Nutrition of the Premature Infant
Presented during the
XXI European Congress of
Perinatal Medicine, Istanbul
Thursday, 11 September 2008
10:45 - 12:30 / Hall A
Thursday, 11 September 2008 10:45 - 12:30
Prof. J.B. (Hans) Goudoever, Netherlands
Allergy Prevention During Pregnancy: The Role of Nutrition
Prof. Seppo Salminen, Finland
Nutritional Needs of the Premature Infant: What do We Know?
Prof. J.B. (Hans) Goudoever, Netherlands
Personalized Nutrition of the Premature Infant
Prof. Staffan Polberger, Sweden
Allergy Prevention During Pregnancy:
The Role of Nutrition
Prof. Seppo Salminen,
Functional Foods Forum, University of Turku,
Finland and Universität Bodenkultur,
The western societies are faced with increased allergic eczema, other studies have failed to support this. One
diseases. This phenomenon is also recognised in reason lies behind the probiotic strain used in particular
the paediatric population. Evidence for programming populations: specific strain differences and method-
effects by early nutrition has been established in ological differences may be causes of confusion.
several epidemiological and experimental studies. The term “probiotic” is often used inappropriately to
Nutrition in the foetal period has accordingly been include bacterial strains with no documented immuno-
shown to influence the risk of atopic and other diseases modulatory capacity, no impact on microbiota compo-
of the infant later in life. Mother’s nutrition, especially sition and activity or no controlled human studies to
during pregnancy and breastfeeding, is of great impor- support the claims. Probiotics have been linked to a
tance. Dietary counselling towards a healthy balanced number of beneficial health effects, many of which may
diet is the basic target during pregnancy. Other targets be mediated by effects on host immune responses.
are dependent on atopic diseases in parents or siblings Administration of probiotics from the prenatal period
and the consequent risk of atopic diseases to the infant. through to the first months of life has been shown
For atopic diseases a major risk factor is deviated to lead to a reduced incidence of atopic eczema or
microbiota. Especially significant is the state of mothers’ IgE-associated eczema. Administration of probiotics to
microbiota prior to and immediately after birth as the the pregnant mother and to the infants during the first
first inoculum and breastfeeding significantly influ- months of life also influence the development of infant
ence the development of microbiota in the newborn Bifidobacterium microbiota. Since maternal intestinal
infant. This source of exposure to microbes through the microbiota at birth is a known source of infant gut
developing intestinal microbiota has been identified as microbes, it appears feasible that administering specific
the stimulus for normal development of the immune defined probiotics or prebiotics to the mother during
system. Aberrancies in the early gut microbiota develop- pregnancy may beneficially influence the development
ment may lead to changes in immune responsiveness of infant Bifidobacterium microbiota. Especially the
and subsequent development of disorders. Altered administration of specific probiotic strains Lactobacil-
intestinal microbiota has been demonstrated to precede lus rhamnosus GG or Bifidobacterium lactis to mothers
the development of atopic eczema in infants. In particu- during late pregnancy may influence the transfer of
lar, species composition differences in the Bifidobac- microbiota from the mother to infant and the coloni-
terium microbiota and deviations in Clostridum micro- zation of their infants by the genus Bifidobacterium
biota have been associated with an increased risk of directing the development towards the direction of
allergic disease. Furthermore, the transferred and further healthy breast-fed infant microbiota and avoidance of
developed bifidobacteria isolated from infants either be- atopic eczema in early years of life. This is an important
coming later allergic or suffering from allergies possess target which has been also recognized by scientific
different adhesion and immune modulatory properties bodies. The evidence has been reviewed in a recent
compared to bifidobacteria from healthy infants. meta-analysis and also in recommendations for
The transfer of microbiota from mothers to their new- probiotic use in the United States.
born is significantly influenced by the diet and nutritional
habits of the mother prior to delivery. These define also
the balance of microbiota in the mother. The proposed
role of microbial colonization in the development of
childhood diseases including atopic diseases provides
a rationale for therapies (?Nutritional interventions?)
aimed at modulation of the first microbial inoculum and
the early development of the gut microbiota.
This rationale has addressed the effects of probiotic
bacteria on immune development and their role in the
treatment and prevention of allergic disease. Although
there is a sound theoretical basis for anticipating ben-
efits, there are conflicting results. Furthermore, although
several studies show a benefit in prevention of atopic
Nutritional needs of premature
infant: What do we know?
Prof. J. B. (Hans) Goudoever
Sophia Children’s Hospital
Erasmus Medical Center
Rotterdam, The Netherlandss
References Recent developments in neonatal care have
increased survival rates of preterm babies,
Floch M, Walker A, Guandalini S, Hibbert M, Gorbach S, Surawicz C,
Sanders ME, Garcia-Tsao G, Quigley E, Isolauri E, Fedorak C, Diele- but has also increased the number of infants
man L. Recommendations for probiotic use 2008. J Clin Gastroenterol with neurodevelopmental deficits in later life.
