Background: Extrauterine growth restriction is common among very low birth weight infants (VLBW, BW <1,500 g). Optimal postnatal nutrient supply is essential to limit growth restriction and ensure adequate growth and neurodevelopment. Objectives: We compared an enhanced postnatal nutrient supply to a standard supply and evaluated the effects on growth velocity, head circumference growth and cerebral maturation - the latter by magnetic resonance diffusion tensor imaging (DTI). We hypothesized increased growth velocity, head circumference growth and decreased mean diffusivity (MD) in cerebral white matter (WM) areas, suggesting improved cerebral maturation among infants on the enhanced nutrient supply. Methods: In this randomized controlled trial, infants on the enhanced nutrient supply received increased amounts of energy, protein, fat, essential fatty acids and vitamin A until discharge. DTI was performed close to term equivalent age. Outcomes were growth velocity, head circumference growth and WM mean diffusivity. Results: Among the 50 included infants, 14 in the intervention group and 11 controls underwent a successful DTI. Infants on the enhanced diet achieved improved growth velocity (16.5 vs. 13.8 g/kg/day, p = 0.01) and increased head circumference (Δz score: 0.24 vs. -0.12, p = 0.15). A significantly lower MD was seen in a large WM area such as the superior longitudinal fasciculi (1.19 × 10-3 vs. 1.24 × 10-3 mm2/s, p = 0.04, adjusted for age when scanned). Conclusions: Enhanced nutrient supply to VLBW infants is associated with improved growth velocity, increased head circumference growth and decreased regional WM mean diffusivity, suggesting improved maturation of cerebral connective tracts.

Keywords:
Premature infants, Growth and nutrition, Brain imaging, Brain maturation, Diffusion tensor imaging, Mean diffusivity
1.
Bhutta AT, Cleves MA, Casey PH, Cradock MM, Anand KJ: Cognitive and behavioral outcomes of school-aged children who were born preterm: a meta-analysis. JAMA 2002;288:728-737.
2.
Embleton NE, Pang N, Cooke RJ: Postnatal malnutrition and growth retardation: an inevitable consequence of current recommendations in preterm infants? Pediatrics 2001;107:270-273.
3.
de Curtis M, Rigo J: The nutrition of preterm infants. Early Hum Dev 2012;88(suppl 1):S5-S7.
4.
Stephens BE, Walden RV, Gargus RA, et al: First-week protein and energy intakes are associated with 18-month developmental outcomes in extremely low birth weight infants. Pediatrics 2009;123:1337-1343.
5.
Tan M, Abernethy L, Cooke R: Improving head growth in preterm infants - a randomised controlled trial. II. MRI and developmental outcomes in the first year. Arch Dis Child Fetal Neonatal Ed 2008;93:F342-F346.
6.
Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE: Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006;355:685-694.
7.
Ramel SE, Demerath EW, Gray HL, Younge N, Boys C, Georgieff MK: The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology 2012;102:19-24.
8.
Tamnes CK, Fjell AM, Ostby Y, et al: The brain dynamics of intellectual development: waxing and waning white and gray matter. Neuropsychologia 2011;49:3605-3611.
9.
Shim SY, Jeong HJ, Son DW, et al: Altered microstructure of white matter except the corpus callosum is independent of prematurity. Neonatology 2012;102:309-315.
10.
Feldman HM, Yeatman JD, Lee ES, Barde LH, Gaman-Bean S: Diffusion tensor imaging: a review for pediatric researchers and clinicians. J Dev Behav Pediatr 2010;31:346-356.
11.
Vinall J, Grunau RE, Brant R, et al: Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns. Sci Transl Med 2013;5:168ra8.
12.
Moltu SJ, Blakstad EW, Strommen K: Enhanced feeding and diminished postnatal growth failure in very-low-birth-weight infants: a randomized controlled trial. J Pediatr Gastroenterol Nutr 2014;58:344-351.
13.
Moltu SJ, Strommen K, Blakstad EW, et al: Enhanced feeding in very-low-birth-weight infants may cause electrolyte disturbances and septicemia - a randomized, controlled trial. Clin Nutr 2013;32:207-212.
14.
Agostoni C, Buonocore G, Carnielli VP, et al: Enteral nutrient supply for preterm infants: commentary from the European Society of Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition. J Pediatr Gastroenterol Nutr 2010;50:85-91.
15.
Yendiki A, Koldewyn K, Kakunoori N, Kanwisher N, Fischl B: Spurious group differences due to head motion in a diffusion MRI study. Neuroimage 2013, Epub ahead of print.
16.
Henriksen C, Westerberg AC, Ronnestad A, et al: Growth and nutrient intake among very-low-birth-weight infants fed fortified human milk during hospitalisation. Br J Nutr 2009;102:1179-1186.
17.
Klein CJ: Nutrient requirements for preterm infant formulas. J Nutr 2002;132:1395S-1577S.
18.
Chaddock-Heyman L, Erickson KI, Voss MW, et al: White matter microstructure is associated with cognitive control in children. Biol Psychol 2013;94:109-115.
19.
Ghods E, Kreissl A, Brandstetter S, Fuiko R, Widhalm K: Head circumference catch-up growth among preterm very low birth weight infants: effect on neurodevelopmental outcome. J Perinat Med 2011;39:579-586.
20.
Lepomaki V, Paavilainen T, Matomaki J, et al: Effect of antenatal growth and prematurity on brain white matter: diffusion tensor study. Pediatr Radiol 2012;42:692-698.
21.
Lapillonne A, Griffin IJ: Feeding preterm infants today for later metabolic and cardiovascular outcomes. J Pediatr 2013;162:S7-S16.
22.
Schulzke SM, Patole SK, Simmer K: Long-chain polyunsaturated fatty acid supplementation in preterm infants. Cochrane Database Syst Rev 2011;2:CD000375.
23.
Deoni SC, Dean DC III, Piryatinksy I, et al: Breastfeeding and early white matter development: a cross-sectional study. Neuroimage 2013;82:77-86.
24.
Woodward LJ, Clark CA, Bora S, Inder TE: Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children. PLoS One 2012;7:e51879.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.