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PEDIATRICS Vol. 113 No. 4 April 2004, pp. 846-857

Early Experience Alters Brain Function and Structure

Heidelise Als, PhD*, Frank H. Duffy, MD{ddagger}, Gloria B. McAnulty, PhD*, Michael J. Rivkin, MD*,{ddagger},§, Sridhar Vajapeyam, PhD§, Robert V. Mulkern, PhD§, Simon K. Warfield, PhD§, Petra S. Huppi, MD{ddagger},||, Samantha C. Butler, PhD*, Nikk Conneman, MD*, Christine Fischer, MD*, Eric C. Eichenwald, MD,#

* Departments of Psychiatry
{ddagger} Neurology
§ Radiology
Newborn Medicine, Harvard Medical School and Children’s Hospital Boston, Boston, Massachusetts
|| Department of Newborn Medicine, University of Geneva, Geneva, Switzerland
# Newborn Intensive Care Nursery, Brigham and Women’s Hospital, Boston, Massachusetts

Objective. To investigate the effects of early experience on brain function and structure.

Methods. A randomized clinical trial tested the neurodevelopmental effectiveness of the Newborn Individualized Developmental Care and Assessment Program (NIDCAP). Thirty preterm infants, 28 to 33 weeks’ gestational age (GA) at birth and free of known developmental risk factors, participated in the trial. NIDCAP was initiated within 72 hours of intensive care unit admission and continued to the age of 2 weeks, corrected for prematurity. Control (14) and experimental (16) infants were assessed at 2 weeks’ and 9 months’ corrected age on health status, growth, and neurobehavior, and at 2 weeks’ corrected age additionally on electroencephalogram spectral coherence, magnetic resonance diffusion tensor imaging, and measurements of transverse relaxation time.

Results. The groups were medically and demographically comparable before as well as after the treatment. However, the experimental group showed significantly better neurobehavioral functioning, increased coherence between frontal and a broad spectrum of mainly occipital brain regions, and higher relative anisotropy in left internal capsule, with a trend for right internal capsule and frontal white matter. Transverse relaxation time showed no difference. Behavioral function was improved also at 9 months’ corrected age. The relationship among the 3 neurodevelopmental domains was significant. The results indicated consistently better function and more mature fiber structure for experimental infants compared with their controls.

Conclusions. This is the first in vivo evidence of enhanced brain function and structure due to the NIDCAP. The study demonstrates that quality of experience before term may influence brain development significantly.


Key Words: preterm infants • NIDCAP • neurobehavior • spectral coherence • diffusion tensor imaging • transverse relaxation time • Bayley Scales of Infant Development • APIB

Abbreviations: NICU, newborn intensive care unit • NIDCAP, Newborn Individualized Developmental Care and Assessment Program • MRI, magnetic resonance imaging • EEG, electroencephalogram • APIB, Assessment of Preterm Infants’ Behavior • Prechtl, Prechtl Neurologic Examination of the Fullterm Newborn Infant • Bayley II, Bayley Scales of Infant Development, Second Edition • MDI, mental developmental index • PDI, psychomotor developmental index • BRS, Behavior Rating Scale • T2*, transverse relaxation time • DTI, diffusion tensor imaging • ROI, region(s) of interest • E1, principal eigenvalue • E3, tertiary eigenvalue • RA, relative anisotropy • MANOVA, multivariate analysis of variance


Received for publication Jun 17, 2003; Accepted Dec 29, 2003.


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