Association of Pediatric Buccal Epigenetic Age Acceleration With Adverse Neonatal Brain Growth and Neurodevelopmental Outcomes Among Children Born Very Preterm With a Neonatal Infection
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».