United Kingdom Oscillation Study Research Articles

Longitudinal changes in lung function in very prematurely born young people receiving high-frequency oscillation or conventional ventilation from birth.

ObjectiveTo examine changes in lung function over time in extremely prematurely born adolescents.Working HypothesisChanges in lung function during adolescence would vary by ventilation mode immediately after birth.Study DesignLongitudinal follow‐up study.Patient Subject SelectionParticipants from the United Kingdom Oscillation Study who were randomized at birth to high‐frequency oscillation (HFO) or conventional ventilation (CV) were assessed at 11–14 years (n = 319) and at 16–19 years (n = 159).MethodologyForced expiratory flow (FEF), forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and lung volumes including functional residual capacity (FRC) were reported as z‐scores. The diffusion capacity of the lungs for carbon monoxide (DLCO) was measured. Lung function trajectories were compared by mode of ventilation using mixed models. Changes in z‐scores were scaled to 5‐year average follow‐up.ResultsThere were significant changes in the mean FEF75, FEF50, FEF25, FEV1, FVC, and DLCO z‐scores within the CV and HFO cohorts, but no significant differences in the changes between the two groups. The mean FRC z‐score increased in both groups, with an average change of greater than one z‐score. The mean FEV1/FVC z‐score increased significantly in the CV group, but not in the HFO group (difference in slopes: p = 0.02). Across the population, deterioration in lung function was associated with male sex, white ethnicity, lower gestational age at birth, postnatal corticosteroids, oxygen dependency at 36 weeks postmenstrual age, and lower birth weight, but not ventilation mode.ConclusionsThere was little evidence that the mode of ventilation affected changes in lung function over time.

Lung function and exercise capacity in prematurely born young people.

To determine if lung function abnormalities in young people born very prematurely routinely exposed to antenatal corticosteroids and postnatal surfactant were associated with reduced exercise capacity. In the current era, lung function abnormalities would not be associated with exercise intolerance STUDY DESIGN: Follow-up of young people from the United Kingdom Oscillation study (UKOS). One hundred twenty-six young people of 797 recruited to UKOS, born at a mean gestational age of 27 weeks were assessed at a mean age of 17 years. Forced expiratory flow at 75% of the expired vital capacity (FEF75 ), forced expiratory volume in 1 second (FEV1 ) and lung volumes (forced vital capacity [FVC]) and residual volume (RV) and functional residual capacity (FRCpleth ) were assessed. Abnormal lung function was below the fifth centile and very abnormal lung function below the 2.5th centile. Exercise capacity was assessed using a modified shuttle sprint test and self-reported hours of exercise. Thirty-nine young people had an abnormal FEF75 with an adjusted reduction in sprint distance of 114 m (P = .018) and an adjusted difference in self-reported exercise of 0.73 hours (P = .036). Twenty-seven young people had a very abnormal FEF75 with an adjusted reduction in sprint distance of 159 m (P = .002) and adjusted reduction in self-reported exercise of 1.15 hours (P = .002). Very prematurely born young people with abnormal airway function had a significant reduction in exercise capacity.

Lung function and respiratory outcomes in teenage boys and girls born very prematurely.

Male sex in prematurely born infants has been associated with worse respiratory outcomes in early childhood. Respiratory outcomes at 11 to 14 years of age in children born very prematurely and routinely exposed to antenatal corticosteroids and postnatal surfactant would differ according to sex. Analysis of follow-up data. Three hundred and nineteen children born before 29 weeks of gestational age from the United Kingdom Oscillation Study. Spirometry was used to assess forced expiratory flow at 75%, 50%, and 25% of expired vital capacity (FEF75 , FEF50 , and FEF25 ), forced expiratory volume in 1 second (FEV1 ), peak expiratory flow (PEF), and forced vital capacity (FVC). Lung volumes were measured using a helium dilution technique (FRCHe ) and by plethysmography (FRCpleth ). Total lung capacity (TLC) and residual volume (RV) were calculated. Mean lung function measurements were compared using linear mixed models and reported as unadjusted and adjusted for neonatal and age 11 to 14 years factors. The participants also completed health questionnaires and provided a urine sample for assessment of passive or active smoking. Three (FEF25 , FEF25-75 , FEV1 ) lung function measures showed significant differences in favor of females after adjustment. The percentage of children with abnormal lung function (below 5th centile for normal) had adjusted differences between 10 and 30 percentage points, for example, for FEF25 15% females compared with 26% males. Among extremely prematurely born school children airway function was significantly worse in males.

