Systemic responses of preterm newborns with presumed or documented bacteraemia
Alan Leviton, T Michael O'Shea, Francis J Bednarek, Elizabeth N Allred, Raina N Fichorova, Olaf Dammann, ELGAN Study Investigators
Acta Paediatr. 2012;101:355-9
Newborns with presumed early (week 1) bacteraemia had ↑ concentrations of only a few inflammation-related proteins, while those who had presumed late (weeks 2-4) bacteraemia did not have any elevations. In contrast, newborns who had documented early bacteraemia or late bacteraemia had a strong inflammatory signal with more protein concentrations elevated on two separate occasions a week apart.
Antenatal antecedents of cognitive impairment at 24 months in extremely low gestational age newborns
Jennifer B Helderman, Thomas M O'Shea, Karl C K Kuban, Elizabeth N Allred, Jonathan L Hecht, Olaf Dammann, Nigel Paneth, T F McElrath, Andrew Onderdonk, Alan Leviton, ELGAN study Investigators
Pediatrics. 2012;129:494-502
103 infants (11%) had MDI <55, and 99 (11%) an MDI between 55-69. No associations between placental orgs & dev delay. Factors strongly associated with MDI <55: fetal vessel thrombosis (OR 3.1; 95% CI 1.2, 7.7), maternal BMI >30 (OR 2.0; 95% CI 1.1, 3.5), mat ed ≤12 years (OR 3.4; 95% CI 1.9, 6.2), nonwhite (OR 2.2; 95% CI 1.3, 3.8), birth wt z score < -2 (OR 2.8; 95% CI 1.1, 6.9), male (OR 2.7; 95% CI 1.6, 4.5).
Fetal-placental inflammation, but not adrenal activation, is associated with extreme preterm delivery
Sunita Trivedi, Maria Joachim, Thomas McElrath, Harvey J Kliman, Elizabeth N Allred, Raina N Fichorova, Andrew Onderdonk, Fernanda Heitor, Leila Chaychi, Alan Leviton, Joseph A Majzoub, Extremely Low Gestational Age Newborns (ELGAN) study investigators
Am J Obstet Gynecol. 2012;206:236.e1-8
Among ELGANs, spontaneous (vs induced) delivery was associated with less placental CRH expression and more frequent placental inflammation and infection.
Inflammation and infection, rather than premature activation of the fetal adrenal axis, should be the major focus of research to prevent extremely preterm human birth.
Elevated concentrations of inflammation-related proteins in postnatal blood predict severe developmental delay at 2 years of age in extremely preterm infants
T Michael O'Shea, Elizabeth N Allred, Karl C K Kuban, Olaf Dammann, Nigel Paneth, Raina Fichorova, Deborah Hirtz, Alan Leviton, Extremely Low Gestational Age Newborn (ELGAN) Study Investigators
J Pediatr. 2012;16):395-401
For 17 of 25 inflammation-related proteins, 1 or more significant associations (P<.01) was found between an ↑ blood level of protein and developmental impairment at age 2 years. ↑s on multiple days were more often associated with developmental impairment than on only 1 day. The highest number of ↑s was found in day-14 blood.
Intraventricular hemorrhage and developmental outcomes at 24 months of age in extremely preterm infants
T Michael O'Shea, Elizabeth N Allred, Karl C K Kuban, Deborah Hirtz, Barbara Specter, Sara Durfee, Nigel Paneth, Alan Leviton, ELGAN Study Investigators
J Child Neurol. 2012;27:22-9
In logistic regression models that adjusted for GA, sex, and SES, isolated iVH was associated with visual fixation difficulty but no other adverse outcome. Infants with WM lesion unaccompanied by IVH were at increased risk of CP, low MDI and PDI scores, and visual and hearing impairments. Isolated IVH is associated with a modest increase (and possibly no increase) in risk of adverse developmental outcome during infancy.
Relationships among the concentrations of 25 inflammation-associated proteins during the first postnatal weeks in the blood of infants born before the 28th week of gestation
Alan Leviton, Elizabeth N Allred, Hidemi Yamamoto, Raina N Fichorova, ELGAN Study Investigators
Cytokine. 2012 Jan;57:182-90.
On each of 3 days assessed, ↑ concentrations of 17 proteins were associated with ↑ concentrations of 15 or more of the other 24 proteins. An ↑ concentration of eight proteins on day 1 predicted ↑ concentration of 10 or more proteins on day 7, while an ↑ concentration of two proteins on day 7 were associated with ↑ 
10 or more proteins on day-14. Few associations seen between days 1 & 14.: Inflammation is a diffuse process in ELGANs, with ↑ concentrations of proteins on same and subsequent days
Neonatal bacteremia and retinopathy of prematurity: the ELGAN study
Kristi Washburn Tolsma, Elizabeth N Allred, Minghua L Chen, Jay Duker, Alan Leviton, Olaf Dammann
Arch Ophthalmol. 2011;129:1555-63
In MVA, newborns with presumed late bacteremia were at ↑ risk for prethreshold-threshold ROP (OR, 1.8; 95% CI, 1.02-3.2), and those with definite late bacteremia were at ↑ risk for prethreshold-threshold ROP and plus disease ROP (1.8; 1.1-2.9).
Cluster analysis of placental inflammatory proteins can distinguish preeclampsia from preterm labor and premature membrane rupture in singleton deliveries < than 28 wks of gestation
Jessica M Faupel-Badger, Raina N Fichorova, Elizabeth N Allred, Jonathan L Hecht, Olaf Dammann, Alan Leviton, Thomas F McElrath
Am J Reprod Immunol. 2011;66:488-94
Placentas from PE had high levels of VEGF combined with low levels of acute inflammatory proteins (IL-1β, IL-18, IL-6, TNF-α), low IL-1 RA, and high transforming growth factor β (TGF-β). PL and pPROM had higher anti-inflammatory IL-1 RA and thrombomodulin combined with lower. Half of the PL and pPROM cases of heightened inflammatory responses (lower TGF-β & higher intensity of inflammatory mediators).
Blood protein concentrations in the first two postnatal weeks associated with early postnatal blood gas derangements among ELGANs. The ELGAN Study
Alan Leviton, Elizabeth N Allred, Karl C K Kuban, Olaf Dammann, Raina N Fichorova, T Michael O'Shea, Nigel Paneth, ELGAN Study Co-Investigators
Cytokine. 2011;56:392-8
Blood gas derangements on two days were much more likely to be accompanied or followed by sustained or recurrent systemic inflammation than a derangement on only one day. This was most evident for acidemia, and slightly less so for hypercapnia.
Placenta microbiology and histology and the risk for severe retinopathy of prematurity
Minghua L Chen, Elizabeth N Allred, Jonathan L Hecht, Andrew Onderdonk, Deborah VanderVeen, David K Wallace, Alan Leviton, Olaf Dammann, ELGAN Study
Invest Ophthalmol Vis Sci. 2011 1;52:7052-8
The co-occurrence of bacteria and inflammation was associated with an increased risk for ROP in zone I (OR, 3.1; 95% CI, 1.02-9.5). Among 339 infants with any placental bacteria, the co-occurrence of (1) inflammation and a GA of 23 – 24 weeks and (2) inflammation and hyperoxia were associated with increased risk for all severe ROP.