Mark Orlando

The New York State universal newborn hearing screening demonstration project: Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention

Objective: To determine the ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention through a multi‐center, state‐wide universal newborn hearing screening project. Design: Universal newborn hearing screening was conducted at eight hospitals across New York State. All infants who did not bilaterally pass hearing screening before discharge were recalled for outpatient retesting. Inpatient screening and outpatient rescreening were done with transient evoked otoacoustic emissions and/or auditory brain stem response testing. Diagnostic testing was performed with age appropriate tests, auditory brain stem response and/or visual reinforcement audiometry. Infants diagnosed with permanent hearing loss were considered for hearing aids and early intervention. Ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention were investigated regarding nursery type, risk status, unilateral versus bilateral hearing loss, loss type, loss severity, and state regions. Results: The prevalence of infants diagnosed with permanent hearing loss was 2.0/1000 (85 of 43,311). Of the 85 infants with hearing loss, 61% were from neonatal intensive care units (NICUs) and 67% were at risk for hearing loss. Of the 36 infants fitted with hearing aids, 58% were from NICUs and 78% were at risk for hearing loss. The median age at identification and enrollment in early intervention was 3 mo. Median age at hearing aid fitting was 7.5 mo. Median ages at identification were less for infants from the well‐baby nurseries (WBNs) than for the NICU infants and for infants with severe/profound than for infants with mild/moderate hearing loss, but were similar for not‐at‐risk and at‐risk infants. Median ages at hearing aid fitting were less for well babies than for NICU infants, for not‐at‐risk infants than for at‐risk infants, and for infants with severe/profound hearing loss than for infants with mild/moderate hearing loss. However, median ages at early intervention enrollment were similar for nursery types, risk status, and severity of hearing loss. Conclusions: Early ages of hearing loss identification, hearing aid fitting, and enrollment in early intervention can be achieved for infants from NICUs and WBNs and for infants at risk and not at risk for hearing loss in a large multi‐center universal newborn hearing screening program.

The New York State universal newborn hearing screening demonstration project: outpatient outcome measures.

Objective: To investigate outpatient outcome measures of a multi‐center, state‐wide, universal newborn hearing screening project. Design: Eight hospitals participated in a 3‐yr, funded project. Each hospital designed its own protocol using common criteria for judging whether an infant passed a hearing screening. Infants were tested in the hospital, and those either failing the in‐hospital screening or who were not tested in the hospital (missed) were asked to return 4 to 6 wk after hospital discharge for outpatient rescreening. Those infants failing the outpatient rescreening were referred for diagnostic auditory brain stem response testing. Each hospital used its own audiological equipment and criteria to determine whether a particular infant had a hearing loss. All data were collected and analyzed for individual hospitals, as well as totaled across all hospitals. Data were analyzed in terms of year of program operation, nursery type, and geographic region. Results: Seventy‐two percent of infants who failed the in‐hospital screening returned for outpatient testing. The percentage of in‐hospital fails returning for retesting was significantly higher than the percentage of in‐hospital misses returning for retesting. The percentage of infants returning for retesting increased with successive years of program operation. Some differences were noted in the percentage of infants returning for retesting among hospitals and geographic regions of the state. Some differences in outpatient outcome measures also were noted between infants originally born into the neonatal intensive care unit (NICU) and the well‐baby nursery (WBN). The percentage of infants from the NICU who returned for retesting was slightly higher than that for infants from the WBN. The percentage of infants from the WBN passing the outpatient rescreening was higher than that for the NICU infants. The overall prevalence of hearing loss was 1.96/1000, with that in the NICU being 8/1000 and that in the WBN being 0.9/1000. Positive predictive value for permanent hearing loss based on inpatient screening was approximately 4% and based on outpatient rescreening was approximately 22%. Conclusions: Several outpatient outcome measures changed with successive years of program operation, suggesting that programs improve over time. Also, some outpatient outcome measures differ between NICU and WBN populations. The differences noted across regions of the state in the percentage of infants returning for outpatient retesting require further research to determine whether differences are due to demographic and/or procedural differences.

New York State universal newborn hearing screening demonstration project: effects of screening protocol on inpatient outcome measures.

