Postnatal steroids for chronic lung disease

Postnatal steroids for chronic lung disease
Chronic lung disease (CLD) remains a major problem in neonatal intensive care units. Steroidsgiven either soon after birth to prevent CLD, or later to reduce its severity, are effective, but thereare acute and long-term adverse effects. When steroids are given early (first 4 days) there is anincreased risk of cerebral palsy in surviving infants which precludes their use at this time.
Dexamethasone may be effective in far lower doses than used in most of the randomised trialsto date. There are probably situations where its use is associated with more benefit than harm.
There is no convincing evidence that inhaled steroids alter the course of CLD. More research isneeded into ways of preventing or reducing CLD in at risk preterm infants.
Henry L Halliday
Chronic lung disease
arrested development, also known as ‘the respiratory distress syndrome (RDS) in the 1990s, survival rates of preterm babies have Department of Child HealthQueen’s University Belfast modest effect on reducing the incidence of translates into an increased overall number dysplasia (BPD) are used interchangeably, academic difficulties, delayed speech and until recently there has been no consistent definition of these conditions5. The best CLD persist into adolescence with reduced Keywords
corrected age of 36 weeks after efforts have been made to ensure that oxygen is indeed significantly different from very preterm dysplasia; corticosteroids; dexamethasone; 88%; the so called ‘physiologic definition’6.
sequelae are important it is not surprising Key points
weight and gestational age, with rates of less than 5% in infants weighing more than Halliday, H.L. (2007) Postnatal steroids for
1500 grams, increasing to 85% in those of chronic lung disease Infant 3(2): 78-81.
less than 700 grams7. Overall at least 20% 1. Chronic lung disease is associated with respiratory outcomes would be expected.
described by Bill Northway and colleagues History of postnatal steroids
in 1967 as a severe sequela of mechanical There is a long history of use of postnatal ventilation – the so called ventilator lung disease8 (FIGURE 1). Pathologically in classic
was first reported in 1956 in the US as a BPD there is severe alveolar fibrosis and potential treatment for respiratory distress 3. Inhaled steroids have little effect on the in infants of diabetic mothers15. Later in strategies of mechanical ventilation, the RDS16, but the first randomised controlled infants with significant chronic lungdisease or at high risk of developing it.
trial was not reported until 197217. This V O L U M E 3 I S S U E 2 2 0 0 7 infant
Subjects
RR (95%CI)
NNT (95%CI)
and perforation. Some of these arepotentially reversible after corticosteroid treatment has been discontinued.
However, the long term adverse increased risk of cerebral palsy after early
treatment with postnatal steroids (TABLE 2).
It appears that this increased risk in earlytreated infants is due to their lower risk of steroids is weighted towards harm ratherthan benefit. With risks of CLD below 35% corticosteroid treatment significantlyincreases the chance of death or cerebral RR=relative risk, CI=confidence interval, NNT=number needed to treat, CLD=chronic lung disease, PDA=persistent ductus arteriosus. Data derived from Cochrane 65%, it reduces the chance of these adverse TABLE 1 Beneficial effects of systemic postnatal steroids.
used dexamethasone but the dose andduration varied considerably23. The most Systematic reviews of systemic
corticosteroids
reducing course over two to six weeks.
increased risk of severe intraventricular postnatal steroids were first published in results of these systematic reviews is the problems20. As a result of these concerns cross over effect of the use of open label about serious long term adverse effects of reviews are classified according to postnatal corticosteroids in the control groups.
age at the start of treatment: early (<96 high dose dexamethasone was used to treat delayed (>3 weeks). Postnatal steroids, babies and this had the effect of reducing ventilator-dependent infants with CLD 21,22.
whether started early, moderately early or late, facilitate earlier extubation and reduce the risk of developing CLD at 36 weeks’ corrected age (TABLE 1). Neonatal mortality
studies with less than 30% cross over (or significant long term benfits. Few adverse effects were reported in these early studies about the safety of postnatal steroids and steroids was first shaken in 1998 with thepublication of a large multicentre follow- up study from Taiwan25. This study showed infants (TABLE 1).
lems and a doubling of the risk of cerebral palsy at two years in infants who had been treated with a 4 week course of dexametha- sone, started within 12 hours of birth. This study and others that followed in 1999 and steroids (TABLE 2).
postnatal corticosteroids to prevent CLD.
FIGURE 1 Ventilator-dependent baby with chronic lung disease.
infant VO L U M E 3 I S S U E 2 2 0 0 7
prevent CLD and later to treat babies with inhaled and systemic corticosteroids, again cerebral palsy was as high as one for every both early (<2 weeks)38 and late (>2 four treated infants30. It seems likely that included five randomised controlled trials that outweigh its benefits. Its initial choice but did not show any reduction in CLD36.
suggesting that either the doses used were risk of hyperglycaemia. In summary, there safe, or alternatively were ineffective. A second systematic review also included five physiological secretion rate of cortisol in effective for prevention and treatment of corticosteroids have been used infrequently dexamethasone in reducing ventilation and Other systemic corticosteroids
Methylprednisolone has been compared
with dexamethasone in a non-randomised
Subjects
RR (95%CI)
NNH (95%CI)
preterm infants at risk31. Although therewere no differences in oxygen requirements or in the rate of weaning from ventilation, the methylprednisolone-treated infantshad better weight gain, less hyperglycaemia than those treated with dexamethasone.
However, there have been no randomisedtrials with methylprednisolone, nor withbetamethasone, a drug commonly used antenatally to mature the fetal lungs.
Hydrocortisone, prescribed in a
relatively low dose as prophylaxis againstadrenal insufficiency, appeared to reduce the risk of CLD in a small pilotrandomised trial32. However, two larger early because of an excess ofgastrointestinal perforations in the cause of these perforations may have beenan interaction between early hydro- cortisone treatment and prophylacticindomethacin. Hydrocortisone has also been compared with dexamethasone fortreatment of CLD in non-randomised outcome may be better with hydro-cortisone. These findings need to be confirmed in randomised comparativetrials before alternative steroids can be Inhaled steroids
RR = relative risk, CI = confidence interval, NNH = number needed to harm. HCM = These should have direct beneficial effects hypertrophic cardiomyopathy, GI = gastrointestinal, CP = cerebral palsy. Data derived from Cochrane systematic reviews26-28.
systemic effects of dexamethasone. Inhaledsteroids have been used early to try to TABLE 2 Adverse effects of systemic postnatal steroids.
V O L U M E 3 I S S U E 2 2 0 0 7 infant
membrane disease: Bronchopulmonary dysplasia.
29. Doyle L.W., Halliday H.L., Ehrenkranz R.A., Davis
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infant VO L U M E 3 I S S U E 2 2 0 0 7

Source: http://www.neonatalnurse.co.uk/pdf/inf_014_scd.pdf