Altered local cerebellar and brainstem development in preterm infants

BACKGROUND: Premature birth is associated with high prevalence of neurodevelopmental impairments in surviving infants. The putative role of cerebellar and brainstem dysfunction remains poorly understood, particularly in the absence of overt structural injury. METHOD: We compared in-utero versus ex-utero global, regional and local cerebellar and brainstem development in healthy fetuses (n ​= ​38) and prematurely born infants without evidence of structural brain injury on conventional MRI studies (n ​= ​74) that were performed at two time points: the first corresponding to the third trimester, either in utero or ex utero in the early postnatal period following preterm birth (30-40 weeks of gestation; 38 control fetuses; 52 premature infants) and the second at term equivalent age (37-46 weeks; 38 control infants; 58 premature infants). We compared 1) volumetric growth of 7 regions in the cerebellum (left and right hemispheres, left and right dentate nuclei, and the anterior, neo, and posterior vermis); 2) volumetric growth of 3 brainstem regions (midbrain, pons, and medulla); and 3) shape development in the cerebellum and brainstem using spherical harmonic description between the two groups. RESULTS: Both premature and control groups showed regional cerebellar differences in growth rates, with the left and right cerebellar hemispheres showing faster growth compared to the vermis. In the brainstem, the pons grew faster than the midbrain and medulla in both prematurely born infants and controls. Using shape analyses, premature infants had smaller left and right cerebellar hemispheres but larger regional vermis and paravermis compared to in-utero control fetuses. For the brainstem, premature infants showed impaired growth of the superior surface of the midbrain, anterior surface of the pons, and inferior aspects of the medulla compared to the control fetuses. At term-equivalent age, premature infants had smaller cerebellar hemispheres bilaterally, extending to the superior aspect of the left cerebellar hemisphere, and larger anterior vermis and posteroinferior cerebellar lobes than healthy newborns. For the brainstem, large differences between premature infants and healthy newborns were found in the anterior surface of the pons. CONCLUSION: This study analyzed both volumetric growth and shape development of the cerebellum and brainstem in premature infants compared to healthy fetuses using longitudinal MRI measurements. The findings in the present study suggested that preterm birth may alter global, regional and local development of the cerebellum and brainstem even in the absence of structural brain injury evident on conventional MRI.