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Postnatal steroids in preterm infants

Review
Results
Comment

Corticosteroids are prescribed in neonatal intensive care to reduce ventilator dependence and the rate of chronic lung disease in preterm infants. Given that neonatal intensive care is a highly specialised area, and given that there are already five good systematic reviews, including three super Cochrane reviews from Belfast [1-5], what interest could there be in examining a sixth?

sixth [6] addresses itself specifically to the question of long term neuro-development impairment, and suggests that short term benefits of corticosteroids may be more than outweighed by long term harm.

Review


The review used previous literature searches, supplemented by updating to September 2000, and supplemented by additional information provided by reviewers. For inclusion trials had to be randomised trials of glucocorticoids for the treatment or prevention of bronchopulmonary dysplasia. Children had to be premature infants of less than 32 weeks of gestation. The outcome sought was long term information on neuro-developmental impairment at one year or later, as well as mortality.

Results


There were eight included studies, all described in some detail, especially the definitions of impairment used in each study. One problem was that steroids may have been used in control infants. The proportion was unknown in three, known not to be present in two, and present to some degree in three.

Mortality was 28% in both groups (Figure 1, Table 1).

Figure 1: Mortality at one year


Table 1: Results for mortality and neuro-developmental impairment at one year

Outcome Babies with outcome (%)    
Among all babies randomised Steroids N=539 Control N=513 Relative risk (95% CI) NNT/H (95% CI)
Died 149 (28) 143 (28) 1.0 (0.8 to 1.2) -432 (-18 to 19)
Impaired neurodevelopment 140 (26) 104 (20) 1.3 (1.01 to 1.6) 17 (9.3 to 161)
Cerebral palsy 107 (20) 52 (10) 1.9 (1.4 to 2.6) 10 (7.2 to 18)
Among all babies survived Steroids N=339 Control N=340    
Impaired neurodevelopment 140 (41) 104 (31) 1.3 (1.1 to 1.6) 9.3 (5.6 to 28)
Cerebral palsy 107 (32) 52 (15) 2.0 (1.5 to 2.7) 6.2 (4.4 to 10)

Among all randomised babies the risk of neurodevelopment impairment, and cerebral palsy (Figure 2), was higher in those given steroids than those not given steroids. For every 10 babies treated with steroids, one additional baby would develop cerebral palsy by one year.

Figure 2: Cerebral palsy at one year



Among all babies who survived the risk of neurodevelopment impairment, and cerebral palsy, was higher in those given steroids than those not given steroids. For every six babies treated with steroids, one additional baby would develop cerebral palsy by one year.

Comment


Several of the reviews comment that the result might not be too much of a surprise, as animal experiments have shown that steroid use in the early postnatal period is associated with impaired brain growth and development, and that it impairs head growth in premature infants. This is in contrast to antenatal steroid use which has been shown not to be harmful.

The Canadian review [6] is forthright in its conclusion: that any short term benefits are outweighed by long term harm, and that the use of postnatal steroids should be abandoned. The paper is available on-line at BioMed Central, with its prepublication history, and the reviewers agree. Authors of other reviews sound notes of caution.

So what to make of it? These reviews collectively make an interesting teaching set. But mostly they inform clinical governance and quality management issues. Not everyone will agree that postnatal steroids should not be used. The arguments may be cogent and pressing, but they need to be made and noted to protect babies, professionals and institutions.

References:

  1. HL Halliday & RA Ehrenkranz. Early postnatal (<96 hours) postnatal corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review) In: The Cochrane Library, 1999, Issue 1, Oxford: Update Software.
  2. HL Halliday & RA Ehrenkranz. Moderately early (7-14 days) postnatal corticosteroids for preventing chronic ling disease in preterm infants (Cochrane Review) In: The Cochrane Library, 2001, Issue 3, Oxford: Update Software.
  3. HL Halliday & RA Ehrenkranz. Delayed (>3 weeks) postnatal corticosteroids for chronic lung disease in preterm infants (Cochrane Review) In: The Cochrane Library, 2001, Issue 3, Oxford: Update Software.
  4. LW Doyle & PG Davis. Postnatal corticosteroids in preterm infants: systematic review of effects on mortality and motor function. J Paediatric Child Health 2000 36: 101-107.
  5. T Bhuta & T Ohlsson. Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease. Arch Dis Child Fetal Neonatal Ed 1998 79: F26-F33.
  6. KJ Barrington. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. BMC Pediatrics 2001 1:1 ( www.biomedcentral.com/1471-2431/1/1 )
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