Letters to the Editor
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Given the inherent weaknesses in this type of retrospective study, the omission of a significant number of cases as well as important covariates in the analysis, and the weight of previously published data relevant to this important clinical question, the authors should exert extreme caution in interpreting their findings. In a recent review on this precise topic, I concluded ‘there is no valid evidence for a mortality benefit of one surfactant preparation over another’.5 This study by Ramanathan et al. has not altered my assessment. Conflict of interest Dr Cummings has served as a consultant for ONY, manufacturer of calfactant, and for Discovery Labs, manufacturer of lucinactant. He currently has no financial interests with any surfactant manufacturer.
JJ Cummings Pediatrics and Physiology, East Carolina University, The Brody School of Medicine, Greenville, NC, USA E-mail:
[email protected]
References 1 Ramanathan R, Bhatia JJ, Sekar K, Ernst FR. Mortality in preterm infants with respiratory distress syndrome treated with poractant alfa, calfactant, or beractant: a retrospective study. J Perinatol 2013; 33: 119–125. 2 Bhatia J, Saunders WB, Friedlich P, Lavin PT, Sekar KC, York JM et al. Differences in mortality among infants treated with three different natural surfactants for respiratory distress syndrome. E-PAS 2007; 617935.16 (abstract). 3 Sekar KC, Bhatia J, Ernst FR, Saunders WB, Lavin PT, Ramanathan R. Resource use in preterm neonates with respiratory distress syndrome (RDS) treated with one of three difference natural surfactants: analyses using a large hospital discharge database. Acta Paediatr 2007; 96(Suppl 456): 109 (abstract). 4 Trembath AN, Clark RH, Bloom BT, Smith PB, Bose C, Laughon M. Trends in surfactant use in the United States: changes in clinical practice. E-Journal Neo Res 2011; 1(1): 23–30. 5 Holm B, Cummings JJ. Is there evidence for a mortality difference between exogenous surfactant preparations in neonatal RDS? J Appl Res 2008; 8(2): 78–83. 6 Carnielli VP, Zimmermann LJ, Hamvas A, Cogo PE. Pulmonary surfactant kinetics of the newborn infant: novel insights from studies with stable isotopes. J Perinatol 2009; 29: S29–S37. 7 Ramanathan R, Rasmussen MR, Gerstmann DR, Finer N, Sekar K, North American Study Group. A randomized, multicenter, masked comparison trial of poractant alfa (Curosurf) versus beractant (Survanta) in the treatment of respiratory distress syndrome in preterm infants. Am J Perinatol 2004; 21(3): 109–119. 8 Halliday HL, Tarnow-Mordi WO, Corcoran JD, Patterson CC. Multicentre randomized trial comparing high and low dose surfactant regimens for the treatment of respiratory distress syndrome (the Curosurf 4 trial). Arch Dis Child 1993; 69: 276–280.
Response to Cummings Journal of Perinatology (2013) 33, 162–165; doi:10.1038/jp.2011.197; published online 16 February 2012
We would like to thank Dr Cummings for giving us the opportunity to explain our study results. Results from nine randomized, controlled, trials (RCTs),1–9 including the one that has been just published (e-pub ahead of print) by Dizdar et al.9 and meta-analyses10–12 comparing animal-derived surfactants, namely, poractant alfa (PA), beractant (BE), bovactant (BO) and/or calfactant (CA), have consistently shown faster weaning of oxygen and mean airway pressure, less need for redosing, fewer days on oxygen and mechanical ventilation, shorter length of stay (LOS) as well as survival advantage in babies treated with PA. These advantages with PA over BE, CA or BO are likely related to major biological and/or biochemical differences between these animal-derived surfactant preparations. PA contains the highest amount of phospholipids when compared with BE or CA. Higher amount of phospholipids has been shown to downregulate oxidative functions in monocytes and confer better anti-inflammatory properties.13 In addition, bacterial growth in different surfactant preparations is influenced by microbial species and the composition Journal of Perinatology
and dose of the surfactant. PA was bactericidal in a dose-dependent fashion and differed from BE and BO, a surfactant preparation similar to CA.14 PA contains the highest amount of plasmalogens (PL) when compared with BE.15 BO contains the lowest amount of PL.15 PL are anti-oxidant phospholipids and presence of higher amounts of PL in the tracheal aspirates from pre-term infants has been shown to be associated with a lower risk for bronchopulmonary dysplasia (BPD).16 Also, the amount of surfactant-associated protein B (SP-B) is highest in PA when compared with BE or CA. SP-B is the most important SP in helping the phospholipids to rapidly adsorb at the air–liquid interphase and in decreasing surface tension. Furthermore, the phospholipid molecular species of PA is much closer to that of human surfactant.17,18 In our paper,19 we have clearly acknowledged the limitations of the retrospective study and took steps to minimize any shortcomings. The major finding of lower mortality in PA-treated infants is consistent with results from previously published small RCTs as well as meta-analyses comparing PA and BE. None of the studies comparing BE with CA have shown any differences in the need for redosing, days on oxygen or mechanical ventilation, BPD or mortality. Interestingly, Bloom et al.1 reported a higher mortality rate in infants with a birth weight
