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ARTICLES: Deanne Wilson-Costello, Michele C. Walsh, John C. Langer, Ronnie Guillet, Abbot R. Laptook, Barbara J. Stoll, Seetha Shankaran, Neil N. Finer, Krisa P. Van Meurs, William A. Engle, Abhik Das for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Months' Adjusted Age: Effects of Dose, Timing, and Risk of Bronchopulmonary Dysplasia in Extremely Low Birth Weight Infants Pediatrics 2009; 123: e430-e437 [Abstract] [Full text] [PDF]

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Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Month’s Adjusted Age

Wes Onland, Martin Offringa, Anne P. De Jaegere, and Anton H. van Kaam.   (27 March 2009)

Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Month’s Adjusted Age 27 March 2009
Wes Onland, physician Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherl, Martin Offringa, Anne P. De Jaegere, and Anton H. van Kaam. Send letter to journal: Re: Impact of Postnatal Corticosteroid Use on Neurodevelopment at 18 to 22 Month’s Adjusted Age w.onland{at}amc.uva.nl Wes Onland, et al.	To the Editor,-- With interest we have read the prospective cohort study by Wilson- Costello et al. in which the authors assessed the impact of postnatal steroid dose and timing on neurodevelopmental outcome in 366 steroid exposed extremely low birth weight infants compared with 1992 nonexposed infants(1). Based on their findings, the authors conclude that “a higher steroid dose was associated with increased neurodevelopmental impairment” and that “there is no “safe” window for steroid use.” Although we commend the authors in their attempt to resolve some of the issues on postnatal steroid use in preterm infants, we feel the non- randomized design of the study does not allow for such strong conclusions. Tables 1 and 2 clearly show that steroid exposed and nonexposed infants are not comparable in respect to patient characteristics and neonatal morbidity that determine their risk profile for neurodevelopmental impairment (NDI). Although the authors made an effort to adjust their analysis for some of these group difference, they failed do so for bronchopulmonary dysplasia (BPD) and the duration of mechanical ventilation, two variables that are seen as independent risk factors for NDI(2,3). Therefore, this study cannot answer the question if steroid use and cumulative dose are merely markers for significant lung disease and subsequent NDI or if steroid use is a true cause of NDI. The relationship between steroid use and NDI is probably ‘confounded by indication’. The mean age at the start of steroid treatment was 5 weeks, indicating that only a few patients were treated in the moderately early time window of 7 – 14 days after birth. It therefore seems inappropriate to conclude that there is no “safe” window for steroid use in preterm infants at risk for BPD. We recently performed a systematic review of all randomized evidence on dexamethasone use in preterm infants and showed that moderately early administration resulted in significant reduction in BPD without an increased risk for NDI(4). In this same analysis we also showed that higher cumulative dexamethasone doses started in the second week of life were associated with an increased risk reduction of BPD and, more importantly, with a reduced risk of NDI. These results suggest that there is indeed a safe window for administering steroids. We support the authors’ conclusion that a large randomized controlled trial is needed to find the optimal dose and timing of steroid treatment in ventilated preterm infants at risk for BPD. Based on the evidence from randomized trials, steroids should be started in the moderately early time window, and higher doses should not be expelled. The evidence presented in their present study is insufficient to change this recommendation, or to guide current clinical practice. Wes Onland, MD Martin Offringa, MD PhD Anne P. De Jaegere, MD Anton H. van Kaam, MD PhD Department of Neonatology, Emma Children’s Hospital, Academic Medical Center, Amsterdam, The Netherlands Center for Pediatric Clinical Epidemiology, Emma Children’s Hospital, Academic Medical Center, University of Amsterdam, The Netherlands References 1.Wilson-Costello D, Walsh MC, Langer JC, Guillet R, Laptook AR, Stoll BJ, et al. Impact of postnatal corticosteroid use on neurodevelopment at 18 to 22 months' adjusted age: effects of dose, timing, and risk of bronchopulmonary dysplasia in extremely low birth weight infants. Pediatrics 2009 Mar;123(3):e430-e437. 2.Walsh MC, Morris BH, Wrage LA, Vohr BR, Poole WK, Tyson JE, et al. Extremely low birthweight neonates with protracted ventilation: mortality and 18-month neurodevelopmental outcomes. J Pediatr 2005 Jun;146(6):798- 804. 3.Schmidt B, Asztalos EV, Roberts RS, Robertson CM, Sauve RS, Whitfield MF. Impact of bronchopulmonary dysplasia, brain injury, and severe retinopathy on the outcome of extremely low-birth-weight infants at 18 months: results from the trial of indomethacin prophylaxis in preterms. JAMA 2003 Mar 5;289(9):1124-9. 4.Onland W, Offringa M, De Jaegere AP, van Kaam AH. Finding the optimal postnatal dexamethasone regimen for preterm infants at risk of bronchopulmonary dysplasia: a systematic review of placebo-controlled trials. Pediatrics 2009 Jan;123(1):367-77. Conflict of Interest: None declared