Extreme prematurity and attention deficit: epidemiology and prevention
T Michael O'Shea, L Corbin Downey, Karl K C Kuban
Front Hum Neurosci 2013;7:578.
ELGANs have an increased risk of attention problems. Perinatal systemic inflammation, an antecedent of structural and functional brain disorders in ELGANs, appears to be an antecedent of attention problems. Interventions to prevent initiators of inflammation or modulate systemic inflammation might decrease the risk of attention problems among children born extremely preterm.
Antecedents of perinatal cerebral WMD with & without IVH in very preterm newborns
J Wells Logan, Sjirk J Westra, Elizabeth N Allred, T Michael O'Shea, Karl Kuban, Nigel Paneth, Alan Leviton, ELGAN Study investigators
Pediatr Neurol. 2013;49:88-96.
Risk of hypoechoic (HE) lesion with IVH (N = 61) associated with gestation <25 weeks, high SNAP, early recurrent or prolonged acidemia, analgesic exposure, & mech vent at 1 week. Risk of a HE lesion w/o IVH differs from HE lesion with IVH (~PVHI). Suggests HE lesions w/ IVH may have different causal pathway than HE lesions w/o IVH, (~PVL(
Systemic inflammation associated with severe intestinal injury in extremely low gestational age newborns
Camilia R Martin, Melissa Bellomy, Elizabeth N Allred, Raina N Fichorova, Alan Leviton
Fetal Pediatr Pathol. 2013 ;32:222-34
On days 7 & 14, infants with NEC had ↑ levels of CRP, SAA, IL-6 and IL-8. Infants with intestinal perf had ↑ levels of CRP and IGF binding protein-1 on day 7 and elevated CRP, SAA, TNF-receptor-2 and MMP-9 on day 14.
Early nutrition and weight gain in preterm newborns and the risk of retinopathy of prematurity
Deborah K VanderVeen, Camilia R Martin, Reshma Mehendale, Elizabeth N Allred, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
PLoS One. 2013 May 29;8(5):e64325.
Greater risk for Type 1 ROP found for infants with lowest ¼ ile receipt of lipids (2.1/1.1, 3.8), total calories (2.2/1.4, 3.6), and carbohydrates (1.7/1.1, 2.9). Zone 1 ROP was associated with lowest quartile lipid or total calorie intake; stage 3 ROP associated with lowest ¼ ile of total calorie. GV in lowest ¼ ile associated with increased risk of ROP, including type 1 ROP. ROP Risk might be reduced by improving nutritional support.
Pregnancy disorders appear to modify risk for retinopathy of prematurity associated with neonatal hyperoxemia and bacteremia
Jennifer W Lee, Thomas McElrath, Minghua Chen, David K Wallace, Elizabeth N Allred, Alan Leviton, Olaf Dammann
J Matern Fetal Neonatal Med. 2013 May;26(8):811-8
Compared to preterm labor, infants delivered after pPROM had reduced risk of plus ds (0.4, 0.2-0.8) and prethreshold/threshold ROP (0.5, 0.3-0.8). Delivery after abruption had reduced risk of zone I ROP and prethreshold/threshold ROP (0.3, 0.1-0.7). Infants born after placental dysfunction had higher severe ROP risks ass’ed with postnatal hyperoxemia & bacteremia than after inflammation-associated pregnancy disorders.
Two-hit model of brain damage in very preterm newborn: fetal growth restriction & postnatal systemic inflammation
Alan Leviton, Raina N Fichorova, T Michael O'Shea, Karl Kuban, Nigel Paneth, Olaf Dammann, Elizabeth N Allred, ELGAN Study Investigators
Pediatr Res. 2013 73:362-70.
SGA newborns who did not have systemic were at a greater risk of an MDI <55 than those with neither SGA nor systemic inflammation. SGA infants with elevated (IL)-1β, TNF-α, or IL-8 in first 2 weeks were at even higher risk of an MDI <55 than SGA peers without systemic inflammation and non-SGA peers with systemic inflammation.
Inflammation-initiating illnesses, inflamm-related proteins, and cognitive impairment in extremely preterm infants
T Michael O'Shea, Bhavesh Shah, Elizabeth N Allred, Raina N Fichorova, Karl C K Kuban, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Brain Behav Immun. 2013 ;29:104-12
The combo of NEC & vent on day 14, and of bacteremia & vent on day 14 elevated risk of MDI <55. Persistently or recurrently elevated concentration of each of the following proteins provided additional information about an increased risk of MDI <55: CRP, SAA, IL-6, TNF-alpha, IL-8, MIP-1beta, ICAM-1, E-SEL, and IGFBP-1.
Systemic inflammation associated with mechanical ventilation among extremely preterm infants
Carl L Bose, Matthew M Laughon, Elizabeth N Allred, T Michael O'Shea, Linda J Van Marter, Richard A Ehrenkranz, Raina N Fichorova, Alan Leviton, ELGAN Study Investigators
Cytokine. 2013;61:315-22
Newborns ventilated for 7-13 days and 14 days (N=330) (v. < 7 days (N=247), were more likely to have ↑ IL-1β & TNF-α, IL-8, MCP-1ICAM-1, and MMP-9, and less likely to have elevated RANTES & MIP-1β, MMP-1, and VEGF. These relationships were not confounded by chorioamnionitis, antenatal corticosteroid exposure, or bacteremia.
Brain damage in preterm newborns and maternal medication:the ELGAN Study
Crystal P Tyler, Nigel Paneth, Elizabeth N Allred, Deborah Hirtz, Karl Kuban, Thomas McElrath, T Michael O'Shea, Cindy Miller, Alan Leviton, ELGAN Study Investigators
Am J Obstet Gynecol. 2012;207:192.e1-9
After adjustment for potential confounding the risk of QP CP remained elevated among infants of mothers who consumed aspirin ([OR, 3.0; 95 CI, 1.3-6.9) and NSAIDs (OR, 2.4; 95% CI, 1.04-5.8). The risk of DP CP was also associated with NSAID, but only if consumption was not approved by a physician (OR, 3.5; 95% CI 1.1-11.0).
Birth wt- and fetal wt-growth restriction: impact on neurodevelopment
Iris G Streimish, Richard A Ehrenkranz, Elizabeth N Allred, T Michael O'Shea, Karl C K Kuban, Nigel Paneth, Alan Leviton, ELGAN Study Investigators
Early Hum Dev. 2012;88:765-71
Only girls with the most severe growth restriction were at ↑ risk of neurodevelopmental impairment at 24 mos CA in the total sample. Neurosensory limitations appear to interfere with assessing growth restriction effects in both girls and boys born preterm.