NZ719159B2 - Lipid composition for improving body composition during catch-up growth - Google Patents
Lipid composition for improving body composition during catch-up growth Download PDFInfo
- Publication number
- NZ719159B2 NZ719159B2 NZ719159A NZ71915914A NZ719159B2 NZ 719159 B2 NZ719159 B2 NZ 719159B2 NZ 719159 A NZ719159 A NZ 719159A NZ 71915914 A NZ71915914 A NZ 71915914A NZ 719159 B2 NZ719159 B2 NZ 719159B2
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- New Zealand
- Prior art keywords
- lipid
- infants
- infant
- growth
- adipose tissue
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- 229940062780 lacto-N-neotetraose Drugs 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N lactose group Chemical group OC1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@H](O)[C@@H](O)[C@@H](O)[C@H](O2)CO)[C@H](O1)CO GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
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Abstract
The invention relates to nutritional compositions comprising specifically designed lipid globules that are especially suited for preterm infants, small for gestational age infants and infants with retarded growth due to physical or mental stress after birth, for promoting catch-up growth and/or for use in improving body composition, improving adipose tissue distribution, decreasing visceral adipose tissue based on body weight and/or on total adipose tissue, and/or decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in such infants, and/or providing nutrition to such infants. In a particular embodiment the nutritional composition further comprises 2.1 to 4.1 g protein per 100 kcal and 1.7 to 3.3 g protein per 100 ml. use in improving body composition, improving adipose tissue distribution, decreasing visceral adipose tissue based on body weight and/or on total adipose tissue, and/or decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in such infants, and/or providing nutrition to such infants. In a particular embodiment the nutritional composition further comprises 2.1 to 4.1 g protein per 100 kcal and 1.7 to 3.3 g protein per 100 ml.
Description
Lipid composition for improving body composition during catch-up growth
FIELD OF THE INVENTION
The invention s to nutritional compositions for preterm or low birth weight infants
BACKGROUND OF THE INVENTION
Human milk is generally recognized as the ideal feeding for infants due to its overall nutritional
composition. For a preterm infant and/or infant small for gestational age (SGA infant), however,
the milk of their own mother does not always meet their complete nutritional needs, even though
1O the milk of mothers of preterm infants appears to be d to the specific needs of preterms.
Therefore, for these infants special nutritional formulae have been designed and marketed, which
differ in composition from standard infant formula. lly such preterm formulae have a
higher energy and n content, to enable an increased growth rate. A review on the
ESPGHAN nutritional guidelines for such formulae is given in Agostoni et al, JPGN 2010,
50 285—91.
After birth, initially these preterm and/or SGA infants grow more rapidly than term infants. The
growth patterns of SGA infants compensate for the growth retardation which they have
developed in utero and this compensation by a sudden spurt of growth is known as ”catch-up
2O ”. It is desirable to ensure that reduced growth is compensated, but is also important that
catch-up growth should not be ive as there are indications that periods of very rapid and/or
very extensive up growth, particularly during infancy, may be linked with a risk of future
obesity and/or diabetes type 2. It is also important that during catch-up growth no excessive
e tissue, in ular Visceral adipose tissue, is formed.
s to a method of increasing lean body mass and reducing fat body mass
in infants, said method comprising administration to an infant a nutritional formula comprising a
source of docosahexaenoic acid (DHA) and arachidonic acid (ARA) without impacting the total
overall growth of the infant. This method is disclosed to be especially useful in preterm infants.
WO 17 relates to a method for enhancing the growth of preterm infants involving the
administration of certain long chain polyunsaturated fatty acids (LC-PUFA). It is preferred that
2014/050761
the infants are administered an infant formula containing a combination of DHA and ARA.
relates to a nutritional formulation comprising an n3 LC—PUFA, a prebiotic
fibre and a probiotic bacterial strain to promote catch-up growth in young mammals whose
growth has been retarded because the young mammal has been subjected to physical or mental
stress. discloses a human milk fortifier with DHA for use in preventing
visceral adiposity. WO 27259 discloses a nutritional composition for infants and/or
toddlers comprising a lipid component which has a large lipid globule size. The composition can
be used to prevent obesity and/or improve body composition later in life. A similar good growth
and development early in life, with no effect on adipose tissue mass early in life was observed,
1O which was found to be advantageous for infants and young children in general.