Objective: To examine differences among various test protocols on the fail rate at hospital discharge for infants in the well‐baby nursery (WBN) and neonatal intensive care unit (NICU) who received hearing screening through a universal newborn hearing screening demonstration project. Design: The outcomes of several screening protocols were examined. Two technologies were used: transient evoked otoacoustic emissions (TEOAEs) alone or in combination with the auditory brain stem response (ABR). The performance of test protocols in both nurseries within eight hospitals was examined over a 2‐ to 3‐yr period. In the WBN, six hospitals used a screening protocol of TEOAE technology first followed by an ABR (automated or conventional) technology screening for newborns who referred on TEOAE screening. Two hospitals used TEOAE only in the WBN. Seven hospitals used screening protocols in the NICU that used a combination of TEOAE and ABR technologies (TEOAE technology administered first or second, before or after TEOAE, or TEOAE and ABR tests on all infants). Only one hospital used TEOAE technology exclusively for hearing screening. Results: Significant differences among screening protocols were found across hospitals in the first, second, and third years of the program. The combination of TEOAE technology and ABR technology (a two‐technology screening protocol) resulted in a significantly lower fail rate at hospital discharge than the use of a single‐technology (TEOAE). Fail rates at discharge were twice as high using the one‐technology protocol versus two‐technology protocol, even when the best outcomes from program year 3 were considered exclusively. Results of two‐technology versus one‐technology protocols were similar in the NICU. Use of a second technology for screening TEOAE fails significantly reduced every hospital that used the protocols fail rate at discharge. Conclusions: A two‐technology screening protocol resulted in significantly lower fail rates at hospital discharge in both the WBN and NICU nurseries than use of a single‐technology (TEOAE) hearing screening protocol.

In Utero Iron Status and Auditory Neural Maturation in Premature Infants as Evaluated by Auditory Brainstem Response

OBJECTIVE To determine whether cord ferritin (CF) concentration, an index of in utero iron status, is associated with auditory neural maturation in premature infants. STUDY DESIGN A prospective cohort study was performed to compare auditory neural maturation in infants with latent iron deficiency (CF 11-75 ng/mL) and infants with normal iron status (CF > 75 ng/mL) at birth. Our inclusion criteria were infants of 27-33 weeks gestational age who were admitted to the neonatal intensive care unit between July 2007 and November 2008 within 12 hours after birth and had cord blood collected. Infants with TORCH infections (toxoplasmosis, other infections, rubella, cytomegalovirus infection, and herpes simplex), chromosomal disorders, craniofacial anomalies, culture-proven sepsis, and/or unstable conditions were excluded. CF level was measured using a chemiluminescence immunoassay method. Bilateral monaural auditory brainstem evoked response (ABR) was assessed using 80-dB nHL click stimuli at a repetition rate of 29.9/seconds within 48 hours after birth. RESULTS Of the 80 infants studied, 35 had latent iron deficiency. After controlling for confounders, the infants with latent iron deficiency had significantly prolonged absolute wave latencies I, III, and V and decreased frequency of mature ABR waveforms compared with the infants with normal iron status. CONCLUSION Premature infants with in utero latent iron deficiency have abnormal auditory neural maturation compared with infants with normal in utero iron status.

The contribution of spontaneous otoacoustic emissions to the click evoked otoacoustic emissions

Objective This investigation determines whether spontaneous otoacoustic emissions (SOAE) contribute to click evoked otoacoustic emissions (EOAE). Design Bilateral SOAEs and click EOAEs were recorded for 81 normal-hearing subjects by using an IL088 Otodynamic Analyzer. Results Results suggest that several factors from SOUS contribute to the level and the shape of the click EOAE. The number, frequency, and level of SOAEs all appear to affect the click EOAE. In addition, as the number of SOAEs increased, the click EOAE response level significantly increased. For the majority of subjects with SOAEs in only one ear, the click EOAE response level was higher in the same ear. Conclusions These findings suggest that SOAEs add to the overall EOAE response level. This likely occurs from the synchronous capturing of SOAEs during click EOAE data collection. Therefore, SOAEs play an important role in the click EOAE measurement.

