Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm / Hudson P. Jr SANTOS in Molecular Autism, 11 (2020)  

Public ISBD [article]  inMolecular Autism > 11 (2020) Titre : Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm Type de document : Texte imprimé et/ou numérique Auteurs : Hudson P. Jr SANTOS, Auteur ; Arjun BHATTACHARYA, Auteur ; Robert M. JOSEPH, Auteur ; Lisa SMEESTER, Auteur ; Karl C. K. KUBAN, Auteur ; Carmen J. MARSIT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur Langues : Anglais (eng) Mots-clés : Differential expression analysis  Epigenome-wide association  Multi-omic aggregation  Placental gene regulation  Prenatal neurodevelopmental programming  Social and cognitive impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Children born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes. METHODS: We examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS. RESULTS: Genes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status. LIMITATIONS: The ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited. CONCLUSIONS: Aggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic. En ligne : http://dx.doi.org/10.1186/s13229-020-00402-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438 [article] Evidence for the placenta-brain axis: multi-omic kernel aggregation predicts intellectual and social impairment in children born extremely preterm [Texte imprimé et/ou numérique] / Hudson P. Jr SANTOS, Auteur ; Arjun BHATTACHARYA, Auteur ; Robert M. JOSEPH, Auteur ; Lisa SMEESTER, Auteur ; Karl C. K. KUBAN, Auteur ; Carmen J. MARSIT, Auteur ; T. Michael O'SHEA, Auteur ; Rebecca C. FRY, Auteur. Langues : Anglais (eng) in Molecular Autism > 11 (2020) Mots-clés : Differential expression analysis  Epigenome-wide association  Multi-omic aggregation  Placental gene regulation  Prenatal neurodevelopmental programming  Social and cognitive impairment Index. décimale : PER Périodiques Résumé : BACKGROUND: Children born extremely preterm are at heightened risk for intellectual and social impairment, including Autism Spectrum Disorder (ASD). There is increasing evidence for a key role of the placenta in prenatal developmental programming, suggesting that the placenta may, in part, contribute to origins of neurodevelopmental outcomes. METHODS: We examined associations between placental transcriptomic and epigenomic profiles and assessed their ability to predict intellectual and social impairment at age 10 years in 379 children from the Extremely Low Gestational Age Newborn (ELGAN) cohort. Assessment of intellectual ability (IQ) and social function was completed with the Differential Ability Scales-II and Social Responsiveness Scale (SRS), respectively. Examining IQ and SRS allows for studying ASD risk beyond the diagnostic criteria, as IQ and SRS are continuous measures strongly correlated with ASD. Genome-wide mRNA, CpG methylation and miRNA were assayeds with the Illumina Hiseq 2500, HTG EdgeSeq miRNA Whole Transcriptome Assay, and Illumina EPIC/850 K array, respectively. We conducted genome-wide differential analyses of placental mRNA, miRNA, and CpG methylation data. These molecular features were then integrated for a predictive analysis of IQ and SRS outcomes using kernel aggregation regression. We lastly examined associations between ASD and the multi-omic-predicted component of IQ and SRS. RESULTS: Genes with important roles in neurodevelopment and placental tissue organization were associated with intellectual and social impairment. Kernel aggregations of placental multi-omics strongly predicted intellectual and social function, explaining approximately 8% and 12% of variance in SRS and IQ scores via cross-validation, respectively. Predicted in-sample SRS and IQ showed significant positive and negative associations with ASD case-control status. LIMITATIONS: The ELGAN cohort comprises children born pre-term, and generalization may be affected by unmeasured confounders associated with low gestational age. We conducted external validation of predictive models, though the sample size (N = 49) and the scope of the available out-sample placental dataset are limited. Further validation of the models is merited. CONCLUSIONS: Aggregating information from biomarkers within and among molecular data types improves prediction of complex traits like social and intellectual ability in children born extremely preterm, suggesting that traits within the placenta-brain axis may be omnigenic. En ligne : http://dx.doi.org/10.1186/s13229-020-00402-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=438

Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years / Robert M. JOSEPH in Autism Research, 10-2 (February 2017)  

Public ISBD [article]  inAutism Research > 10-2 (February 2017) . - p.224-232 Titre : Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years Type de document : Texte imprimé et/ou numérique Auteurs : Robert M. JOSEPH, Auteur ; Thomas M. O'SHEA, Auteur ; Elizabeth N. ALLRED, Auteur ; Tim HEEREN, Auteur ; Deborah HIRTZ, Auteur ; Nigel PANETH, Auteur ; Alan LEVITON, Auteur ; Karl C. K. KUBAN, Auteur Article en page(s) : p.224-232 Langues : Anglais (eng) Mots-clés : diagnosis  epidemiology – descriptive  intellectual disability  pre- and perinatal risk factors  prevalence  sex differences Index. décimale : PER Périodiques Résumé : We sought to estimate the prevalence of autism spectrum disorder (ASD) in children born extremely preterm relative to the U.S. population risk of 1.5% [CDC, 2014] using the best-available diagnostic procedures and minimizing confounding with other neurodevelopmental impairments. Eight hundred and eighty nine of 966 (92%) 10-year-old children from the Extremely Low Gestational Age Newborn birth cohort, delivered at 23–27 weeks gestation in 2002–2004, participated. Children meeting ASD screening criteria on the Social Communication Questionnaire were evaluated with the Autism Diagnostic Interview–Revised (ADI-R). Those meeting ADI-R criteria were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). A positive ADOS-2 score was the criterion for ASD. Twenty-six participants were not assessed for ASD because of severe sensory or motor impairment. In the remaining sample, 61 children met criteria for ASD, resulting in a prevalence of 7.1% (95% CI?=?5.5–9.0). ASD risk decreased with increasing gestational age, from 15.0% (95% CI?=?10.0–21.2) for 23–24 weeks, 6.5% (95% CI?=?4.2–9.4) for 25–26 weeks, to 3.4% (95% CI?=?1.6–6.1) for 27 weeks gestational age, and this association was independent of IQ. Among children with ASD, 40% had intellectual disability. The male-to-female ratio of children with ASD was 2.1:1 (95% CI?=?1.2:1–3.5:1), lower than in the general population (4:1). ASD prevalence in the ELGAN cohort was four times higher than in the general population, and was strongly associated with gestational age, underscoring the need for enhanced ASD screening of children born preterm, and suggesting that some risk factors associated with preterm birth may also play a role in the etiology of autism. En ligne : http://dx.doi.org/10.1002/aur.1644 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303 [article] Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years [Texte imprimé et/ou numérique] / Robert M. JOSEPH, Auteur ; Thomas M. O'SHEA, Auteur ; Elizabeth N. ALLRED, Auteur ; Tim HEEREN, Auteur ; Deborah HIRTZ, Auteur ; Nigel PANETH, Auteur ; Alan LEVITON, Auteur ; Karl C. K. KUBAN, Auteur . - p.224-232. Langues : Anglais (eng) in Autism Research > 10-2 (February 2017) . - p.224-232 Mots-clés : diagnosis  epidemiology – descriptive  intellectual disability  pre- and perinatal risk factors  prevalence  sex differences Index. décimale : PER Périodiques Résumé : We sought to estimate the prevalence of autism spectrum disorder (ASD) in children born extremely preterm relative to the U.S. population risk of 1.5% [CDC, 2014] using the best-available diagnostic procedures and minimizing confounding with other neurodevelopmental impairments. Eight hundred and eighty nine of 966 (92%) 10-year-old children from the Extremely Low Gestational Age Newborn birth cohort, delivered at 23–27 weeks gestation in 2002–2004, participated. Children meeting ASD screening criteria on the Social Communication Questionnaire were evaluated with the Autism Diagnostic Interview–Revised (ADI-R). Those meeting ADI-R criteria were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). A positive ADOS-2 score was the criterion for ASD. Twenty-six participants were not assessed for ASD because of severe sensory or motor impairment. In the remaining sample, 61 children met criteria for ASD, resulting in a prevalence of 7.1% (95% CI?=?5.5–9.0). ASD risk decreased with increasing gestational age, from 15.0% (95% CI?=?10.0–21.2) for 23–24 weeks, 6.5% (95% CI?=?4.2–9.4) for 25–26 weeks, to 3.4% (95% CI?=?1.6–6.1) for 27 weeks gestational age, and this association was independent of IQ. Among children with ASD, 40% had intellectual disability. The male-to-female ratio of children with ASD was 2.1:1 (95% CI?=?1.2:1–3.5:1), lower than in the general population (4:1). ASD prevalence in the ELGAN cohort was four times higher than in the general population, and was strongly associated with gestational age, underscoring the need for enhanced ASD screening of children born preterm, and suggesting that some risk factors associated with preterm birth may also play a role in the etiology of autism. En ligne : http://dx.doi.org/10.1002/aur.1644 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=303