WC 73486 s to the use of specifically designed lipid for an early in life diet for
ing the pment of a healthy body ition, in ular prevention of obesity,
later in life.
SUMMARY OF THE INVENTION
Using a model with intrauterine growth restricted (IUGR) animals, which is representative for
infants undergoing catch up growth, in particular for SGA infants and/or for preterm infants, the
inventors found that a ional composition comprising large lipid globules and/or lipid
globules coated with phospholipids ated globules) promoted controlled catch-up growth
2O after birth.
Animals having enced catch-up growth on a standard, control diet with small lipid
globules and no phospholipid coating developed an increased absolute amount and an increased
relative amount of adipose , in particular visceral adipose tissue, during up growth.
Surprisingly, in animals having experienced catch-up growth on the present experimental diet
with large lipid globules and/or PL-coated lipid globules, an improved body ition was
observed compared to animals receiving a control formula. The improved body composition
observed was revealed as a decreased absolute amount and a decreased relative amount of
adipose tissue (based on body weight), and most importantly especially a decreased relative
amount of visceral adipose tissue (based on body weight or total adipose tissue mass), while on
the other hand the relative amount of subcutaneous adipose tissue was sed. In the context
of the present invention this is called ‘promoting controlled catch-up growth’. Even more
surprisingly, the decreased relative amount of visceral adipose tissue mass concomitant with
increased relative amount of aneous adipose tissue mass observed during catch-up
growth with the experimental diet was highest in the IUGR rats, and higher than compared to
l rats or sham operated rats having consumed the experimental diet. This shows that the
experimental diet is especially beneficial and more effective in this specific group.
Preterm and/or SGA infants, as well as other infants experiencing catch-up growth (e.g.
escing infants), already have an extra risk for development of visceral obesity, insulin
resistance and/or metabolic disease. However, the presence of subcutaneous adipose tissue is
of crucial importance for a healthy development of growth in infants, especially in preterm
and/or SGA infants. Subcutaneous fat is not associated with health problems, and is
furthermore ary for a good start in life in providing energy reserves, and thermal and
mechanical protection in this vulnerable group. Therefore a mere reduction in overall adipose
tissue mass and/or an se in lean body mass alone is not a way to solve the problems of
increased risk of developing obesity and associated ers in infants, and especially not in
preterm and/or SGA infants. The reduced amount of al adipose tissue, while having an
increase in subcutaneous adipose tissue, as specifically observed during catch-up growth in the
IUGTR group, is therefore very ageous for infants undergoing catch up growth, such as
preterm infants, SGA infants, and/or infants with retarded growth due to physical or mental
stress after birth (e.g. convalescing infants).
DETAILED DESCRIPTION OF THE INVENTION
Thus in particular embodiments provided herein is:
(1) Use of lipid for the ation of a ional composition for improving adipose
tissue distribution in an infant selected from the group consisting of preterm infants, small for
gestational age infants and s with retarded growth due to physical or mental stress after
birth, wherein the lipid is present in lipid globules, having:
(a) a volume-weighted mode diameter of at least 1.0 µm; and
(b) a phospholipid coating, wherein the nutritional composition comprises at least 0.5 wt.%
phospholipids based on total lipid,
and wherein the nutritional ition further ses 2.1 to 4.1 g protein per 100 kcal and
1.7 to 3.3 g protein per 100 ml.
(followed by page 3A)
(2) The use ing to (1), wherein ing adipose tissue distribution occurs during
or directly after catch-up growth.
(3) The use according to (1) or (2), wherein the lipid globules have a volume-weighted
mode diameter of at least 1.0 µm.
