Elevated blood levels of inflammation-related proteins are associated with an attention problem at age 24 mo in extremely preterm infants
T Michael O'Shea, Robert M Joseph, Karl C K Kuban, Elizabeth N Allred, Janice Ware, Taryn Coster, Raina N Fichorova, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Pediatr Res. 2014;75:781-7.
A single-day ↑ of ICAM-3 associated w/↑ risk of an attention problem; also persistent-recurrent ↑ of myeloperoxidase, IL-6, TNF-RI, IL-8, ICAM-3, VEGF-R1, and VEGF-R2.
Early blood gas predictors of bronchopulmonary dysplasia in extremely low gestational age newborns
Sudhir Sriram, Joy Condie, Michael D Schreiber, Daniel G Batton, Bhavesh Shah, Carl Bose, Matthew Laughon, Linda J Van Marter, Elizabeth N Allred, Alan Leviton
Int J Pediatr. 2014;2014:210218.
In models that did not adjust for ventilation, hypoxemia was associated with ↑ risk of severe and very severe BPD; infants with hypercapnea were at increased risk of very severe BPD only. Infants with hypocapnea were at reduced risk of severe BPD. Including ventilation for 14 or more days eliminated associations with hypoxemia and hypercapnea and made the decreased risk of very severe BPD statistically significant.
Intermittent or sustained systemic inflammation and the preterm brain
Olaf Dammann, Alan Leviton
Pediatr Res. 2014 Mar;75(3):376-80.
We discuss evidence in support of contention that the preterm newborn is capable of intermittent or sustained systemic inflammation (ISSI), and appears to contribute more to adverse neurodevelopmental outcomes than does shorter duration inflammation.
Comparison of frozen and unfrozen blood spots for gene expression studies
Changshuai Wei, Qing Lu, Sok Kean Khoo, Madeleine Lenski, Raina N Fichorova, Alan Leviton, Nigel Paneth
J Pediatr 2014;164:189-191.E1.
We studied gene expression in 9 pairs newborn blood spots stored 8-10 yrs in frozen or unfrozen state. Fewer genes expressed in unfrozen spots, but avg correlation coeff for gene expression for frozen & unfrozen state was 0.771 (95% CI, 0.700-0.828).
Social-emotional delays at 2 years in ELGA survivors: correlates of impaired orientation-engagement and emotional regulation
Lauren A C Boyd, Michael E Msall, T Michael O'Shea, Elizabeth N Allred, Gail Hounshell, Alan Leviton
Early Hum Dev. 2013;89:925-30.
31% of children had a non-optimal (14%) or questionable (17%) Behavior Rating Scale score for Emotional Regulation, and 27% for Orientation/Engagement (O/E). These children were more likely to have MDI and PDI scores <70 and be unable to walk. Antecedents of low scores include multi-fetal pregnancy, indicators of socioeconomic disadvantage, and male sex. Over 25% of children born extremely premature exhibit socio-emotional delays during developmental assessment at age 2 years.
Is maternal obesity associated with sustained inflammation in extremely low gestational age newborns?
Jelske W van der Burg, Elizabeth N Allred, Thomas F McElrath, Raina N Fichorova, Karl Kuban, T Michael O'Shea, Olaf Dammann, Alan Leviton
Early Hum Dev. 2013;89:949-55.
Among infants delivered for spontaneous indications, maternal BMI was not related to elevated concentrations of any protein. Among infants delivered for maternal (i.e., preeclampsia) or fetal indications, those whose mother was overweight or obese were more likely than others to have elevated concentrations of inflammation proteins.
Systemic inflammation, intraventricular hemorrhage, and white matter injury
Alan Leviton, Elizabeth N Allred, Olaf Dammann, Stephen Engelke, Raina N Fichorova, Deborah Hirtz, Karl C K Kuban, Laura R Ment, T Michael O'shea, Nigel Paneth, Bhavesh Shah, Michael D Schreiber, ELGAN Study Investigators
J Child Neurol. 2013;28:1637-45
Infants with both IVH and WMI were more likely to have ↑ concentrations of CRP and IL-8 on days 1, 7, and 14, and ↑ SAA and TNF-α on 2 of these days. IVH should be viewed as 2 entities: with-w/o WMI. Each is associated with inflammation, but the combination has a stronger inflammatory signal than hemorrhage alone.
Gene Targets for IVH Study Group. Candidate Gene Analysis: Severe Intraventricular Hemorrhage in Inborn Preterm Neonates
Ulrika Adén, Aiping Lin, Waldemar Carlo, Alan Leviton, Jeffrey C Murray, Mikko Hallman, Richard P Lifton, Heping Zhang, Laura R Ment, Gene Targets for Intraventricular Hemorrhage Study Group
J Pediatr 2013;163(5):1503-6.e1
IVH is a disorder of complex etiology. We analyzed genotypes for 7 genes from 224 inborn preterm neonates treated with antenatal steroids and grade 3-4 IVH and 389 matched controls. Only methylenetetrahydrofolate reductase was more prevalent in cases of IVH, emphasizing the need for more comprehensive genetic strategies.
Risk factors and correlates of neonatal growth velocity in extremely low gestational age newborns: the ELGAN Study
Julie Bartholomew, Camilia R Martin, Elizabeth Allred, Minghua L Chen, Richard A Ehrenkranz, Olaf Dammann, Alan Leviton
Neonatology. 2013;104(4):298-304.
In MV model, only ventilator dependence on day 7 (OR 2.2, 95% CI 1.5-3.2), early persistent pulmonary dysfunction (OR 1.8, 95% CI 1.3-2.5), and postnatal exposure to dex (OR 2.8, 95% CI 1.2-6.5) were associated with increased risk of being in lowest GV quartile. Low caloric intake was not associated with low GV (OR 1.3, 95% CI 0.9-1.9). Variables associated with severe pulmonary disease convey more information about risk of reduced GV in first 28 postnatal days than does low caloric intake.
Perinatal systemic inflammatory responses of growth-restricted preterm newborns
T F McElrath, E N Allred, L Van Marter, R N Fichorova, A Leviton, ELGAN Study Investigators
Acta Paediatr. 2013 Oct;102(10):e439-42.
Severe SGAs (B Wt Z-score <-2) were not at increased risk of systemic inflammation on day 1. On day 14, however, they were more likely to have elevated CRP, IL-1β, IL-6, TNF-α, IL-8, MCP-4, ICAM-1, ICAM-3, E-SEL, MMP-9, VEGF-R2 and/or IGFBP-1, not attributable to delivery indication, bacteremia or ventilation duration.