Recently we have shown that one out of eight
Gueimonde M, Sakata S, Kalliomäki M, Isolauri E, Benno Y, Salminen of the infants born prematurely 20 years ago,
S. Effect of maternal consumption of lactobacillus GG on transfer
and establishment of fecal bifidobacterial microbiota in neonates.
had moderate to severe problems in cognitive or
J Pediatr Gastroenterol Nutr. 2006;42:166-70. neurosensory functioning1 Adequate nutritional
support in early postnatal life of preterm infants
Huurre A, Laitinen K, Rautava S, Korkeamäki M, Isolauri E. Impact of
maternal atopy and probiotic supplementation during pregnancy on has been associated with improved functional
infant sensitization: a double-blind placebo-controlled study. Clin Exp outcome2. Thus, nutrition in the first few weeks
Allergy. 2008 May 7.
of life should deserve a lot of attention from the
Huurre A, Kalliomäki M, Rautava S, Rinne M, Salminen S, Isolauri E. professionals taking care of these infants.
Mode of delivery - effects on gut microbiota and humoral immunity.
Neonatology. 2008;93:236-40. The optimal supply of nutrients to premature
Isolauri E, Kalliomäki M, Laitinen K, Salminen S. Modulation of the
infants should be based upon the supply the
maturing gut barrier and microbiota: a novel target in allergic disease. foetus receives in utero, while allowing for the
Curr Pharm Des. 2008;14:1368-75. different circumstances premature infants face
Kalliomäki M, Salminen S, Poussa T, Isolauri E. Probiotics during in the NICU. However, hardly anything is known
the first 7 years of life: a cumulative risk reduction of eczema in about the umbilical supply of the foetus so it is
a randomized, placebo-controlled trial. J Allergy Clin Immunol.
hard to estimate the exact needs.
Lee J, Seto D, Bielory L. Meta-analysis of clinical trials of probiotics Consequently, the composition of the nutrition
for prevention and treatment of pediatric atopic dermatitis. J Allergy which is provided to the premature infant is
Clin Immunol. 2008;121:116-121.
mainly based on the composition of human milk
Piirainen T, Isolauri E, Lagström H, Laitinen K. Impact of dietary and the infants’ presumed needs for growth.
counselling on nutrient intake during pregnancy: a prospective cohort
study. Br J Nutr. 2006;96:1095-104. Adequate nutrition starts with the provision
of parenteral nutrition from postnatal day 1
onwards. In utero, the foetus receives glucose,
amino acids and, depending on the gestational
age, an increasing amount of lipids. Thus, the
immature foetus receives a high amino acid
nutritional supply, whereas the preterm newborn
receives a fat dominated nutritional supply.
Increasing amino acid intake just after birth
results in a faster regain of birth weight and
improved nitrogen balance by an increased rate
of protein synthesis3. Our recent studies show
an impressive effect of early amino acid supply
on anti-oxidant defense mechanisms including
Although enteral nutrition should prevail,
tolerance is a major problem for preterm
infants. Early enteral feeding with relatively
small amounts has been shown to reduce the
incidence of necrotising enterocolitis5. Some data
show an advantage of hydrolyze formula over
regular formula with regard to advancement of
of the Premature Infant
Prof. Staffan Polberger
Neonatal Intensive Care Unit
Department of Paediatrics
enteral nutrition6. Additional growth factors to The increasing number of surviving extremely preterm
improve intestinal function has not been proven infants with gestational age from 23 weeks and birth
beneficial in infants, although good results have weights from 400 grams yields a new challenge to neo-
been obtained from animal studies7,8. natal nutrition. The vast majority of extremely low birth
weight (ELBW; < 1000 g) infants will survive if they are
In conclusion, parenteral and enteral nutrition in
born and taken care of at a hospital with a tertiary neo-
early postnatal life should be of major interest to
natal intensive care unit. Preterm infants should be given
all who take care of preterm infants. Although
optimal nutrition for brain growth and development.
enteral nutrition is the preferred way, tolerance is
Nutrition during the vulnerable preterm period, preferably
a huge problem, which is still largely unresolved.
based on human milk, shall lead to adequate growth,
at least corresponding to the intrauterine growth rate.
In Sweden, an individualized feeding system has been
1. Hille, E.T. et al. Functional outcomes and participation
in young adulthood for very preterm and very low developed during the last 10-15 years. Most ELBW
birth weight infants: the Dutch Project on Preterm and infants are fed according to the scheme: 1. Mother´s
Small for Gestational Age Infants at 19 years of age.
Pediatrics 120, e587-95 (2007).
own milk (preferred), 2. Banked milk (if mother’s milk is
not available), 3. Preterm infant formula (if human milk
2. Lucas, A., Morley, R. & Cole, T.J. Randomised trial
of early diet in preterm babies and later intelligence is not available), 4. Supplementary parenteral nutrition
quotient. Bmj 317, 1481-7 (1998). (starting at birth).
