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.
Patterns of blood protein concentrations of ELGANs classified by three patterns of respiratory disease in the first 2 postnatal weeks
Matthew Laughon, Carl Bose, Elizabeth N. Allred, T. Michael O’Shea, Richard A. Ehrenkranz, Linda J. Van Marter, Alan Leviton, and for the ELGAN Study Investigators
Pediatr Res. 2011 ;70:292-6
Two patterns of early lung disease: early and persistent pulmonary dysfunction (EPPD) and nl pulmonary function followed by pulmonary deterioration (PD). 38% (n = 347) of our cohort had PD, and 43% (n = 383) had EPPD. On d 14, elevated RANTES and VEGF associated with ↓ risk of PD. Risk of EPPD ↓ with elevated RANTES, MMP-1, and VEGF on d 14. Risk of EPPD was ↑ if on d 14 IL-8 & ICAM-1 were ↑. Inflammation might influence EPPD and PD risk, or be a consequence of lung damage or therapies.
Early postnatal hypotension and developmental delay at 24 months of age among extremely low gestational age newborns
J Wells Logan, T Michael O'Shea, Elizabeth N Allred, Matthew M Laughon, Carl L Bose, Olaf Dammann, Daniel G Batton, Stephen C Engelke, Alan Leviton, ELGAN Study Investigators
Arch Dis Child Fetal Neonatal Ed. 2011;96:F321-8
78% of infants in cohort received volume expansion or pressors;. 26% had MDI <70 & 32% had PDI <70. Low MDI & PDI associated with low GA, which in turn, was associated with pressor treatment. After adjusting for potential confounders, none of the indicators of hypotension associated with MDI <70 or PDI <70.
Persistence after birth of systemic inflammation associated with umbilical cord inflammation
Alan Leviton, Jonathan L Hecht, Elizabeth N Allred, Hidemi Yamamoto, Raina N Fichorova, Olaf Dammann, ELGAN Study Investigators
J Reprod Immunol. 2011 ;90:235-43
Seven of nine proteins [CRP, myeloperoxidase , IL1β, IL8, TNFα, ICAM3, and MMP9) were elevated on d 7 among infants with funisitis. Adjusting for GA, SGA, and three postnatal exposures (ventilation on day 7, early bacteremia, and Bell stage III NEC) did not diminish the elevated OR of ↑ MPO, IL1β, TNFα, IL8, ICAM3, and MMP9. The persistence of a relationship between umbilical cord inflammation and inflammation-related proteins on postnatal day 7 suggests sustained systemic inflammation.