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Circulatory insulin-like growth factor-I and brain volumes in relation to neurodevelopmental outcome in very preterm infants

Journal article
Authors Ingrid Hansen-Pupp
Holger Hovel
Chatarina Löfqvist
Lena Hellstrom-Westas
Vineta Fellman
Petra S. Huppi
Ann Hellström
David Ley
Published in Pediatric Research
Volume 74
Issue 5
Pages 564-569
ISSN 0047-2506
Publisher International Pediatric Research Foundation, Inc.
Publication year 2013
Published at Institute of Neuroscience and Physiology, Department of Clinical Neuroscience and Rehabilitation
Pages 564-569
Language en
Subject categories Ophthalmology


Background: To evaluate the relationships between postnatal change in circulatory insulin-like growth factor-I (IGF-I) concentrations, brain volumes, and developmental outcome at 2 y of age in very preterm infants. Methods: IGF-I was measured weekly, and nutritional intake was calculated daily from birth until a postmenstrual age (PMA) of 35 wk. Individual β coefficients for IGF-I, IGF-I(B), representing the rate of increase in IGF-I from birth until a PMA of 35 wk were calculated. Brain magnetic resonance imaging was performed at term age, with segmentation into total brain, cerebellar, gray matter, and unmyelinated white matter volume (UWMV). Developmental outcome was evaluated using Bayley Scales of Infant Development-II. Results: Forty-nine infants, with mean gestational age (GA) of 26.0 wk, were evaluated at mean 24.6 mo corrected age. Higher IGF-I(B), UWMV, and cerebellar volume were associated with a decreased risk for a Mental Developmental Index (MDI) < 85 (odds ratio (95% confidence interval): 0.6 (0.4–0.9), 0.96 (0.94–0.99), and 0.78 (0.6–0.96), respectively). In multivariate analysis, higher IGF-I(B) and higher UWMV combined with female gender constituted the two models with the highest predictive value for MDI > 85. Conclusion: A higher rate of increase in circulating IGF-I is associated with a decreased risk for subnormal MDI at 2 y of corrected age. This relationship is in part dependent on brain volume at term age. Impaired neurodevelopment after very preterm birth remains a major concern. Combinations of risk factors interfere with growth and maturation of the immature brain during the early postnatal period (1). Decreased brain volumes and impaired developmental outcome have been observed not only after extremely preterm birth but also in moderately or late preterm infants (2,3,4), suggesting a deleterious effect of other factors than only gestational age (GA). Delayed maturation of white matter structures has been suggested to be a result of postnatal events rather than gestational age per se (5). Reduced longitudinal growth velocity and decreased nutritional intake during the first postnatal week after very preterm birth have been associated with later developmental delay (6,7). Fetal and postnatal growth is regulated not only by nutritional intake but also by several endogenous growth factors. Insulin-like growth factor-I (IGF-I) plays a crucial role in brain development (8). Immediately after birth, circulatory IGF-I concentrations decrease rapidly, and in preterm infants, low concentrations persist during several weeks, as compared with corresponding intrauterine concentrations (9,10,11). In preterm infants, postnatal circulatory IGF-I concentrations have been positively associated with longitudinal growth (10,12,13). We have previously shown that low postnatal IGF-I concentrations are related to decreased brain volumes at term age (14). As a consequence, we hypothesized that a lower rate of increase in IGF-I concentrations and lower brain volumes may be associated with impaired later neurodevelopment. We explored this by relating postnatal development of circulating IGF-I and brain growth as determined by magnetic resonance imaging at term age to neurodevelopment at 2 y of age.

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