Preterm cerebellar growth impairment after postnatal exposure to glucocorticoids

Abstract

As survival rates of preterm newborns improve as a result of better medical management, these children increasingly show impaired cognition. These adverse cognitive outcomes are associated with decreases in the volume of the cerebellum. Because animals exhibit reduced preterm cerebellar growth after perinatal exposure to glucocorticoids, we sought to determine whether glucocorticoid exposure and other modifiable factors increased the risk for these adverse outcomes in human neonates. We studied 172 preterm neonatal infants from two medical centers, the University of British Columbia and the University of California, San Francisco, by performing serial magnetic resonance imaging examinations near birth and again near term-equivalent age. After we adjusted for associated clinical factors, antenatal betamethasone was not associated with changes in cerebellar volume. Postnatal exposure to clinically routine doses of hydrocortisone or dexamethasone was associated with impaired cerebellar, but not cerebral, growth. Alterations in treatment after preterm birth, particularly glucocorticoid exposure, may help to decrease risk for adverse neurological outcome after preterm birth.

Figure 1

Cerebellar growth is decreased associated with A. postnatal hydrocortisone and B. postnatal dexamethasone. Results are from a generalized estimated equation for repeated measures, adjusting for gestational age at birth, postmenstrual age at time of MRI, severity of intraventricular hemorrhage, cerebellar hemorrhage, duration of intubation, presence of hypotension requiring intervention, and study site.

Figure 2

Change in cerebellar volume associated with various clinical factors. A. The univariate models adjusting for postmenstrual age at time of MRI scan and study site. B. The multivariate model considering all variables. Statistical significance for this analysis was defined as a mean magnitude of change in cerebellar volume >0.5cm³ (dotted lines) and P<0.1 (whiskers not crossing zero).