Chronic lung disease of the neonate; Pathophysiology and treatment after the first weeks of life

Chronic lung disease of the neonate sometimes occurs as a residual condition following respiratory distress in preterm infants. - Improvements in neonatal intensive care treatment will in future lead to a greater number of children surviving chronic lung disease and reaching adulthood. - The symptoms of the disease are hypoxaemia, hypercapnia, tachypnoea, subcostal and intercostal retractions, fluid retention, a reduced exertion tolerance and hyperreactive airways. - The treatment after the first weeks of life is symptomatic and consists of: - providing supplemental oxygen via a nasal mask or cannula (0,1-1 l/min); rapid downward adjustment of oxygen therapy may lead to more complaints and poorer growth; - a normal fluid therapy; if there is a tendency towards fluid retention, then diuretic therapy is indicated and in severe cases fluid restriction as well; - in the case of bronchial hyperreactivity: inhaled corticosteroids (the lowest effective dose for a period of several months) and a trial treatment with beta-agonists; in the case of persistent complaints or functional limitations, lung function tests can distinguish obstructive and restrictive disorders; - vaccinations according to the national programme; consider vaccinations against influenza (age: 6-12 months) and respiratory syncytial virus (age &lt; 2 years).</p

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

Lung Volume, Breathing Pattern and Ventilation Inhomogeneity in Preterm and Term Infants

BACKGROUND: Morphological changes in preterm infants with bronchopulmonary dysplasia (BPD) have functional consequences on lung volume, ventilation inhomogeneity and respiratory mechanics. Although some studies have shown lower lung volumes and increased ventilation inhomogeneity in BPD infants, conflicting results exist possibly due to differences in sedation and measurement techniques. METHODOLOGY/PRINCIPAL FINDINGS: We studied 127 infants with BPD, 58 preterm infants without BPD and 239 healthy term-born infants, at a matched post-conceptional age of 44 weeks during quiet natural sleep according to ATS/ERS standards. Lung function parameters measured were functional residual capacity (FRC) and ventilation inhomogeneity by multiple breath washout as well as tidal breathing parameters. Preterm infants with BPD had only marginally lower FRC (21.4 mL/kg) than preterm infants without BPD (23.4 mL/kg) and term-born infants (22.6 mL/kg), though there was no trend with disease severity. They also showed higher respiratory rates and lower ratios of time to peak expiratory flow and expiratory time (t(PTEF)/t(E)) than healthy preterm and term controls. These changes were related to disease severity. No differences were found for ventilation inhomogeneity. CONCLUSIONS: Our results suggest that preterm infants with BPD have a high capacity to maintain functional lung volume during natural sleep. The alterations in breathing pattern with disease severity may reflect presence of adaptive mechanisms to cope with the disease process

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

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