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Schanler 1999 Preterm Fortifikasi-Form Preterm PDF
Schanler 1999 Preterm Fortifikasi-Form Preterm PDF
Richard J. Schanler, MD*‡; Robert J. Shulman, MD*§; and Chantal Lau, PhD§
ABSTRACT. Background. In a large-scale study of feeding tolerance between groups. Milk intakes of in-
feeding strategies in premature infants (early vs later fants fed FHM were significantly greater than those fed
initiation of enteral feeding, continuous vs bolus tube- PF (180 6 13 vs 157 6 10 mL z kg21 z day21). The intakes of
feeding, and human milk vs formula), the feeding of nitrogen and copper were higher and magnesium and
human milk had more effect on the outcomes measured zinc were lower in group FHM versus PF. Fat and energy
than any other strategy studied. Therefore, this report absorption were lower and phosphorus, zinc, and copper
describes the growth, nutritional status, feeding toler- absorption were higher in group FHM versus PF. The
ance, and health of participating premature infants who postnatal retention (balance) surpassed the intrauterine
were fed fortified human milk (FHM) in comparison accretion rate of nitrogen, phosphorus, magnesium, zinc,
with those who were fed exclusively preterm formula and copper in the FHM group, and of nitrogen, magne-
(PF). sium, and copper in the PF group.
Methods. Premature infants were assigned randomly Conclusions. Although the study does not allow a
in a balanced two-way design to early (gastrointestinal comparison of FHM with unfortified human milk, the
priming for 10 days) versus late initiation of feeding data suggest that the unique properties of human milk
(total parenteral nutrition only) and continuous infusion promote an improved host defense and gastrointestinal
versus intermittent bolus tube-feeding groups. The type function compared with the feeding of formula. The
of milk was determined by parental choice and infants to benefits of improved health (less sepsis and necrotizing
receive their mother’s milk were randomized separately enterocolitis) associated with the feeding of FHM out-
from those to receive formula. The duration of the study weighed the slower rate of growth observed, suggesting
spanned the entire hospitalization of the infant. To eval- that the feeding of FHM should be promoted actively in
uate human milk versus formula feeding, we compared premature infants. Pediatrics 1999;103:1150 –1157; forti-
outcomes of infants fed >50 mL z kg21 z day21 of any fied human milk, preterm formula, premature infants, nu-
human milk (averaged throughout the hospitalization) tritional support.
with those of infants fed exclusively PF. Growth, feeding
tolerance, and health status were measured daily. Serum
indices of nutritional status were measured serially, and ABBREVIATIONS. GI, gastrointestinal; FHM, fortified human
72-hour nutrient balance studies were conducted at 6 and milk; NEC, necrotizing enterocolitis; PF, preterm formula; GRV,
9 weeks postnatally. gastric residual volume; TPN, total parenteral nutrition; Ca, cal-
Results. A total of 108 infants were fed either >50 cium; P, phosphorus; Mg, magnesium; Zn, zinc; Cu, copper.
mL z kg21 z day21 human milk (FHM, n 5 62) or exclu-
sively PF (n 5 46). Gestational age (28 6 1 weeks each),
T
he American Academy of Pediatrics’ recent
birth weight (1.07 6 0.17 vs 1.04 6 0.19 kg), birth length
and head circumference, and distribution among feeding statement on the recommendations for breast-
strategies were similar between groups. Infants fed FHM feeding full-term infants acknowledges the
were discharged earlier (73 6 19 vs 88 6 47 days) despite benefits of human milk in the management of pre-
significantly slower rates of weight gain (22 6 7 vs 26 6 mature infants.1 The beneficial effects generally re-
6 g z kg21 z day21), length increment (0.8 6 0.3 vs 1.0 6 0.3 late to improvements in host defense, digestion and
cm z week21), and increment in the sum of five skinfold absorption of nutrients, neurodevelopment, gastro-
measurements (0.86 6 0.40 vs 1.23 6 0.42 mm z week21) intestinal (GI) function, as well as psychological ef-
than infants fed PF. The incidence of necrotizing entero- fects on the mother.2 Human milk, especially, is suit-
colitis and late-onset sepsis was less in the FHM group. able for meeting many needs of premature infants,
Overall, there were no differences in any measure of
providing that their nutritional status is monitored
carefully.2 The exclusive feeding of unfortified hu-
man milk in premature infants, however, has been
From the *Children’s Nutrition Research Center and Sections of ‡Neona-
tology and §Pediatric Gastroenterology, Department of Pediatrics, Baylor associated with poorer rates of growth and nutri-
College of Medicine, Houston, Texas. tional deficits during and beyond the period of hos-
This work is a publication of the USDA/ARS Children’s Nutrition Research pitalization.3–12 As the goal for nutritional support is
Center, Department of Pediatrics, Baylor College of Medicine and Texas to meet the intrauterine rates of growth and nutrient
Children’s Hospital, Houston, Texas.
