The DC-IDDRC Research Project relates to one of several focus themes identified as an area of research in need in intellectual and developmental disabilities (IDD) by NICHD. Our research project relates to the focus theme Developing Biomarkers of Premature Brain Injury. The project showcases the best research at our center and reflects our strengths in a specific research area. The research project is new and not previously funded by any mechanism.

The Vulnerable Preterm Cerebellum: Elucidating Mechanisms and Consequences of Injury

Principal Investigator: Catherine Limperopoulos, Ph.D., Developing Brain Institute at Children's National Hospital

Premature birth is a major public health problem associated with a personal, familial and societal burden of staggering proportions. The potentially lifelong cognitive, learning and affective-behavioral consequences have become the major determinant of quality of life in children who survive preterm birth, with up to 50% of very premature infants experiencing dysfunction in these domains by school age. Impaired cerebellar development recently has been implicated in this dysfunction. 

We have described a clinically important, previously under-recognized form of prematurity-related cerebellar parenchymal injury in up to 20% in extremely preterm infants. Recently, our observations have extended beyond the role of parenchymal cerebellar injury to a broader and more prevalent spectrum of cerebellar developmental impairments. 

We have shown that cerebellar development is

  1. markedly accelerated during the third trimester, but
  2. significantly impeded after premature birth, even in the absence of direct cerebellar injury. 

We refer to this impaired growth as cerebellar developmental impairment (CDI). Complementing this intriguing set of structural observations are our findings of a distinctive long-term neuropsychological profile of cognitive, language affective and social deficiency, which we have termed the developmental cerebellar cognitive affective disorder. The onset and underlying mechanisms and consequences of prematurity-related CDI remain poorly understood, which in turn have complicated the search for potential therapeutic interventions.

We are leveraging serial, advanced MRI techniques to elucidate the timing, evolution, mechanisms and risk factors of CDI in preterm infants born ≤30 weeks’ gestational age. Our overarching goal is to identify early MR imaging biomarkers of prematurity-related CDI and the associated clinical factors that lead to specific development disabilities. We are tapping one of the world’s largest imaging databases of normal fetal development to compare cerebellar growth trajectories during pregnancy and after childbirth. These findings inform specific targets, interventions and timing of neuroprotective strategies, advance clinical practices and improve neurodevelopmental outcomes. 

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