Early postnatal hypotension is not associated with indicators of white matter damage or cerebral palsy in extremely low gestational age newborns
J W Logan, T M O'Shea, E N Allred, M M Laughon, C L Bose, O Dammann, D G Batton, K C Kuban, N Paneth, A Leviton, ELGAN Study Investigators
J Perinatol. 2011;31:524-34
21 % of survivors had lowest BP in lowest ¼ ile for GA, 24% txed with pressors & 24% had labile BP . Among these infants, 10% % developed VM and 7% developed an EL lesion. At 2 years, 6% had QP, 4% DP and 2% HP. After adjusting for confounders, no association between indicators of hypotension, and indicators of cerebral WMD or CP.
The M-CHAT in ELGANs: individual items associated with motor, cognitive, vision and hearing limitations
Rhiannon J Luyster, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Elizabeth N Allred, Alan Leviton, ELGAN Study investigators
Paediatr Perinat Epidemiol. 2011;25:366-76
M-CHAT items were failed more frequently by children with concurrently identified impairments (motor, cognitive, vision and hearing). In addition, the frequency of item failure increased with the severity of impairment. Importantly, four of the six M-CHAT ‘critical items’ were commonly affected by impairments. This suggests that impairments might give rise to false positive M-CHAT screening.
The relationship between early concentrations of 25 blood proteins and cerebral white matter injury in preterm newborns: the ELGAN study
Alan Leviton, Karl Kuban, T Michael O'Shea, Nigel Paneth, Raina Fichorova, Elizabeth N Allred, Olaf Dammann
J Pediatr. 2011;158:897-903.e1-5
VEGF receptor 1, SAA, and MIP 1β on day 1 and IL-8 on day 7 were associated with increased risk of VM. Elevated MIP 1β on day 1 and ICAM-1 on day 7 were associated with risk of EL lesion. Elevated inflammation-related proteins on two separate days were at significantly ↑ risk for VM, & modestly ↑ risk for EL.
Blood protein profiles of infants born before 28 weeks differ by pregnancy complication
Thomas F McElrath, Raina Nakova Fichorova, Elizabeth N Allred, Jonathan L Hecht, Mahmoud A Ismail, Huaiping Yuan, Alan Leviton, ELGAN Study Investigators
Am J Obstet Gynecol. 2011;204:418.e1-418.e12
Cytokines (IL-1β, IL-6, TNFα), cytokine receptors (IL-6R, TNF-R1, TNF-R2), systemic inflammatory proteins (CRP, SAA, MPO), chemokines (IL-8, MCP-1, MCP-4, MIP-1β, RANTES, I-TAC), adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin), and metalloproteinases (MMP-1, MMP-9) were ↑ after preterm labor, membrane rupture, abruption, and cervical insufficiency. Such pattern not seen after PE or fetal indication-growth restriction. Inflammatory profiles were also associated with maternal vaginitis.
Early postnatal blood concentrations of inflammation-related proteins & microcephaly at two years in infants born before the 28th post-menstrual week
Alan Leviton, Karl C K Kuban, Elizabeth N Allred, Raina N Fichorova, T Michael O'Shea, Nigel Paneth, ELGAN Study Investigators
Early Hum Dev. 2011;87:325-30
↑ SAA on day 1 and ↑of five proteins on day 14, (IL-6, TNF-R2, IL-8, MCP-1, and ICAM-1) increased risk of microcephaly. The ten proteins ↑ on two separate days a week apart predicted microcephaly, but not when elevated on only one day, were CRP, SAA, IL-1β, IL-6, TNF-α, IL-8, MCP-1, ICAM-1, E-SEL, IGFBP-1.
