Antecedents of inflammation biomarkers in preterm newborns on days 21 and 28
Alan Leviton, Elizabeth N Allred, Raina N Fichorova, Karl C K Kuban, T Michael O'Shea, Olaf Dammann, ELGAN Study Investigators
Acta Paediatr. 2016 Mar;105(3):274-80.
The purpose of this study was to identify antecedents of systemic inflammation evident during postnatal weeks three and four. We measured protein in blood spots collected on postnatal days 21 (N = 176) and 28 (N = 157) from ELGANs and found that infants born for maternal and fetal indications were more likely than peers to have top quartile concentrations of IL-beta, IL-8, TNF-alpha, and ICAM-1 on days 21 and 28. Similarly, infants whose B. Wt. Z-score was < -2 or between -1 and -2 were also more likely to have elevated concentrations of these proteins.
Strabismus at Age 2 Years in Children Born Before 28 Weeks’ Gestation: Antecedents and Correlates
Deborah K VanderVeen, Elizabeth N Allred, David K Wallace, Alan Leviton, ELGAN Study Investigators
J Child Neurol. 2016 Mar;31(4):451-60.
We evaluated perinatal factors associated with strabismus at age 2 years in ELGANs. Overall, 14% (n = 141) of children had strabismus at 2 yrs, and 80% of these children had esotropia. Characteristics associated with strabismus were birth before 26 weeks’ gestation, severe FGR, maternal Hx of aspirin ingestion. Postnatal factors included a SNAP-II Score ≥30, Vmeg, type I ROP, and ventilator-dependent severe BPD.
The Development of Extremely Preterm Infants Born to Women Who Had Genitourinary Infections During Pregnancy
Alan Leviton, Elizabeth N Allred, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Andrew B Onderdonk, Raina N Fichorova, Olaf Dammann, ELGAN Study Investigators
Am J Epidemiol. 2016 Jan 1;183(1):28-35
The mothers of 989 ELGAN infants who reported a UTI were less likely than others to have a very low MDI (adjusted odds ratio = 0.5; 95% confidence interval: 0.3, 0.8), whereas infants born to women who reported a CVI were more likely than others to have a low PDI (adjusted odds ratio = 1.7; 95% confidence interval: 1.04, 2.7). In this high-risk sample, maternal gestational CVI, but not UTI, was associated with a higher risk of impaired motor development at 2 yrs of age. The apparent protective effect of UTI might be spurious, reflect confounding due to untreated asymptomatic bacteriuria among women who were not given a diagnosis of UTI, or reflect preconditioning.
Weight Status in First 2 Years of Life and Neurodevelopmental Impairment in ELGANs
Mandy B Belfort, Karl C K Kuban, T Michael O'Shea, Elizabeth N Allred, Richard A Ehrenkranz, Stephen C Engelke, Alan Leviton, Extremely Low Gestational Age Newborn (ELGAN) Study Investigators
J Pediatr. 2016 Jan;168:30-35.
We examined extent of weight gain and weight status in first 2 yrs of life relate to risk of neurodevelopmental impairment in EP infants. Weight gain in lowest quartile from 7-28 days was not associated with ↑risk of adverse outcomes. Children w/12-mo wt z-score <-2 were at ↑risk for all adverse outcomes in girls, and for MC and GMFCS ≥1 in boys. Excluding children with motor impairment attenuated all associations except wt z-score <-2 w/MC in girls. Most associations of low wt z-score at 24 mos with adverse outcomes were attenuated when excluding children w/motor impairment.
Brain disorders associated with corticotropin releasing hormone expression in the placenta among children born before the 28th week of gestation
Alan Leviton, Elizabeth N Allred, Karl C K Kuban, Thomas Michael O'Shea, Nigel Paneth, Joseph Majzoub, ELGAN Study Investigators
Acta Paediatr. 2016 Jan;105(1):e7-e11.
To evaluate relationship between placenta CRH expression & brain structure and function abnormalities in Eps, we evaluated relationship between CRH expression in placenta and risk of HUS abnormalities, low scores on BSID of 900 children at age two years and HC > one and two SD below mean. Infants w/low placenta CRH m-RNA were at ↑risk of VMeg on HUS. ↑placenta CRH mRNA also associated w/↑risk of inability to walk at 2 years, and a Bayley PDI 3 SD < mean. Placenta CRH mRNA conveys risk information about brain damage in ELGANs.
Systemic inflammation on postnatal days 21 and 28 and indicators of brain dysfunction 2years later among children born before the 28th week of gestation
Alan Leviton, Elizabeth N Allred, Raina N Fichorova, Karl C K Kuban, T Michael O'Shea, Olaf Dammann, ELGAN study investigators
Early Hum Dev. 2015 Dec 28;93:25-32.
