Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants

Many preterm babies who survive, having had respiratory distress syndrome (RDS) or not, go on to develop chronic lung disease (CLD). This is probably due to persistence of inflammation in the lung. Corticosteroids have powerful anti-inflammatory effects and have been used to treat established CLD. However it is unclear whether any beneficial effects outweigh the adverse effects of these drugs.

To determine if late (usually > 3 weeks) postnatal corticosteroid treatment vs control (placebo or nothing) is of benefit in the treatment of chronic lung disease (CLD) in the preterm infant.

Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, MEDLINE 1966 through October 2002, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. Authors of all studies were contacted, where possible, to confirm details of reported follow-up studies, or to obtain any information about long-term follow-up where none had been reported.

Randomised controlled trials of postnatal corticosteroid treatment initiated at predominantly > 3 weeks of age in preterm infants with CLD were selected for this review.

Data regarding clinical outcomes including mortality, CLD (including need for home oxygen, or need for late rescue with corticosteroids), death or CLD, failure to extubate, complications in the primary hospitalisation (including infection, hyperglycaemia, glycosuria, hypertension, echodensities on ultrasound scan of brain, necrotising enterocolitis (NEC), gastrointestinal bleeding, intestinal perforation, and severe retinopathy of prematurity (ROP)), and long term outcome (including blindness, deafness, cerebral palsy and major neurosensory disability), were abstracted and analysed using RevMan 4.1.

Nine trials enrolling a total of 562 participants were eligible for this review. Delayed steroid treatment had no significant effect on mortality. Beneficial effects of delayed steroid treatment included reductions in failure to extubate by 7 or 28 days, chronic lung disease at 36 weeks, need for late rescue treatment with dexamethasone, discharge to home on oxygen therapy, and death or CLD at 36 wk. There was no evidence of increase in risk of infection, necrotising enterocolitis, or gastrointestinal bleeding. Short-term adverse affects included glycosuria and hypertension. There was an increase in severe retinopathy of prematurity, of borderline significance, but no significant increase in blindness. The trend to an increase in cerebral palsy was partly offset by a trend in the opposite direction in death before late follow-up. The combined rate of death or cerebral palsy was not significantly different between steroid and control groups. Major neurosensory disability, and the combined rate of death or major neurosensory disability, were not significantly different between steroid and control groups.

The benefits of late corticosteroid therapy may not outweigh actual or potential adverse effects. Although there continues to be concern about an increased incidence of adverse neurological outcomes in infants treated with postnatal steroids (see also review of Early postnatal corticosteroids), this review of postnatal corticosteroid treatment for CLD initiated predominantly after three weeks of age suggests that late or delayed therapy may not significantly increase the risk of adverse long-term neurodevelopmental outcomes. However, the methodological quality of the studies determining the long-term outcome is limited in some cases, the children have been assessed predominantly before school age, and no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes. Given the evidence of both benefits and harms of treatment, and the limitations of the evidence at present, it appears prudent to reserve the use of late corticosteroids to infants who cannot be weaned from mechanical ventilation, and to minimise the dose and duration of any course of treatment.