Outcomes of the Neonatal Trial of High-Frequency Oscillation at 16 to 19 Years

Abstract

We previously reported superior lung function and teacher ratings of school performance in young persons who had received high-frequency oscillatory ventilation (HFOV) as neonates.1 In a multicenter, randomized trial, HFOV was compared with conventional ventilation that commenced within an hour of birth in infants born before 29 weeks of gestation.2 We hypothesized that the positive outcomes of HFOV would persist after the onset of puberty and now report the results of a reassessment of this cohort at the ages of 16 to 19 years. Comprehensive lung-function assessments were undertaken and questionnaires completed regarding respiratory health, health-related quality of life, and lung function (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). As in our previous assessment of children 11 to 14 years of age,1 the primary outcome was forced expiratory flow at 75% of the expired vital capacity (FEF75). Because some children were unable to complete all the lung-function tests, we used multiple imputation with chained equations to impute missing data. Table 1. Lung-Function Test Results According to Ventilation Group. A total of 161 young people were evaluated, and 159 underwent lung-function assessment (Fig. S1 in the Supplementary Appendix). Baseline characteristics were similar among those who were assessed and those who were not (Table S1). Participant characteristics did not differ significantly between the ventilation groups when assessed as infants or at 16 to 19 years of age (Table S2). The results with respect to the primary outcome did not differ significantly between the ventilation groups at 16 to 19 years of age: mean (±SD) FEF75 z score of −1.07±1.21 with conventional ventilation and −0.94±1.33 with HFOV (adjusted difference in mean z scores, 0.19; 95% confidence interval [CI], −0.18 to 0.56) (Table 1 and Table S3). These differences remained nonsignificant after multiple imputation (P=0.11) (Table S4). The majority of the mean FEF75 results reported when participants were 16 to 19 years of age were below the lower limit of normal (59% with HFOV and 65% with conventional ventilation). Other measures of lung function also did not differ significantly between the ventilation groups (Table 1 and Table S3). However, 15% of participants in the HFOV group received a diagnosis of asthma, whereas only 3% of participants in the conventional ventilation group had such a diagnosis (adjusted difference, 11 percentage points; 95% CI, 3 to 23). Similarly, inhalers were prescribed for asthma treatment in 13% of those in the HFOV group as compared with 3% of those in the conventional ventilation group (adjusted difference, 11 percentage points; 95% CI, 2 to 21) (Table S5). Our follow-up study of infants who had been enrolled in a randomized trial in which two types of ventilation were prescribed showed that the use of HFOV in the neonatal period was not associated with superior respiratory or functional outcomes at 16 to 19 years of age. Longer-term follow-up is required to determine whether there will be premature onset of chronic pulmonary disease in this vulnerable population.