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Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study.

ABSTRACT: Inflammatory phenomena seem to contribute to the occurrence of perinatal cerebral white matter damage and CP. The stimulus that initiates the inflammation remains obscure. One thousand two hundred forty-six infants born before the 28th postmenstrual week had a protocol ultrasound scan of the brain read concordantly by two independent sonologists. Eight hundred ninety-nine of the children had a neurologic examination at approximately 24-mo postterm equivalent. The placenta of each child had been biopsied under sterile conditions and later cultured. Histologic slides of the placenta were examined specifically for this study. Recovery of a single microorganism predicted an echolucent lesion, whereas polymicrobial cultures and recovery of skin flora predicted both ventriculomegaly and an echolucent lesion. Diparetic CP was predicted by recovery of a single microorganism, multiple organisms, and skin flora. Histologic inflammation predicted ventriculomegaly and diparetic CP. The risk of ventriculomegaly associated with organism recovery was heightened when accompanied by histologic inflammation, but the risk of diparetic CP was not. Low-virulence microorganisms isolated from the placenta, including common skin microflora, predict ultrasound lesions of the brain and diparetic CP in the very preterm infant. Organism recovery does not seem to be needed for placenta inflammation to predict diparetic CP.

SUBMITTER: Leviton A

PROVIDER: S-EPMC2794973 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study.

Leviton Alan A Allred Elizabeth N EN Kuban Karl C K KC Hecht Jonathan L JL Onderdonk Andrew B AB O'shea T Michael TM Paneth Nigel N

Pediatric research 20100101 1

Inflammatory phenomena seem to contribute to the occurrence of perinatal cerebral white matter damage and CP. The stimulus that initiates the inflammation remains obscure. One thousand two hundred forty-six infants born before the 28th postmenstrual week had a protocol ultrasound scan of the brain read concordantly by two independent sonologists. Eight hundred ninety-nine of the children had a neurologic examination at approximately 24-mo postterm equivalent. The placenta of each child had been ...[more]

PMID: 19745780

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Project description:BackgroundChildren 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.MethodsWe 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.ResultsGenes 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.LimitationsThe 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.ConclusionsAggregating 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.

Dataset Information

Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study.

Publications

Microbiologic and histologic characteristics of the extremely preterm infant's placenta predict white matter damage and later cerebral palsy. the ELGAN study.

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