Format

Send to

Choose Destination
J Pediatr. 2017 Jan;180:116-123.e1. doi: 10.1016/j.jpeds.2016.09.054. Epub 2016 Oct 24.

Circulating Inflammatory-Associated Proteins in the First Month of Life and Cognitive Impairment at Age 10 Years in Children Born Extremely Preterm.

Author information

1
Department of Pediatrics, Boston Medical Center, Boston, MA. Electronic address: karl.kuban@bmc.org.
2
Department of Anatomy and Neuroanatomy, Boston University School of Medicine, Boston, MA.
3
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of North Carolina, Chapel Hill, NC.
4
Department of Biostatistics, Boston University School of Public Health, Boston, MA.
5
Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
6
Department of Pediatrics, Boston Medical Center, Boston, MA.
7
Department of Radiology, Boston University School of Medicine, Boston, MA.
8
Department of Psychiatry, University of Massachusetts Medical School/ University of Massachusetts Memorial Health Care, Worcester, MA.
9
National Institute of Neurological Disorders and Stroke, Bethesda, MD.
10
Department of Epidemiology and Biostatistics and Pediatrics, Michigan State University, East Lansing, MI.

Abstract

OBJECTIVES:

To evaluate whether in children born extremely preterm, indicators of sustained systemic inflammation in the first month of life are associated with cognitive impairment at school age.

STUDY DESIGN:

A total of 873 of 966 eligible children previously enrolled in the multicenter Extremely Low Gestational Age Newborn Study from 2002 to 2004 were evaluated at age 10 years. We analyzed the relationship between elevated blood concentrations of inflammation-associated proteins in the first 2 weeks ("early elevations"; n = 812) and the third and fourth week ("late elevations"; n = 532) of life with neurocognition.

RESULTS:

Early elevations of C-reactive protein, tumor necrosis factor-α, interleukin (IL)-8, intercellular adhesion molecule (ICAM)-1, and erythropoietin were associated with IQ values >2 SD below the expected mean (ORs: 2.0-2.3) and with moderate to severe cognitive impairment on a composite measure of IQ and executive function (ORs: 2.1-3.6). Additionally, severe cognitive impairment was associated with late protein elevations of C-reactive protein (OR: 4.0; 95% CI 1.5, 10), IL-8 (OR: 5.0; 1.9, 13), ICAM-1 (OR: 6.5; 2.6, 16), vascular endothelial growth factor-receptor 2 (OR: 3.2; 1.2, 8.3), and thyroid-stimulating hormone (OR: 3.1; 1.3, 7.3). Moderate cognitive impairment was most strongly associated with elevations of IL-8, ICAM-1, and vascular endothelial growth factor-receptor 2. When 4 or more inflammatory proteins were elevated early, the risk of having an IQ <70 and having overall impaired cognitive ability was more than doubled (ORs: 2.1-2.4); the presence of 4 or more inflammatory protein elevated late was strongly linked to adverse cognitive outcomes (ORs: 2.9-4.8).

CONCLUSIONS:

Extremely preterm children who had sustained elevations of inflammation-related proteins in the first postnatal month are more likely than extremely preterm peers without such elevations to have cognitive impairment at 10 years.

KEYWORDS:

cognition; extremely preterm infants; inflammation-related proteins; school age

PMID:
27788929
PMCID:
PMC5183478
DOI:
10.1016/j.jpeds.2016.09.054
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center