Publications

Neonatal Cranial Ultrasound Lesions and Developmental Delays at 2 Years of Age Among Extremely Low Gestational Age Children

T Michael O'Shea, Karl C K Kuban, Elizabeth N Allred, Nigel Paneth, Marcello Pagano, Olaf Dammann, Lisa Bostic, Kara Brooklier, Samantha Butler, Donald J Goldstein, Gail Hounshell, Cecelia Keller, Susan McQuiston, Alice Miller, Steve Pasternak, Susan Plesha-Troyke, Joan Price, Elaine Romano, Katherine M Solomon, Amanda Jacobson, Sjirk Westra, Alan Leviton, Extremely Low Gestational Age Newborns Study Investigators

Pediatrics 2008;122:e662-e669

PubMed Link

26% of all children had MDI < 70, and 31% had PDI < 70. HUS more associated with low PDI than with low MDI. Children w/o HUS abnormality had lowest probability (23% and 26%) of delayed development. Mod/severe Vmeg associated with 4-fold risk of low PDI and 3-fold risk of low MDI. EL was next best predictor of delay At particularly high risk were infants with bilat cerebellar hemorrhage, Vmeg and bilat/post EL

Colonization of second trimester placenta parenchyma

Andrew B Onderdonk, Jonathan L Hecht, Thomas F McElrath, Mary L Delaney, Elizabeth N Allred, Alan Leviton, ELGAN Study Investigators

Am J Obstet Gynecol 2008;199:52.e1-52.e10

PubMed Link

Bx specimens of chorion from 1083 placentas cultured, and placentas examined. Placentas delivered by c/s w/ PET had lowest bacteria (25%). Preterm labor had highest rates, which ↓with ↑GA from 79% at 23 weeks to 43% at 27 wks. Microorgs in placenta associated w/wbc in fetal stem vessels of chorion or in vessels of umb cord.

Histologic characteristics of singleton placentas delivered before the 28th week of gestation

Jonathan L Hecht, Elizabeth N Allred, Harvey J Kliman, Eduardo Zambrano, Barbara J Doss, Aliya Husain, Solveig M V Pflueger, Chung-Ho Chang, Chad A Livasy, Drucilla Roberts, Ina Bhan, Dennis W Ross, Patricia Kaman Senagore, Alan Leviton, Elgan Study Investigators

Pathology 2008;40:372-6

PubMed Link

Lesions of uteroplacental circulation (abruption, extensive infarction/thrombosis, basal or perivillous fibrin deposition, ↑syncytial knots) inversely related to membrane & cord inflammation. Earlier GA favored inflamm; older age favored charact of ↓blood flow. Inflammation of chorionic plate in 43%, cord in 19%, & chorionic plate vessels in 30%. Of placentas w/umb cord inflammation, 8% had no inflammation of chorionic plate.

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

PubMed Link

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

PubMed Link

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.

PubMed Link

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

PubMed Link

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

PubMed Link

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.

PubMed Link

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

PubMed Link

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).

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