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Placental DNA methylation changes and the early prediction of autism in full-term newborns.

ABSTRACT: Autism spectrum disorder (ASD) is associated with abnormal brain development during fetal life. Overall, increasing evidence indicates an important role of epigenetic dysfunction in ASD. The placenta is critical to and produces neurotransmitters that regulate fetal brain development. We hypothesized that placental DNA methylation changes are a feature of the fetal development of the autistic brain and importantly could help to elucidate the early pathogenesis and prediction of these disorders. Genome-wide methylation using placental tissue from the full-term autistic disorder subtype was performed using the Illumina 450K array. The study consisted of 14 cases and 10 control subjects. Significantly epigenetically altered CpG loci (FDR p-value <0.05) in autism were identified. Ingenuity Pathway Analysis (IPA) was further used to identify molecular pathways that were over-represented (epigenetically dysregulated) in autism. Six Artificial Intelligence (AI) algorithms including Deep Learning (DL) to determine the predictive accuracy of CpG markers for autism detection. We identified 9655 CpGs differentially methylated in autism. Among them, 2802 CpGs were inter- or non-genic and 6853 intragenic. The latter involved 4129 genes. AI analysis of differentially methylated loci appeared highly accurate for autism detection. DL yielded an AUC (95% CI) of 1.00 (1.00-1.00) for autism detection using intra- or intergenic markers by themselves or combined. The biological functional enrichment showed, four significant functions that were affected in autism: quantity of synapse, microtubule dynamics, neuritogenesis, and abnormal morphology of neurons. In this preliminary study, significant placental DNA methylation changes. AI had high accuracy for the prediction of subsequent autism development in newborns. Finally, biologically functional relevant gene pathways were identified that may play a significant role in early fetal neurodevelopmental influences on later cognition and social behavior.

SUBMITTER: Bahado-Singh RO

PROVIDER: S-EPMC8279352 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceAntibiotic treatment saves lives in newborns with early-onset sepsis (EOS), but unwarranted antibiotic use is associated with resistant bacteria and adverse outcomes later in life. Surveillance is needed to optimize treatment strategies.ObjectiveTo describe antibiotic use in association with the incidence and mortality from EOS among late-preterm and full-term newborns.Design, setting, and participantsThe Sweden Neonatal Antibiotic Use study was a nationwide observational study that included all late-preterm and full-term neonates born from January 1, 2012, to December 31, 2020, in neonatal units of all levels. All hospital live births from 34 weeks' gestation during the study period were included in the study. Data were collected from the Swedish Neonatal Quality Register and the Swedish Medical Birth Register. Data were analyzed from August 2022 to May 2023.ExposureAdmission for neonatal intensive care during the first week of life.Main outcomes and measuresThe main outcomes were the usage of intravenous antibiotics during the first week of life, the duration of antibiotic therapy, the rate of culture-proven EOS, and mortality associated with EOS.ResultsA total of 1 025 515 newborns were included in the study; 19 286 neonates (1.88%; 7686 girls [39.9%]; median [IQR] gestational age, 40 [38-41] weeks; median [IQR] birth weight, 3610 [3140-4030] g) received antibiotics during the first week of life, of whom 647 (3.4%) had EOS. The median (IQR) duration of antibiotic treatment in newborns without EOS was 5 (3-7) days, and there were 113 antibiotic-days per 1000 live births. During the study period there was no significant change in the exposure to neonatal antibiotics or antibiotic-days per 1000 live births. The incidence of EOS was 0.63 per 1000 live births, with a significant decrease from 0.74 in 2012 to 0.34 in 2020. Mortality associated with EOS was 1.39% (9 of 647 newborns) and did not change significantly over time. For each newborn with EOS, antibiotic treatment was initiated in 29 newborns and 173 antibiotic-days were dispensed.Conclusions and relevanceThis large nationwide study found that a relatively low exposure to antibiotics is not associated with an increased risk of EOS or associated mortality. Still, future efforts to reduce unwarranted neonatal antibiotic use are needed.

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Placental DNA methylation changes and the early prediction of autism in full-term newborns.

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