Characterization of chorioamnionitis in second trimester C-section placentas and correlation with microorganism recovery from subamniotic tissues

Jonathan L Hecht, Andrew Onderdonk, Mary Delaney, Elizabeth N Allred, Harvey J Kliman, Eduardo Zambrano, Solveig M Pflueger, Chad A Livasy, Ina Bhan, Alan Leviton, ELGAN Study Investigators

Pediatr Dev Pathol 2008;11:15-22

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Subamniotic parenchyma of 835 placentas delivered by c/s cultured and evaluated in blinded fashion. Microbes recovered from 41% of placentas. Microbes found more frequently in placentas with high-grade chorionic plate inflammation: Actinomyces, Prevotella bivia, Corynebacterium sp., Escherichia coli, Peptostreptococcus magnus, multiple species of Streptococci, and Mycoplasma sp., including Ureaplasma urealyticum. These microorganisms were also associated with fetal vasculitis.

Detection of Bacteria in Placental Tissues Obtained from Extremely Low Gestational Age Neonates (ELGAN)

Andrew B Onderdonk, Mary L Delaney, Andrea M DuBois, Elizabeth N Allred, Alan Leviton, Extremely Low Gestational Age Newborns (ELGAN) Study Investigators

Am J Obstet Gynecol 2008;198:110.e1-7

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The culture + rate was higher for vaginal deliveries (333/489; 68%) than for cesarean sections (363/876; 41%). 30% of culture-positive samples had only aerobic bacteria, 21% had only anaerobic bacteria, and 9% had only Mycoplasma/Ureaplasma. Staph and Corynebacterium & organisms associated w/bacterial vaginosis most frequently recovered. Approximately 1/2 of 2nd trimester placentas had orgs w/i chorionic plate.

Observer variability assessing US scans of the preterm brain: The ELGAN Study

Karl Kuban, Ira Adler, Elizabeth N Allred, Daniel Batton, Steven Bezinque, Bradford W Betz, Ellen Cavenagh, Sara Durfee, Kirsten Ecklund, Kate Feinstein, Lynn Ansley Fordham, Frederick Hampf, Joseph Junewick, Robert Lorenzo, Roy McCauley, Cindy Miller, Joanna Seibert, Barbara Specter, Jacqueline Wellman, Sjirk Westra, Alan Leviton

Pediatric Radiology 2007;37:1201-8.

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We sought to evaluate observer variability among experienced neurosonologists. We collected all protocol US scans of 1,450 infants born before the 28th postmenstrual week. Each set of scans read by 2 sonologists for presence of IVH and mod/sev vmeg, & EL &EG: in WM. Scans read discordantly sent to a tie-breaking third sonologist.

Vmeg, EL and IVH had similar rates of positive agreement (68-76%), negative agreement (92-97%), and kappa values (0.62 to 0.68). EG had lower values of positive agreement (48%), negative agreement (84%), and kappa (0.32).

Perturbation of gene expression of the chromatin remodeling pathway in premature newborns at risk for BPD

Jennifer Cohen, Linda J Van Marter, Yao Sun, Elizabeth Allred, Alan Leviton, Isaac S Kohane

Genome Biol 2007;8:R210

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To evaluate expression profiling in umbilical cord tissue to discover molecular signatures for staging and determine risk for BPD, we conducted cross-sectional study of ELGANs (n = 54). Sections of umb cord obtained at birth f/ 20 infants w/BPD & 34 peers who did not. Infants who developed BPD had distinct signatures involving chromatin remodeling and histone acetylation pathways, implicated in adult lung ds.

Reference weights for placentas delivered before the 28th week of gestation

J L Hecht, H J Kliman, E N Allred, S M Pflueger, C-H Chang, B J Doss, D Roberts, C A Livasy, I Bhan, E Zambrano, D W Ross, P Senagore, A N Husain, A Leviton

Placenta 2007;28:987-90

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We measured the weight of 930 singleton placentas delivered < 28th week, and examined distributions of wts. We excluded 90 IUGR, resulting in normative sample of 840 placentas. Placenta weight varied with B Wt. Placentas from pregnancies ending due to preeclampsia, fetal indications or with poor perfusion on histology were among smallest and weights correlated with the smallest birth weights for gestational age.

