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Section of Neonatology and Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030
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INTRODUCTION |
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 TOP INTRODUCTION Human milk and host...Intestinal responses to feedingSUMMARYREFERENCES |
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).
Human milk may be of special benefit to the premature infant because of
the interrelationships among nutritional support, gastrointestinal
maturity and host defense. In particular, the high rates of infection
and septicemia in the immunosuppressed premature infant are the direct
results of exposure to the numerous pathogens in the nursery
environment. In addition, circulatory instability and apnea are common
factors that are thought to interact with feeding and bacterial
colonization to contribute to the development of necrotizing
enterocolitis (NEC)3
. Thus, by incorporating both
nutritional and host defense benefits, human milk may protect the
premature infant.
A recent report from the National Institute of Child Health and Human
Development Neonatal Research Network (Stoll et al. 1996
) indicated the importance of the problem of late-onset
sepsis in premature infants and its association with NEC, commenting
that these conditions accounted for major morbidity and mortality,
prolonged hospitalization and tremendous economic burden. Of note was
the variation in incidence among the 12 centers in the Network, but no
data were provided on the use of human milk in the nurseries at the
study sites. Efforts directed at partially reducing the incidence of
these medical conditions, potentially through the feeding of human
milk, therefore, would significantly affect the cost of medical care
(Gaynes et al. 1996
, Kliegman et al. 1993
, Stoll et al. 1996
).
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Human milk and host defense in premature infants |
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TOPINTRODUCTIONHuman milk and host...Intestinal responses to feedingSUMMARYREFERENCES |
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, Goldman and Frawley 1996
, Hambraeus 1977
,
Lindblad et al. 1978
, Newburg 1996
,
Raiha et al. 1976
, Rassin et al. 1977
,
Telemo and Hanson 1996
), but the specific mechanism(s)
for this protection is unclear. One investigation reported a decreased
incidence of NEC in premature infants fed a preparation of
immunoglobulins (Ig) A and G derived from serum (Eibl et al. 1988
). The infants fed the IgA-IgG also had a significantly
higher fecal excretion of immunologically active IgA than control
infants, suggesting a local protective effect throughout the
gastrointestinal tract. In our studies at the Children’s Nutrition
Research Center, we demonstrated greater fecal and urinary IgA and
lactoferrin excretion in premature infants fed human milk vs. formula
(Goldblum et al. 1989
, Schanler et al. 1986
). Further studies in our Center indicated that human
milk–derived lactoferrin was absorbed intact and excreted in the urine
of premature infants, suggesting local as well as systemic action
(Hutchens et al. 1991
).
Nonrandomized clinical studies report a lower incidence of a variety of
infections in premature infants fed human milk, regardless of whether
the milk was fresh, frozen, pasteurized or co-administered with
formula (Contreras-Lemus et al. 1992
, El-Mohandes et al. 1995
, Hylander et al. 1998
,
Narayanan et al. 1980
, 1983
and 1984
). The devastating
acute gastrointestinal inflammatory disease in premature infants, NEC,
is reportedly a less frequent occurrence when the prior diet was human
milk compared with formula or no milk (Yu et al. 1981
).
Lucas and Cole (1990)
reported a markedly lower
incidence of NEC in a large nonrandomized study of hospitalized
premature infants fed human milk exclusively or partially, compared
with formula only. That study reported clinical cases as well as
confirmed cases (via surgical or autopsy specimen); in both
circumstances, the incidence of NEC was significantly lower in
premature infants fed human milk, even if they received supplements of
donor human milk or formula. Because that study was conducted in the
early 1980s, the infants received only unfortified human milk. A
follow-up randomized trial investigated the incidence of sepsis and
NEC in premature infants fed multinutrient-fortified human milk
compared with partially supplemented human milk (containing only
additional phosphorus, sodium and vitamins) (Lucas et al. 1996
). The study was complicated by the large quantity of
preterm formula given to infants because of poor maternal milk
production (Schanler 1996
). Thus, the study was unable
to evaluate exclusive human milk feeding. The study reported no
significant differences in the incidence of sepsis or NEC. However,
when both outcomes were grouped together (sepsis plus NEC), the infants
fed multinutrient-fortified human milk had a greater incidence of
the combined morbidities than the infants fed partially supplemented
human milk. It is difficult to draw specific conclusions regarding the
risks of sepsis and NEC from that investigation until a confirmatory
investigation of exclusive fortified human milk feeding or a
dose-response evaluation is conducted.
