds with developmental problems. Kerstjens thinks that helping these children during the first four years of their lives may improve their opportunities in the future. She is also predicting more attention world-wide for moderately preterm-born children. Kinderen die 4 tot 8 weken te vroeg worden geboren, hebben meer kans op ontwikkelingsproblemen dan eerder werd gedacht. Dit blijkt uit de Pinkeltje-studie die UMCG-kinderarts en neonatoloog Jorien Kerstjens heeft opgezet. “Zo’n 7% van alle kinderen in Nederland wordt te vroeg geboren en het overgrote deel daarvan (70-85%) valt in deze groep,” vertelt Kerstjens. “Het is een ‘vergeten’ groep die helemaal geen extra ontwikkelings-follow-up krijgt binnen de kindergeneeskunde, in tegenstelling tot kinderen die meer dan acht weken te vroeg worden geboren, de ‘echte’ prematuren.” Kerstjens pleit voor meer bewustwording van het risico op ontwikkelingsproblemen bij matig te vroeg geborenen omdat juist in deze laatste fase van de zwangerschap nog zo’n 35% van de hersenontwikkeling plaatsvindt. Kerstjens promoveert op 13 mei 2013 aan de Rijksuniversiteit Groningen. Kerstjens vergeleek de ontwikkeling van matig te vroeg geboren kinderen met die van op tijd geboren kinderen en ernstig-vroeggeborenen (minder dan 32 weken zwangerschap). Op vierjarige leeftijd vond zij bij 8,3% van de matig te vroeg geboren kinderen ontwikkelingsproblemen, twee keer zoveel als bij op-tijd geboren kinderen. Bij ernstig-vroeggeborenen kwam dit voor bij 14,9% van de kinderen. Op zevenjarige leeftijd scoorden de matig te vroeg geboren kinderen in vergelijking met op-tijd geborenen minder goed qua IQ, ontwikkeling van visueel-ruimtelijke vaardigheden zoals puzzels leggen, aandacht, en selectief kunnen focussen op wat belangrijk is. “Lang werd gedacht dat het altijd wel goed zou komen met de ontwikkeling van matig te vroeg geboren kinderen, maar mijn onderzoek laat zien dat er bij een deel van deze kinderen wel degelijk sprake is van een langdurige ontwikkelingsachterstand”, aldus Kerstjens.

Frequency and Prognostic Significance of Hemoptysis in Pediatric Pulmonary Arterial Hypertension

<p>Data concerning the prevalence, risk factors, and prognostic significance of hemoptysis in pediatric pulmonary arterial hypertension (PAH) are scarce. A Dutch national cohort of 74 children with either idiopathic or heritable PAH (IPAH/HPAH, n = 43) or PAH associated with congenital heart disease (PAH-CHD, n = 31) were followed from 1993 to 2012. During a median follow-up of 3.5 years (range 0.1 to 19.2), hemoptysis occurred in 13 children (17.6%). The hemoptysis event rate was 9.9 per 100 patient-years, equally divided between IPAH/HPAH and PAH-CHD (p = 0.824). The median age at first hemoptysis was 12.5 years, and the median time since PAH diagnosis to first hemoptysis was 6.1 years. Patients with hemoptysis had longer time since PAH diagnosis (p = 0.001) and more frequently used anticoagulant therapy (p = 0.006). Univariate Cox regression analysis indicated that older age (hazard ratio [HR] 1.15, 95% confidence interval [CI] 1.01 to 1.30, p = 0.031), World Health Organization functional class IV (HR 0.28, 95% CI 0.08 to 0.95, p = 0.042), higher mean pulmonary arterial pressure (HR 1.04, 95% CI 1.00 to 1.07, p = 0.028), and higher indexed pulmonary vascular resistance (HR 1.08, 95% CI 1.02 to 1.15, p = 0.009), all at the time of PAH diagnosis, were associated with increased risk of hemoptysis during follow-up. Ten of 13 patients with hemoptysis died or underwent (heart-) lung transplantation; in 6 patients, this was directly related to hemoptysis. In conclusion, the occurrence of hemoptysis in pediatric IPAH/HPAH and PAH-CHD increases with time since diagnosis, is a serious condition, and is, in case of life-threatening hemoptysis, associated with poor outcome. (C) 2013 Elsevier Inc. All rights reserved.</p>