Participant retention in follow-up studies of prematurely born children

BackgroundFollow-up studies of infants born prematurely are essential to understand the long-term consequences of preterm birth and the efficacy of interventions delivered in the neonatal period. Retention of participants for follow-up studies, however, is challenging, with attrition rates of up to 70%. Our aim was to examine retention rates in two follow-up studies of prematurely born children and identify participant or study characteristics that were associated with higher attrition, and to discuss retention strategies with regard to the literature.MethodsData from children recruited at birth to one of two studies of prematurely born infants were assessed. The two studies were the United Kingdom Oscillation Study (UKOS, a randomised study comparing two modes of neonatal ventilation in infants born less than 29 weeks of gestational age (GA)), and an observational study examining the impact of viral lower respiratory tract infections in infancy in those born less than 36 weeks of GA (virus study). The UKOS participants, but not those in the virus study, had regularly been contacted throughout the follow-up period. UKOS subjects were followed up at 11 to 14 years of age and subjects in the virus study at 5–7 years of age. At follow up in both studies, pulmonary function and respiratory morbidity were assessed. Retention rates to follow-up in the two studies and baseline characteristics of those who were and were not retained were assessed.ResultsRetention was significantly higher in UKOS than the virus study (61% versus 35%, p < 0.0001). Subjects lost to UKOS follow up had greater deprivation scores (p < 0.001), a greater likelihood of intrauterine tobacco exposure (p = 0.001) and were more likely to be of non-white ethnicity (p < 0.001). In the virus study, those lost to follow-up had higher birth weights (p = 0.036) and were less likely to be oxygen dependent at hospital discharge (p = 0.003) or be part of a multiple birth (p = 0.048).ConclusionsHigher retention was demonstrated when there was regular contact in the follow-up period. Both social factors and initial illness severity affected the retention into follow-up studies of prematurely born infants, though these factors were not consistent across the two studies.

An in vitro investigation of the inflammatory response to the strain amplitudes which occur during high frequency oscillation ventilation and conventional mechanical ventilation

Children randomised in the neonatal period to high frequency oscillatory ventilation (HFOV) or conventional mechanical ventilation (CMV) in the United Kingdom Oscillation study (UKOS) had superior lung function at 11 to 14 years of age. During HFOV, much smaller tidal volumes, but a higher mean airway distending pressure is delivered, hence, a possible explanation for a volume dependent effect on long term lung function could be an increase in inflammation in response to higher tidal volumes and strains. We tested that hypothesis by assessing interleukin-6 (IL-6) and -8 (IL-8) release from A549 alveolar analogue cells following biaxial mechanical strain applied at 0.5 Hz occurring during conditions mimicking strain during CMV (5–20% strain) and conditions mimicking strain during HFOV (17.5% ± 2.5% strain) for up to 4 h. Cyclic strain of 5–20%, occurring during CMV, increased levels of both IL-6 and IL-8 compared to unstrained controls, while 17.5% ± 2.5% strain, occurring during HFOV, was associated with significantly lower levels of IL-6 (46.31 ± 2.66 versus 56.79 ± 3.73 pg/mL) and IL-8 (1340.2 ± 74.9 versus 2522 ± 248 pg/mL) secretion compared to conditions occurring during CMV at four hours. These results may provide a possible explanation for the superior lung function in 11–14-year-old children who had been supported in the neonatal period by HFOV.

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.

P09 Pulmonary artery pressures in school age children born very prematurely

AimBronchopulmonary dysplasia, which occurs most frequently in extremely prematurely born infants, can be complicated by pulmonary hypertension due to dysregulation of angiogenesis and increased muscularisation of the pulmonary arteries. (1)...

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

BackgroundVery 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...

