PEDIATRICS Vol. 108 No. 3 September 2001, pp. 761-763

COMMENTARY:
Use of Continuous Positive Airway Pressure in Preterm Infants: Comments and Experience From New Zealand

The role of continuous positive airway pressure (CPAP) in the care of preterm newborns with respiratory disease has long been debated in the neonatal literature, with much early interest focused on the multicenter study of Avery et al.¹ This study demonstrated a significantly lower incidence of chronic lung disease (CLD) in preterm infants at 28 days of life at Columbia Presbyterian Medical Center in New York, a center that used CPAP extensively. Despite valid criticisms of the limitations of that multicenter observational study design and a lack of good quality studies looking at the role of CPAP versus other respiratory support in the interim, interest has been rekindled by, among others, the recent study of Van Marter et al.² This again revealed a substantially lower incidence of CLD at Columbia versus 2 centers in Boston, in this case at 36 weeks' corrected gestational age. Additional analysis showed that despite multiple variations in details of care and respiratory support, neonatal intensive care unit (NICU)-specific risk of CLD was predominantly associated with the decision to use mechanical ventilation.

A number of questions have arisen, many of which can be answered at best only in part, and some not at all.

1. Is the success with CPAP of the Columbia group reproducible at other centers?

In a recent paper,³ the authors report in a historical cohort study the results of rigorously introducing a Columbia model of respiratory support into a Level 3 NICU (Middlemore Hospital) in Auckland, New Zealand, that previously practiced a conventional approach to respiratory support. Using a total of 116 infants weighing between 1000 and 1499 g at birth between 1993 and 1998, and comparing outcomes before (1993 to May 1996) and after (June 1996 to 1998) the change in respiratory support policy, the study showed a significant reduction in the number of infants ventilated (65% to 14%) and receiving surfactant (40% to 12%), and in the median days of ventilation (6 to 2) and oxygen (4 to 2). There were decreases in CLD at 28 days (11% to 0%) and in death or CLD at 28 days (16% to 3%). The study design and larger subgroup of very low birth weight (VLBW) infants studied must caution against placing too much emphasis on the outcomes, which nonetheless do suggest that a CPAP-based approach may decrease the invasiveness and duration of respiratory support, and may decrease the incidence of adverse respiratory outcomes. Approximately 5 years each of continuous medical and nursing experience in the Columbia NICU were available to ensure accurate and thorough introduction of the Columbia methods. Given the difficulties reported by many centers when trying to adopt a CPAP-based approach, this experience may well have proven critical to the successful introduction of this approach. Similar changes in outcomes have been noted over a 2-year period at the first author's current institution, including in the extremely low birth weight population, but the study outcomes can not automatically be extrapolated to include these smaller infants. Nor can claims be made that it is proven that the Columbia approach can be successfully and repeatedly reproduced until this is done in a well-designed, prospective and randomized fashion.

2. Are there increases in adverse nonrespiratory outcomes with a CPAP-based approach?

In the New Zealand study after the change in respiratory support policy, there were decreases in the use of pressor support (34% to 7%), incidence of necrotizing enterocolitis (11% to 0%), time to reach full oral feeds (17.3 to 13.2 days), discharge weight (2569 to 2314 g) and average length of stay (61 to 52.9 days). Some of these differences clearly related to changes over time in other aspects of care, such as discharge criteria. There were no differences in neurosonographic or other morbidity outcomes. All such outcomes in the CPAP-era cohort were at the desirable end of the ranges commonly reported in the literature. Specifically, the incidence of severe intracranial hemorrhage (grade 3-4) was 2%, and of periventricular leukomalacia, hydrocephalus, and severe retinopathy of prematurity (stage 3 or worse) were all 0%. These data should again be interpreted with caution, but the lack of any observed increase in nonrespiratory morbidities suggests that prospective studies of a CPAP-based strategy may be done safely without an unreasonable increased risk of adverse nonrespiratory outcomes.

3. What are the long-term outcomes associated with this approach?

There is an alarming lack of data looking at the long-term outcomes, most importantly neurodevelopmental, of preterm infants managed with a primarily CPAP-based approach. No such data has been published by the Columbia group. The New Zealand cohorts are currently being followed and neurodevelopmental data collected, but the small study size, the larger VLBW subgroup studied, and the itinerant nature of the population served by Middlemore Hospital (with associated difficulties in adequate follow-up of sufficient numbers of study patients) may render this data of limited value. It is encouraging that a number of short-term interventions/outcomes (need for ventilation, incidence of CLD) that correlate with higher risk for adverse neurodevelopmental outcome may be reduced with a CPAP-based approach, and that no increases in short-term neurosonographic imaging outcomes have been documented in the sparse neonatal literature available. However, there are no longitudinal studies to confirm any improvement in long-term outcome that might potentially reflect these findings. Such studies following-up 1 or more large randomized, controlled trials of the use of neonatal CPAP are imperative to clarify this issue.

