Systemic Inflammation in the Extremely Low Gestational Age Newborn Following Maternal Genitourinary Infections
Raina N Fichorova, Noah Beatty, Rita R S Sassi, Hidemi S Yamamoto, Elizabeth N Allred, Alan Leviton, ELGAN Investigators
Am J Repro Immunol 2015;73(2):162-74
Compared to their peers whose mother had no UTI or CVI, infants whose mother reported a CVI were more likely on day 1 to have a concentration in the top quartile of CRP, SAA, MPO, IL-1β, IL-6, IL-6R, TNF-α, RANTES, ICAM-3, E-selectin and VEGF-R2. Infants whose mother reported UTI were more likely on d 7 to have concentration in the top quartile of MPO, IL-6R, TNF-R1, TNF-R2, and RANTES. Associations were no longer significant 14 days after birth. GU infections in pregnancy appear to increase the very preterm newborn’s risk of systemic inflammation
The breadth and type of systemic inflammation and the risk of adverse neurological outcomes in extremely low gestation newborns
Karl C K Kuban, T Michael O'Shea, Elizabeth N Allred, Raina N Fichorova, Tim Heeren, Nigel Paneth, Deborah Hirtz, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Pediatr Neurol 2015;52(1):42-8.
We evaluated associations between number and type of proteins elevated on two occasions a week apart and diagnoses of VMeg, MC, MDI < 55, CP, MCHAT+, and sxs of ADHD on CBCL Increasing breadth of early neonatal inflammation, indexed by number of protein elevations or number of protein functional classes elevated, is associated with ↑ risk of d/o of brain structure and function in ELGANS. The risk for most outcomes did not rise until at least four proteins in at least two functional categories were ↑. When focused on 10 proteins previously found associated w/ neurological outcomes, we found risk of low MDI on Bayley Scales, MC, and CBCL-defined ADHD ↑ w/higher numbers of recurrently and/or persistently elevated proteins.
Antecedents and correlates of visual field deficits in children born extremely preterm
Mari Holm, Michael E Msall, Jon Skranes, Olaf Dammann, Elizabeth Allred, Alan Leviton
Eur J Paediatr Neurol. 2015 Jan;19:56-63.
The VF of 1023 infants assessed by confrontation at age 2 yrs. We compared ante-and postnatal characteristics and exposures of 65 infants with a VFD to peers w/o a VFD. In final regression model, VFD was associated with maternal aspirin use during pregnancy, recurring/persistent acidemia in first 3 postnatal days, cerebral Vmeg, prethreshold ROP, supplemental O2, and vent dependence at 36 wks. Birth before the 27th week was also associated with increased risk, but was diminished by the addition of postnatal variables. Our study supports a multifactorial cause of these deficits.
Antenatal and early postnatal antecedents of parent-reported attention problems at 2 years of age
L Corbin Downey, T Michael O'Shea, Elizabeth N Allred, Karl Kuban, Thomas F McElrath, Diane D Warner, Janice Ware, Jonathan L Hecht, Andrew Onderdonk, Alan Leviton, Extremely Low Gestational Age Newborn (ELGAN) Study
Journal of Pediatrics 2015 166:20-25.
Antenatal antecedents of attention problems included birth to an unmarried mother, maternal secondhand smoke exposure, severe fetal growth restriction, thrombosis of fetal stem vessels in the chorionic plate, and recovery of an organism from placenta. All but severe SGA were associated with ADHPDSM, too. Multiple gestation was associated with a lower risk of ADHPDSM. The only postnatal risk factor for attention problems was recovery of bacteria from a tracheal aspirate. Conclusion: Among ELGANs several potentially modifiable antenatal and perinatal antecedents are associated with increased risk for attention problems and ADHPDSM at 2 years.
Pre-threshold retinopathy in premature infants with intra-uterine growth restriction
Jennifer W Lee, Deborah VanderVeen, Elizabeth N Allred, Alan Leviton, Olaf Dammann
Acta Paediatrica 2015;104(1):27-31.
Low GA (23-24 weeks, OR 11.6 (2.9, 47); 25-26 weeks, 8.1 (2.1, 32)) and severe growth restriction (birth weight Z-score <-2, OR 9.1 (1.1, 76)) were associated with increased risk of pre-threshold ROP. A sample defined by B. Wt. has an excess of gestationally-older, SGA newborns. Conclusion: In this sample, low GA and severe growth restriction were associated with increased risk of pre-threshold ROP.