The Epidemiology Of Germinal Matrix Hemorrhage During The First Half-Day Of Life / Alan LEVITON in Developmental Medicine & Child Neurology, 33-2 (February 1991)

Public ISBD [article]  inDevelopmental Medicine & Child Neurology > 33-2 (February 1991) . - p.138-145 Titre : The Epidemiology Of Germinal Matrix Hemorrhage During The First Half-Day Of Life Type de document : Texte imprimé et/ou numérique Auteurs : Alan LEVITON, Auteur ; Marcello PAGANO, Auteur ; Karl C. K. KUBAN, Auteur ; Kalpathy S. KRISHNAMOORTHY, Auteur ; Kathleen F. SULLIVAN, Auteur ; Elizabeth N. ALLRED, Auteur Année de publication : 1991 Article en page(s) : p.138-145 Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Epidémiologie des hémorragies manifestes de la couche germinative durant la première demi-journée de vie Les caractéristiques personnelles et maternelles de 27 nourrissons présentant une hémorragie précoce de la couche germinative (EGMH) ont été comparées à celles de 280 nourrissons avec échographies craniennes normales, observés dans un service clinique séparé. Aucune des mères n'avait présenté d'hypertension artérielle ou d'éclampsie durant la grossesse. Un âge conceptuel de moins de 30 semaines et un pH initial inférieur à 7,2 traduisaient un risque accru et l'administration de corticoïdes stéroïdiens a la mère, un risque diminué d'EGMH. Ainsi, les facteurs prénataux et périnataux précoces paraissent fournir l'essentiel de l'information sur le risque d'EGMH. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=135 [article] The Epidemiology Of Germinal Matrix Hemorrhage During The First Half-Day Of Life [Texte imprimé et/ou numérique] / Alan LEVITON, Auteur ; Marcello PAGANO, Auteur ; Karl C. K. KUBAN, Auteur ; Kalpathy S. KRISHNAMOORTHY, Auteur ; Kathleen F. SULLIVAN, Auteur ; Elizabeth N. ALLRED, Auteur . - 1991 . - p.138-145. Langues : Anglais (eng) in Developmental Medicine & Child Neurology > 33-2 (February 1991) . - p.138-145 Index. décimale : PER Périodiques Résumé : Epidémiologie des hémorragies manifestes de la couche germinative durant la première demi-journée de vie Les caractéristiques personnelles et maternelles de 27 nourrissons présentant une hémorragie précoce de la couche germinative (EGMH) ont été comparées à celles de 280 nourrissons avec échographies craniennes normales, observés dans un service clinique séparé. Aucune des mères n'avait présenté d'hypertension artérielle ou d'éclampsie durant la grossesse. Un âge conceptuel de moins de 30 semaines et un pH initial inférieur à 7,2 traduisaient un risque accru et l'administration de corticoïdes stéroïdiens a la mère, un risque diminué d'EGMH. Ainsi, les facteurs prénataux et périnataux précoces paraissent fournir l'essentiel de l'information sur le risque d'EGMH. Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=135

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