Auditory brainstem response forward-masking recovery functions in older humans with normal hearing

We investigated the auditory brainstem response (ABR) recovery from forward masking using toneburst maskers and probes. Two subject groups matched for hearing thresholds were evaluated: normal-hearing young adults (21-40 years) and older subjects (63-77 years) with normal audiometric thresholds. Stimuli consisted of 1, 4 and 8 kHz tonebursts, with 2-4 cycle rise/fall time and no plateau. Forward maskers were tonebursts of the same frequency, with a 5 ms rise/fall time and a 20 ms plateau time. Probes were presented at 40 dB above threshold, and the forward masker was adjusted to a level that just eliminated the ABR to the 40 dB sensation level toneburst when the probe onset occurred at masker offset. Forward-masker intervals varied from 2 to 64 ms. ABR wave V latencies were similar for the young and old age groups regardless of toneburst frequency. Under forward-masking conditions, wave V latency was prolonged for the shorter intervals, and recovered to baseline latency by 64 ms. The forward-masker recovery functions were nearly identical for the two age groups for the 1 kHz toneburst. In contrast, there were clear differences in the recovery functions for the two age groups for the 4 and 8 kHz tonebursts. Specifically, the mean latency shift was greater for the aged group for forward-masker intervals of 16 ms or less. The two age groups showed identical latency shifts for longer forward-masker intervals. These data demonstrate prolonged recovery from forward masking in older human subjects. As these subjects had audiometric thresholds within normal limits, one plausible interpretation of this finding is that the prolonged recovery time is a manifestation of an aging effect on the central auditory nervous system rather than the periphery.

Morphological changes in serial auditory brain stem responses in 24 to 32 weeks' gestational age infants during the first week of life.

OBJECTIVE The purpose of this investigation was to describe and quantify the sequential morphological changes in the auditory brain stem response (ABR) during the first postnatal week of life in very premature infants < or = 32 wk gestational age. These normative data could be useful in predicting neurological outcome in infants with perinatal risk factors. DESIGN Sequential ABRs were recorded on a total of 135 infants on 5 out of the first 7 days of life. For analysis, data were grouped by gestational age in 2 wk intervals. In addition, a unique system was devised to categorize waveform response types in premature infants: type 1, a response with normal morphology and replicable waves III and V; type 2, a replicable response with either a wave III or wave V; type 3, a replicable response with neither a wave III or wave V; type 4, a response with no replicable waveform. RESULTS The frequency of detection of waves improves over the first week of life with the detectability of waves III and V being more frequent than wave I at all gestational ages. There was a gradual improvement in response types in infants > 26 wk with the greatest improvement occurring during the 28 to 29 wk gestation. ABRs were predominantly types 3 and 4 at 24 to 25 wk, type 3 at 26 to 27 wk, type 2 at 28 to 29 wk, and types 1 and 2 at 30 to 31 wk. Absolute wave latencies and interwave latencies also progressively decreased during the first postnatal week. In some infants there was a transient increase in latencies or worsening of response type on the second to third test day. CONCLUSIONS There is progressive improvement in frequency of detection of waves I, III, and V with increasing gestational age. Response types gradually mature over the first postnatal week, particularly in premature infants 28 to 32 wk gestational age.

Impact of maternal and neonatal iron status on placental transferrin receptor expression in pregnant adolescents.

OBJECTIVE To elucidate the role of maternal and neonatal iron status on placental transferrin receptor (TfR) expression. STUDY DESIGN AND OUTCOMES: Ninety-two healthy pregnant adolescents (ages 14-18 years) were followed across pregnancy. Maternal iron status (hemoglobin, hematocrit, serum ferritin, TfR, and total body iron) was assessed in mid-gestation (21-25 wks) and at delivery in the mother and neonate. Placental TfR protein expression was assessed by western blot in placental tissue collected at delivery. RESULTS Placental TfR expression was inversely associated with maternal iron status at mid-gestation (hemoglobin p = 0.046, R(2) = 0.1 and hematocrit p = 0.005, R(2) = 0.24) and at delivery (serum ferritin p = 0.02, R(2) = 0.08 and total body iron p = 0.02, R(2) = 0.07). Mothers with depleted body iron stores had significantly greater placental expression of TfR than mothers with body iron stores greater than zero (p = 0.003). Neonatal iron stores were also inversely associated with the expression of placental TfR (p = 0.04, R(2) = 0.06). Neonates with serum ferritin values ≤ 34 μg/L had significantly greater protein expression of placental TfR compared to neonates with cord serum ferritin values >34 μg/L (p = 0.01). CONCLUSIONS Expression of placental TfR is associated with both maternal and neonatal iron demands. Increased expression of placental TfR may be an important compensatory mechanism in response to iron deficiency in otherwise healthy pregnant women.

