NCT05298748

Brief Summary

The aim of this proposal is to characterize the acute effect of early postnatal sound exposure on neuronal maturation of the respiratory control regions of the brain in preterm infants.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
34

participants targeted

Target at P25-P50 for not_applicable

Timeline
6mo left

Started Sep 2022

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress88%
Sep 2022Nov 2026

First Submitted

Initial submission to the registry

March 8, 2022

Completed
20 days until next milestone

First Posted

Study publicly available on registry

March 28, 2022

Completed
6 months until next milestone

Study Start

First participant enrolled

September 16, 2022

Completed
4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2026

Expected
1 month until next milestone

Study Completion

Last participant's last visit for all outcomes

November 1, 2026

Last Updated

December 5, 2025

Status Verified

December 1, 2025

Enrollment Period

4 years

First QC Date

March 8, 2022

Last Update Submit

December 4, 2025

Conditions

BradycardiaApnea of PrematurityIntermittent Hypoxemia

Keywords

apnea, intermittent hypoxemia, bradycardia, audio recording

Outcome Measures

Primary Outcomes (6)

  • cardiorespiratory events

    Apnea (\>20 seconds or shorter with intermittent hypoxemia \<85% or bradycardia \<80bpm)

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

  • intermittent hypoxemia

    falls in oxygen saturation \<85%

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

  • mean heart rate

    mean heart rate

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

  • bradycardia

    heart rate \<80bpm

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

  • body motion

    non-cardiac alterations in the oximeter plethysmograph waveform

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

  • respiratory pauses

    Respiratory pauses of \>5sec will be documented to increase the chance of capturing small alterations in respiratory stability.

    During the 24 hour period of randomized blocks of womb sound recordings and ambient noise

Study Arms (2)

Ambient noise followed by Womb sound

OTHER

At 34 weeks corrected age, preterm infants (29-33 weeks gestational age at birth), who are off respiratory support \>1.5 lpm, will be exposed to alternating 6-hour periods of a recording of ambient noise followed by commercially available womb sounds over a 24-hour period for a combined total of 12 hours of womb sounds and 12 hours of ambient noise.

Other: Womb sound recordings

Womb sound recordings followed by ambient noise

OTHER

At 34 weeks corrected age, preterm infants (29-33 weeks gestational age at birth), who are off respiratory support \>1.5 lpm, will be exposed to alternating 6-hour periods of a recording of commercially available womb sounds followed by ambient noise over a 24-hour period for a combined total of 12 hours of womb sounds and 12 hours of ambient noise.

Other: Womb sound recordings

Interventions

Womb sound recordingsOTHER

Womb sounds will be chosen from commercially available (Amazon) womb recordings using a recording that most closely resembles the womb including maternal heart rate, fetal heartbeat, respiratory sounds, bowel "popping" sounds and frequency spectra as described by Parga, Daland 2018 et al.

Ambient noise followed by Womb soundWomb sound recordings followed by ambient noise

Eligibility Criteria

Age1 Week - 5 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • preterm infants 29-33 weeks gestational age at birth
  • weeks corrected age
  • off respiratory support \>1.5 lpm

You may not qualify if:

  • on respiratory support \>1.5 lpm
  • congenital anomalies

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106-7061, United States

RECRUITING

Related Publications (32)

  • Noise: a hazard for the fetus and newborn. American Academy of Pediatrics. Committee on Environmental Health. Pediatrics. 1997 Oct;100(4):724-7. No abstract available.

    PMID: 9836852BACKGROUND

  • Jobe AH, Bancalari E. An All-Inclusive Perspective on Bronchopulmonary Dysplasia. J Pediatr. 2021 Jul;234:257-259. doi: 10.1016/j.jpeds.2021.03.063. Epub 2021 Apr 1. No abstract available.

    PMID: 33811871BACKGROUND

  • White RD, Smith JA, Shepley MM; Committee to Establish Recommended Standards for Newborn ICU Design. Recommended standards for newborn ICU design, eighth edition. J Perinatol. 2013 Apr;33 Suppl 1:S2-16. doi: 10.1038/jp.2013.10.

    PMID: 23536026BACKGROUND

  • Almadhoob A, Ohlsson A. Sound reduction management in the neonatal intensive care unit for preterm or very low birth weight infants. Cochrane Database Syst Rev. 2015 Jan 30;1:CD010333. doi: 10.1002/14651858.CD010333.pub2.

    PMID: 25633155RESULT

  • Barateiro A, Brites D, Fernandes A. Oligodendrocyte Development and Myelination in Neurodevelopment: Molecular Mechanisms in Health and Disease. Curr Pharm Des. 2016;22(6):656-79. doi: 10.2174/1381612822666151204000636.

    PMID: 26635271RESULT

  • Benzaquen S, Gagnon R, Hunse C, Foreman J. The intrauterine sound environment of the human fetus during labor. Am J Obstet Gynecol. 1990 Aug;163(2):484-90. doi: 10.1016/0002-9378(90)91180-k.

