Update on Postnatal Steroids

Abstract

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention.

European Consensus Guidelines on the Management of Respiratory Distress Syndrome – 2019 Update

“…Breaking this cycle using systemic corticosteroids is possible, and there are now over 50 randomised controlled trials studying the risks and benefits of various corticosteroid regimens [133, 134]. Dexamethasone increases the chance of successful extubation and reduces BPD but at the expense of increased risk of neurodevelopmental sequelae if used in the first week [133, 135]. We previously recommended that the smallest effective dose should be used and only for babies at highest risk of BPD such as those who remain ventilator-dependent after 1–2 weeks.…”

Postnatal steroids: still a dilemma for neonatologists and parents?

“…These two small studies used sequential analysis and appeared to show benefit as regards weaning from ventilation but apart from infection4 adverse effects were not reported. In the next decade or so high-dose dexamethasone was studied in many randomised trials given early (in the first week) to try to prevent BPD or later (after the first week) to treat it 6. Meta-analyses of randomised controlled trials (RCTS) showed that dexamethasone facilitated extubation from ventilation and reduced BPD, although adverse effects of hypertension, hyperglycaemia and growth failure were considered to be both tolerable and reversible on stopping steroids.…”

“…Comparison of the early and late dexamethasone Cochrane systematic reviews suggests that early treatment is more harmful than late as regards cerebral palsy and the outcome ‘abnormal CNS examination’ 6. In 2005, we proposed that the reason that early treatment was more harmful was related to the risk of developing BPD if untreated 10.…”

“…I think what was meant was ‘early initiation’ (less than 7 days) and ‘high dose’ (over 3.0 mg/kg accumulated dose of dexamethasone) was beneficial 16. This seems counter-intuitive from results derived from individual meta-analyses where later (over 7 days) treatment seems both effective and safer than early treatment with dexamethasone 6. High-dose dexamethasone may be more effective than low dose but is it safer?…”

“…For example, the studies included were from 1966 to June 2016, almost 2 years ago and all the steroid Cochrane reviews have been updated in 2017. When I presented an update on postnatal steroids in June 2017, I could find 60 RCTs which enrolled 6818 subjects 6. By October 2017, this had increased to 78 RCTs and 8801 subjects although this included infants treated with steroid/surfactant combinations and those where inhaled steroids were compared with systemic.…”