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Neonatology 2012;102:59–60
DOI: 10.1159/000336865

Received: January 25, 2012
Accepted: January 28, 2012
Published online: April 11, 2012

Is Lung Surfactant Ready ‘to Protect and
to Serve’ in Necrotizing Enterocolitis?
Commentary on F.E. Canpolat et al.: Effects of Enterally Administered Surfactant in a Rat
Model of Necrotizing Enterocolitis (Neonatology 2012;102:53–58)

Frans J. Walther
Division of Neonatology, Department of Pediatrics, Willem-Alexander Children’s Hospital, Leiden University
Medical Center, Leiden, The Netherlands

Necrotizing enterocolitis (NEC) is a common gastrointestinal emergency in the neonatal intensive care unit
and associated with a high mortality. The precise pathogenesis of NEC is incompletely understood, but is clearly
multifactorial [1]. Prematurity is the most important risk
factor that, in combination with formula feeding, intestinal hypoxic-ischemic injury, and colonization of the gut
with pathogenic bacteria, may lead to activation of the
inflammatory cascade that precipitates NEC. Antenatal
glucocorticoids, early feeding with human breast milk,
careful feeding advancement, and prophylactic probiotic
administration reduce the risk of NEC in preterm infants, but primary prevention continues to be a holy grail
in neonatology.
In this issue of Neonatology, Canpolat et al. [2] examine whether 5 days of enteral administration of high doses of lung surfactant (400 mg/kg of Curosurf 쏐 per day)
protect against the development of NEC in newborn rats
exposed to 5 min of hypoxia, followed by 5 min of hyperoxia. Enteral treatment with lung surfactant did not protect against the histological changes of NEC, but increased superoxide dismutase (SOD) and glutathione
peroxidase (GPx) activity and reduced malondialdehyde
(MDA) levels. The increase in antioxidant enzyme activity in the gut of surfactant-treated rats probably reflects
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the SOD and GPx content of the porcine surfactant
(Curosurf) used [3], whereas the lower MDA levels, which
reflect reduced lipid peroxidation, may be due to an overload of surfactant lipids in the gut. All in all, enteral surfactant administration increased antioxidant enzyme activity and decreased lipid peroxidation, and tipped the
balance between the production of reactive oxygen species and the gut’s ability to detoxify them in favor of reduced oxidative stress. However, this did not result in less
histological damage to the gut and suggests that oxidative
stress in the pathogenesis of NEC is not due to a deficient
antioxidant capacity, but the result of an excess production of reactive oxygen species.
What if the authors would have used lung surfactant
for its antioxidant properties? In that case, the same result
could have been obtained by administering a less-expensive liposomal preparation of SOD, catalase, and/or GPx.
Davis et al. [4] showed for example that intratracheal administration of recombinant human CuZn SOD (rhSOD)
to preterm infants increases the concentration and activity of SOD in tracheal aspirates and serum and may reduce early pulmonary injury. Likewise, early intratracheal rhSOD treatment improves oxygenation in premature
lambs with RDS and prevents the development of pulmonary hypertension [5]. What if the authors decided to give
Frans J. Walther
Division of Neonatology, Department of Pediatrics
Willem-Alexander Children’s Hospital, Leiden University Medical Center, J6-S
Albinusdreef 2, NL–2333 ZA Leiden (The Netherlands)
Tel. +31 71 526 2957, E-Mail fwalther @

Kassem N. Corsini I.102:59–60 5 Kinsella JP. So. Goldstein AM. Buonocore G. but lack SP-A and SP-D which play an important role in innate immunity of the lung and might have slowed the inflammatory cascade in the gut. 2 Canpolat FE. Richter SE. Horowitz S: Safety and pharmacokinetics of multiple doses of recombinant human CuZn superoxide dismutase administered intratracheally to premature neonates with respiratory distress syndrome. preferably.44:1125–1131. Pediatrics 1997. and glucocorticoids [1]. 3 Dani C. N Engl J Med 2011. Gewolb IH. prevention of NEC will have a greater impact on mortality and morbidity than treatment when the gut is already on fire. Walker WA: The mechanism of excessive intestinal inflammation in necrotizing enterocolitis: an immature innate immune response. growth factors. Uauy R. 6 Nanthakumar N. Yurdakök M. Carlo WA.364:255–264. use of enteral antibiotics. Parad MR. Pediatr Pulmonol 2009. interrupt the inflammatory cascade. Neonatology 2012. And what if the authors decided to give lung surfactant for its surfactant proteins (SP)? Clinical surfactants contain a total of 2(–3)% of SPB and SP-C which are essential for optimal surface activity of surfactant and normal lung function. Tierney J. and administration of probiotic and/or prebiotic agents.lung surfactant for its high lipid concentration? In that case.172:745–749. Recent insights about the facilitating function of Toll-like receptor 4 (TLR4) may offer a new window of opportunity here [6]. Felici C. Claud EC. [2] does not resolve how to prevent and treat NEC. More research in this field is badly needed as clinical surfactant is not ready to protect and serve in NEC. Spitzer AR. Couser RJ. Rosenfeld WN. Price A. Zhu W. but does not slow down the destruction of the bowels during NEC. Walker WA: Necrotizing enterocolitis. Lu L. Longini M. 60 4 Davis JM. Until the magic bullet comes along. Rodriguez A. Neonatology 2012. Meng D. PLoS One 2011. Ersin SC: Effects of enterally administered surfactant in a rat model of necrotizing enterocolitis.100:24–30. Walther . Parker TA. Llanos A. Davis JM. Am J Respir Crit Care Med 2005. anticytokine agents. the high phospholipid content of Curosurf (80 mg/ ml) could contribute to gut protection through a barrier action or anti-bacterial activity. use of a native instead of a clinical surfactant might have worked better through the presence of SP-A and SP-D. Abman SH: Superoxide dismutase improves gas exchange and pulmonary hemodynamics in premature lambs. Flaster E. in retrospect. current thinking about prevention focuses on feeding the infant with the mother’s expressed breast milk. Rubaltelli FF: Superoxide dismutase and catalase activity in naturally derived commercial surfactants. Edwards L.102:53–58. Without any doubt.6:e17776. The central question in NEC is of course how to slow or. but is a fine example of thinking outside the box: enteral administration of lung sur- factant increases the gut’s defense against reactive oxidative species. References 1 Neu J. The paper by Canpolat et al.

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