Neurodevelopment in Children Born Small for Gestational Age: A Randomized Trial of Nutrient-Enriched Versus Standard Formula and Comparison With a Reference Breastfed Group
* Medical Research Council Childhood Nutrition Research Centre, Institute of Child Health, London, United Kingdom
Clinical Epidemiology and Biostatistics Unit and Murdoch Children’s Research Institute, Royal Children’s Hospital, Melbourne, Australia
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom
|| Academic Division of Child Health, University Hospital, Nottingham, United Kingdom
¶ Paediatric Department, Stirling Royal Infirmary National Health Service Trust, Stirling, United Kingdom
Objective. Many studies have shown that children born small for gestational age (SGA) are at a neurodevelopmental disadvantage. We have shown that nutrient enrichment of formula fed to term SGA infants improves their growth and hypothesized that it also would improve their neurodevelopmental outcome.
Design. A randomized, controlled trial of standard term-infant (n = 147) or nutrient-enriched (n = 152) formula for the first 9 months. A reference group of 175 breastfed SGA infants was also recruited.
Setting. Subjects were recruited in 5 maternity hospitals in Cambridge, Nottingham, and Leicester, all in the United Kingdom.
Participants. Healthy, term infants (gestation: 
37 weeks) with birth weight <10th centile.
Outcome Measures. Bayley mental and psychomotor scores at 18 months (primary) and developmental scores from Knobloch, Pasamanick, and Sherrard’s developmental screening inventory at 9 months (secondary).
Results. There was no significant intergroup difference in Bayley Mental Development Index (MDI) or Psychomotor Development Index (PDI) scores at 18 months. However, at 9 months, children fed the enriched formula had a significantly lower developmental quotient (99.5 vs 102.0; 95% confidence interval [CI] for difference: –4.6, –0.4). A significant disadvantage was seen in girls (–5.1; 95% CI: –7.8, –2.4) but not in boys (0.9; 95% CI: –2.4, 4.2).
Breastfed infants had significantly higher MDI and PDI scores at 18 months than formula-fed infants. Confounding factors accounted for 
34% of the observed association between breastfeeding and MDI score and none of the association between breastfeeding and PDI score.
Conclusions. The previously reported enhanced linear growth in SGA children fed enriched formula was not matched by a neurodevelopmental advantage. At 9 months, girls fed the enriched formula had a significant developmental disadvantage, although this was not seen at 18 months. Later follow-up will determine any long-term effects on health or development. Meanwhile, use of enriched formula for term SGA children should not be promoted.
It seems that breastfeeding may be especially beneficial for neurodevelopment in children born SGA.
Key Words: term infant • small for gestational age • postnatal nutrition • neurodevelopment • randomized trial
Abbreviations: SGA, small for gestational age • MDI, Mental Development Index • PDI, Psychomotor Development Index • SD, standard deviation • IQ, intelligence quotient • CI, confidence interval
Received for publication Dec 16, 2002; Accepted Jun 4, 2003.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Facebook 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  B. J. Lew, L. L. Collins, M. A. O'Reilly, and B. P. Lawrence Activation of the Aryl Hydrocarbon Receptor during Different Critical Windows in Pregnancy Alters Mammary Epithelial Cell Proliferation and Differentiation Toxicol. Sci., September 1, 2009; 111(1): 151 - 162. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-L. Funkquist, T. Tuvemo, B. Jonsson, F. Serenius, and K. H. Nyqvist Feeding Regimens and Catch-Up Growth in Premature and Full-Term Small for Gestational Age Infants ICAN: Infant, Child, & Adolescent Nutrition, April 1, 2009; 1(2): 66 - 72. [Abstract] [PDF]
|
|
|
|
 |
|
 L Corvaglia, B Battistini, V Paoletti, A Aceti, M G Capretti, and G Faldella Near-infrared reflectance analysis to evaluate the nitrogen and fat content of human milk in neonatal intensive care units Arch. Dis. Child. Fetal Neonatal Ed., September 1, 2008; 93(5): F372 - F375. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Singhal, T. J. Cole, M. Fewtrell, K. Kennedy, T. Stephenson, A. Elias-Jones, and A. Lucas Promotion of Faster Weight Gain in Infants Born Small for Gestational Age: Is There an Adverse Effect on Later Blood Pressure? Circulation, January 16, 2007; 115(2): 213 - 220. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S M Montgomery, A Ehlin, and A Sacker Breast feeding and resilience against psychosocial stress Arch. Dis. Child., December 1, 2006; 91(12): 990 - 994. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sacker, M. A. Quigley, and Y. J. Kelly Breastfeeding and Developmental Delay: Findings From the Millennium Cohort Study Pediatrics, September 1, 2006; 118(3): e682 - e689. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. C. Daniels and L. S. Adair Breast-Feeding Influences Cognitive Development in Filipino Children J. Nutr., November 1, 2005; 135(11): 2589 - 2595. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C McCann and B. N Ames Is docosahexaenoic acid, an n-3 long-chain polyunsaturated fatty acid, required for development of normal brain function? An overview of evidence from cognitive and behavioral tests in humans and animals Am. J. Clinical Nutrition, August 1, 2005; 82(2): 281 - 295. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. desRobert, R. Lane, N. Li, and J. Neu Neonatal Nutrition and Consequences on Adult Health NeoReviews, May 1, 2005; 6(5): e211 - e219. [Full Text] [PDF]
|
|
|
|
 |
|
 23 Apr 2004 to 23 Jul 2004 Evid. Based Nurs., October 1, 2004; 7(4): e4 - e4. [Full Text] [PDF]
|
|
|
|
 |
|
 Other articles noted Evid. Based Med., September 1, 2004; 9(5): e5 - e5. [Full Text] [PDF]
|
|
|
|
 |
|
 Yet Another Reason to Breast-Feed Journal Watch Pediatrics and Adolescent Medicine, April 26, 2004; 2004(426): 2 - 2. [Full Text]
|
|
eLetters:
Read all eLetters
- formula should contain prolactin or DHEA
- James M. Howard
- Pediatrics Online, 8 Mar 2004 [Full text]