4. What (if any) is the key component of a CPAP-based strategy?

Not only has a CPAP-based approach as a whole not been well-studied in a comparative fashion, but the issue of what constitutes good or effective CPAP has not been adequately addressed. Different studies and reviews have suggested possible advantages of different ways of generating CPAP (such as bubble CPAP and flow-drivers), of delivering CPAP (such as binasal prongs versus nasopharyngeal tubes, and various CPAP pressure levels),^4-7 and of the prevention of mouth leaks,⁸ to name only a few. Of at least equal importance might be the timing and duration of CPAP use. Much speculation has centered on the initial use (that is, in the first hours and days of life) of CPAP versus more invasive ventilatory support, most commonly intubation, surfactant administration, and positive pressure ventilation. However, there is evidence that ongoing CPAP support for relatively prolonged periods (as, for example, using CPAP, often without supplemental oxygen, in lieu of oxygen without positive pressure support, as in the form of oxyhood or low-flow nasal cannula) may enhance lung growth, potentially aiding in the recovery of the injured lung.⁹ Might this component of the respiratory support strategy at Columbia and other similar centers be at least as important as the initial interventions in determining respiratory outcomes?

It should be a priority of those who would advance the role of CPAP in the preterm population to attempt to address these and other questions. It is our strong belief that a CPAP-based strategy similar to that practiced at Columbia can and will produce a consistent, reliable and reproducible decrease in the incidence of adverse respiratory outcomes (and may improve some nonrespiratory outcomes, including neurodevelopmental) if applied comprehensively and meticulously, but also that this needs to be rigorously tested and proven (or disproven) in a prospective fashion. We also believe that no single study could adequately address all (or even many) of these questions simultaneously, and that it may be necessary to test individual components and strategies in a series of studies to tease out an overall best approach. Long-term neurodevelopmental follow-up needs to be a priority of any such trials.

Alan M. de Klerk, MBChB
Department of Pediatrics
Infants' and Children's Hospital of Brooklyn at Maimonides Brooklyn, NY 11219

Rosemary K. de Klerk, RNC
Department of Nursing (Neonatal)
New York Presbyterian Hospital (Columbia Presbyterian Medical Center) New York, NY 10032

FOOTNOTES

Received for publication Jan 3, 2001; accepted May 29, 2001.

Address correspondence to Alan M. de Klerk, MBChB, Department of Pediatrics, Infants' and Children's Hospital of Brooklyn at Maimonides, 4802 10th Ave, Brooklyn, NY 11219. E-mail: adeklerk{at}maimonidesmed.org

ABBREVIATIONS

CPAP, continuous positive airway pressure; CLD, chronic lung disease; NICU, neonatal intensive care unit; VLBW, very low birth weight.

REFERENCES

1. Avery ME, Tooley WH, Keller JB, Is chronic lung disease in low birth weight infants preventable? A survey of eight centers. Pediatrics 1987; 79:26-30 [Abstract/Free Full Text]
2. Van Marter LJ, Allred EN, Pagano M, Do clinical markers of barotrauma and oxygen toxicity explain interhospital variation in rates of chronic lung disease? The Neonatology Committee for the Developmental Network. Pediatrics. 2000; 105:1194-1201 [Abstract/Free Full Text]
3. De Klerk AM, De Klerk RK Nasal continuous positive airway pressure and outcomes of preterm infants. J Paediatr Child Health. 2001; 37:161-167 [CrossRef][Medline]
4. Lee KS, Dunn MS, Fenwick M, Shennan AT A comparison of underwater bubble continuous positive airway pressure with ventilator-derived continuous positive airway pressure in premature neonates ready for extubation. Biol Neonate 1998; 73:69-75 [CrossRef][Medline]
5. Moa G, Nilsson K Nasal continuous positive airway pressure: experiences with a new technical approach. Acta Paediatr Scand 1993; 82:210-211
6. Klausner JF, Lee AY, Hutchison AA Decreased imposed work with a new nasal continuous positive airway pressure device. Pediatr Pulmonol 1996; 22:188-194 [CrossRef][Medline]
7. Davis PG, Henderson-Smart DJ. Nasal continuous positive airways pressure immediately after extubation for preventing morbidity in preterm infants. In: Sinclair J, Bracken M, Soll RF, Horbar JD, eds. Neonatal Module of The Cochrane Database of Systematic Reviews. Available in The Cochrane Library [database on disk and CD ROM]. The Cochrane Collaboration; 2000;2:CD000143. Oxford, United Kingdom: Update Software. Updated quarterly. Available from BMJ Publishing Group, London.
8. Richards GN, Cistulli PA, Ungar RG, Berthon-Jones M, Sullivan CE Mouth leak with nasal continuous positive airway pressure increases nasal airway resistance. Am J Respir Crit Care Med 1996; 154:182-186 [Abstract]
9. Zhang S, Garbutt V, McBride JT Strain-induced growth of the immature lung. J App Physiol 1996; 81:1471-1476 [Abstract/Free Full Text]