Article

Inflammation-related proteins in the blood of extremely low gestational age newborns. The contribution of inflammation to the appearance of developmental regulation.

Neurology Department, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
Cytokine (Impact Factor: 2.87). 10/2010; 53(1):66-73. DOI: 10.1016/j.cyto.2010.09.003
Source: PubMed

ABSTRACT We wanted to assess to what extent concentrations of circulating proteins appear to be developmentally regulated, and to what extent such regulation is influenced by intra-uterine inflammation.
We measured 22 proteins in blood obtained on postnatal days 1, 7, and 14 from 818 children born before the 28th week of gestation for whom we also had information about placenta morphology.
Within the narrow gestational age range of this sample, some protein concentrations increase in blood with increasing gestational age. More commonly, the concentrations of inflammation-related proteins decrease with increasing gestational age. We observed this inverse pattern both in children whose placenta was and was not inflamed. CONCLUSIONS/INFERENCES: Regardless of whether or not the placenta is inflamed, the concentrations of inflammation-related proteins in early blood specimens appear to be developmentally regulated with the most common pattern being a decrease with increasing gestational age.

0 Followers
 · 
100 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Elevated thyrotropin (TSH) levels in critically ill extremely premature infants have been attributed to transient hypothyroidism of prematurity or non-thyroidal illness syndrome. We evaluated the hypothesis that relatively high TSH levels in the first 2 postnatal weeks follow recovery from systemic inflammation, similar to non-thyroidal illness syndrome. The study was conducted in 14 Neonatal Intensive Care Units and approved by each individual Institutional Review Board. We measured the concentrations of TSH and 25 inflammation-related proteins in blood spots obtained on postnatal days 1, 7, and 14. We then evaluated the temporal relationships between hyperthyrotropinemia (HTT), defined as a TSH concentration in the highest quartile for gestational age and postnatal day, and elevated levels of inflammation-related proteins. 880 newborns less than 28 weeks of gestation were included. Elevated concentrations of inflammation-related proteins during the first or second week did not precede day-14 HTT. Systemic inflammation on day 7 was associated with day-14 HTT only if inflammation persisted through the end of the 2 week period. HTT frequently accompanied elevated concentrations of inflammation-related proteins on the same day. The hypothesis that HTT follows recovery from severe illness, defined as preceding systemic inflammation, is weakly supported by our study. Our findings more prominently support the hypothesis that TSH conveys information about concomitant inflammation in the extremely premature newborn.
    Endocrine 07/2014; 48(2). DOI:10.1007/s12020-014-0329-4 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ProblemGestational genitourinary infections are associated with lifelong disabilities, but it is unknown if neonatal inflammation is involved. Method Mothers of 914 infants born before 28th gestation week reported cervical/vaginal infection (CVI), and/or urine/bladder/kidney infection (UTI), or neither. Inflammation proteins measured in baby's blood on postnatal days 1, 7, and 14 were considered elevated if in the top quartile for gestational age. Logistic regression models adjusting for potential confounders assessed odds ratios. ResultsCompared to mothers with neither UTI/CVI, those with CVI were more likely to have infants with elevated CRP, SAA, MPO, IL-1, IL-6, IL-6R, TNF-, RANTES, ICAM-3, E-selectin, and VEGF-R2 on day 1; those with UTI were more likely to have infants with elevated MPO, IL-6R, TNF-R1, TNF-R2, and RANTES on day 7. Placental anaerobes and genital mycoplasma were more common in pregnancies with CVI. Conclusion Gestational UTI/CVI should be targeted for preventing systemic inflammation in the very preterm newborn.
    American journal of reproductive immunology (New York, N.Y.: 1989) 08/2014; 73(2). DOI:10.1111/aji.12313 · 2.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We hypothesized that the risk of brain damage in extremely preterm neonates increases with the breadth and type of systemic inflammation, indexed by the number of elevated inflammation-related proteins and the number of functional categories of inflammation-related proteins exhibiting an elevated concentration. In blood from 881 infants born before 28 weeks gestation, we measured the concentrations of 25 inflammation-related proteins, representing six functional categories (cytokines, chemokines, growth factors, adhesion molecules, metalloproteinases, and liver-produced acute phase reactant proteins) on postnatal days 1, 7, and 14. We evaluated associations between the number and type of proteins whose concentrations were elevated on two separate occasions a week apart and the diagnoses of ventriculomegaly as a neonate, and at 2 years, microcephaly, impaired early cognitive functioning, cerebral palsy, and autism risk as assessed with the Modified Checklist for Autism in Toddlers screen, and in a subset of these children from 12 of 14 sites (n = 826), an attention problem identified with the Child Behavior Checklist. The risk of abnormal brain structure and function overall was increased among children who had recurrent and/or persistent elevations of the 25 proteins. The risk for most outcomes did not rise until at least four proteins in at least two functional categories were elevated. When we focused our analysis on 10 proteins previously found to be associated consistently with neurological outcomes, we found the risk of low Mental Development Index on the Bayley Scales of Infant Development-II, microcephaly, and a Child Behavior Checklist-defined attention problem increased with higher numbers of these recurrently and/or persistently elevated proteins. Increasing breadth of early neonatal inflammation, indexed by the number of protein elevations or the number of protein functional classes elevated, is associated with increasing risk of disorders of brain structure and function among infants born extremely preterm. Copyright © 2014 Elsevier Inc. All rights reserved.
    Pediatric Neurology 10/2014; 52(1). DOI:10.1016/j.pediatrneurol.2014.10.005 · 1.50 Impact Factor

Full-text (2 Sources)

Download
27 Downloads
Available from
Jun 1, 2014