Long-Term Variability of Distortion-Product Otoacoustic Emissions in Infants and Children and Its Relation to Pediatric Ototoxicity Monitoring

Objective: Distortion-product otoacoustic emissions (DPOAEs) provide a rapid, noninvasive measure of outer hair cell damage associated with chemotherapy and are a key component of pediatric ototoxicity monitoring. Serial monitoring of DPOAE levels in reference to baseline measures is one method for detecting ototoxic damage. Interpreting DPOAE findings in this context requires that test-retest differences be considered in relation to normal variability, data which are lacking in children. This study sought to (1) characterize normal test-retest variability in DPOAE level over the long time periods reflective of pediatric chemotherapy regimens for a variety of childhood ages and f2 primary frequencies using common clinical instrumentation and stimulus parameters; (2) develop level-shift reference intervals; and (3) account for any age-related change in DPOAE level or measurement error that may occur as the auditory system undergoes maturational change early in life. Design: Serial DPOAE measurements were obtained in 38 healthy children (25 females and 13 males) with normal hearing and ranging in age from one month to 10 years at the initial (baseline) visit. On average, children were tested 5.2 times over an observation period of 6.5 months. Data were collected in the form of DP grams, in which DPOAE level was measured for f2 ranging from 1.4 to 10 kHz, using a fixed f2/f1 ratio of 1.22 and stimulus level of 65/55 dB SPL for L1/L2. Age effects on DPOAE level and measurement error were estimated using Bayesian regression of the longitudinal data. The raw and model-based distribution of DPOAE test-retest differences were characterized using means and standard error of the measurement for several ages and f2's. Results: DPOAE test-retest differences for the children in this study are at the high end of those previously observed in adults, as reflected in the associated shift reference intervals. Further, although we observe substantial child-specific variation in DPOAE level, the pattern of age-related changes is highly consistent across children. Across a wide range of f2's, DPOAE level decreases by 3 to 4 dB from 1 to 13 months of age followed by a more gradual decline of <1 dB/year. An f2 of 6 kHz shows the smallest decrease during the early rapid maturation period. DPOAE measurement error is fairly constant with age. It is 3 to 4 dB at most f2's and is greater (indicating poorer reliability) at 1.5, 8, and 10 kHz. Conclusions: DPOAE level decreases with childhood age, with the greatest changes observed in the first year of life. Maturational effects during infancy and greater measurement error at very low and high f2's affect test-retest variability in children. An f2 of 6 kHz shows minimal maturation and measurement error, suggesting it may be an optimal sentinel frequency for ototoxicity monitoring in pediatric patients. Once validated with locally developed normative data, reference intervals provided herein could be used to determine screen fail criteria for serial monitoring using DPOAEs. Employing state-of-the-art calibration techniques might reduce variability, allowing for more sensitive screen fail criteria.