Latent Iron Deficiency In Utero Is Associated with Abnormal Auditory Neural Myelination in ≥35 Weeks Gestational Age Infants

OBJECTIVE To determine whether cord serum ferritin level is associated with auditory brainstem evoked response interpeak latencies, an index of auditory neural myelination, in infants at ≥ 35 weeks gestational age (GA). STUDY DESIGN This prospective study compared auditory neural myelination in infants with latent iron deficiency (cord serum ferritin, 11-75 ng/mL) and infants with normal iron status (cord serum ferritin, >75 ng/mL) at birth. Our inclusion criteria were infants born at ≥ 35 weeks GA who had cord blood collected soon after birth and had 1 or more of the following risk factors for poor in utero iron status: maternal diabetes mellitus, pregnancy-induced hypertension, and intrauterine growth restriction. Cord serum ferritin level was measured using the chemiluminescence immunoassay method. Auditory brainstem evoked response was measured using 80-dB normal hearing level click stimuli at a rate of 69.9/second within 48 hours after birth to evaluate interpeak latencies, a measure of nerve conduction velocity or myelination. RESULTS Of the 45 infants studied, 12 had latent iron deficiency. On repeated-measures ANCOVA using interpeak latencies I-III, III-V, and I-V as multiple outcomes, infants with latent iron deficiency had significantly prolonged interpeak latencies (P = .01) compared with infants with normal iron status after controlling for confounders. CONCLUSION In utero latent iron deficiency is associated with abnormal auditory neural myelination at birth in infants born at ≥ 35 weeks GA.

Maternal Inflammation at Delivery Affects Assessment of Maternal Iron Status

Pregnant adolescents (aged ≤ 18 y, n = 253) were followed from ≥ 12 wk of gestation to delivery to assess longitudinal changes in anemia and iron status and to explore associations between iron status indicators, hepcidin, and inflammatory markers. Hemoglobin, soluble transferrin receptor (sTfR), ferritin, serum iron, erythropoietin (EPO), hepcidin, C-reactive protein, interleukin-6 (IL-6), folate, and vitamin B-12 were measured, and total body iron (TBI) (milligrams per kilogram) was calculated using sTfR and ferritin values. Anemia prevalence increased from trimesters 1 and 2 (3-5%, <28 wk) to trimester 3 (25%, 33.2 ± 3.7 wk, P < 0.0001). The prevalence of iron deficiency (sTfR > 8.5 mg/L) doubled from pregnancy to delivery (7% to 14%, P = 0.04). Ferritin and hepcidin concentrations at delivery may have been elevated as a consequence of inflammation because IL-6 concentrations at delivery were 1.6-fold higher than those obtained at 26.1 ± 3.3 wk of gestation (P < 0.0001), and a positive association was found between IL-6 and both hepcidin and ferritin at delivery (P < 0.01). EPO was consistently correlated with hemoglobin (r = -0.36 and -0.43, P < 0.001), ferritin (r = -0.37 and -0.32, P < 0.0001), sTfR (r = 0.35 and 0.25, P < 0.001), TBI (r = -0.44 and -0.37, P < 0.0001), and serum iron (r = -0.22 and -0.16, P < 0.05) at mid-gestation and at delivery, respectively. EPO alone explained the largest proportion of variance in hemoglobin at 26.0 ± 3.3 wk of gestation (R(2) = 0.13, P = 0.0001, n = 113) and at delivery (R(2) = 0.19, P < 0.0001, n = 192). Pregnant adolescents are at high risk of anemia. EPO is a sensitive indicator of iron status across gestation, is not affected by systemic inflammation, and may better predict risk of anemia at term. The trial was registered at clinicaltrials.gov as NCT01019902.