The contents of this publication do not necessarily reflect the views or
retention, nutrient supplementation is necessary to
policies of the USDA, nor does mention of trade names, commercial prod- optimize the use of human milk in the feeding of
ucts, or organizations imply endorsement by the US government. premature infants.13–15
Received for publication Sep 18, 1998; accepted Jan 20, 1999. There is a concern, however, that nutrient supple-
Reprint requests to (R.J.S.) 1100 Bates St, Houston, TX 77030-2600. E-mail:
schanler@bcm.tmc.edu
mentation of human milk might affect the intrinsic
PEDIATRICS (ISSN 0031 4005). Copyright © 1999 by the American Acad- host defense properties of the milk.16,17 A recent ran-
emy of Pediatrics. domized comparison of premature infants fed forti-
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TABLE 3. Clinical Outcomes .007. The FHM group had significantly more stools
Fortified Preterm than the PF group; the median number throughout
Human Milk Formula hospitalization was 164 versus 127, respectively,
Oxygen therapy (days)† 19 6 21* 33 6 41 P 5 .02.
NEC, n (%)‡ 1 (1.6) 6 (13)
NEC surgery (n) 0 3
Late-onset sepsis, n (%)§ 19 (31) 22 (48) Indices of Nutritional Status
Late-onset sepsis (no. of episodes 0.3 6 0.5 0.6 6 0.7 There were no differences between groups in the
per infant)\
Positive blood cultures (no. per 0.5 6 0.9 1.2 6 1.7 mean or the number of abnormal values for serum
infant)‡ Ca, P, Mg, alkaline phosphatase activity, albumin,
NEC or late-onset sepsis, n (%)‡ 19 (31) 25 (54) sodium, or blood urea nitrogen. However, the FHM
Abbreviation: NEC, necrotizing enterocolitis. group had significantly more serum bicarbonate val-
* Values are mean 6 SD. ues ,20 mmol/L than the PF group, P 5 .04. A
†,‡,§,\ Differences between groups: † P 5 .02, ‡ P # .01, § P 5 .07,
\ P 5 .03.
hematocrit ,25% also was more common in FHM
than PF groups, P 5 .001. In addition, the FHM
group received more supplementation with enteral
lates were Staphylococcus coagulase–negative, 24% acetate preparations for low serum bicarbonate con-
Staphylococcus aureus, 6% Escherichia coli, 4% Entero- centrations (34% vs 15%; P 5 .03) and more sodium
coccus, 4% Klebsiella, 4% Enterobacter, 2% Serratia, and supplementation for low serum sodium concentra-
2% Candida.
tions (39% vs 22%; P 5 .06).
There were significant differences in feeding toler-
ance during the advancement of feedings, from day
15 to the attainment of complete tube-feeding. Dur- Milk and Nutrient Intakes
ing this interval, there were fewer GRVs .2 Total fluid intake differed between groups, pri-
mL z kg21 (3 6 7% vs 7 6 9% of any GRV) and .50% marily a result of the greater intake of human milk
of 3 hours of feeding (0.3 6 0.8% vs 0.9 6 2.0% of any
prescribed to meet desired goals for minimum gains
GRV) in FHM than PF, respectively, P , .05. There
in body weight (Table 4). The FHM group received
were significantly fewer hours when feeding was
84 6 20% of all their milk as human milk (median
withheld in FHM than PF (47% vs 69% of infants, P ,
.04). For the entire study, however, there were no 93%); 22 infants received 100% human milk through-
significant differences between groups in the follow- out hospitalization. Human milk fortifier was used
ing assessments of feeding tolerance: the median for 37 6 13 days (range, 15 to 79 days). The average
number of episodes of emesis, abdominal distention, milk and nutrient intakes during and between the
GRV, bilious GRV, number of hours feedings were balance studies, while infants were receiving full
withheld, and abnormal abdominal radiographs. enteral nutrition, are given in Table 4. There were no
However, despite the overall absence of major dif- differences in fluid, energy, or nutrient intake be-
ferences in feeding tolerance, fewer of the FHM tween the first and the second balance study, at 6 and
group received antigastroesophageal reflux medica- 9 weeks’ postnatal age. Significant differences be-
tions (eg, metoclopramide, bethanecol, ranitidine, tween the FHM and PF group, however, were noted
and cisapride), 16% versus 39%, respectively, P 5 for intakes of milk, nitrogen, Mg, Zn, and Cu.
