Sandy Calvert

Randomised trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: respiratory and neurological outcomes at 2 years

Background: The long term outcome of children entered into neonatal trials of high frequency oscillatory ventilation (HFOV) or conventional ventilation (CV) has been rarely studied. Objective: To evaluate respiratory and neurodevelopmental outcomes for children entered into the United Kingdom Oscillation Study, which was designed to evaluate these outcomes. Methods: Surviving infants were followed until 2 years of age corrected for prematurity. Study forms were completed by local paediatricians at routine assessments, and parents were asked to complete a validated neurodevelopmental questionnaire. Results: Paediatricians’ forms were returned for 73% of the 585 surviving infants. Respiratory symptoms were common in all infants, and 41% had received inhaled medication. Mode of ventilation had no effect on frequency of any symptoms. At 24 months of age, severe neurodevelopmental disability was present in 9% and other disabilities in 38% of children, but the prevalence of disability was similar in children who received HFOV or CV (relative risk 0.93; 95% confidence interval 0.74 to 1.16). The prevalence of disability did not vary by gestational age, but boys were more likely to have overall disability. Developmental scores were unaffected by mode of ventilation (relative risk 1.13; 95% confidence interval 0.78 to 1.63) and were lower in infants born before 26 weeks gestation compared with babies born at 26–28 weeks. Conclusions: Initial mode of ventilation in very preterm infants has no impact on respiratory or neurodevelopmental morbidity at 2 years. HFOV and CV appear equally effective for the early treatment of respiratory distress syndrome.

Frequent wheeze at follow up of very preterm infants: which factors are predictive?

Objective: To determine if chest radiograph appearance at 28 days or 36 weeks postmenstrual age (PMA) can predict recurrent wheeze or cough at follow up in prematurely born infants more effectively than readily available clinical data. Design: Chest radiographs of infants entered into the UKOS trial, who had had a chest radiograph at 28 days and 36 weeks PMA and completed six months of follow up, were assessed for the presence of fibrosis, interstitial shadows, cystic elements, and hyperinflation. At 6 months of corrected age, the occurrence and frequency of wheeze and cough since discharge were determined using a symptom questionnaire. Patients: A total of 185 infants with a median gestational age of 26 (range 23–28) weeks. Results: Thirty seven infants wheezed more than once a week, compared with the rest of the cohort. These infants had significantly higher chest radiograph scores at 28 days (p = 0.020) and 36 weeks PMA (p = 0.005), with significantly higher scores at 28 days for fibrosis (p = 0.017) and at 36 weeks PMA for fibrosis (p = 0.001) and cystic elements (p = 0.0007). They had also been ventilated for longer (p = 0.013). Forty four infants coughed more than once a week; they did not differ significantly from the rest of the cohort. An abnormal chest radiograph score at 36 weeks PMA had the largest area under the receiver operator characteristic curve with regard to prediction of frequent wheeze. Conclusion: An abnormal chest radiograph appearance at 36 weeks PMA predicts frequent wheeze at follow up and appears to be a better predictor than readily available clinical data.

Prediction of respiratory outcome in extremely low gestational age infants.

Background: Bronchopulmonary dysplasia (BPD) is a commonly used outcome for randomized neonatal trials. Objectives: The aim of the present study was to determine whether a diagnosis of BPD or respiratory morbidity (RM1 or RM2) at 12 months corrected age better predicted subsequent RM in extremely low gestational age infants (23-28 weeks of gestation). Methods: Initial analysis was undertaken in a development cohort of 76 infants who underwent pulmonary function tests (PFTs) at 12 months corrected age. Parents completed infant respiratory diaries 2 weeks before the PFTs. Analysis was then undertaken in a validation cohort of 227 infants whose parents completed a 4-week respiratory diary when their infant was 12 months corrected age. BPD at 28 days (BPD28d) and 36 weeks post-menstrual age (BPD36w), RM1 (≥3 days and/or nights of cough, wheeze, and/or medicine use) and RM2 (≥4 days and/or nights of cough, wheeze, and/or respiratory medicine use) each week for 2 weeks at 12 months corrected age were assessed with regard to prediction of respiratory outcomes at 24 months documented by respiratory health questionnaires. Results: BPD28d and BPD36w were not significantly associated with any respiratory outcome. Areas under the receiver operating characteristic curves were significantly better for either definition of RM than BPD28d or BPD36w for all outcomes. Conclusions: RM documented by parental completed diaries at 12 months corrected age better predicted respiratory outcome at 24 months corrected age than BPD regardless of diagnostic criteria.

Plethysmograph and interrupter resistance measurements in prematurely born young children.