(4) The use according to (3), wherein the lipid globules have a volume-weighted mode
er of 3.0 to 8.0 µm.
(5) The use according to any one of (1) to (4), wherein the phospholipids are derived from
milk.
(6) The use according to any one of (1) to (5), wherein the infant is a small for gestational
age infant.
(7) The use according to (6), wherein the small for gestational age infant is an intrauterine
growth restricted infant.
(8) The use according to any one of (1) to (7), wherein the nutritional composition
comprises 0.3 to 0.7 wt.% arachidonic acid, based on total lipid.
(9) An infant a selected from a preterm formula, a low birthweight formula or a
tric formula for catch-up growth sing protein, carbohydrates and lipid, n:
(i) the caloric density is 50 to 200 kcal per 100 ml;
(ii) lipid is present in 4.4 to 6.0 g per 100 kcal;
(iii) protein is present in 2.1 to 4.1 g per 100 kcal and in 1.7 to 3.3 g per 100 ml;
(iv) carbohydrates are present in 10 to 12 g per100 kcal,
(v) the lipid is present in lipid globules, having:
(a) a volume-weighted mode diameter of at least 1.0 µm; and
(b) a phospholipid coating, wherein the composition comprises at least 0.5 wt.%
phospholipids based on total lipid.
(followed by page 3B)
(10) The infant formula according to (9), which is a preterm formula or a low eight
formula, comprising 2.6 to 3.4 g protein per 100 kcal and 1.7 to 3.1 g protein per 100 ml.
(11) The infant formula according to (9), which is a paediatric formula for catch-up ,
comprising 2.4 to 2.8 g protein per 100 kcal and 1.7 to 3.1 g protein per 100 ml.
(12) The infant formula according to any one of (9) to (11), comprising 0.3 to 0.7 wt.%
arachidonic acid, based on total lipid.
(13) The infant formula according to any one of (9) to (12), comprising 0.3 to 0.5 wt.%
docosahexaenoic acid, based on total lipid.
(14) A non-therapeutic method for providing nutrition to an infant selected from the group
consisting of preterm infants, small for gestational age infants and infants with retarded growth
due to physical or mental stress after birth, comprising administering the nutritional
composition according to any one of (9) to (13) to said infant.
Other aspects and embodiments of the ion are also described herein for completeness.
Thus the present ion concerns a method for promoting controlled catch-up growth in an
infant selected from the group ting of preterm infants, small for ional age infants
and infants with retarded growth due to physical or mental stress after birth, comprising
administering to said infant a nutritional composition comprising lipid, n the lipid is
present in lipid globules having:
(a) a volume-weighted mode diameter of at least 1.0 m; and/or
(b) a phospholipid coating, n the nutritional composition comprises at least 0.5
wt.% phospholipids based on total lipid.
(followed by page 4)
Thus, the invention concerns a method for promoting controlled catch-up growth in an infant
selected from the group consisting of m infants, small for gestational age s and
infants with retarded growth due to physical or mental stress after birth, comprising
stering to said infant a nutritional composition comprising lipid, wherein the lipid is
present in lipid es, having a volume-weighted mode diameter of at least 1.0 pm.
The invention also concerns a method for ing controlled catch-up growth in an infant
selected from the group consisting of preterm infants, small for gestational age infants and
infants with retarded growth due to physical or mental stress after birth, comprising
administering to said infant a nutritional composition comprising lipid, wherein the lipid is
1O present in lipid globules, having a phospholipid coating, wherein the ional composition
comprises at least 0.5 wt.% phospholipids based on total lipid.
The invention also ns a method for promoting controlled catch-up growth in an infant
selected from the group ting of preterm infants, small for gestational age infants and
infants with retarded growth due to physical or mental stress after birth, comprising
administering to said infant a ional composition comprising protein, carbohydrates and
lipid, wherein the lipid is present in lipid globules, having a volume-weighted mode diameter of
at least 1.0 um, and having a phospholipid coating, wherein the nutritional composition
comprises at least 0.5 wt.% phospholipids based on total lipid.
