Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep

Judith Rittenschober-Böhm, Jennifer Rodger, Alan H. Jobe, Suhas G. Kallapur, Dorota A. Doherty, Boris W. Kramer, Matthew S. Payne, Michael Archer, Christian Rittenschober, John P. Newnham, Yuichiro Miura, Angelika Berger, Stephen G. Matthews, Matthew W. Kemp, Wilhelmina Mulders

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: Antenatal corticosteroids (ACS) improve preterm neonatal outcomes. However, uncertainty remains regarding the safety of ACS exposure for the developing fetus, particularly its neurosensory development. Objectives: We investigated the effect of single and multiple ACS exposures on auditory nerve development in an ovine model of pregnancy. Methods: Ewes with a single fetus (gestational age [GA] 100 days) received an intramuscular injection of 150 mg medroxyprogesterone-acetate, followed by intramuscular (i) betamethasone (0.5 mg/kg) on days 104, 111, and 118 GA; (ii) betamethasone on day 104 and saline on days 111 and 118 GA; or (iii) saline on days 104, 111, and 118 GA, with delivery on day 125 GA. Transmission electron microscope images of lamb auditory nerve preparations were digitally analyzed to determine auditory nerve morphology and myelination. Results: Relative to the control, mean auditory nerve myelin area was significantly increased in the multiple-treatment group (p < 0.001), but not in the single-treatment group. Increased myelin thickness was significantly changed only in a subgroup analysis for those axons with myelin thickness greater than the median value (p < 0.001). Morphological assessments showed that the increased myelin area was due to an increased likelihood of decompacted areas (p = 0.005; OR = 2.14, 95% CI 1.26–3.63; 31.6 vs. 18.2% in controls) and irregular myelin deposition (p = 0.001; OR = 5.91, 95% CI 2.16–16.19; 49.0 vs. 16.8% in controls) in the myelin sheath. Conclusions: In preterm sheep, ACS exposure increased auditory nerve myelin area, potentially due to disruption of normal myelin deposition.

Original languageEnglish
Pages (from-to)62-68
Number of pages7
JournalNeonatology
Volume114
Issue number1
DOIs
Publication statusE-pub ahead of print - 2018

Fingerprint

Cochlear Nerve
Myelin Sheath
Sheep
Adrenal Cortex Hormones
Gestational Age
Betamethasone
Fetus
Medroxyprogesterone Acetate
Intramuscular Injections
Uncertainty
Axons
Electrons
Safety
Pregnancy
Therapeutics

Cite this

Rittenschober-Böhm, Judith ; Rodger, Jennifer ; Jobe, Alan H. ; Kallapur, Suhas G. ; Doherty, Dorota A. ; Kramer, Boris W. ; Payne, Matthew S. ; Archer, Michael ; Rittenschober, Christian ; Newnham, John P. ; Miura, Yuichiro ; Berger, Angelika ; Matthews, Stephen G. ; Kemp, Matthew W. ; Mulders, Wilhelmina. / Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep. In: Neonatology. 2018 ; Vol. 114, No. 1. pp. 62-68.
@article{d3d24cfa81764aa9ae5fbdd502c9e3c6,
title = "Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep",
abstract = "Background: Antenatal corticosteroids (ACS) improve preterm neonatal outcomes. However, uncertainty remains regarding the safety of ACS exposure for the developing fetus, particularly its neurosensory development. Objectives: We investigated the effect of single and multiple ACS exposures on auditory nerve development in an ovine model of pregnancy. Methods: Ewes with a single fetus (gestational age [GA] 100 days) received an intramuscular injection of 150 mg medroxyprogesterone-acetate, followed by intramuscular (i) betamethasone (0.5 mg/kg) on days 104, 111, and 118 GA; (ii) betamethasone on day 104 and saline on days 111 and 118 GA; or (iii) saline on days 104, 111, and 118 GA, with delivery on day 125 GA. Transmission electron microscope images of lamb auditory nerve preparations were digitally analyzed to determine auditory nerve morphology and myelination. Results: Relative to the control, mean auditory nerve myelin area was significantly increased in the multiple-treatment group (p < 0.001), but not in the single-treatment group. Increased myelin thickness was significantly changed only in a subgroup analysis for those axons with myelin thickness greater than the median value (p < 0.001). Morphological assessments showed that the increased myelin area was due to an increased likelihood of decompacted areas (p = 0.005; OR = 2.14, 95{\%} CI 1.26–3.63; 31.6 vs. 18.2{\%} in controls) and irregular myelin deposition (p = 0.001; OR = 5.91, 95{\%} CI 2.16–16.19; 49.0 vs. 16.8{\%} in controls) in the myelin sheath. Conclusions: In preterm sheep, ACS exposure increased auditory nerve myelin area, potentially due to disruption of normal myelin deposition.",
keywords = "Antenatal corticosteroids, Auditory nerve, Myelination, Neurosensory development, Preterm lamb",
author = "Judith Rittenschober-B{\"o}hm and Jennifer Rodger and Jobe, {Alan H.} and Kallapur, {Suhas G.} and Doherty, {Dorota A.} and Kramer, {Boris W.} and Payne, {Matthew S.} and Michael Archer and Christian Rittenschober and Newnham, {John P.} and Yuichiro Miura and Angelika Berger and Matthews, {Stephen G.} and Kemp, {Matthew W.} and Wilhelmina Mulders",
year = "2018",
doi = "10.1159/000487914",
language = "English",
volume = "114",
pages = "62--68",
journal = "Neonatalogy",
issn = "0006-3126",
publisher = "S Karger AG",
number = "1",