    PMID: 2386134RESULT

  • Brockmann PE, Wiechers C, Pantalitschka T, Diebold J, Vagedes J, Poets CF. Under-recognition of alarms in a neonatal intensive care unit. Arch Dis Child Fetal Neonatal Ed. 2013 Nov;98(6):F524-7. doi: 10.1136/archdischild-2012-303369. Epub 2013 May 28.

    PMID: 23716498RESULT

  • Coleman RJ, Beharry KD, Brock RS, Abad-Santos P, Abad-Santos M, Modanlou HD. Effects of brief, clustered versus dispersed hypoxic episodes on systemic and ocular growth factors in a rat model of oxygen-induced retinopathy. Pediatr Res. 2008 Jul;64(1):50-5. doi: 10.1203/PDR.0b013e31817307ac.

    PMID: 18344903RESULT

  • Corrigan MJ, Keeler JR, Miller HD, Ben Khallouq BA, Fowler SB. Music therapy and retinopathy of prematurity screening: using recorded maternal singing and heartbeat for post exam recovery. J Perinatol. 2020 Dec;40(12):1780-1788. doi: 10.1038/s41372-020-0719-9. Epub 2020 Jul 17.

    PMID: 32681063RESULT

  • Decker MJ, Rye DB. Neonatal intermittent hypoxia impairs dopamine signaling and executive functioning. Sleep Breath. 2002 Dec;6(4):205-10. doi: 10.1007/s11325-002-0205-y.

    PMID: 12524574RESULT

  • Di Fiore JM, Bloom JN, Orge F, Schutt A, Schluchter M, Cheruvu VK, Walsh M, Finer N, Martin RJ. A higher incidence of intermittent hypoxemic episodes is associated with severe retinopathy of prematurity. J Pediatr. 2010 Jul;157(1):69-73. doi: 10.1016/j.jpeds.2010.01.046. Epub 2010 Mar 20.

    PMID: 20304417RESULT

  • Di Fiore JM, Kaffashi F, Loparo K, Sattar A, Schluchter M, Foglyano R, Martin RJ, Wilson CG. The relationship between patterns of intermittent hypoxia and retinopathy of prematurity in preterm infants. Pediatr Res. 2012 Dec;72(6):606-12. doi: 10.1038/pr.2012.132. Epub 2012 Oct 4.

    PMID: 23037873RESULT

  • Doheny L, Hurwitz S, Insoft R, Ringer S, Lahav A. Exposure to biological maternal sounds improves cardiorespiratory regulation in extremely preterm infants. J Matern Fetal Neonatal Med. 2012 Sep;25(9):1591-4. doi: 10.3109/14767058.2011.648237. Epub 2012 Feb 2.

    PMID: 22185623RESULT

  • Emery L, Hamm EL, Hague K, Chorna OD, Moore-Clingenpeel M, Maitre NL. A randomised controlled trial of protocolised music therapy demonstrates developmental milestone acquisition in hospitalised infants. Acta Paediatr. 2019 May;108(5):828-834. doi: 10.1111/apa.14628. Epub 2018 Dec 7.

    PMID: 30375661RESULT

  • Jiang NM, Cowan M, Moonah SN, Petri WA Jr. The Impact of Systemic Inflammation on Neurodevelopment. Trends Mol Med. 2018 Sep;24(9):794-804. doi: 10.1016/j.molmed.2018.06.008. Epub 2018 Jul 11.

    PMID: 30006148RESULT

  • Jobe AH, Kallapur SG. Long term consequences of oxygen therapy in the neonatal period. Semin Fetal Neonatal Med. 2010 Aug;15(4):230-5. doi: 10.1016/j.siny.2010.03.007. Epub 2010 May 10.

    PMID: 20452844RESULT

  • Lahav A, Skoe E. An acoustic gap between the NICU and womb: a potential risk for compromised neuroplasticity of the auditory system in preterm infants. Front Neurosci. 2014 Dec 5;8:381. doi: 10.3389/fnins.2014.00381. eCollection 2014.

    PMID: 25538543RESULT

  • Loewy J, Stewart K, Dassler AM, Telsey A, Homel P. The effects of music therapy on vital signs, feeding, and sleep in premature infants. Pediatrics. 2013 May;131(5):902-18. doi: 10.1542/peds.2012-1367. Epub 2013 Apr 15.

    PMID: 23589814RESULT

  • Parga JJ, Bhatt RR, Kesavan K, Sim MS, Karp HN, Harper RM, Zeltzer L. A prospective observational cohort study of exposure to womb-like sounds to stabilize breathing and cardiovascular patterns in preterm neonates. J Matern Fetal Neonatal Med. 2018 Sep;31(17):2245-2251. doi: 10.1080/14767058.2017.1339269. Epub 2017 Jun 22.

    PMID: 28587528RESULT

  • Parga JJ, Daland R, Kesavan K, Macey PM, Zeltzer L, Harper RM. A description of externally recorded womb sounds in human subjects during gestation. PLoS One. 2018 May 10;13(5):e0197045. doi: 10.1371/journal.pone.0197045. eCollection 2018.