2O In other words, the t invention concerns the use of lipid for the preparation of a nutritional
composition for promoting controlled catch-up growth in an infant selected from the group
consisting of preterm s, small for gestational age infants and infants with retarded growth
due to physical or mental stress after birth, wherein the lipid is present in lipid globules, having:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the nutritional ition comprises at least 0.5
wt.% phospholipids based on total lipid.
Thus, the invention concerns the use of lipid for the preparation of a nutritional compositions for
promoting controlled catch-up growth in an infant selected from the group consisting of preterm
infants, small for gestational age infants and infants with retarded growth due to physical or
WO 65193
mental stress after birth, wherein the lipid is t in lipid globules, having a volume-weighted
mode diameter of at least 1.0 um.
The ion also concerns the use of lipid for the preparation of a nutritional compositions for
promoting controlled catch-up growth in an infant selected from the group consisting of preterm
infants, small for gestational age infants and infants with retarded growth due to physical or
mental stress after birth, wherein the lipid is present in lipid es, having a phospholipid
coating, wherein the nutritional composition comprises at least 0.5 wt.% phospholipids based on
total lipid.
The invention also concerns the use of lipid for the preparation of a nutritional compositions for
1O promoting controlled catch-up growth in an infant selected from the group consisting of preterm
infants, small for gestational age infants and infants with retarded growth due to al or
mental stress after birth, wherein the lipid is present in lipid globules, having a volume-weighted
mode diameter of at least 1.0 um, and having a phospholipid coating, wherein the nutritional
composition comprises at least 0.5 wt.% phospholipids based on total lipid.
The present invention can also be worded as a nutritional composition comprising lipid, wherein
the lipid is t in lipid globules, having:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the nutritional composition comprises at least 0.5
2O wt.% phospholipids based on total lipid,
for use in promoting controlled catch-up growth in an infant selected from the group consisting
of preterm infants, small for ional age infants and s with retarded growth due to
physical or mental stress after birth.
Thus, the invention concerns a nutritional compositions comprising lipid, wherein the lipid is
present in lipid es, having a volume-weighted mode diameter of at least 1.0 um, for use in
promoting controlled catch-up growth in an infant selected from the group consisting of m
infants, small for gestational age infants and s with retarded growth due to al or
mental stress after birth.
The invention also concerns a nutritional composition comprising lipid, wherein the lipid is
present in lipid globules, having a phospholipid coating, wherein the nutritional composition
WO 65193 2014/050761
comprises at least 0.5 wt.% phospholipids based on total lipid, for use in ing controlled
catch-up growth in an infant selected from the group consisting of preterm infants, small for
gestational age infants and infants with ed growth due to physical or mental stress after
birth.
The invention also concerns a nutritional composition comprising lipid, wherein the lipid is
present in lipid globules, having a volume-weighted mode diameter of at least 1.0 um, and
having a phospholipid coating, wherein the nutritional composition comprises at least 0.5 wt.%
phospholipids based on total lipid, for use in promoting controlled catch-up growth in an infant
selected from the group consisting of preterm infants, small for gestational age infants and
1O infants with retarded growth due to physical or mental stress after birth.
Thus the t invention concerns a method for (i) improving body composition, (ii) improving
adipose tissue distribution, (iii) decreasing visceral adipose tissue based on body weight and/or
on total adipose tissue, and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous
adipose tissue, in an infant selected from the group consisting of m infants, small for
gestational age infants and infants with retarded growth due to al or mental stress after
birth, comprising administering to said infant a nutritional composition comprising lipid, wherein
the lipid is present in lipid globules having:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
2O (b) a phospholipid coating, wherein the nutritional ition comprises at least 0.5
wt.% phospholipids based on total lipid.
