Published online April 2, 2007
PEDIATRICS Vol. 119 No. 4 April 2007, pp. 818-820 (doi:10.1542/peds.2006-3026)

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COMMENTARY

Is There a Strategy for Preventing Bronchopulmonary Dysplasia? Absence of Evidence Is Not Evidence of Absence

Hany Aly, MD, FAAP

Department of Newborn Services, George Washington University and Children's National Medical Center, Washington, DC

Abbreviations: BPD, bronchopulmonary dysplasia • CPAP, continuous positive airway pressure • GWU, George Washington University

Bronchopulmonary dysplasia (BPD) is a serious health problem associated with mortality and high morbidity among graduates of the NICU.¹ The cost of BPD is tremendous. It is associated with prolonged hospitalization of the preterm infant, multiple rehospitalizations during the first few years of life, and survival with developmental delay and/or cerebral palsy.^1,2 It becomes, therefore, a major goal for the neonatal community to prevent or at least partially control the incidence of BPD. In an effort to scientifically ameliorate the incidence of BPD, Walsh et al³ examined the 3 best-performing NICUs among the 17 units of the National Institute of Child Health and Human Development Neonatal Network. The study team determined some practices in these 3 units that they could adopt in a clinical trial. They then initiated a cluster-randomized, controlled trial among the remaining 14 units; 7 of these units changed their practices accordingly, and the other 7 units continued their routine care. Early administration of surfactant, use of vitamin A, and maintaining lower oxygen saturation were among the adopted practices in this randomized trial. Early nasal continuous positive airway pressure (CPAP) was not one of the targeted practices to change, because there was "insufficient evidence" to support its use. In fact, when compared with the control group, the 7 NICUs in the intervention group used more endotracheal intubation (77% vs 66%) and less CPAP (16% vs 27%) in the delivery room. During the first week of life, mechanical ventilation was more prolonged in the intervention-group infants (4 vs 3.5 days). Despite the overtly scientific approach and the tedious efforts and resources spent to ensure quality of care and compliance with policies, the incidence of BPD did not change in the 4095 recruited infants.³

BPD is caused by an inflammatory process that results in either airway injury and parenchymal fibrosis of the lung alternating with emphysema (classical BPD)⁴ or cessation of alveolar septum formation (the new BPD).⁵ This inflammation is driven by the use of mechanical ventilation and oxygen.⁶ The liberal use of oxygen has been shown to induce lung injury and produce BPD.⁷ For decades, not only has mechanical ventilation alone been shown to damage healthy lungs and even lead to death in animal studies,⁸ but the use of elective ventilation for even a few breaths also clearly causes significant damage to premature animal lungs.⁹ In addition, mechanical ventilation by itself poses an independent risk for cerebral palsy and learning disability in premature infants.^1,10 Therefore, to control BPD, it is imperative to avoid ventilator injury.

Despite the clear cause-and-effect relationship between the ventilator and lung injury, studies have not been designed to avoid intubation and instead have been conducted to test every possible strategy for reducing lung injury in already-intubated and -ventilated infants. In addition, even more desperate efforts are spent trying different drugs on ventilated infants: glucocorticoids, vitamin A, superoxide dismutase, or even inhaled nitric oxide. A simple search at the National Library of Medicine can identify at least 800 well-designed trials that were performed mostly on ventilated premature lungs. Injury starts immediately after the first few mechanical breaths in the delivery room, so it is puzzling to find that such continued efforts against BPD are still concentrating on those already-intubated infants.

Logically, more studies should be performed with the aim of avoiding lung injury in the first place, but such simple logic has not gained ground because it is not "evidence based." In fact, evidence-based critical thinking should urge us to explore whether the practice of elective intubation in the delivery room has any supportive biological or physiologic proof compared with CPAP use.

With this frustration of not having a "silver bullet" to prevent or control BPD, an increasing number of NICUs are reporting their experience of less BPD when using CPAP. In 1985, Avery et al¹¹ reported less BPD (4%) at Columbia University (in New York) when compared with 8 other centers. Columbia University is known for its strategy of early use of CPAP. A later comparison conducted at Columbia University confirmed the decreased incidence of BPD.¹² NICUs in and outside the United States have reported their experiences with lower incidence of BPD using CPAP when compared with their own historical outcomes or current national benchmark values.^2,13–15 The strength of evidence of these reports is not adequate, because they were not originally designed as randomized, controlled trials. However, it is important to remember that the absence of evidence is not evidence of absence.

In an effort to validate such CPAP claims, Finer et al¹⁶ conducted a randomized trial and proved the feasibility of the application of CPAP in the delivery room even with the lowest birth weight categories (<1000 g). In that pilot trial, the overall majority of these infants ended up being intubated shortly after birth. On the basis of these reports, it is fair to conclude that the use of CPAP in the delivery room is possible but requires tedious training and bedside nursing experience to ensure its success.

A collaborative effort to achieve satisfactory levels of training and experience might have made CPAP clinical trials more meaningful. A randomized, controlled trial without adequate CPAP training might seem to demonstrate the absence of efficacy of CPAP in the prevention of BPD but would not differentiate whether the failure occurred with CPAP itself as a "tool" or was a result of lack of experience in the hands of the "carpenter." However, this does not explain why units experienced with CPAP have a much lower incidence of BPD than the national average.

I strongly believe that we need to collaborate to decrease the incidence of BPD. Units that have used CPAP successfully should step forward and share their experiences with other units that are willing to use CPAP for a scientific trial or as a standard of practice. The ability to reproduce CPAP experience in different units would be the best proof of its effectiveness and should be a prerequisite before any meaningful trials can start.

Eight years ago, the incidence of BPD at the George Washington University (GWU) had been steady at 33% in infants <1500 g. The early use of CPAP in the delivery room was initially associated with an unfavorable trend during the first year of its application. The incidence of BPD has been declining steadily for 8 consecutive years (Fig 1). A favorable trend has also been established in infants <1000 g.¹⁷ To control BPD and ensure safer management of preterm infants everywhere, we need to share our resources and experiences. We have been contacted by several units that are eager to reproduce a successful CPAP experience. This interest led us to start a health initiative called "the CPAP rescue team" at GWU that aims to share experiences and teach hands-on care to nurses and physicians, which allows interested NICUs to reproduce their own successful experience. We envision this move to be in the right direction; it will transform debates into actions and skepticism into hands-on care. We invite NICU advocates to move forward and join with us to stop the suffering of those we are caring for.

View larger version (9K): [in this window] [in a new window]   FIGURE 1 BPD rates from 1998 to 2005 in infants <1500 g at GWU.

 

	ACKNOWLEDGMENTS

 
I thank Cynthia Poindexter for reviewing this commentary.

	FOOTNOTES

 
Accepted Dec 8, 2006.

Address correspondence to Hany Aly, MD, 900 23rd St NW, Suite G2092, Washington, DC 20037. E-mail: haly{at}mfa.gwu.edu

The author has indicated he has no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.

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PEDIATRICS (ISSN 1098-4275). ©2007 by the American Academy of Pediatrics

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