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J Pediatr. 2018 Oct;201:40-48.e4. doi: 10.1016/j.jpeds.2018.05.021. Epub 2018 Jul 18.

Among Children Born Extremely Preterm a Higher Level of Circulating Neurotrophins Is Associated with Lower Risk of Cognitive Impairment at School Age.

Author information

1
Department of Pediatrics, Division of Pediatric Neurology, Boston Medical Center, Boston, MA. Electronic address: karl.kuban@bmc.org.
2
Department of Biostatistics, Boston University School of Public Health, Boston, MA.
3
Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of North Carolina, Chapel Hill, NC.
4
Department of Anatomy and Neuroanatomy, Boston University School of Medicine, 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, Division of Pediatric Neurology, Boston Medical Center, Boston, MA.
7
Department of Radiology, Boston University School of Medicine, Boston, MA.
8
Department of Psychiatry, Eunice Kennedy Shriver Center, UMASS Medical School/ University of Massachusetts Memorial Health Care, Worcester, MA.
9
National Institute of Neurological Disorders and Stroke, Bethesda, MD.
10
Department of Pediatrics, Case Western Reserve University, Cleveland, OH.
11
Department of Epidemiology and Biostatistics and Pediatrics & Human Development, Michigan State University, East Lansing, MI.
12
ELGAN Study Boston Children's Hospital, Boston, MA.
13
Tufts Medical Center, Boston, MA.
14
Baystate Medical Center, Springfield, MA.
15
University of Massachusetts Medical School, Worcester, MA.
16
Yale University School of Medicine, New Haven, CT.
17
Wake Forest University Baptist Medical Center, Winston-Salem, NC.
18
University Health Systems of Eastern Carolina, Greenville, NC.
19
North Carolina Children's Hospital, Chapel Hill, NC.
20
Helen DeVos Children's Hospital, Grand Rapids, MI.
21
Sparrow Hospital, Lansing, MI.
22
University of Chicago Medical Center, Chicago, IL.
23
William Beaumont Hospital, Royal Oak, MI.
24
Brigham and Women's Hospital, Boston, MA.

Abstract

OBJECTIVES:

To test the hypothesis that higher blood levels of neurotrophic proteins (proteins that support neuronal survival and function) in the first 2 weeks of life are associated with a lower risk of cognitive impairment at 10 years.

STUDY DESIGN:

We evaluated 812 10-year-old children with neonatal blood specimens enrolled in the multicenter prospective Extremely Low Gestational Age Newborn Study, assessing 22 blood proteins collected on 3 days over the first 2 weeks of life. Using latent profile analysis, we derived a cognitive function level based on standardized cognitive and executive function tests. We defined high exposure as the top quartile neurotrophic protein blood level on ≥2 days either for ≥4 proteins or for a specific cluster of neurotrophic proteins (defined by latent class analysis). Multinomial logistic regression analyzed associations between high exposures and cognitive impairment.

RESULTS:

Controlling for the effects of inflammatory proteins, persistently elevated blood levels of ≥4 neurotrophic proteins were associated with reduced risk of moderate (OR, 0.35; 95% CI, 0.18-0.67) and severe cognitive impairment (OR, 0.22; 95% CI, 0.09-0.53). Children with a cluster of elevated proteins including angiopoietin 1, brain-derived neurotrophic factor, and regulated upon activation, normal T-cell expressed, and secreted had a reduced risk of adverse cognitive outcomes (OR range, 0.31-0.6). The risk for moderate to severe cognitive impairment was least with 0-1 inflammatory and >4 neurotrophic proteins.

CONCLUSIONS:

Persisting elevations of circulating neurotrophic proteins during the first 2 weeks of life are associated with lowered risk of impaired cognition at 10 years of age, controlling for increases in inflammatory proteins.

KEYWORDS:

early life risks and protectors of later cognition; extreme prematurity; inflammation and neurotrophins

PMID:
30029870
DOI:
10.1016/j.jpeds.2018.05.021
[Indexed for MEDLINE]

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