The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs.
BACKGROUND
Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants. This systematic review was performed with the objective of determining whether glucocorticoid therapy, to prevent or treat bronchopulmonary dysplasia, impairs neuro-developmental outcomes in preterm infants.


METHODS
A systematic review of the literature was performed. Medline was searched and articles retrieved using predefined criteria. Data from randomized controlled trials with adequate neuro-developmental follow up (to at least one year) were entered into a meta-analysis to determine the effects of postnatal treatment of preterm infants with glucocorticoids. Cerebral palsy rates, and neuro-developmental impairment (developmental score more than 2SD below the mean, or cerebral palsy or blindness) were analyzed. The studies were divided into 2 groups according to the extent of contamination of the results by treatment of controls with steroids after the initial study period, those with less than 30% contamination, and those with more than 30% contamination or size of contamination not reported.


RESULTS
Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment. The studies with less contamination show a greater effect of the steroids, consistent with a real direct toxic effect of steroids on the developing central nervous system. The typical relative risk for the development of cerebral palsy derived from studies with less than 30% contamination is 2.86 (95% CI 1.95, 4.19). The typical relative risk for the development of neuro-developmental disability among followed up infants from studies with less than 30% contamination is 1.66 (95% CI 1.26, 2.19). From this subgroup of studies, the number of premature infants who need to be treated to have one more infant with cerebral palsy (number needed to harm, NNH) is 7; to have one more infant with neuro-developmental impairment the NNH is 11.


CONCLUSIONS
Postnatal pharmacologic steroid treatment for prevention or treatment of bronchopulmonary dysplasia is associated with dramatic increases in neuro-developmental impairment. As there is no clear evidence in the literature of long term benefit, their use for this indication should be abandoned.
Barrington
K J
KJ
Royal Victoria Hospital, 687 Pine Ave W, Room C7.68, Montreal, Quebec, H3A 1A1 Canada. kbarri@po-box.mcgill.ca
D000305:Adrenal Cortex Hormones / Q000009:adverse effects* / Q000627:therapeutic use; D001997:Bronchopulmonary Dysplasia / Q000209:etiology / Q000517:prevention & control*; D002547:Cerebral Palsy / Q000139:chemically induced / Q000453:epidemiology; D002908:Chronic Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000188:drug therapy*; D008171:Lung Diseases / Q000188:drug therapy; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000401:mortality; D018570:Risk Assessment; D015996:Survival Rate
D000305:Adrenal Cortex Hormones