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Fig 4. Percent absorption of minerals at 6 and
9 weeks. Significant differences between
groups, *P , 0.001, **P , 0.01. Significant dif-
ferences over time, †P 5 .03, ††P 5 .05. Values
are mean 6 SEM.
feeding, using donor human milk if mother’s milk is gest that infants in group FHM were leaner than
unavailable. those in group PF. The lesser rate of growth might be
The low incidence of NEC and late-onset sepsis in detrimental if it prolonged hospitalization, but, par-
group FHM is compatible with other reports of pro- adoxically, group FHM had a significantly shorter
tective effects of human milk in premature in- hospitalization. Thus, we question the relevance of
fants.9,36 –38 The mechanism underlying the protective the lower rate of weight gain in the FHM group.
effects is unknown. Some reports suggest that the Further investigations of the growth outcomes in this
protective effects are related to the high immuno- group are ongoing.
globulin A content of human milk.39 The numerous There are many factors that affect the duration of
bioactive substances in human milk also may play a hospitalization. Similar objective criteria in each
role in the local protective effects of human milk.40,41 group were used for discharge. Infants fed FHM
The protection afforded by FHM also may be ex- were healthier, having less NEC and late-onset sep-
plained, at least partially, by the more frequent ses- sis, but also, these infants had more interaction with
sions of skin-to-skin contact between mother and their parents, through visits, holding, and skin-to-
infant in the FHM group. Skin-to-skin contact can be skin contact. However, we did not observe any rela-
viewed as the neonatal nursery equivalent of the tionship between parent interaction and the duration
enteromammary pathway for host defense of the of hospitalization. Thus, our data do not support the
infant.42 Frequent skin-to-skin sessions may stimu- enhanced bonding effect of parental contact.43 There
late maternal antibody production to produce a milk- is no way to assess whether these parenting oppor-
containing antibody against nosocomial pathogens. tunities affected, in other ways, the decision for hos-
Therefore, there are several possible explanations for pital discharge. Nevertheless, a shorter hospitaliza-
the reduced episodes of NEC and late-onset sepsis in tion has tremendous economic advantages in terms
the FHM group. of the cost of health care.
Our large study suggests that more attention to the The balance study data indicate that the net reten-
nutritional aspects of fortification is warranted. We tion of most nutrients was significantly above intra-
observed slower rates of weight gain and linear uterine references and that Mg, Zn, and Cu are in
growth in the FHM group compared with the PF excess in the FHM group versus the PF group. These
group. The lesser increments in skinfold thickness, in data support the formulation of human milk fortifi-
conjunction with the greater nitrogen retention, sug- ers with less of these nutrients.
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18. Lucas A, Fewtrell MS, Morley R, et al. Randomized outcome trial of 32. Roy RN, Chance GW, Radde IC, Hill DE, Willis DM, Sheepers J. Late
human milk fortification and developmental outcome in preterm in- hyponatremia in very low birthweight infants. Pediatr Res. 1976;526 –53l
fants. Am J Clin Nutr. 1996;64:142–151 33. Polberger SKT, Axelsson IA, Raiha NCR. Growth of very low birth
19. Schanler RJ. Human milk fortification for premature infants. Am J Clin weight infants on varying amounts of human milk protein. Pediatr Res.
Nutr. 1996;64:249 –250 1989;25:414 – 419
20. Schanler RJ, Shulman RJ, Lau C, Smith EO, Heitkemper MM. Feeding 34. Schanler RJ, Burns PA, Abrams SA, Garza C. Bone mineralization
strategies for premature infants: randomized trial of gastrointestinal outcomes in human milk-fed preterm infants. Pediatr Res. 1992;31:
priming and tube-feeding method. Pediatrics. 1999;103:434 – 439 583–586
21. Schanler RJ. The low birth weight infant: perinatal nutrition. In: Walker 35. Metcalf R, Dilena B, Gibson R, Marshall P, Simmer K. How appropriate
WA, Watkins JB. eds. Nutrition in Pediatrics: Basic Science and Clinical are commercially available human milk fortifiers? J Paediatr Child Health.
