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Antenatal Steroids
Multiple Courses of Antenatal Corticosteroids are Associated with Severe Lung Disease in Preterm Neonates. Banks BA, Macones G, Cnaan A, et al. J Perinatol (March 2002); 22:101-7.
A post hoc analysis was conducted on 595 premature neonates (26-32 weeks gestation) who were enrolled in a trial of thyrotropin releasing hormone (TRH) for the prevention of RDS. In the TRH study, an association was noted between > 2 courses of antenatal corticosteroids (ANCS) and mortality (9.2% vs. 4.8% after 1 or 2 courses of ANCS). This association was not explained by maternal factors, or other common preterm morbidities. However, 15/141 (10.6%) of infants receiving > 2 courses of ANCS had early severe lung disease with 10 deaths, compared to 16/454 (3.5%) of the 1-2 course infants with 7 deaths (odds ratio 3.5, p<0.001).
Comment. The early studies of ANCS suggested that the optimal benefits persisted for only 7 days, so it became popular to re-dose patients at risk for preterm delivery on a weekly basis. Recently, there have been increasing concerns about possible deleterious effects of multiple courses of ANCS, especially in light of findings that postnatal treatment of premature infants with dexamethasone is associated with a 3-4 fold increased risk of cerebral palsy (see NeoNotes, Vol. 2, Issue 12). While this study does not prove that multiple courses of ANCS causes early severe lung disease or increased mortality in premature babies, the association is very concerning. Previous studies have associated multiple courses of ANCS with growth retardation and decreased head circumference. The early severe lung disease seen in this group of babies was not necessarily related to RDS and its complications. It is equally likely that prolonged exposure to ANCS interferes with fetal lung growth and alveolarization. In the present study, pulmonary hypoplasia was identified in 5 of the 13 infants who died after multiple courses of ANCS. The current recommendation of the NIH Consensus group on ANCS is that repeat or rescue doses of should be avoided.
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