Thus, the invention ns a method for (i) ing body composition, (ii) improving
adipose tissue distribution, (iii) decreasing visceral adipose tissue based on body weight and/or
on total adipose tissue, and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous
adipose , in an infant ed from the group consisting of preterm infants, small for
gestational age infants and infants with retarded growth due to physical or mental stress after
birth, comprising stering to said infant a nutritional composition comprising lipid, wherein
the lipid is present in lipid globules, having a volume-weighted mode diameter of at least 1.0 um.
The invention also concerns a method for (i) improving body composition, (ii) improving
adipose tissue distribution, (iii) decreasing visceral adipose tissue based on body weight and/or
2014/050761
on total adipose tissue, and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous
adipose tissue, in an infant selected from the group consisting of m infants, small for
ional age infants and infants with retarded growth due to physical or mental stress after
birth, comprising administering to said infant a nutritional composition comprising lipid, wherein
the lipid is present in lipid globules, having a phospholipid coating, wherein the nutritional
composition comprises at least 0.5 wt.% phospholipids based on total lipid.
The invention also concerns a method for (i) improving body composition, (ii) improving
e tissue distribution, (iii) decreasing visceral adipose tissue based on body weight and/or
on total adipose , and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous
1O e tissue, growth in an infant selected from the group consisting of preterm infants, small
for gestational age s and s with retarded growth due to physical or mental stress after
birth, comprising administering to said infant a nutritional composition comprising protein,
carbohydrates and lipid, n the lipid is present in lipid globules, having a volume-weighted
mode diameter of at least 1.0 pm, and having a phospholipid coating, wherein the nutritional
composition ses at least 0.5 wt.% phospholipids based on total lipid.
In one embodiment, the method for (i) ing body composition, (ii) improving adipose
tissue distribution, (iii) decreasing visceral adipose tissue based on body weight and/or on total
adipose tissue, and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous adipose
2O tissue, in an infant selected from the group of preterm infants, small for gestational age infants
and infants with retarded growth due to al or mental stress after birth, is a non-therapeutic
method or a non-medical method.
In other words, the present invention concerns the use of lipid for the preparation of a nutritional
composition for (i) improving body composition, (ii) improving adipose tissue distribution, (iii)
decreasing visceral adipose tissue based on body weight and/or on total adipose tissue, and/or
(iv) decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in an infant
selected from the group consisting of preterm infants, small for gestational age s and
infants with retarded growth due to physical or mental stress after birth, wherein the lipid is
present in lipid globules, having:
2014/050761
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the nutritional composition comprises at least 0.5
wt.% phospholipids based on total lipid.
Thus, the invention concerns the use of lipid for the preparation of a nutritional itions for
(i) improving body composition, (ii) improving adipose tissue distribution, (iii) decreasing
visceral adipose tissue based on body weight and/or on total adipose , and/or (iv)
decreasing the ratio visceral adipose tissue to subcutaneous e tissue, in an infant selected
from the group consisting of preterm infants, small for gestational age infants and infants with
1O retarded growth due to physical or mental stress after birth, wherein the lipid is present in lipid
globules, having a volume-weighted mode diameter of at least 1.0 pm.
The invention also concerns the use of lipid for the preparation of a nutritional itions for
(i) improving body composition, (ii) improving adipose tissue distribution, (iii) decreasing
visceral adipose tissue based on body weight and/or on total adipose tissue, and/or (iv)
decreasing the ratio visceral adipose tissue to subcutaneous e tissue, in an infant selected
from the group consisting of preterm infants, small for gestational age infants and infants with
retarded growth due to physical or mental stress after birth, wherein the lipid is present in lipid
globules, having a phospholipid coating, wherein the nutritional composition ses at least
0.5 wt.% phospholipids based on total lipid.