Blood protein concentrations in the first two postnatal weeks that predict BPD among infants born before the 28th week of gestation
Carl Bose, Matthew Laughon, Elizabeth N Allred, Linda J Van Marter, T Michael O'Shea, Richard A Ehrenkranz, Raina Fichorova, Alan Leviton, Elgan Study Investigators
Pediatr Res. 2011;69:347-53
BPD Risk was associated with ↑ blood cytokines, adhesion molecules, and proteases. ↓ risk was associated with chemokine, RANTES. ↑ of inflammatory proteins associated with BPD risk occurred in first days and intensified thereafter. Exposures that promote inflammation after first days may be more critical in the pathogenesis of BPD. Fetal growth restriction was not accompanied by proteins elevations
Antecedents of chronic lung disease following three patterns of early respiratory disease in preterm infants
Matthew Laughon, Carl Bose, Elizabeth N Allred, T Michael O'Shea, Richard A Ehrenkranz, Linda J Van Marter, Alan Leviton, ELGAN Study Investigators
Arch Dis Child Fetal Neonatal Ed. 2011;96:F114-20
CLD 69% of infants with EPPD, 52% with PD, and 17% in the Low FiO(2) group. Birth weight z score <-1 conveyed information about CLD risk in all three groups and was the major risk factor for infants in the Low FiO(2) group (OR 27; 95% CI 7 to 95). MV at 7 days associated with ↑ risk in PD (OR 4.2, 95% CI 2.5 to 6.9) and EPPD groups (OR 2.7, 95% CI 1.5 to 4.7), but not Low FiO(2) group. Among infants with little exposure to oxygen, fetal growth restriction, not MV, is factor with strongest association with CLD
Early cranial ultrasound lesions predict microcephaly at age 2 years in preterm infants
Kalpathy S Krishnamoorthy, Karl C K Kuban, T Michael O'Shea, Sjirk J Westra, Elizabeth N Allred, Alan Leviton, ELGAN Study Co-investigators
J Child Neurol. 2011;26:188-94
OR (95% CI) for MC associated with different HUS images were IVH, 1.5 (0.8-3.0); VM, 3.3 (1.8-6.0); an ED, 1.6 (0.7-3.5); and EL, 3.1 (1.5-6.2). VM and EL had similar low PPV (24% and 27%, respectively) and high NPV (91% and 90%, respectively) for MC. VM had higher sensitivity for MC than did EL (24% vs 16%, respectively). Focal WM lesion (EL) and diffuse WMD (VM) predict increased risk of MC.
Blood gases and retinopathy of prematurity: the ELGAN Study
Alisse K Hauspurg, Elizabeth N Allred, Deborah K Vanderveen, Minghua Chen, Francis J Bednarek, Cynthia Cole, Richard A Ehrenkranz, Alan Leviton, Olaf Dammann
Neonatology. 2011;99:104-11
MVA indicate exposure to PCO(2) in highest quartile predicts ROP (stage 3- 5: OR = 1.6, – 1.1-2.3); zone 1: 2.0, 1.1-3.6; prethreshold/threshold: 1.9, 1.2-3.0; plus disease: 1.8, 1.1-2.9). Estimates similar for a low pH for zone 1 (2.1, 1.2-3.8), and prethreshold-threshold (1.8, 1.1-2.8). A PaO(2) in highest quartile for GA on at least 2 postnatal days associated with doubled risk of ROP, and 70% risk ↑ for plus disease.
Maternal microbe-specific modulation of inflammatory response in extremely low-gestational-age newborns
Raina N Fichorova, Andrew B Onderdonk, Hidemi Yamamoto, Mary L Delaney, Andrea M DuBois, Elizabeth Allred, Alan Leviton, Extremely Low Gestation Age Newborns (ELGAN) Study Investigators
MBio. 2011 18;2:e00280-10
Mixed bacterial vaginosis (BV) organisms were associated with a proinflammatory pattern similar to facultative anaerobes. Prevotella and Gardnerella species, anaerobic streptococci, peptostreptococci, and genital mycoplasmas associated with different patterns of elevated inflammation-related proteins. Lactobacillus associated with low inflammatory response. Microorganisms colonizing placenta provoke distinctive newborn inflammatory responses & Lactobacillus may suppress these responses.