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Re: RSV infection in prematurely born infants

RSV infection in prematurely born infants

We thank Drs Clifford and Deshpande for their comments on our paper [1]. Both are concerned about the cost-effectiveness of Palivizumab. Our paper, however, was not about the cost-effectiveness of Palivizumab but to examine prospectively healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants. Importantly, we demonstrated an effect not only on hospital admission, but also on GP attendances and subsequent cough and wheeze.

In response to Dr Clifford’s specific comments:
• We take conflicts of interest statements very seriously.
• We cannot comment on the percentage of smokers in the non-consenters, as it would be unethical to collect detailed data on parents who had refused to take part in the study.
• It is a pity Dr Clifford did not contact us directly as we would have been very pleased to have given him our raw data, if he wished to undertake an appropriately designed cost effectiveness study, and contacting us would have revealed that the two infants who received Palivizumab and had an RSV LRTI were not admitted to hospital.
• We agree it is very important to find effective ways to stop antenatal women and house-holders of premature babies smoking. As our data demonstrate current methods are clearly ineffective.

In response to Dr Deshpande:
• We apologise the duration of oxygen therapy was given in a confusing fashion, as postmenstrual age (wks), not as number of weeks since birth.
• The 40% rate of BPD at 36 weeks post menstrual age is very similar to the 46% reported recently [2].
• We have recently reported [3] that diminished lung function is a risk factor for RSV infection and subsequent respiratory morbidity, but in that paper also report that RSV infection is an independent risk factor for days of cough and wheeze.

In conclusion, we emphasize our study was not about the cost- effectiveness of Palivizumab, but to assess health care utilisation and respiratory morbidity following RSV infection. From the results of all studies, hypotheses are generated and need to be tested – hence our comments regarding consideration of giving Palivizumab to infants who have siblings and whose mothers smoked during pregnancy. We hope our comments will encourage researchers to undertake an appropriately designed study to test this.

References

1 Broughton S, Roberts A, Fox G, Pollina E, Zuckerman M, Chaudhry S, Greenough A. Prospective study of healthcare utilisation and respiratory morbidity due to RSV infection in prematurely born infants. Thorax 2005;60:1039-1044.

2 Ehrenkranz RA, Walsh MC, Vohr BR, Jobe AH, Wright LL, Fanaroff AA, Wrage LA, Poole K. Validation of the National Institutes of Health concensus definition of bronchopulmonary dysplasia. Pediatrics 2005;116:1353-60.

Send letter to journal:
Re: RSV infection in prematurely born infants

Dear Editor,

I read with interest the article by Broughton et al, and wish to offer following comments.

1. The duration of oxygen therapy (in both Table 1 and the text) ranges from 30 to 107 weeks, thus qualifying every baby in the cohort as having BPD. Even if this was in days, it would make every baby oxygen dependent 28 days after birth, compared to 19% in other studies(1).

2. The rate of BPD in this cohort was 40% - much higher than has been reported for babies of similar gestation in recent years(1,2). In view of this high rate of BPD and prolonged oxygen dependency, the studied cohort might have consisted of rather sick infants.

3. Since discharge home on oxygen is mentioned as one of the explanatory variables, it would be helpful to know its frequency and significance in relation to the risk of hospital admission and RSV infection.

4. It is not clear if the healthcare utilisation includes all events after discharge from the neonatal unit, or only those after a RSV infection. The authors have elsewhere suggested that babies with lung function deficits at discharge from the neonatal unit are more likely to sustain symptomatic RSV infections(3). If the healthcare utilisation includes all post-discharge events, then is it possible that the excessive healthcare utilisation of RSV-infected infants a manifestation of their underlying lung deficit rather than effect of RSV?

5. The authors suggest consideration of palivizumab for the two risk factors of RSV LRTI – maternal smoking during pregnancy and presence of school aged siblings. However, palivizumab has been shown to be effective in ‘reducing hospitalisations from RSV’ rather than ‘preventing RSV infection’ itself(4), and the validity of this extrapolation remains to be tested. Indeed, the indicator for healthcare utilisation (GP attendances) just reached significance among non-admitted RSV-infected infants as compared to no LRTI infants, the use of reliever medications being comparable in all three groups. I am not sure widening the indications for palivizumab to the suggested groups will prove to be cost-effective.

Conflict of interest: I have previously questioned the cost- effectiveness of palivizumab in relation to its recommended indications.

References

1. Manktelow BN, Draper ES, Annamalai S, Field D. Factors affecting the incidence of chronic lung disease of prematurity in 1987, 1992, and 1997. Arch Dis Child Fetal Neonatal Ed 2001;85(1):F33-5.

2. Smith VC, Zupancic JA, McCormick MC, Croen LA, Greene J, Escobar GJ, et al. Trends in severe bronchopulmonary dysplasia rates between 1994 and 2002. J Pediatr 2005;146(4):469-73.

3. Broughton S, Bhat R, Roberts A, Zuckerman M, Rafferty G, Greenough A. Diminished lung function, RSV infection, and respiratory morbidity in prematurely born infants. Arch Dis Child 2006;91(1):26-30.

Send letter to journal:
Re: Consideration of Palivizumab not justified

Dear Editor,

Broughton and colleagues state that consideration should be given to use of prophylactic palivizumab to infants born at less than 32 weeks in the case of maternal smoking or even if they have siblings. The authors however present no data from their own or other studies to indicate that this would be in any way cost effective or justified. Certainly the word "consider" is fortunate given the stated funding provided to one author by the manufacturer.

The study demonstrated a relationship between lower respiratory morbidity from RSV and smoking which has been widely shown elsewhere. Numbers of smokers were in fact very small - surprisingly so at 18 per 126 babies given both their prematurity and the catchment population for this hospital although 28 experienced smoking in the home. One wonders if the 61 non-consenters and non-attenders may have comprised a higher proportion.

Perhaps because of the small numbers there was actually very little relationship shown with smoking in pregnancy - the strong relationships were instead with the 28 passive smokers in the home. Were palvizumab to be given to this group the cost would be something over £56,000. I have unfortunately had to extrapolate from other data in the paper which would indicate that about 8 of the 16 hospital admissions (excluding the two who were given palvizumab anyway)would have been from smoking families. Assuming a halving of hospital admission rate from treatment this amounts to £56000 to prevent 4 "admissions" (with a median length of stay of 0 days) whilst 24 babeis would have received 120 needless injections. No savings are likely to acrue from this reduction as the effect on total RSV workload would be miniscule.