3. te Braake, F.W., van den Akker, C.H., Wattimena, D.J.,
Huijmans, J.G. & van Goudoever, J.B. Amino acid There is a trend to a more “aggressive” nutrition of
administration to premature infants directly after birth.
J Pediatr 147, 457-61 (2005). preterm infants, i.e. initiating nutrition early after birth
including administration of not only intravenous glucose
4. van den Akker, C.H. et al. Albumin synthesis in premature
neonates is stimulated by parenterally administered but also amino acids and lipids immediately after birth
amino acids during the first days of life. Am J Clin Nutr or during the first day of life. Enteral feeding, preferably
86, 1003-8 (2007).
with human milk, is also started during the first 2-4
5. Berseth, C.L., Bisquera, J.A. & Paje, V.U. Prolonging small hours of life.
feeding volumes early in life decreases the incidence of
necrotizing enterocolitis in very low birth weight infants.
Pediatrics 111, 529-34 (2003). There is growing evidence that human milk is superior
6. Mihatsch, W.A., Franz, A.R., Hogel, J. & Pohlandt, over infant formula for all newborn infants including the
F. Hydrolyzed protein accelerates feeding advancement ELBW infants. Human milk confers nutritional and
in very low birth weight infants. Pediatrics 110,
1199-203 (2002). non-nutritional advantages, and there is now a worldwide
trend using more human milk for feeding of preterm
7. Burrin, D.G., Wester, T.J., Davis, T.A., Amick, S. & Heath,
J.P. Orally administered IGF-I increases intestinal mucosal infants over infant formula. Outcome data support im-
growth in formula-fed neonatal pigs. Am J Physiol 270, proved neurological development by human milk, even
if the human milk intake has been limited to only a few
8. Corpeleijn, W.E. et al. Effect of enteral IGF-1 weeks during the vulnerable preterm period.
supplementation on feeding tolerance, growth, and gut
permeability in enterally fed premature neonates.
J Pediatr Gastroenterol Nutr 46, 184-90 (2008).
Unfortunately, but still in widespread use over the world References
is the misconception that human milk has a predictable
1. Ziegler EE: Breast-milk fortification. Acta Paediatr 2001;90:720-723.
and uniform composition. However, several studies have
underlined the enormous variation in nutrient composi- 2. Heiman H, Schanler RJ: Enteral nutrition for premature infants:
The role of human milk. Semin Fetal Neonatal Med 2007;12:26-34.
tion of human milk, particularly fat and to a less extent
protein. There is a variation between mothers, during the 3. Michaelsen KF, Skafte L, Badsberg JH, Jørgensen M: Variation
in macronutrients in human bank milk: Influencing factors and
course of lactation, during individual meals and also as implications for human milk banking. J Pediatr Gastroenterol Nutr
a consequence of varying pumping techniques. 1990;11:229-239.
4. Polberger S, Räihä NCR, Juvonen P, Moro GE, Minoli I, Warm A:
To account for this fact, a system with routine macronu- Individualized protein fortification of human milk for preterm infants:
trient analyses of the milk based on infra-red technique is Comparison of ultrafiltrated human milk protein and a bovine whey
fortifier. J Pediatr Gastroenterol Nutr 1999;29:332-338.
used once a week, allowing for optimal intakes of protein
and energy. Analyses are always performed on 24-hour 5. Omarsdottir S, Casper C, Åkerman A, Polberger S, Vanpée M:
collections as spot samples can not be used due to the Breast milk handling routines for preterm infants in Sweden:
a national cross-sectional study. Breastfeed Med 2008 (in press).
enormous meal-to-meal-variation. Also, all banked milk is
analyzed, and the most protein-rich milk is chosen for a
newborn ELBW infant.
To further reduce the variation in nutrient intake of
ELBW infants, mother’s own milk is given in chronologi-
cal order, i.e. in the order it was pumped. Also, all milk
is mixed in 24-hour collections before being given or
frozen. This will substantially reduce the day-to-day and
meal-to-meal-variation in nutrient content, which is likely
to increase the gut tolerance.
When the volumes after a few weeks can not be further
increased, the milk is fortified if a computerized calcu-
lation has shown that the protein and secondly, energy
intakes need to be further increased. Parenteral nutri-
tion is discontinued when the enteral intake constitutes
75-80% of the total volume intake. The goal is to reach
daily protein and energy intakes of 3,5-4 g/kg and 110-
120 kcal/kg, respectively. To further asses the metabolic
capacity to utilize the protein given, markers, e.g. serum
urea and transthyretin are evaluated. Growth is moni-
tored by regular measurements of weight, crown-heel
length and head circumference, preferably by the
same person each time, and fortification is continued
throughout the tube-feeding period until breast-feeding
is initiated before discharge.