Dear Editor,

We read with interest the article by Marlow et al on the long term respiratory and neurodevelopmental outcomes in babies, 28 weeks of gestation or less, in the UKOS trial[1]. It was reassuring to learn that babies in the HFOV arm were no worse than the controls in terms of their long term neurodevelopment outcome. This is contrary to the neurodevelopmental outcomes observed in the HiFi trial [2].

However we have some general queries about the paper;

1.As there is only data from 428 of 529 survivors with almost one third lost to follow-up (164 infants, 27% of survivors), it may be possible that lower rates of neurodevelopmental disability observed in the UKOS trial reflects underreporting. This may represent an ascertainment bias and underreporting of those with the worst neurodevelopment outcomes.[3] .

2.It was not clear why outcome data on 55 infants (13% of survivors) was not included in the analysis even though analysis was on an “intention to treat basis”.

3.In table-1 the number of infants with no outcome data returned (171 infants) doesn’t match the number derived from figure-1(164 infants).

At present those unanswered points may limit the external validity of the study findings.

References:

1.N Marlow, A Greenough,J L Peacock S Limb, A H Jonhson,S A Calvert, for the United Kingdom Oscillatory Study Group. Randomized trial of high frequency oscillatory ventilation or conventional ventilation in babies of gestational age 28 weeks or less: repiratory and neurological outcome at 2 years. (Arch Dis Child Fetal Neonatal Ed 2006; 91 No 5:F320–F326).

2.HiFi study group; High frequency oscillatory ventilation compared with conventional intermittent mechanical ventilation in the treatment of respiratory failure in preterm infants; Neurodevelopmental status at 16-24 months of post term age. J Pediatr 19900; 17:939-946.

3.Win Tin, Susan Fritz, Unni Wariyar, Edmund Hey. Outcome of very preterm birth: children reviewed with ease at 2 years differ from those followed up with difficulty. (Arch Dis Child Fetal Neonatal Ed 1998; 79:F83–F87).

Dear Editor,

Paper from Marlow et al. (1) compares the neurological outcomes of infants of gestational age 28 week or less who were ventilated with high frequency oscillatory ventilation or conventional mechanical ventilation. They concluded that the initial mode of ventilation does not affect neurodevelopmental morbidity at 2 years. However, considering their enrolment criteria [“Infants were eligible for the study if their gestational age was between 23 weeks and 28 weeks plus 6 days; if they were born in a participating center; if they required endotracheal intubation from birth; and if they required ongoing intensive care” (2)] which did not take in account the severity of respiratory distress syndrome, it is difficult to hypothesize that the type of mechanical ventilation could affect alone neurodevelopmental outcome in infants who were ventilated only few hours or days. Probably, it would more useful to distinguish infant with normal, moderate abnormal, and severe abnormal neurological development for evaluating through a multivariate analysis the independent role of all factors (i.e. : the severity of respiratory illness, type of mechanical ventilation, birth weight, etc.) which could exert a detrimental effect on central nervous system.

References:

1. Marlow N, Greenough A, Peacock JL, Marston L, Limb ES, Johnson AH, Calvert SA. 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. Arch Dis Child Fetal Neonatal Ed. 2006;91:F320-6.

2. Johnson AH, Peacock JL, Greenough A, Marlow N, Limb ES, Marston L, Calvert SA; United Kingdom Oscillation Study Group. High-frequency oscillatory ventilation for the prevention of chronic lung disease of prematurity. N Engl J Med. 2002;347:633-42.