Background: Airways obstruction in premature infants is often assessed by plethysmography, which requires sedation. The interrupter (Rint) technique does not require sedation, but has rarely been examined in children under 2 years of age. Objective: To compare Rint results with plethysmographic measurements of airway resistance (Raw) in prematurely born, young children. Design: Prospective study. Setting: Infant and Paediatric Lung Function Laboratories. Patients: Thirty children with a median gestational age of 25–29 weeks and median postnatal age of 13 months. Interventions and main outcome measures: The infants were sedated, airway resistance was measured by total body plethysmography (Raw), and Rint measurements were made using a MicroRint device. Further Raw and Rint measurements were made after salbutamol administration if the children remained asleep. Results: Baseline measurements of Raw and Rint were obtained from 30 and 26 respectively of the children. Mean baseline Rint values were higher than mean baseline Raw results (3.45 v 2.84 kPa/l/s, p  =  0.006). Limits of agreement for the mean difference between Rint and Raw were −1.52 to 2.74 kPa/l/s. Ten infants received salbutamol, after which the mean Rint result was 3.6 kPa/l/s and mean Raw was 3.1 kPa/l/s (limits of agreement −0.28 to 1.44 kPa/l/s). Conclusion: The poor agreement between Rint and Raw results suggests that Rint measurements cannot substitute for plethysmographic measurements in sedated prematurely born infants.

Airway resistance estimation by best fit analysis in very premature infants

Plethysmographic measurement of airway resistance (R(aw)) has been determined by single-point analysis, usually at 50% of maximum inspiratory flow (MIF). Computer-assisted (best fit) analysis, however, allows R(aw) to be calculated by applying a regression line to any portion of the plethysmograph pressure-flow loop. We determined whether the results of best fit analysis using a computer program, sampling at 200 Hz, were influenced by the portion of the inspiratory loop analysed and if best fit or single-point analysis gave more reproducible results. Twenty infants of median gestational age 26 (range 24-28) weeks, were studied at a median age of 12 (12-14) months corrected for prematurity. R(aw) was calculated by best fit analysis between 0 and 33% MIF, 0 and 50% MIF and 0 and 67% MIF and single-point analysis at 50% of MIF. Similar mean R(aw) values were obtained by best fit analysis between 0 and 33% MIF (2.79 kPa/(l/s)) and 0 and 50% MIF (3.01 kPa/(l/s)) and single-point analysis at 50% MIF (2.86 kPa/(l/s)), but best fit analysis between 0 and 67% gave higher results (3.60 kPa/(l/s)), p < 0.0001. Within the linear portion of the inspiratory loop, the mean intrasubject coefficient of variation was lowest for best fit analysis between 0 and 50% MIF. Best fit computerized analysis between 0 and 50% MIF is recommended as the analysis of choice.

Postnatal dexamethasone, respiratory and neurodevelopmental outcomes at two years in babies born extremely preterm

Importance Postnatal dexamethasone is associated with reduction in bronchopulmonary dysplasia. There remains, however, concern that its short-term benefits are accompanied by long-term adverse effects e.g. poorer neurodevelopmental outcomes. Objective Our aim was to determine the effects of administration of postnatal dexamethasone on respiratory and neurodevelopmental outcome at two years of age after adjusting for neonatal and infant risk factors. Materials and methods The study included 412 infants born at 23–28 weeks of gestation, 29% had received postnatal dexamethasone. Two outcomes were examined, respiratory hospital admissions in the past 12 months and neurodevelopmental impairment. Logistic regression, adjusted for sex, birthweight z-score, gestation, maternal smoking, oxygen dependency at 36 weeks, airleak, patent ductus arteriosus, pulmonary haemorrhage, major ultrasound abnormality, mode of ventilation and age at assessment, was undertaken. Results After adjustment, postnatal dexamethasone was associated with significantly increased proportions of both respiratory hospital readmission: (0.35 vs 0.15, difference = 0.20; 95% CI: 0.08, 0.31) and neurodevelopmental impairment (0.59 vs 0.45, difference = 0.14; 95% CI: 0.02, 0.26). Conclusions Postnatal dexamethasone use in extremely preterm infants is associated with increased risks of respiratory hospital admissions and neurodevelopmental impairment. These associations were not explained by excess neonatal morbidities.

Longitudinal assessment of lung function in extremely prematurely born children

To assess longitudinally small airway function in children born extremely prematurely and whether there was a correlation between airway function in infancy and at 11‐14 years.