Systemic Inflammation and Cerebral Palsy Risk in Extremely Preterm Infants
Karl C K Kuban, T Michael O'Shea, Elizabeth N Allred, Nigel Paneth, Deborah Hirtz, Raina N Fichorova, Alan Leviton, ELGAN Study Investigators
J Child Neurol. 2014 Dec;29(12):1692-8
Protein elevations within 3 ds of birth not associated with CP. Elevations of TNF-α, TNF-α-R1, IL-8, and ICAM-1 on at least 2 days were associated with DP. Recurrent-persistent elevations of IL-6, E-selectin, or insulin-like GFBP-1 were associated with HP. DP and HP were more likely with at least 4 of 9 protein elevations previously associated with MDI<55 & and MC. Repeated elevated proteins during first 2 postnatal weeks are associated w/increased CP risk.
Are preterm newborns who have relative hyperthyrotropinemia at increased risk of brain damage?
Steven J Korzeniewski, Carmen L Soto-Rivera, Raina N Fichorova, Elizabeth N Allred, Karl C K Kuban, T Michael O'Shea, Nigel Paneth, Michael Agus, Olaf Dammann, Alan Leviton
J Pediatr Endocrinol Metab. 2014;27:1077-88
In univariable models, hyperthyrotropinemia (HTT) not associated with brain damage indicators. In models of HTT only, intermittent or sustained systemic inflammation (ISSI) only, and HTT+ISSI, children with ISSI or HTT+ISSI were at higher risk of VM (OR) 2-6]. Children with HTT only had a higher risk of QP and those with ISSI alone had a higher risk of HP (ORs 1.6-2.4). Elevated risk of MDI <55 associated with ISSI and HTT+ISSI, whereas PDI < 55 & MC associated with HTT+ISSI. Conclusions: The association of HTT with brain damage depends on the presence or absence of ISSI.
Endogenous erythropoietin varies significantly with inflammation-related proteins in extremely premature newborns
J Wells Logan, Elizabeth N Allred, Raina N Fichorova, Stephen Engelke, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Cytokine. 2014 Sep;69(1):22-8.
We evaluate relationships between endogenous Epo and 25 inflammation-related proteins in ELGANs. The proportion of children with inflammation-associated protein concentrations in top quartile increased with increasing quartile of Epo concentrations on 2 of 3days assessed. The ORs for Epo being in top quartile were significantly elevated among those with an inflammation-related protein concentration in the top quartile. Suggests elevation of Epo is not an epiphenomenon, but instead might promote or reduce inflammation, or promote anti-injury or repair capability.
Impaired Visual Fixation at Age 2 yrs in ELGANs: antecedents & Correlates
Anuradha Phadke, Michael E Msall, Patrick Droste, Elizabeth N Allred, Thomas Michael O'Shea, Karl Kuban, Olaf Dammann, Alan Leviton, ELGAN Study Investigators
Pediatr Neurol. 2014;51:36-42.
Infants with impaired visual fixation were more likely than those without impaired visual fixation to have been born after shortest gestations (OR, 3.2; 99% CI, 1.4-7.5) and exposed to maternal aspirin (OR, 5.2; 99% CI, 2.2-12). They were also more likely to have had prethreshold retinopathy of prematurity (OR, 4.1; 99% CI, 1.8-9.0). At age 2 years, children with impaired fixation were more likely to be unable to walk (OR, 7.5; 99% CI, 2.2-26) and have a MDI < 55 (OR, 3.6; 99% CIl, 1.4-8.2).
Retinopathy of prematurity and brain damage in the very preterm newborn
Elizabeth N Allred, Antonio Capone Jr, Anthony Fraioli, Olaf Dammann, Patrick Droste, Jay Duker, Robert Gise, Karl Kuban, Alan Leviton, T Michael O'Shea, Nigel Paneth, Robert Petersen, Michael Trese, Kathleen Stoessel, Deborah Vanderveen, David K Wallace, Grey Weaver
J AAPOS. 2014 Jun;18:241-7.
The 173 children w/severe ROP (prethreshold ROP or worse) were more likely than peers without ROP to have brain HUS lesions or CP, and twice as likely to have Bayley Scales scores <55. After adjusting for risk factors common to both ROP and brain disorders, infants with severe ROP were at increased risk of low Bayley Scales only. Exposure to anesthesia was not associated with low Bayley Scales.