Factors associated with tx for hypotension in extremely low gestational age newborns during the first postnatal week

Matthew Laughon, Carl Bose, Elizabeth Allred, T Michael O'Shea, Linda J Van Marter, Francis Bednarek, Alan Leviton, ELGAN Study Investigators

Pediatrics 2007;119:273-80.

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The goals to ID the BP of ELGANs that prompt intervention & to ID other infant characteristics of BP therapies. At each GA, the lowest MAP in treated and untreated infants tended to increase with advancing postnatal age. The proportion of infants receiving any tx decreased with increasing GA from 93% at 23 wks to 73% at 27 wks. Lower GA lower B Wt ,male sex, and higher SNAP-II values associated with tx.

Thymus involution and cerebral white matter damage in extremely low gestational age neonates

Joshua David Kuban, Elizabeth N Allred, Alan Leviton

Biol Neonate 2006;90:252-7

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Among newborns who die, those who have cerebral white matter damage are more likely than others to have thymus involution and low thymus weights. We sought to evaluate in a population of preterm newborns who did not die if those who developed a cerebral white matter damage (defined by echolucency) are more likely than others to have thymus involution assessed on chest radiographs. Infants with an EL were more likely to have had early involution than infants without an EL (89% vs. 44%) (p = 0.01).

Video and CD-ROM as a training tool for performing neurologic examinations of 1-year-old children in a multicenter epidemiologic study

Karl C K Kuban, Michael O'Shea, Elizabeth Allred, Alan Leviton, Herbert Gilmore, Adré DuPlessis, Kalpathy Krishnamoorthy, Cecil Hahn, Janet Soul, Sunila E O'Connor, Karen Miller, Paige T Church, Cecilia Keller, Richard Bream, Robin Adair, Alice Miller, Elaine Romano, Haim Bassan, Kathy Kerkering, Steve Engelke, Diane Marshall, Kristy Milowic, Janice Wereszczak, Carol Hubbard, Lisa Washburn, Robert Dillard, Cherrie Heller, Wendy Burdo-Hartman, Lynn Fagerman, Dinah Sutton, Padu Karna, Nick Olomu, Leslie Caldarelli, Melisa Oca, Kim Lohr, Albert Scheiner

J. Child Neurol 2005;20:829-31

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In lieu of traditional training of examiners to identify cerebral palsy on a neurologic examination at age 1 year, we proposed an alternative approach using multimedia training video. Interactive CD-ROM examination training is an efficient and cost-effective means of training both neurologists and non-neurologists to perform structured neurologic examinations in 1-year-old children.

Sex-based differences in placental DNA methylation profiles related to gestational age: an NIH ECHO meta-analysis

Bulka CM, Everson TM, Burt AA, Marsit CJ, Karagas MR, Boyle KE, Niemiec S, Kechris K, Davidson EJ, Yang IV, Feinberg JI, Volk HE, Ladd-Acosta C, Breton CV, O'Shea TM, Fry RC; program collaborators for Environmental influences on Child Health Outcomes.

Epigenetics. 2023 Dec;18(1):2179726. doi: 10.1080/15592294.2023.2179726. PMID: 36840948; PMCID: PMC9980626.

PubMed Link


The placenta undergoes many changes throughout gestation to support the evolving needs of the foetus. There is also a growing appreciation that male and female foetuses develop differently in utero, with unique epigenetic changes in placental tissue. Here, we report meta-analysed sex-specific associations between gestational age and placental DNA methylation from four cohorts in the National Institutes of Health (NIH) Environmental influences on Child Health Outcomes (ECHO) Programme (355 females/419 males, gestational ages 23-42 weeks). We identified 407 cytosine-guanine dinucleotides (CpGs) in females and 794 in males where placental methylation levels were associated with gestational age. After cell-type adjustment, 55 CpGs in females and 826 in males were significant. These were enriched for biological processes critical to the immune system in females and transmembrane transport in males. Our findings are distinct between the sexes: in females, associations with gestational age are largely explained by differences in placental cellular composition, whereas in males, gestational age is directly associated with numerous alterations in methylation levels.