Speech Development and Brain Structure/Function in Infants with Isolated Oral Clefts: Relationship Anesthesia Exposure and Oxygenation

The purpose of this research grant application is to expand a pilot project evaluating the earliest markers of brain and pre-speech development in infants with isolated cleft of the lip and/or palate (iCL/P). Research has documented a high incidence of specific learning disabilities (most notably language or reading deficits) among this population. These disabilities, while not in the range of intellectual dysfunction, do result in academic achievement problems and lower rates of college attendance. Recent work has also documented differences in brain structure and function that is correlated to measures of cognitive and academic functioning. These differences have been identified across child, adolescent, and adult samples. Current theories on the etiology of these structural and functional differences have proposed: 1) early exposure to anesthesia, 2) obstructed airway and resulting reduced oxygenation, and 3) abnormal neural migration as potential contributing factors.
To fully evaluate these theories, imaging work needs to be done on infants before and after their first surgery, with information on early functioning, pre-speech development, oxygenation, and brain structure obtained in tandem. In the proposed study, infants with iCL/P and unaffected controls will undergo assessment at 2, 6-8, and 14-16 months of age; providing pre- and post-surgery measures for infants with iCL/P. At each time point, innovative techniques of brain imaging (through MRI and fNIRS) and multi-modal assessment of speech/language (vocal recordings and clinical ratings) will be combined with continuous overnight pulse oximetry and systematic and structured medical chart review (for information on anesthesia exposure, clinically-mandated sleep studies, medical interventions, and audiology assessments). Through an R56 (NIDCR), the PI and research team has demonstrated feasibility of this protocol, by obtaining data on 9 participants (4 iCL/P and 5 unaffected) at 2 months of age. Initial data validate differential neural activation during the fNIRS language processing task and suggest patterns of immature pre-speech development, lower brain volume due to delayed white matter growth, and increased desaturation events during sleep shortly after birth and before exposure to anesthesia for those with iCL/P. This provides preliminary evidence of a biologically based, developmental etiology where differences are present prior to exposure to anesthesia.
Specific goals of the current project are to: 1) Assess the effects of cleft presence and sex (as well as their interaction) and oxygen level on brain structure/function and pre-speech/language measures at each time point; 2) Evaluate the relationship of early brain structure/function to later brain function and language outcomes; and 3) Assess the potential impact of exposure to anesthesia on developmental trajectories within groups (i.e., iCL, iCP, iCLP, and Unaffected). The results of this study will significantly contribute to the understanding of neuronal development in infants with iCL/P and the impact of exposure to anesthesia and reduced oxygenation have on this development.