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.
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.