    PMID: 29746604RESULT

  • Peng YJ, Prabhakar NR. Effect of two paradigms of chronic intermittent hypoxia on carotid body sensory activity. J Appl Physiol (1985). 2004 Mar;96(3):1236-42; discussion 1196. doi: 10.1152/japplphysiol.00820.2003. Epub 2003 Dec 5.

    PMID: 14660510RESULT

  • Poets CF, Roberts RS, Schmidt B, Whyte RK, Asztalos EV, Bader D, Bairam A, Moddemann D, Peliowski A, Rabi Y, Solimano A, Nelson H; Canadian Oxygen Trial Investigators. Association Between Intermittent Hypoxemia or Bradycardia and Late Death or Disability in Extremely Preterm Infants. JAMA. 2015 Aug 11;314(6):595-603. doi: 10.1001/jama.2015.8841.

    PMID: 26262797RESULT

  • Raffaeli G, Manzoni F, Cortesi V, Cavallaro G, Mosca F, Ghirardello S. Iron Homeostasis Disruption and Oxidative Stress in Preterm Newborns. Nutrients. 2020 May 27;12(6):1554. doi: 10.3390/nu12061554.

    PMID: 32471148RESULT

  • Raffay TM, Dylag AM, Sattar A, Abu Jawdeh EG, Cao S, Pax BM, Loparo KA, Martin RJ, Di Fiore JM. Neonatal intermittent hypoxemia events are associated with diagnosis of bronchopulmonary dysplasia at 36 weeks postmenstrual age. Pediatr Res. 2019 Feb;85(3):318-323. doi: 10.1038/s41390-018-0253-z. Epub 2018 Dec 12.

    PMID: 30538265RESULT

  • Rains ME, Muncie CB, Pang Y, Fan LW, Tien LT, Ojeda NB. Oxidative Stress and Neurodevelopmental Outcomes in Rat Offspring with Intrauterine Growth Restriction Induced by Reduced Uterine Perfusion. Brain Sci. 2021 Jan 8;11(1):78. doi: 10.3390/brainsci11010078.

    PMID: 33435577RESULT

  • Reeves SR, Gozal D. Developmental plasticity of respiratory control following intermittent hypoxia. Respir Physiol Neurobiol. 2005 Nov 15;149(1-3):301-11. doi: 10.1016/j.resp.2005.01.014.

    PMID: 16203218RESULT

  • Reeves SR, Mitchell GS, Gozal D. Early postnatal chronic intermittent hypoxia modifies hypoxic respiratory responses and long-term phrenic facilitation in adult rats. Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1664-71. doi: 10.1152/ajpregu.00851.2005. Epub 2006 Feb 2.

    PMID: 16455761RESULT

  • Smith CV, Satt B, Phelan JP, Paul RH. Intrauterine sound levels: intrapartum assessment with an intrauterine microphone. Am J Perinatol. 1990 Oct;7(4):312-5. doi: 10.1055/s-2007-999511.

    PMID: 2222618RESULT

  • Smith SW, Ortmann AJ, Clark WW. Noise in the neonatal intensive care unit: a new approach to examining acoustic events. Noise Health. 2018 Jul-Aug;20(95):121-130. doi: 10.4103/nah.NAH_53_17.

    PMID: 30136672RESULT

  • Standley J. Music therapy research in the NICU: an updated meta-analysis. Neonatal Netw. 2012 Sep-Oct;31(5):311-6. doi: 10.1891/0730-0832.31.5.311.

    PMID: 22908052RESULT

  • Stokes A, Agthe AG, El Metwally D. Music exposure and maturation of late preterm sleep-wake cycles: a randomised crossover trial. Acta Paediatr. 2018 Apr;107(4):582-586. doi: 10.1111/apa.14079. Epub 2017 Oct 11.

    PMID: 28929527RESULT

  • Volpe JJ. Brain injury in premature infants: a complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009 Jan;8(1):110-24. doi: 10.1016/S1474-4422(08)70294-1.

    PMID: 19081519RESULT

MeSH Terms

Conditions

ApneaBradycardia

Condition Hierarchy (Ancestors)

Respiration DisordersRespiratory Tract DiseasesSigns and Symptoms, RespiratorySigns and SymptomsPathological Conditions, Signs and SymptomsArrhythmias, CardiacHeart DiseasesCardiovascular DiseasesPathologic Processes

Study Officials

  • Cynthia Bearer, MD

    University Hospitals Cleveland Medical Center

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Cynthia Bearer, MD

CONTACT

216 844-3387Cynthia.Bearer@UHhospitals.org

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
The order of the sound exposure will be randomized within each subject. The outcomes assessor (quantifying cardiorespiratory events) will be blinded as to the order of the 6 hour randomization blocks within the 24 hour study.
Purpose
PREVENTION
Intervention Model
SINGLE GROUP
Model Details: This is a single site, single visit study. The order of exposure, two 6 hour periods of ambient noise and two 6 hour periods of sound, will be randomized within each subject for a total of 24hrs of sound exposure.
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 8, 2022

First Posted

March 28, 2022

Study Start

September 16, 2022

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

November 1, 2026

Last Updated

December 5, 2025

Record last verified: 2025-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)