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J Pediatr. 2019 Jul;210:81-90.e3. doi: 10.1016/j.jpeds.2019.03.018. Epub 2019 May 7.

Association of Circulating Proinflammatory and Anti-inflammatory Protein Biomarkers in Extremely Preterm Born Children with Subsequent Brain Magnetic Resonance Imaging Volumes and Cognitive Function at Age 10 Years.

Author information

1
Division of Pediatric Neurology, Department of Pediatrics, Boston Medical Center, Boston, MA. Electronic address: karl.kuban@bmc.org.
2
Department of Radiology, Boston University School of Medicine, Boston, MA.
3
Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of North Carolina, Chapel Hill, NC.
4
Department of Biostatistics, Boston University School of Public Health, Boston, MA.
5
Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA.
6
Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
7
Division of Pediatric Neurology, Department of Pediatrics, Boston Medical Center, Boston, MA.
8
Eunice Kennedy Shriver Center, Department of Psychiatry, UMASS Medical School/University of Massachusetts Memorial Health Care, Worcester, MA.
9
National Institute of Neurological Disorders and Stroke, Bethesda, MD.
10
Department of Psychiatry, University of Massachusetts Medical School, Worcester, MA.
11
Department of Epidemiology and Biostatistics and Pediatrics, Michigan State University, East Lansing, MI.

Abstract

OBJECTIVES:

To examine elevated neonatal inflammatory and neurotrophic proteins from children born extremely preterm in relation to later childhood brain Magnetic Resonance Imaging volumes and cognition.

STUDY DESIGN:

We measured circulating inflammation-related proteins and neurotrophic proteins on postnatal days 1, 7, and 14 in 166 children at 10 years of age (73 males; 93 females). Top quartile levels on ≥2 days for ≥3 inflammation-related proteins and for ≥4 neurotrophic proteins defined exposure. We examined associations among protein levels, brain Magnetic Resonance Imaging volumes, and cognition with multiple linear and logistic regressions.

RESULTS:

Analyses were adjusted for gestational age at birth and sex. Children with ≥3 elevated inflammation-related proteins had smaller grey matter, brain stem/cerebellar, and total brain volumes than those without elevated inflammation-related proteins, adjusted for neurotrophic proteins. When adjusted for inflammation-related proteins, children with ≥4 neurotrophic proteins, compared with children with no neurotrophic proteins, had larger grey matter and total brain volumes. Higher grey matter, white matter, and cerebellum and brainstem volumes were significantly correlated with higher IQ. Grey and white matter volumes were correlated with each other (r = -0.18; P = .021), and cerebellum and brainstem was highly correlated with grey matter (r = 0.55; P < .001) and white matter (r = 0.29; P < .001). Adjusting for other brain compartments, cerebellum and brainstem was associated with IQ (P = .016), but the association with white matter was marginally significant (P = .051). Grey matter was not associated with IQ. After adjusting for brain volumes, elevated inflammation-related proteins remained significantly associated with a lower IQ, and elevated neurotrophic proteins remained associated with a higher IQ.

CONCLUSIONS:

Newborn inflammatory and neurotrophin protein levels are associated with later brain volumes and cognition, but their effects on cognition are not entirely explained by altered brain volumes.

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