2O The invention also concerns the use of lipid for the preparation of a nutritional compositions for
(i) improving body composition, (ii) improving adipose tissue distribution, (iii) decreasing
visceral adipose tissue based on body weight and/or on total e tissue, and/or (iv)
decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in an infant selected
from the group consisting of preterm s, small for gestational age infants and infants with
retarded growth due to physical or mental stress after birth, wherein the lipid is present in lipid
globules, having a volume-weighted mode diameter of at least 1.0 pm, and having a
phospholipid coating, wherein the nutritional composition comprises at least 0.5 wt.%
phospholipids based on total lipid.
The t invention can also be worded as a nutritional composition comprising lipid, wherein
the lipid is present in lipid globules, having:
(a) a -weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid g, wherein the nutritional composition ses at least 0.5
wt.% olipids based on total lipid,
for use in (i) improving body composition, (ii) improving e tissue distribution, (iii)
decreasing visceral e tissue based on body weight and/or on total adipose tissue, and/or
(iv) decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in an infant
selected from the group consisting of preterm infants, small for gestational age infants and
infants with retarded growth due to physical or mental stress after birth.
1O Thus, the invention concerns a nutritional compositions comprising lipid, wherein the lipid is
present in lipid globules, having a volume-weighted mode diameter of at least 1.0 um, for use in
(i) improving body composition, (ii) improving adipose tissue distribution, (iii) decreasing
visceral adipose tissue based on body weight and/or on total e tissue, and/or (iv)
decreasing the ratio visceral adipose tissue to subcutaneous adipose tissue, in an infant selected
from the group consisting of preterm infants, small for gestational age infants and infants with
retarded growth due to physical or mental stress after birth.
The invention also concerns a nutritional composition comprising lipid, wherein the lipid is
t in lipid globules, having a phospholipid coating, wherein the nutritional composition
comprises at least 0.5 wt.% olipids based on total lipid, for use in (i) improving body
2O composition, (ii) improving adipose tissue distribution, (iii) decreasing visceral adipose tissue
based on body weight and/or on total adipose tissue, and/or (iv) sing the ratio visceral
e tissue to subcutaneous adipose tissue, in an infant selected from the group consisting of
preterm infants, small for gestational age infants and infants with retarded growth due to physical
or mental stress after birth.
The invention also concerns a ional composition comprising lipid, wherein the lipid is
present in lipid globules, having a volume-weighted mode diameter of at least 1.0 um, and
having a phospholipid coating, wherein the nutritional composition comprises at least 0.5 wt.%
phospholipids based on total lipid, for use in (i) improving body composition, (ii) improving
adipose tissue distribution, (iii) sing visceral adipose tissue based on body weight and/or
on total adipose tissue, and/or (iv) decreasing the ratio visceral adipose tissue to subcutaneous
adipose , in an infant selected from the group consisting of preterm infants, small for
gestational age infants and infants with retarded growth due to physical or mental stress after
birth.
Preferably, the nutritional ition is an infant formula, more preferably a preterm formula,
low birthweight formula or paediatric a for catch-up growth, which is intended for
providing nutrition to an infant selected from the group consisting of preterm infants, small for
gestational age infants and infants with retarded growth due to al or mental stress after
birth.
1O In another aspect, the invention concerns an infant formula, more preferably a m formula,
low eight formula or paediatric formula for catch-up growth, which is intended for
providing nutrition to an infant selected from the group consisting of preterm infants, small for
gestational age infants and infants with retarded growth due to physical or mental stress after
birth. , a “preterm formula” is to be understood as an infant formula intended for and/or
especially designed for preterm infants. Herein, a “low birthweight formula” is to be understood
as an infant formula ed for and/or especially designed for small for gestational age infants.
Herein, ”
a “paediatric formula for catch-up growt is to be understood as an infant a
intended for and/or especially designed for infants with retarded growth due to physical or
mental stress after birth such as convalescent infants.
In another aspect, the invention concerns the use of the nutritional composition according to the
invention for providing nutrition to an infant selected from the group consisting of preterm
s, small for gestational age infants and infants with retarded growth due to physical or
mental stress after birth.
