Research ArticlePreterm Birth

Preterm Cerebellar Growth Impairment After Postnatal Exposure to Glucocorticoids

Science Translational Medicine  19 Oct 2011:
Vol. 3, Issue 105, pp. 105ra105
DOI: 10.1126/scitranslmed.3002884

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Dangers at the Time of Preterm Birth

Sometimes, it is bad to show up early for an appointment. Babies born before the usual 40-week term of pregnancy are at risk for many problems, including impaired brain development. Despite advances in neonatology, these children experience developmental problems at the same frequency that they did 10 years ago. To pinpoint the causes of these lifelong issues, Tam et al. carefully assessed 172 newborn babies. The researchers documented a long list of clinical factors that the babies experienced and measured the volume of their brains after birth, and then many weeks later, a sensitive index of whether the brain is developing normally. As shown previously in animals, treatment of neonates with the glucocorticoids dexamethasone and hydrocortisone—often given to babies to promote lung development or treat hypotension—is associated with significant decreases in the rate of growth of the cerebellum, suggesting that these steroids should be used with caution.

The authors showed that other things experienced by the babies were also associated with decreased cerebellar volumes: intubation, hypotension, and heart abnormalities—although these effects did not account for the effects of the glucocorticoids, which caused a significant 8 to 10% smaller cerebellum. Brain hemorrhage also affected cerebellar development, as the authors have previously reported. One bit of good news was that treatment of the babies (before birth) with another glucocorticoid, betamethasone, to encourage lung development and prevent hemorrhage had no effect on brain volumes.

The American Academy of Pediatrics presently recommends that high-dose dexamethasone treatment in neonates be avoided, although they have no recommendation against hydrocortisone (the babies treated with dexamethasone in this study were from the University of British Columbia). The authors suggest that clinicians weigh the risks and benefits of glucocorticoid treatment for neonates, taking into account the association with impaired brain development. Other approaches to this problem may be possible, including adjuvant drug treatment given along with the glucocorticoids that could inhibit the detrimental effects of glucocorticoids, while preserving their ability to promote lung development, as reported in the accompanying paper by Heine et al.