}

Rittenschober-Böhm, J, Rodger, J, Jobe, AH, Kallapur, SG, Doherty, DA, Kramer, BW, Payne, MS, Archer, M, Rittenschober, C, Newnham, JP, Miura, Y, Berger, A, Matthews, SG, Kemp, MW & Mulders, W 2018, 'Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep' Neonatology, vol. 114, no. 1, pp. 62-68. https://doi.org/10.1159/000487914

Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep. / Rittenschober-Böhm, Judith; Rodger, Jennifer; Jobe, Alan H.; Kallapur, Suhas G.; Doherty, Dorota A.; Kramer, Boris W.; Payne, Matthew S.; Archer, Michael; Rittenschober, Christian; Newnham, John P.; Miura, Yuichiro; Berger, Angelika; Matthews, Stephen G.; Kemp, Matthew W.; Mulders, Wilhelmina.

In: Neonatology, Vol. 114, No. 1, 2018, p. 62-68.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antenatal Corticosteroid Exposure Disrupts Myelination in the Auditory Nerve of Preterm Sheep

AU - Rittenschober-Böhm, Judith

AU - Rodger, Jennifer

AU - Jobe, Alan H.

AU - Kallapur, Suhas G.

AU - Doherty, Dorota A.

AU - Kramer, Boris W.

AU - Payne, Matthew S.

AU - Archer, Michael

AU - Rittenschober, Christian

AU - Newnham, John P.

AU - Miura, Yuichiro

AU - Berger, Angelika

AU - Matthews, Stephen G.

AU - Kemp, Matthew W.

AU - Mulders, Wilhelmina

PY - 2018

Y1 - 2018

N2 - Background: Antenatal corticosteroids (ACS) improve preterm neonatal outcomes. However, uncertainty remains regarding the safety of ACS exposure for the developing fetus, particularly its neurosensory development. Objectives: We investigated the effect of single and multiple ACS exposures on auditory nerve development in an ovine model of pregnancy. Methods: Ewes with a single fetus (gestational age [GA] 100 days) received an intramuscular injection of 150 mg medroxyprogesterone-acetate, followed by intramuscular (i) betamethasone (0.5 mg/kg) on days 104, 111, and 118 GA; (ii) betamethasone on day 104 and saline on days 111 and 118 GA; or (iii) saline on days 104, 111, and 118 GA, with delivery on day 125 GA. Transmission electron microscope images of lamb auditory nerve preparations were digitally analyzed to determine auditory nerve morphology and myelination. Results: Relative to the control, mean auditory nerve myelin area was significantly increased in the multiple-treatment group (p < 0.001), but not in the single-treatment group. Increased myelin thickness was significantly changed only in a subgroup analysis for those axons with myelin thickness greater than the median value (p < 0.001). Morphological assessments showed that the increased myelin area was due to an increased likelihood of decompacted areas (p = 0.005; OR = 2.14, 95% CI 1.26–3.63; 31.6 vs. 18.2% in controls) and irregular myelin deposition (p = 0.001; OR = 5.91, 95% CI 2.16–16.19; 49.0 vs. 16.8% in controls) in the myelin sheath. Conclusions: In preterm sheep, ACS exposure increased auditory nerve myelin area, potentially due to disruption of normal myelin deposition.

AB - Background: Antenatal corticosteroids (ACS) improve preterm neonatal outcomes. However, uncertainty remains regarding the safety of ACS exposure for the developing fetus, particularly its neurosensory development. Objectives: We investigated the effect of single and multiple ACS exposures on auditory nerve development in an ovine model of pregnancy. Methods: Ewes with a single fetus (gestational age [GA] 100 days) received an intramuscular injection of 150 mg medroxyprogesterone-acetate, followed by intramuscular (i) betamethasone (0.5 mg/kg) on days 104, 111, and 118 GA; (ii) betamethasone on day 104 and saline on days 111 and 118 GA; or (iii) saline on days 104, 111, and 118 GA, with delivery on day 125 GA. Transmission electron microscope images of lamb auditory nerve preparations were digitally analyzed to determine auditory nerve morphology and myelination. Results: Relative to the control, mean auditory nerve myelin area was significantly increased in the multiple-treatment group (p < 0.001), but not in the single-treatment group. Increased myelin thickness was significantly changed only in a subgroup analysis for those axons with myelin thickness greater than the median value (p < 0.001). Morphological assessments showed that the increased myelin area was due to an increased likelihood of decompacted areas (p = 0.005; OR = 2.14, 95% CI 1.26–3.63; 31.6 vs. 18.2% in controls) and irregular myelin deposition (p = 0.001; OR = 5.91, 95% CI 2.16–16.19; 49.0 vs. 16.8% in controls) in the myelin sheath. Conclusions: In preterm sheep, ACS exposure increased auditory nerve myelin area, potentially due to disruption of normal myelin deposition.

KW - Antenatal corticosteroids

KW - Auditory nerve

KW - Myelination

KW - Neurosensory development

KW - Preterm lamb

UR - http://www.scopus.com/inward/record.url?scp=85045763404&partnerID=8YFLogxK

UR - https://www.karger.com/Article/FullText/495278

U2 - 10.1159/000487914

DO - 10.1159/000487914

M3 - Article

VL - 114

SP - 62

EP - 68

JO - Neonatalogy

JF - Neonatalogy

SN - 0006-3126

IS - 1

ER -