This aspect could also be worded as the use of lipid for the preparation of the nutritional
composition according to the invention for providing nutrition to an infant ed from the
group consisting of preterm infants, small for gestational age s and infants with ed
growth due to physical or mental stress after birth.
This aspect could also be worded as a method for ing nutrition to an infant selected from
the group consisting of preterm infants, small for gestational age infants and infants with
retarded growth due to physical or mental stress after birth, comprising stering the
nutritional composition according to the invention to said infant.
This aspect could also be worded as the nutritional composition according to the invention for
use in providing nutrition to an infant selected from the group consisting of preterm infants,
small for gestational age infants and infants with retarded growth due to physical or mental stress
after birth.
Target grow;
The present invention relates to a method for feeding preterm infants, small for gestational age
(SGA) infants, and/or infants with retarded growth due to physical or mental stress after birth,
preferably for feeding premature infants, small for gestational age (SGA) infants and/or
convalescent infants, more preferably for g preterm infants and/or small for gestational age
(SGA) s. A preterm infant relates to an infant born before the standard period of pregnancy
is completed, thus before 37 weeks pregnancy of the mother, i.e. before 37 weeks from the
beginning of the last menstrual period of the mother. Preterm infants are also referred to as
premature infants.
SGA infants are those whose birth weight lies below the 10th percentile for that gestational age.
Reasons for SGA can be several; for example, term or preterm infants can be born SGA because
they have been the subject of intrauterine growth restriction (IUGR). Many preterm infants are
also small for gestational age. ure and/or SGA infants include low birth weight s
(LBW infants), very low birth weight infants (VLBW infants), and ely low birth weight
infants (ELBW infants). LBW s are infants with a birth weight below 2500 g; this group
includes term infants born SGA. VLBW and ELBW infants are almost always born preterm and
are defined as s with a birth weight below 1500 g or 1000 g, respectively.
Infants with retarded growth due to physical or mental stress after birth are infants that need to
recover from a disease state after birth in the first year of life, thus from 0-12 months. Such
recovering s can also be referred to as convalescent infants.
Catch-up growth, also referred to as compensatory , is known in the art to be distinct from
r growth and is defined as the rated growth of subjects following a period of reduced
or lete growth or growth retardation. A practical definiton of catch-up growth is an
WO 65193
increase in weight above 0.67 Standard Deviation (SD) score, as for example can be visualised in
standard growth charts, suitably spanning the first 24 months of life of an infant, by crossing a
centile band. Reduced growth may occur due to nutrient deprivation, e.g. poor maternal nutrition
during pregnancy or lack of adequate oxygen supply to the fetus, leading to intrauterine growth
restriction, or poor nutrition during sickness or chronic s. Also preterm infants, which have
not enced intrauterine growth restriction but are delivered before the rd period of
pregnancy is completed, lly with a lower than average birth weight, usually exhibit catch-
up growth. Growth retardation can also occur due to al or mental stress, for example due
to a disease, in infants in the first year of life. Such infants experiencing growth retardation can
1O have been appropriate for gestational age (AGA) at birth. The body weights of subjects who
experienced reduced or incomplete growth or growth retardation will over time become similar
to those of subjects who did not ence such stress. Such a high compensatory growth rate
may result in overcompensation, where the normal weight is exceeded and the animal in suit
often develops excessive e tissue deposition during catch-up growth. Herein, “subject”
preferably refers to human, and “infant” preferably refers to “human infant”. Human infants are
defined as human subjects between 0 and 12 months of age.
The nutritional composition according to the present invention is thus especially beneficial for
preterm infants, small for gestational age infants and infants with retarded growth due to physical
or mental stress after birth, as those are likely to have experienced reduced or incomplete growth
2O and likely are experiencing or will ence catch-up growth. Thus, the target group for the
present invention is selected from preterm infants, small for gestational age infants (SGA infants,
including IUGR infants) and infants with retarded growth due to al or mental stress after
birth, preferably human infants. Preferably, the target group is selected from m infants and
SGA infants, more preferably SGA infants. A preferred group of SGA infants are the IUGR
(intrauterine growth restricted) infants.
ably, the nutritional composition is an infant formula, more preferably a preterm formula
or low birthweight formula or tric formula for catch-up growth, which is intended for
providing nutrition to an infant selected from the group consisting of preterm s, small for
gestational age infants and infants with retarded growth due to physical or mental stress after
birth.
