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Growth and Development of Premature Infants Fed Predominantly Human Milk, Predominantly Premature Infant Formula, or a Combination of Human Milk and Premature Formula

O'Connor, Deborah L.*; Jacobs, Joan; Hall, Robert; Adamkin, David§; Auestad, Nancy; Castillo, Marcella; Connor, William E.; Connor, Sonja L.; Fitzgerald, Kathleen; Groh-Wargo, Sharon#; Hartmann, E. Eugenie**; Janowsky, Jeri; Lucas, Alan††; Margeson, Dean; Mena, Patricia; Neuringer, Martha; Ross, Gail‡‡; Singer, Lynn§§; Stephenson, Terence∥∥; Szabo, Joanne¶¶; Zemon, Vance***

Journal of Pediatric Gastroenterology and Nutrition: October 2003 - Volume 37 - Issue 4 - p 437-446
Original Articles–Liver and Nutrition

Background In a recent meta-analysis, human milk feeding of low birth-weight (LBW) infants was associated with a 5.2 point improvement in IQ tests. However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice.

Objective To compare the growth, in-hospital feeding tolerance, morbidity, and development (cognitive, motor, visual, and language) of LBW infants fed different amounts of human milk until term chronologic age (CA) with those of LBW infants fed nutrient-enriched formulas from first enteral feeding.

Methods The data in this study were collected in a previous randomized controlled trial assessing the benefit of supplementing nutrient-enriched formulas for LBW infants with arachidonic acid and docosahexaenoic acid. Infants (n = 463, birth weight, 750–1,800 g) were enrolled from nurseries located in Chile, the United Kingdom, and the United States. If human milk was fed before hospital discharge, it was fortified (3,050–3,300 kJ/L, 22–24 kcal/oz). As infants were weaned from human milk, they were fed nutrient-enriched formula with or without arachidonic and docosahexaenoic acids (3,300 kJ/L before term, 3,050 kJ/L thereafter) until 12 months CA. Formula fed infants were given nutrient-enriched formula with or without added arachidonic and docosahexaenoic acids (3,300 kJ/L to term, 3,050 kJ/L thereafter) until 12 months CA. For the purposes of this evaluation, infants were categorized into four mutually exclusive feeding groups: 1) predominantly human milk fed until term CA (PHM-T, n = 43); 2) ≥ 50% energy from human milk before hospital discharge (≥ 50% HM, n = 98); 3) < 50% of energy from human milk before hospital discharge (< 50% HM, n = 203); or 4) predominantly formula fed until term CA (PFF-T, n = 119).

Results PFF-T infants weighed approximately 500 g more at term CA than did PHM-T infants. This absolute difference persisted until 6 months CA. PFF-T infants were also longer (1.0–1.5 cm) and had larger head circumferences (0.3–1.1 cm) than both PHM-T and ≥ 50% HM infants at term CA. There was a positive association between duration of human milk feeding and the Bayley Mental Index at 12 months CA (P = 0.032 full and P = 0.073 reduced, statistical models) after controlling for the confounding variables of home environment and maternal intelligence. Infants with chronic lung disease fed ≥ 50% HM until term CA (n = 22) had a mean Bayley Motor Index about 11 points higher at 12 months CA compared with infants PFF-T (n = 24, P = 0.033 full model).

Conclusion Our data suggest that, despite a slower early growth rate, human milk fed LBW infants have development at least comparable to that of infants fed nutrient-enriched formula. Exploratory analysis suggests that some subgroups of human milk fed LBW infants may have enhanced development, although this needs to be confirmed in future studies.

*University of Toronto and The Hospital for Sick Children, Toronto, Canada; †Ross Products Div, Abbott Labs, Columbus, Ohio; ‡The Children's Mercy Hospital, Kansas City, Missouri; §University of Louisville & Kosair Children's Hospital, Louisville, Kentucky; INTA Univ de Chile, Santiago, Chile; ¶Oregon Health & Sciences University, Portland, Oregon; #MetroHealth Medical Center, Cleveland, Ohio; **Hunter College, New York, New York; ††Institute of Child Health, London, United Kingdom; ‡‡Weill Medical College, Cornell University, New York, New York; §§Rainbow Babies & Children's Hospital, Cleveland, Ohio; ∥∥University of Nottingham, Nottingham, United Kingdom; ¶¶Arkansas Children's Hospital, Little Rock, Arkansas; ***Yeshiva University, Bronx, New York; on behalf of The Ross Preterm Lipid Study Group: R. Carroll and B. Meyer (The Children's Mercy Hospital); P. Radmacher and S. Rafail (Kosair Children's Hospital); A. Blanco Gomez (INTA Univ de Chile); P. Fisher and S. Escoe (Oregon Health & Sciences University); R. Arendt and M. Davillier (Rainbow Babies & Children's Hospital); K. Kennedy (Institute of Child Health); J. Putis (Leeds General Infirmary); S. Newell (St. James' Hospital, Leeds); S. Carlisle (Arkansas Children's Hospital); C. Broestl, C. Downs, Q. Liang, P. Pollack, W. Qiu, and D. Smart (Ross Products Division); J. Deeks, S. Sullivan, R. Tressler (Abbott Labs); S. Buckley (Yeshiva University); J. Gordon and L. Garcia-Quispe (Hunter College); and D. Pinchasik and M. Nesin (Weill Medical College).

Received: September 5, 2002;

revised: March 14, 2003; accepted: April 9, 2003.

Address correspondence and reprint requests to Dr. Deborah L. O'Connor, Associate Professor, Department of Nutritional Sciences, University of Toronto, Senior Associate Scientist, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada Canada, M5G 1X8 (e-mail: Deborah_l.o'connor@sickkids.ca).

© 2003 Lippincott Williams & Wilkins, Inc.