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Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection

IMPORTANCE: Very preterm neonates (24-32 weeks’ gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there i...

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Autores principales: Gomaa, Noha, Konwar, Chaini, Gladish, Nicole, Au-Young, Stephanie H., Guo, Ting, Sheng, Min, Merrill, Sarah M., Kelly, Edmond, Chau, Vann, Branson, Helen M., Ly, Linh G., Duerden, Emma G., Grunau, Ruth E., Kobor, Michael S., Miller, Steven P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631102/
https://www.ncbi.nlm.nih.gov/pubmed/36322087
http://dx.doi.org/10.1001/jamanetworkopen.2022.39796
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author Gomaa, Noha
Konwar, Chaini
Gladish, Nicole
Au-Young, Stephanie H.
Guo, Ting
Sheng, Min
Merrill, Sarah M.
Kelly, Edmond
Chau, Vann
Branson, Helen M.
Ly, Linh G.
Duerden, Emma G.
Grunau, Ruth E.
Kobor, Michael S.
Miller, Steven P.
author_facet Gomaa, Noha
Konwar, Chaini
Gladish, Nicole
Au-Young, Stephanie H.
Guo, Ting
Sheng, Min
Merrill, Sarah M.
Kelly, Edmond
Chau, Vann
Branson, Helen M.
Ly, Linh G.
Duerden, Emma G.
Grunau, Ruth E.
Kobor, Michael S.
Miller, Steven P.
author_sort Gomaa, Noha
collection PubMed
description IMPORTANCE: Very preterm neonates (24-32 weeks’ gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population. OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock—a recently developed tool to measure biological aging—among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks’ gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded. EXPOSURES: The extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age. MAIN OUTCOMES AND MEASURES: Total cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months. RESULTS: Among 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [<28 weeks’ gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = –5356.8; 95% CI, −6899.3 to −2961.7; P = .01) and slower cerebral growth (β = –2651.5; 95% CI, −5301.2 to −1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = –0.4; 95% CI, −0.8 to −0.03; P = .04) and language (β = –0.6; 95% CI, −1.1 to −0.06; P = .02) scores at 18 months. CONCLUSIONS AND RELEVANCE: This cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention.
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spelling pubmed-96311022022-11-28 Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection Gomaa, Noha Konwar, Chaini Gladish, Nicole Au-Young, Stephanie H. Guo, Ting Sheng, Min Merrill, Sarah M. Kelly, Edmond Chau, Vann Branson, Helen M. Ly, Linh G. Duerden, Emma G. Grunau, Ruth E. Kobor, Michael S. Miller, Steven P. JAMA Netw Open Original Investigation IMPORTANCE: Very preterm neonates (24-32 weeks’ gestation) remain at a higher risk of morbidity and neurodevelopmental adversity throughout their lifespan. Because the extent of prematurity alone does not fully explain the risk of adverse neonatal brain growth or neurodevelopmental outcomes, there is a need for neonatal biomarkers to help estimate these risks in this population. OBJECTIVES: To characterize the pediatric buccal epigenetic (PedBE) clock—a recently developed tool to measure biological aging—among very preterm neonates and to assess its association with the extent of prematurity, neonatal comorbidities, neonatal brain growth, and neurodevelopmental outcomes at 18 months of age. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted in 2 neonatal intensive care units of 2 hospitals in Toronto, Ontario, Canada. A total of 35 very preterm neonates (24-32 weeks’ gestation) were recruited in 2017 and 2018, and neuroimaging was performed and buccal swab samples were acquired at 2 time points: the first in early life (median postmenstrual age, 32.9 weeks [IQR, 32.0-35.0 weeks]) and the second at term-equivalent age (TEA) at a median postmenstrual age of 43.0 weeks (IQR, 41.0-46.0 weeks). Follow-ups for neurodevelopmental assessments were completed in 2019 and 2020. All neonates in this cohort had at least 1 infection because they were originally enrolled to assess the association of neonatal infection with neurodevelopment. Neonates with congenital malformations, genetic syndromes, or congenital TORCH (toxoplasmosis, rubella, cytomegalovirus, herpes and other agents) infection were excluded. EXPOSURES: The extent of prematurity was measured by gestational age at birth and PedBE age difference. PedBE age was computed using DNA methylation obtained from 94 age-informative CpG (cytosine-phosphate-guanosine) sites. PedBE age difference (weeks) was calculated by subtracting PedBE age at each time point from the corresponding postmenstrual age. MAIN OUTCOMES AND MEASURES: Total cerebral volumes and cerebral growth during the neonatal intensive care unit period were obtained from magnetic resonance imaging scans at 2 time points: approximately the first 2 weeks of life and at TEA. Bayley Scales of Infant and Toddler Development, Third Edition, were used to assess neurodevelopmental outcomes at 18 months. RESULTS: Among 35 very preterm neonates (21 boys [60.0%]; median gestational age, 27.0 weeks [IQR, 25.9-29.9 weeks]; 23 [65.7%] born extremely preterm [<28 weeks’ gestation]), extremely preterm neonates had an accelerated PedBE age compared with neonates born at a later gestational age (β = 9.0; 95% CI, 2.7-15.3; P = .01). An accelerated PedBE age was also associated with smaller cerebral volumes (β = –5356.8; 95% CI, −6899.3 to −2961.7; P = .01) and slower cerebral growth (β = –2651.5; 95% CI, −5301.2 to −1164.1; P = .04); these associations remained significant after adjusting for clinical neonatal factors. These findings were significant at TEA but not earlier in life. Similarly, an accelerated PedBE age at TEA was associated with lower cognitive (β = –0.4; 95% CI, −0.8 to −0.03; P = .04) and language (β = –0.6; 95% CI, −1.1 to −0.06; P = .02) scores at 18 months. CONCLUSIONS AND RELEVANCE: This cohort study of very preterm neonates suggests that biological aging may be associated with impaired brain growth and neurodevelopmental outcomes. The associations between epigenetic aging and adverse neonatal brain health warrant further attention. American Medical Association 2022-11-02 /pmc/articles/PMC9631102/ /pubmed/36322087 http://dx.doi.org/10.1001/jamanetworkopen.2022.39796 Text en Copyright 2022 Gomaa N et al. JAMA Network Open. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Gomaa, Noha
Konwar, Chaini
Gladish, Nicole
Au-Young, Stephanie H.
Guo, Ting
Sheng, Min
Merrill, Sarah M.
Kelly, Edmond
Chau, Vann
Branson, Helen M.
Ly, Linh G.
Duerden, Emma G.
Grunau, Ruth E.
Kobor, Michael S.
Miller, Steven P.
Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title_full Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title_fullStr Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title_full_unstemmed Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title_short Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
title_sort association of pediatric buccal epigenetic age acceleration with adverse neonatal brain growth and neurodevelopmental outcomes among children born very preterm with a neonatal infection
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9631102/
https://www.ncbi.nlm.nih.gov/pubmed/36322087
http://dx.doi.org/10.1001/jamanetworkopen.2022.39796
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