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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 & Nutrition: October 2003 - Volume 37 - Issue 4 - pp 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 However, in the studies in this meta-analysis, feeding regimens were used (unfortified human milk, term formula) that no longer represent recommended practice.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.

In a recently published meta-analysis, Anderson et al. (1) conclude that breast feeding is associated with higher scores for cognitive development than is formula feeding, even after adjustment for confounding factors. Interestingly, this benefit was greatest for low birth weight (LBW) infants, among whom those fed human milk showed a 5.2 point advantage in IQ. The conclusions of Anderson et al. are consistent with the individual observations of Lucas et al. (2,3) and others (4,5). Lucas et al. reported that LBW infants fed unfortified human milk for 4 weeks after initiation of enteral feeding performed better on standardized tests of development at 18 months corrected age (CA) than did LBW infants fed a significant proportion of total energy via standard term formula. Lucas et al. also reported that LBW infants fed a specially designed nutrient-enriched preterm formula for 4 weeks postnatally had more advanced motor and mental development at 18 months CA than did infants fed term formula. They also observed higher IQ, most notably verbal IQ, in boys 7½ to 8 years of age who were fed nutrient-enriched formula compared with those fed term formula in infancy (6).

In contrast to these comparisons between unfortified human milk and term formula, Lucas et al. (2) found no difference in the developmental outcomes of LBW infants fed unfortified human milk for 4 weeks compared with those fed a specially designed nutrient-enriched preterm formula. These comparisons suggest that human milk feeding and nutrient enrichment may have independent, perhaps additive, effects on the development of infants born prematurely.

In contemplating how these observations might be applied to current clinical practice, the following points are worthy of consideration. First, the American Academy of Pediatrics (7) now recommends that, under most circumstances, fortified human milk is the feeding of choice for hospitalized LBW infants. Neither unfortified human milk nor term formulas are currently recommended during the initial in-hospital course because they do not meet the nutritional requirements of LBW infants, especially those of very LBW infants(<1,500 g) (7,8). Thus, the aforementioned studies compared feeding regimens that no longer represent ideal or recommended feeding practices for LBW infants. Few published data exist to date that directly examine the development of LBW infants fed fortified human milk compared with specially designed nutrient-enriched formulas during and after hospital discharge.

The purpose of this article is to compare the growth, in-hospital feeding tolerance, morbidity, and development at 14 months CA of LBW infants fed different amounts of human milk until term-corrected age (CA) and then fed nutrient-enriched formulas until 12 months CA when weaned with those of LBW infants fed nutrient-enriched formulas from first enteral feeding until 12 months CA.

*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'

© 2003 Lippincott Williams & Wilkins, Inc.