Early Vocal Development in Tuberous Sclerosis Complex

Objective To determine whether entry into the canonical stage, canonical babbling ratios (CBR) and the level of volubility (vocal measures) are delayed in infants with Tuberous Sclerosis Complex (TSC), we completed human coding of their vocalizations at 12 months and compared the results to typically developing infants with no clinical features (TD/NCF). Methods We randomly selected videos from 40 infants with TSC from the TACERN database. All 78 videos were coded in real-time in AACT (Action Analysis, Coding and Training). Results Entry into the canonical stage was delayed in the great majority of the infants with TSC. The CBR for the TD/NCF infants was significantly higher than for the infants with TSC (TD/NCF mean = .346, SE = .19; TSC mean = .117, SE = .023). Volubility level in infants with TSC was less than half that of TD/NCF infants (TD/NCF mean = 9.82, SE = 5.78; TSC mean = 3.99, SE = 2.16). CBR and volubility were also lower in TSC infants than in TD/NCF infants recorded all-day at home. Conclusions Entry into the canonical stage was delayed, while canonical babbling ratios and volubility were low in infants with TSC. Assessing prediction of neurodevelopmental outcome using these vocal measures in combination with non-vocal measures will be the focus of planned studies in this high-risk population. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Institute on Deafness and Other Communication Disorders of the National Institutes of Health [Grant number 3R01DC015108-05S] awarded to TTG and DKO and by the National Institute on Mental Health [Grant number P50 MH100029] awarded to GR. The work was also funded by the parent grant [R01DC015108] and the Plough Foundation, and by the Holly Lane Foundation to GR. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the IRB for human subjects committees of the University of Tennessee Health Sciences Center and Cincinnati Children's Hospital for the TACERN data, and the University of Memphis, and Children's Hospital of Atlanta for the TD/NCF data. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Portions of these data will be made available on the OSF following journal acceptance.