Respiratory morbidity at follow-up of small-for-gestational-age infants born very prematurely

The aim of this study was to determine whether small-for-gestational-age (SGA) infants born very prematurely had increased respiratory morbidity in the neonatal period and at follow-up. Data were examined from infants recruited into the United Kingdom Oscillation Study (UKOS). Of the 797 infants who were born at <29 wk of gestational age, 174 infants were SGA. Overall, 92% were exposed to antenatal corticosteroids and 97% received surfactant; follow-up data at 22-28 mo were available for 367 infants. After adjustment for gestational age and sex, SGA infants had higher rates of supplementary oxygen dependency at 36 wk postmenstrual age (odds ratio (OR): 3.23; 95% confidence interval: 2.03, 5.13), pulmonary hemorrhage (OR: 3.07; 95% CI: 1.82, 5.18), death (OR: 3.32; 95% CI: 2.13, 5.17), and postnatal corticosteroid requirement (OR: 2.09; 95% CI: 1.35, 3.23). After adjustment for infant and respiratory morbidity risk factors, a lower mean birth weight z-score was associated with a higher prevalence of respiratory admissions (OR: 1.40; 95% CI: 1.03, 1.88 for 1 SD change in z-score), cough (OR: 1.28; 95% CI: 1.00, 1.65), and use of chest medicines (OR: 1.32; 95% CI: 1.01, 1.73). SGA infants who were born very prematurely, despite routine use of antenatal corticosteroids and postnatal surfactant, had increased respiratory morbidity at follow-up, which was not due to poor neonatal outcome.

Neonatal and infant outcome in boys and girls born very prematurely

Although important new strategies have improved outcomes for very preterm infants, males have greater mortality/morbidity than females. We investigated whether the excess of adverse later effects in males operated through poorer neonatal profile or if there was an intrinsic male effect. Male sex was significantly associated with higher birth weight, death or oxygen dependency (72% vs. 61%, boys vs. girls), hospital stay (97 vs. 86 days), pulmonary hemorrhage (15% vs. 10%), postnatal steroids (37% vs. 21%), and major cranial ultrasound abnormality (20% vs. 12%). Differences remained significant after adjusting for birth weight and gestation. At follow-up, disability, cognitive delay, and use of inhalers remained significant after further adjustment. We conclude that in very preterm infants, male sex is an important risk factor for poor neonatal outcome and poor neurological and respiratory outcome at follow-up. The increased risks at follow-up are not explained by neonatal factors and lend support to the concept of male vulnerability following preterm birth. Data came from the United Kingdom Oscillation Study, with 797 infants (428 boys) born at 23-28 wk gestational age. Thirteen maternal factors, 8 infant factors, 11 acute outcomes, and neurological and respiratory outcomes at follow-up were analyzed. Follow-up outcomes were adjusted for birth and neonatal factors sequentially to explore mechanisms for differences by sex.

Factors affecting vocabulary acquisition at age 2 in children born between 23 and 28 weeks' gestation

Language development is often slower in preterm children compared with their term peers. We investigated factors associated with vocabulary acquisition at 2 years in a cohort of children born at 28 weeks' gestation or less. For children entered into the United Kingdom Oscillation Study, language development was evaluated by using the MacArthur-Bates Communicative Development Inventories score, completed by parents as part of a developmental questionnaire. The effect of demographic, neonatal, socioeconomic factors, growth, and disability were investigated using multifactorial random effects modelling. Questionnaires were returned by 288 participants (148 males, 140 females). The mean number of words vocalized was 42 (SD 29). Multifactorial analysis showed only four factors were significantly associated with vocabulary acquisition. These were: (1) level of disability (mean words: no disability, 45; other disability, 38; severe disability, 30 [severe disability is defined as at least one extreme response in one of the following clinical domains: neuromotor, vision, hearing, communication, or other physical disabilities]; 95% confidence interval [CI] for the difference between no and severe disability 7- 23); (2) sex (39 males, 44 females; 95% CI 0.4-11); (3) length of hospital stay (lower quartile, 47; upper quartile, 38; 95% CI -12 to -4); and (4) weight SD score at 12 months (lower quartile, 39; upper quartile, 44; 95% CI 1-9). There was no significant association between gestational age and vocabulary after multifactorial analysis. There was no significant effect of any socioeconomic factor on vocabulary acquisition. We conclude that clinical factors, particularly indicators of severe morbidity, dominate the correlates of vocabulary acquisition at age 2 in children born very preterm.

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...

Respiratory function of very prematurely born infants at follow up: influence of sex

Objective: To test the hypothesis that male compared with female prematurely born infants would have worse lung function at follow up. Design: Prospective follow up study. Setting: Tertiary neonatal intensive...

Risk factors for respiratory morbidity in infancy after very premature birth

Objectives: To determine the occurrence of respiratory morbidity during infancy after very premature birth and to identify risk factors. Design: Prospective follow up study. Setting: The United Kingdom oscillation study....