Late (>7 days) post corticosteroids for chronic lung disease in preterm infants

Halliday HL, Ehrenkranz RA, Doyle LW

Published Online:

January 21, 2009

Corticosteroids can reduce lung inflammation in newborns with chronic lung disease (CLD) but there are major adverse effects of the drugs. CLD is a major problem for newborn babies in neonatal intensive care units, and is associated with both a higher death rate and worse long-term outcomes in survivors. Persistent inflammation of the lungs is the most likely cause of CLD. Because of their strong anti-inflammatory effects corticosteroid drugs have been used to either prevent or treat CLD, particularly in babies who cannot be weaned from assisted ventilation. This review of trials found that giving corticosteroids to infants at least seven days old produces short-term benefits of reducing the need for assisted ventilation and the rate of CLD, perhaps also reducing death in the first 28 days of life. However, high doses in particular are associated with short-term side effects such as bleeding from the stomach or bowel, higher blood pressure and difficulty tolerating glucose. In contrast with early use of corticosteroids in the first week of life, there is little evidence for long-term complications; however, it is not certain that there are no long-term problems. It seems wise to limit the use of late corticosteroids to those babies who cannot be weaned from assisted ventilation and to minimise the dose and duration of any course of treatment.

Abstract (click to read)

Background:

Many preterm infants who survive go on to develop chronic lung disease (CLD). This is true in infants who have had respiratory distress syndrome (RDS) and in infants without RDS. 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.

Objectives:

To determine the effect of late (> 7 days) postnatal corticosteroid treatment compared to control (placebo or nothing) in the preterm infant with CLD.

Search strategy:

Randomised controlled trials of postnatal corticosteroid therapy were sought from the Cochrane Central Register of Controlled Trials (The Cochrane Library), MEDLINE 1966 through May 2008, hand searching paediatric and perinatal journals, examining previous review articles and information received from practising neonatologists. When possible, authors of all studies were contacted 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 (RCTs) of postnatal corticosteroid treatment initiated after seven days after birth in preterm infants with or developing CLD were selected for this review.

Data collection and analysis:

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 (GI) bleeding, GI perforation, intraventricular hemorrhage (IVH), severe retinopathy of prematurity (ROP), and long-term outcomes (including blindness, deafness, cerebral palsy and major neurosensory disability), were abstracted and analysed using RevMan 5

Main results:

Nineteen RCTs enrolling a total of 1345 participants were eligible for this review. Late steroid treatment was associated with a reduction in neonatal mortality (at 28 days) but not mortality at discharge or latest reported age. Beneficial effects of delayed steroid treatment included reductions in failure to extubate by 3, 7 or 28 days, CLD at both 28 days and 36 weeks' postmenstrual age (overall and in survivors), need for late rescue treatment with dexamethasone, discharge to home on oxygen therapy, and death or CLD at both 28 days and 36 weeks' postmenstrual age (PMA). There was a trend towards an increase in risk of infection and GI bleeding but not NEC. Short-term adverse affects included hyperglycaemia, glycosuria and hypertension. There was an increase in severe ROP (overall and a trend in survivors) but no significant increase in blindness. There was trend towards a reduction in severe IVH but only 247 infants were enrolled in five studies reporting this outcome. The trends to an increase in cerebral palsy or abnormal neurological examination were 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. There were no substantial differences between groups for other outcomes in later childhood, including respiratory health or function, blood pressure, or growth.

Authors' conclusions:

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 for preventing chronic lung disease in preterm infants"), this review of postnatal corticosteroid treatment for CLD initiated after seven days of age suggests that late therapy may reduce neonatal mortality without significantly increasing 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; in some studies the surviving children have only been assessed before school age when some important neurological outcomes cannot be determined with certainty, and no study was sufficiently powered to detect increased rates of 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.

This record should be cited as:

Halliday HL, Ehrenkranz RA, Doyle LW. Late (>7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database of Systematic Reviews 2009, Issue 1. Art. No.: CD001145. DOI: 10.1002/14651858.CD001145.pub2

Assessed as up to date:

November 6, 2008

Find the research

Get full text at The Cochrane Library

Primary Review Group:

Neonatal Group

Health topics:

Neonatal care > Bronchopulmonary dysplasia

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Late (>7 days) post corticosteroids for chronic lung disease in preterm infants

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