# Brain Development and Pre-Speech Function in Infants with Isolated Oral Clefts: Relationship to Anesthesia Exposure and Oxygenation

> **NIH NIH R56** · UNIVERSITY OF IOWA · 2022 · $510,462

## Abstract

Project Summary/Abstract
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) – before their
first exposure to anesthesia. 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 among people with an isolated
oral cleft that is correlated to measures of cognitive and academic functioning. These differences have been
identified across child, adolescent, young adult, 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.
The PI conducted a pilot study, obtaining structural MRI scans and vocal recording in infants with (n = 4; 2 with
successful MRI) and without (n = 4) isolated oral clefts at 2 months of age (prior to any exposure to
anesthesia). Results demonstrated a trend of reduced volume of myelinated white matter and reduced vocal
complexity (pre-speech marker of language development) in infants with iCL/P compared to unaffected
controls. While preliminary, these findings suggest that differences in infants with iCL/P may be present shortly
after birth and prior to exposure to anesthesia – supporting a stronger role of genetics and development in the
progression of structural and functional differences identified later in life.
The proposed study will expand the pilot by recruiting a larger sample from two sites, obtaining vocal and
neuronal measures at three different time points (before and after surgery for those with iCL/P), utilizing both
MRI and functional near-infrared spectroscopy (fNIRS) for neural measurement, and obtaining measures of
oxygenation. 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.

## Key facts

- **NIH application ID:** 10427075
- **Project number:** 1R56DE030075-01A1
- **Recipient organization:** UNIVERSITY OF IOWA
- **Principal Investigator:** Amy Lynn Conrad
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $510,462
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10427075

## Citation

> US National Institutes of Health, RePORTER application 10427075, Brain Development and Pre-Speech Function in Infants with Isolated Oral Clefts: Relationship to Anesthesia Exposure and Oxygenation (1R56DE030075-01A1). Retrieved via AI Analytics 2026-05-30 from https://api.ai-analytics.org/grant/nih/10427075. Licensed CC0.

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