Applications. Hamilton, Ontario, Canada: BC Decker Inc; 1996:387– 407 1994;30:350 –355
22. American Academy of Pediatrics, Committee on Fetus and Newborn. 36. Lucas A, Cole TJ. Breast milk and neonatal necrotizing enterocolitis.
Hospital discharge of the high-risk neonate: proposed guidelines. Pedi- Lancet. 1990;336:1519 –1523
atrics. 1998;102:411– 417 37. El-Mohandes AE, Picard MB, Simmens SJ, Keiser JF. Use of human milk
23. Hurst NM, Myatt A, Schanler RJ. Growth and development of a hos- in the intensive care nursery decreases the incidence of nosocomial
pital-based lactation program and mother’s own milk bank. J Obstet sepsis. J Perinatol. 1998;17:130 –134
Gynecol Neonatal Nurs. 1998;27:503–510 38. Hylander MA, Strobino DM, Dhanireddy R. Human milk feedings and
24. Schanler RJ, Abrams SA. Postnatal attainment of intrauterine mac- infection among very low birth weight infants. Pediatrics. 1998;102(3).
romineral accretion rates in low birth weight infants fed fortified human URL: http://www.pediatrics.org/cgi/content/full/102/3/e38
milk. J Pediatr. 1995;126:441– 447 39. Eibl MM, Wolf HM, Furnkranz H, Rosenkranz A. Prevention of necro-
25. Michaelsen KF, Skov L, Badsberg JH, Jorgensen M. Short-term measure- tizing enterocolitis in low-birth-weight infants by IgA-IgG feeding.
ment of linear growth in preterm infants: validation of a hand-held N Engl J Med. 1988;319:1–7
knemometer. Pediatr Res. 1991;30:464 – 468 40. Goldman AS. Immunologic system in human milk. J Pediatr Gastroen-
26. Stoll BJ, Gordon T, Korones SB, et al. Late-onset sepsis in very low birth terol Nutr. 1986;5:343–345
weight neonates: a report from the National Institute of Child Health 41. Goldman AS, Frawley S. Bioactive components of milk. J Mammary
and Human Development Neonatal Research Network. J Pediatr. 1996; Gland Biol Neoplasia. 1996;1:241–242
129:63–71 42. Kleinman RE, Walker WA. The enteromammary immune system. Dig
27. Wauben IP, Atkinson SA, Grad TL, Shah JK, Paes B. Moderate nutrient Dis Sci. 1979;24:876 – 882
supplementation of mother’s milk for preterm infants supports ade- 43. Tessier R, Cristo M, Velez S, et al. Kangaroo mother care and the
quate bone mass and short-term growth: a randomized, controlled trial. bonding hypothesis. Pediatrics. 1998;102(2). URL: http://www.
Am J Clin Nutr. 1998;67:465– 472 pediatrics.org/cgi/content/full/102/2/e17
28. Abrams SA, Schanler RJ, Garza C. Bone mineralization in former very 44. Whyte RK, Campbell D, Stanhope R, Bayley HS, Sinclair JC. Energy
low birth weight infants fed either human milk or commercial formula. balance in low birth weight infants fed formula of high or low medium-
J Pediatr. 1988;112:956 –962 chain triglyceride content. J Pediatr. 1986;108:964 –971
29. Abrams SA, Schanler RJ, Tsang RC, Garza C. Bone mineralization in 45. Chappell JE, Clandinin MT, Kearney-Volpe C, Reichman B, Sawyer PW.
former very low birth weight infants fed either human milk or com- Fatty acid balance studies in premature infants fed human milk or
mercial formula: one year follow-up observation. J Pediatr. 1989;114: formula: effect of calcium supplementation. J Pediatr. 1986;108:439 – 447
1041–1044 46. Boehm G, Muller DM, Senger H, Borte M, Moro G. Nitrogen and fat
30. Schanler RJ, Garza C. Improved mineral balance in very low birth balances in very low birth weight infants fed human milk fortified with
weight infants fed fortified human milk. J Pediatr. 1987;112:452– 456 human milk or bovine milk protein. Eur J Pediatr. 1993;152:236 –239
31. Kumar SP, Sacks LM. Hyponatremia in very low-birth-weight infants 47. Kildeberg P, Engel K, Winters RW. Balance of net acid in growing
and human milk feedings. J Pediatr. 1978;93:1026 –1027 infants. Acta Paediatr Scand. 1969;58:321–329
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