Effect of dexamethasone exposure on the neonatal unit on the school age lung function of children born very prematurely

The objective of this study was to determine the impact of postnatal dexamethasone treatment on the neonatal unit on the school age lung function of very prematurely born children. Children born prior to 29 weeks of gestational age had been entered into a randomised trial of two methods of neonatal ventilation (United Kingdom Oscillation Study). They had comprehensive lung function measurements at 11 to 14 years of age. One hundred and seventy-nine children born at a mean gestational age of 26.9 (range 23–28) weeks were assessed at 11 to 14 years; 50 had received postnatal dexamethasone. Forced expiratory flow at 75% (FEF75), 50%, 25% and 25–75% of the expired vital capacity, forced expiratory volume in one second, peak expiratory flow and forced vital capacity and lung volumes including total lung capacity and residual volume were assessed. Lung function outcomes were compared between children who had and had not been exposed to dexamethasone after adjustment for neonatal factors using linear mixed effects regression. After adjustment for confounders all the mean spirometry results were between 0.38 and 0.87 standard deviations lower in those exposed to dexamethasone compared to the unexposed. For example, the mean FEF75 z-score was 0.53 lower (95% CI 0.21 to 0.85). The mean lung function was lower as the number of courses of dexamethasone increased. In conclusion, postnatal dexamethasone exposure was associated with lower mean lung function at school age in children born extremely prematurely. Our results suggest the larger the cumulative dose the greater the adverse effect on lung function at follow-up.

Pulmonary Artery Pressures in School-Age Children Born Prematurely

Objectives To test the hypothesis that pulmonary artery pressures were higher in school aged children born extremely premature than those born at term. We also wanted to assess whether pulmonary artery pressures differed between children born prematurely with or without bronchopulmonary dysplasia (BPD) or between those randomized in the neonatal period to different ventilation modes. Study design Transthoracic echocardiography was performed on 193 children born extremely premature (106 had BPD) and 110 children born at term when they were 11–14 years of age. Ninety‐nine children born extremely premature had been supported by high‐frequency oscillation and 94 by conventional ventilation. Tricuspid regurgitation was assessed in the apical 4‐chamber and modified parasternal long‐axis views. Continuous‐wave Doppler of the peak regurgitant jet velocity was used to estimate the right‐ventricular‐to‐right‐atrial systolic pressure gradient. Results Tricuspid regurgitation was measurable in 71% (137/193) of the children born preterm and 75% (83/110) of the children born at term (P .23). The children born prematurely compared with the children born at term had a greater peak tricuspid regurgitation velocity (2.21 vs 1.95 m/s, P < .001) and the children born prematurely who had BPD vs those without BPD had a greater peak tricuspid regurgitation velocity (P = .023). There were no significant differences in pulmonary artery pressures according to neonatal ventilation mode. Conclusions Pulmonary artery pressures were estimated to be greater in 11‐ to 14‐year‐old children born extremely prematurely compared with those born at term and in those born prematurely who developed BPD compared with those who did not but did not differ significantly by neonatal ventilation mode.

G155 Small For Gestational Age at Birth and Lung Function at School Age in Very Prematurely Born Children

Background Very prematurely born infants who were small for gestation age (SGA) at birth, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity in infancy – increased rates of BPD and hospital readmissions for respiratory disorders (1). Aim To test the hypothesis that amongst children born very prematurely, those who were SGA would have greater lung function abnormalities at school age. Methods Lung function was assessed at 12 to 13 years of age in 204 children born <29 weeks of gestational age; 50 were SGA (<10th centile for weight). They had been entered into the United Kingdom Oscillation Study and randomised within one hour after birth to receive high frequency oscillation or conventional ventilation. There were no significant differences in short term outcomes (2), hence the results of the children in the two arms were pooled for this study. Forced expiratory volume in one second (FEV1), forced vital capacity (FVC), FEV1:FVC, residual volume (RV), diffusion factor for carbon monoxide (DLCO), functional residual capacity (FRCpleth) and maximum expiratory flow at 24, 50, 75% of vital capacity (MEF25,50,75) were assessed. The results were expressed as z-scores. The response to a cold air challenge (CACh) was considered positive if FEV1 fell by >10% of baseline. Results At the time of assessment, compared to the non SGA children, the SGA children had lower weight (p < 0.001) and height (p = 0.002). The SGA children had lower mean z-scores for FEV1 (p < 0.001), FEV1/FVC (P = 0.009), DLCO (p = 0.013), MEF25 (p = 0.005), MEF50 (p = 0.002) and MEF75 (p < 0.001) and a higher mean FRCpleth z-score (p = 0.010). There was no significant difference regarding the proportion of SGA and non SGA children responding to a CACh (p = 0.091). Conclusion These results suggest that amongst very prematurely born children, being SGA at birth is associated with greater restrictive and obstructive (particularly of small airways) lung function abnormalities at school age. References Peacock J, Marston L, Marlow N, et al Neonatal and infant outcome in boys and girls born very prematurely. Ped Res 2012; 71:305–310. Johnson AH, Peacock JL, Greenough A, et al High frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity. New Engl J Med 2002; 347:633–642.