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Record W4225264846 · doi:10.1080/15622975.2021.2016955

Newborn differential DNA methylation and subcortical brain volumes as early signs of severe neurodevelopmental delay in a South African Birth Cohort Study

2021· article· en· W4225264846 on OpenAlexaff
Anke Hüls, Catherine J. Wedderburn, Nynke A. Groenewold, Nicole Gladish, Meaghan J. Jones, Nastassja Koen, Julia L. MacIsaac, David Lin, Katia E. Ramadori, Michael P. Epstein, Kirsten A. Donald, Michael S. Kobor, Heather J. Zar, Dan J. Stein

Bibliographic record

VenueThe World Journal of Biological Psychiatry · 2021
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEpigenetics and DNA Methylation
Canadian institutionsBC Children's HospitalUniversity of ManitobaChildren's Hospital Research Institute of ManitobaPacific Centre for Reproductive MedicineUniversity of British Columbia
FundersEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institute of Environmental Health SciencesNational Institute on Alcohol Abuse and AlcoholismDeutsche ForschungsgemeinschaftHarry Crossley FoundationNational Institute of General Medical SciencesSouth African Medical Research CouncilWellcome TrustDiscovery Eye Foundation
KeywordsCohortBrain sizeDNA methylationSigns and symptomsMedicinePediatricsPsychologyNeuroscienceBiologyGeneticsInternal medicineMagnetic resonance imagingGene

Abstract

fetched live from OpenAlex

Objectives Early detection of neurodevelopmental delay is crucial for intervention and treatment strategies. We analysed associations between newborn DNA methylation (DNAm), neonatal magnetic resonance imaging (MRI) neuroimaging data, and neurodevelopment.Methods Neurodevelopment was assessed in 161 children from the South African Drakenstein Child Health Study at 2 years of age using the Bayley Scales of Infant and Toddler Development III. We performed an epigenome-wide association study of neurodevelopmental delay using DNAm from cord blood. Subsequently, we analysed if associations between DNAm and neurodevelopmental delay were mediated by altered neonatal brain volumes (subset of 51 children).Results Differential DNAm at SPTBN4 (cg26971411, Δbeta = −0.024, p-value = 3.28 × 10−08), and two intergenic regions (chromosome 11: cg00490349, Δbeta = −0.036, p-value = 3.02 × 10−08; chromosome 17: cg15660740, Δbeta = −0.078, p-value = 6.49 × 10−08) were significantly associated with severe neurodevelopmental delay. While these associations were not mediated by neonatal brain volume, neonatal caudate volumes were independently associated with neurodevelopmental delay, particularly in language (Δcaudate volume = 165.30 mm3, p = 0.0443) and motor (Δcaudate volume = 365.36 mm3, p-value = 0.0082) domains.Conclusions Differential DNAm from cord blood and increased neonatal caudate volumes were independently associated with severe neurodevelopmental delay at 2 years of age. These findings suggest that neurobiological signals for severe developmental delay may be detectable in very early life.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.033
Threshold uncertainty score0.065

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.013
GPT teacher head0.261
Teacher spread0.248 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations25
Published2021
Admission routes1
Has abstractyes

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