Early hydrocortisone improves survival without bronchopulmonary dysplasia in extremely preterm born infants.

Abstract

Commentary on: Baud O, Maury L, Lebail F, Ramful D,El Moussawi F, Nicaise C, Zupan-Simunek V, Coursol A, Beuchée A, Bolot P, Andrini P, Mohamed D, Alberti C, PREMILOC trial study group. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): a double-blind, placebo-controlled, multicentre, randomised trial. Lancet. 2016 Apr 30;387 (10030): 1827–36. https://doi.org/10.1016/s0140-6736(16)00202-6. Epub 2016 Feb 23. Olivier Baud and colleagues investigated in a large RCT the effect of a 10-day course of low-dose prophylactic hydrocortisone given to extremely preterm infants born between 24 and 27 weeks of gestational age. Survival without bronchopulmonary dysplasia (BPD) was significantly higher in the group of infants receiving hydrocortisone than in controls receiving placebo. This effect was most pronounced in females and in infants exposed to chorioamnionitis before birth. For the secondary outcomes, the treatment group exhibited lower odds for PDA ligation, higher numbers of patients extubated on day 10 and higher proportion of patients weaned from any supplemental oxygen at 36 weeks of postmenstrual age. Despite recommendations against the use of postnatal steroids because of adverse long-term neurodevelopmental outcomes, neonatologists across the world use these drugs to treat BPD 1. The fact that ELBW infants can suffer from adrenal insufficiency, particular the sickest ones, has been shown earlier and might make early supplementation reasonable 2. Furthermore, the connection between low cortisol levels and early inflammation promoting the development of BPD from early on has been described previously and potentially justifies the treatment with steroids 3. This well-designed trial is one of the largest on this subject and provides us with important information on short-term outcome as well as on the safety of hydrocortisone treatment. It seems promising that even the lowest dose ever tested had a beneficial effect on primary outcome of survival without BPD. This trial also gives assurance with the regard to the feared side effect of gastrointestinal perforation, and very fortunately, even the two-year follow-up data are available and giving reassurance with regard to neurodevelopmental outcome 4, 5. Caution is warranted with regard to the higher incidence of late-onset sepsis in the treatment group. Although not statistically significant, a six percent difference between the groups might be of clinical interest. Treatment with postnatal steroids to prevent BPD seems to be a hot topic. The recent trial by Bassler et al. and the updated Cochrane review are suggesting a benefit for using early inhaled steroids in extreme preterm infants 6, 7. However, the long-term risk/benefit ratio for treatment with steroids still needs to be identified for either application way even beyond the two-year data currently available for this trial. A weakness might be the fact that the study was discontinued prior to targeted sample size of 786 infants. Nevertheless, the sequential analytical design allowed appropriate analysis after the fourth interim analysis anyway. Neonatologists around the world are faced with an increasingly immature population consequently leading to a higher prevalence of BPD, which makes prevention and treatment strategies inevitable. Early supplementation with hydrocortisone as described in this trial might be a promising way forward. The question whether this treatment strategy could be particularly beneficial in infants not exposed to antenatal steroids has not been addressed here. Further studies on this subject focusing on type of steroid, timing of treatment, dosage and duration of treatment are needed. https://ebneo.org/2017/09/early-hydrocortisone-improves-survival-without-bronchopulmonary-dysplasia-in-extremely-preterm-born-infants/ None. None.