A recent investigation of feeding strategies in premature infants (time
of initiation, method of tube-feeding and type of milk fed) is
pertinent to the above observations (Schanler et al. 1999b
). Of all of the strategies investigated, the study
outcomes were most affected by the type of milk fed, specifically, the
quantity of human milk received. The average (and cumulative) intake of
human milk (predominantly fortified human milk) was associated
significantly with less need for parenteral nutrition; more rapid
attainment of complete tube-feeding; better feeding tolerance; lower
incidence of positive blood cultures, late-onset sepsis episodes
and NEC; less need for antibiotics; and a shorter duration of
hospitalization (Schanler et al. 1999a
). Late-onset
sepsis and NEC occurred in 31 and 2%, respectively, of infants fed
predominantly fortified human milk compared with 48 and 13%,
respectively, in infants fed preterm formula. The study also reported
that the more human milk consumed, the lower the number of episodes of
late-onset sepsis and/or the number of positive blood cultures
(Schanler et al. 1999a
). These results differ from the
multicenter study of fortified vs. partially supplemented human milk by
such a magnitude that further investigations are mandated.
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Intestinal responses to feeding |
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TOPINTRODUCTIONHuman milk and host...Intestinal responses to feedingSUMMARYREFERENCES |
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). Feeding premature infants (gestational age 28 wk, birth
weight ~1 kg) small volumes of milk, ~20 mL/(kg·d), beginning at
4 d of age appears to stimulate endogenous lactase activity, which
remains greater until d 50 compared with that of infants receiving only
parenteral nutrition for 14 d (Shulman et al. 1998a
). Human milk increases the effect of milk on endogenous
lactase activity (Shulman et al. 1998a
).
Gastrointestinal permeability also appears to be affected by human
milk. Premature infants, ~28 wk gestation with birth weights of ~1
kg, have lower permeability than infants fed formula (Shulman et al. 1998b
). Postnatal age and the receipt of glucocorticoids
antenatally enhance the effect of human milk on gastrointestinal
permeability (Shulman et al. 1998b
). Thus, human milk
may modify the gastrointestinal tract in such a way that the barrier to
infectious agents is protected. |
SUMMARY |
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TOPINTRODUCTIONHuman milk and host...Intestinal responses to feedingSUMMARYREFERENCES |
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 Support by the National Institute of Child Health and Human Development, Grant No. RO-1-HD-28140 and the General Clinical Research Center, Baylor College of Medicine/Texas Children’s Hospital Clinical Research Center, Grant No. MO-1-RR-00188, National Institutes of Health is acknowledged. Partial funding also has been provided from the USDA/ARS under Cooperative Agreement No. 58–6250-6–001. This work is a publication of the USDA/ARS Children’s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine and Texas Children’s Hospital, Houston, TX. The contents of this publication do not necessarily reflect the views or policies of the USDA, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government.
3 Abbreviations used: Ig, immunoglobulin; NEC, necrotizing enterocolitis; sIgA, secretory immunoglobulin A.
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REFERENCES |
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TOPINTRODUCTIONHuman milk and host...Intestinal responses to feedingSUMMARYREFERENCES |
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1.
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3. Eibl M. M., Wolf H. M., Furnkranz H., Rosenkranz A. Prevention of necrotizing enterocolitis in low-birth-weight infants by IgA-IgG feeding. N. Engl. J. Med. 1988;319:1-7[Abstract]
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Narayanan I., Prakash K., Verma R. K., Gujral V. V. Administration of colostrum for the prevention of infection in the low birth weight infants in a developing country. J. Trop. Pediatr. 1983;29:197-200
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28. Shulman R. J., Schanler R. J., Lau C., Heitkemper M. A., Ou C.-N., Smith E. O. Early feeding, antenatal glucocorticoids, and human milk decrease intestinal permeability in preterm infants. Pediatr. Res. 1998b;44:519-523[Medline]
29. Stoll B. J., Gordon T., Korones S. B., Shankaran S., Tyson J. E., Bauer C. R., Fanaroff A. A., Lemons J. A., Donovan E. F., Oh W., Stevenson D. K., Ehrenkranz R. A., Papile L.-A., Verter J., Wright L. L. Late-onset sepsis in very low birth weight neonates: a report from the National Institute of Child Health and Human Development Neonatal Research Network. J. Pediatr. 1996;129:63-71[Medline]
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