We measured the concentrations of 16 inflammation-related proteins in blood spots collected on postnatal days 21 (N=749) & 28 (N=697) from ELGAN Study infants. Top quartile concentrations of CRP, IL-1β, IL-6, IL-6R, TNF-R2, IL-8, ICAM-1, and TSH on both days 21 and 28 were associated with neonatal VMeg and MC at 2yrs. Top quartile concentrations of CRP, SAA, IL-6, TNF-R2, IL-8, and ICAM-1 were associated with MDI<55, while top quartile concentrations of CRP, TNF-α (inversely), IL-8, and ICAM-1 were associated with PDI<55. Systemic inflammation during third and fourth postnatal weeks increased risk of VM and MC, and low Bayley Scale scores.
Antecedents of the Child Behavior Checklist-Dysregulation Profile in Children Born Extremely Preterm
Jean A Frazier, Mollie E Wood, Janice Ware, Robert M Joseph, Karl C Kuban, Michael O'Shea, Elizabeth N Allred, Alan Leviton, ELGAN Study Investigators
J Am Acad Child Adolesc Psychiatry. 2015 Oct;54:816-23
We evaluated antenatal & early postnatal antecedents that might mediate association between EP and emotional and behavioral dysregulation (DP) at age 2 years. 9% of 826 ELGAN Study children had a CBCL-DP. Only low maternal education, passive smoking, and recovery of Mycoplasma from placenta were associated with ↑risk, whereas histologic chorioamnionitis was associated with ↓risk, raising possibility that modifiable antenatal and early postnatal phenomena contribute to risk of DP.
Maternal obesity and development of the preterm newborn at 2 years
Jelske W van der Burg, Elizabeth N Allred, Karl Kuban, T Michael O'Shea, Olaf Dammann, Alan Leviton
Acta Paediatr. 2015 Sep;104(9):900-3.
Compared to mothers with nl BMIs, newborns of obese mothers, but not overweight mothers, were more likely to have Bayley Scales indices > – 3Z-score (mental: OR = 2.1; 95% CI: 1.3, 3.5) (motor: OR = 1.7; 95% CI: 1.1, 2.7). These associations were more prominent in children without intermittent- sustained systemic inflammation (mental: OR = 4.6; 95% CI: 1.6, 14) (motor: OR = 3.7; 95% CI: 1.5, 8.9).Some of impaired development cannot be attributed to confounding due to immaturity, socio-economic correlates, or neonatal systemic inflammation.
Elevated Endogenous Erythropoietin Concentrations Are Associated with Increased Risk of Brain Damage in Extremely Preterm Neonates
Steven J Korzeniewski, Elizabeth Allred, J Wells Logan, Raina N Fichorova, Stephen Engelke, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Mari Holm, Olaf Dammann, Alan Leviton, ELGAN study investigators
PLoS One. 2015 Mar 20;10(3):e0115083
We sought to determine whether elevated perinatal (EPO) is associated with risks ofbrain damage, and whether this risk differs by co-occurrence of (ISSI).
Newborns with hyperEPO, regardless of ISSI, were more than twice as likely as those without to have very low (< 55) MDI (OR 2.3; 95% CI 1.5-3.5) and/or PDI (OR 2.4; 95% CI 1.6-3.7) Development Indices, and MC at 2 yrs (OR 2.4; 95%CI 1.5-3.8). Newborns with both hyperEPO and ISSI had significantly increased risks of VMeg, CP-HP MC, and MDI & PDI < 55 (ORs ranged from 2.2-6.3), but not WM lesions or other CP forms.
The relationship between TSH and systemic inflammation in extremely preterm newborns
Carmen L Soto-Rivera, Raina N Fichorova, Elizabeth N Allred, Linda J Van Marter, Bhavesh Shah, Camilia R Martin, Michael S D Agus, Alan Leviton
Endocrine. 2015 Mar;48(2):595-602
Elevated TSH in ill ELGANs attributed to THOP. We evaluated whether high TSH in first 2 weeks follow recovery from inflammation, similar to non-thyroidal illness synd. We evaluated relationships between hyperthyrotropinemia (HTT), TSH in highest quartile, and elevated inflammation-related proteins. Elevated inflammation-related proteins in 1st 2 weeks did not precede day-14 HTT. Inflammation on day 7 associated with day-14 HTT if inflammation persisted for 2 weeks. Hypothesis that HTT follows recovery from severe illness (preceding systemic inflammation), is weakly supported. Findings support hypothesis that TSH conveys info about concomitant inflammation.