Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants

Abstract

Background: Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to either prevent or treat CLD because of their potent anti-inflammatory effects.

Objectives: To determine if postnatal corticosteroid treatment is of benefit in the prevention of chronic lung disease (CLD) in the preterm infant. This review examines the outcome of trials where preterm infants at risk of CLD were given postnatal steroids within 96 hours after birth.

Search strategy: Randomised controlled trials of postnatal corticosteroid therapy were sought from the Oxford Database of Perinatal Trials, the Cochrane Controlled Trials Register, MEDLINE (1966 - 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.

Selection criteria: Randomised controlled trials of postnatal corticosteroid treatment within 96 hours of birth (early) in high risk preterm infants were selected for this review.

Data collection and analysis: Data regarding clinical outcomes including mortality, CLD (including late rescue with corticosteroids, and need for home oxygen therapy), death or CLD, failure to extubate, complications during the primary hospitalisation (including infection, hyperglycaemia, hypertension, pulmonary air leak, patent ductus arteriosus (PDA), severe intraventricular haemorrhage (IVH), periventricular leucomalacia (PVL), necrotising enterocolitis (NEC), gastrointestinal bleeding, intestinal perforation, 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.

Main results: Twenty-one randomised controlled trials enrolling a total of 3072 participants were eligible for inclusion in this review. A meta-analysis of these trials demonstrated significant benefits as regards earlier extubation and decreased risks of CLD at both 28 days and 36 weeks, death or CLD at 28 days and 36 weeks, PDA and severe ROP. There were no significant differences in the rates of neonatal or subsequent mortality, infection, severe IVH, PVL, NEC or pulmonary haemorrhage. Gastrointestinal bleeding and intestinal perforation were important adverse effects and the risks of hyperglycaemia and hypertension were also increased. In the nine trials which have reported late outcomes, several adverse neurological effects were found at follow-up examinations of survivors treated with early steroids: developmental delay (not defined), cerebral palsy and abnormal neurological exam. However, major neurosensory disability was not significantly increased, either overall in the 4 studies where this outcome could be determined, or in the 2 individual studies where the rate of cerebral palsy and abnormal neurological exam were significantly increased. Moreover, the rate of the combined outcome of death or major neurosensory disability was not significantly increased.

Reviewer's conclusions: The benefits of early postnatal corticosteroid treatment (< 96 hours) may not outweigh the known or potential adverse effects of this treatment. Although early steroid treatment facilitates extubation and reduces the risk of chronic lung disease, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Long-term follow-up studies report an increased risk of abnormal neurological exam and cerebral palsy. 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. There is a compelling need for the long term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. The role of inhaled steroids remains to be elucidated.