2014/050761
Body adigose tissue distribution, visceral adigosity
The term ‘Visceral adiposity‘ refers to a condition wherein the subject has increased visceral
tissue mass. The term visceral adiposity is also referred to as visceral obesity, intra-abdominal
obesity or l y. Visceral adiposity is typically caused by (accumulation of) excessive
visceral tissue mass. Visceral tissue, also known as visceral fat, organ fat, abdominal fat,
peritoneal fat or central fat is normally located inside the peritoneal cavity as opposed to
subcutaneous fat which is found underneath the skin and intramuscular fat which is found
interspersed in skeletal muscles. Visceral fat includes mesenteric fat, perirenal fat and
retroperitoneal fat. Visceral fat stores can suitably be investigated by g techniques such as
1O computed tomography (CT), ic resonance g (MRI) and ultrasonography. Total
adipose tissue mass can be determined by DEXA (dual-energy X-ray absorptiometry). Internal
abdominal adipose tissue is a synonym for intra-abdominal adipose tissue or visceral adipose
tissue, and is the adipose tissue that surrounds the internal organs.
In the present invention, improving body composition or improving adipose tissue distribution
may encompass a se in visceral e tissue mass, based on body weight and/or based
on total adipose , an increase in subcutaneous adipose tissue mass, based on total e
tissue, and/or a decrease in the weight ratio of visceral adipose tissue to subcutaneous e
tissue. Thus, a reduction of total adipose tissue mass is not aimed for.
2O In one particular embodiment, the present invention is also for the prevention of, in particular
prevention of accumulation of, excessive visceral adipose tissue mass or for the prevention of
visceral adiposity. , the term “prevention” can also be referred to as ing the risk or
occurrence of” for example visceral adiposity. Herein, each of “preventing visceral adiposity”
ving body composition”, “improving adipose tissue distribution’,3 “decreasing visceral
adipose tissue mass”, “increasing subcutaneous adipose tissue mass”, and “decreasing the weight
ratio of visceral adipose tissue to subcutaneous e tissue”, is compared to the situation
regarding preterm infants, SGA infants and infants with retarded growth due to physical or
mental stress after birth which are not administered with a nutritional composition according to
the present invention, i.e. administered with a conventional nutritional composition. Thus, the
occurrence of visceral adiposity, the body composition, the adipose tissue distribution, the
visceral adipose tissue mass, the subcutaneous adipose tissue mass and/or the weight ratio of
visceral adipose tissue to subcutaneous adipose tissue is more like the situation regarding healthy
breast-fed term born infants with the same gestational age having a weight and size appropriate
for ional age.
The present nutritional composition comprises lipid in the form of lipid globules. Preferably
more than 95 wt.% of the lipid present in the nutritional composition is in the form of lipid
globules, ably more than 98 wt.% of the lipid present in the nutritional composition is in
the form of lipid globules. The lipid that is present in the nutritional composition provides
preferably 30 to 60 % of the total calories of the composition. More preferably the present
nutritional composition ses lipid providing 35 to 55 % of the total calories, even more
preferably the present composition comprises lipid providing 40 to 50 % of the total calories. Per
100 kcal, the nutritional composition preferably comprises 4.4 to 6.0 g lipid, more preferably 4.6
to 5.5 g lipid. When in liquid form, e.g. as a ready-to-feed liquid, the nutritional composition
preferably comprises 2.1 to 6.5 g lipid per 100 ml, more preferably 3.0 to 6.0 g per 100 ml. In
case the present nutritional composition is a preterm formula or low eight formula, it is
red that the composition comprises 3.0 to 5.0 g lipid per 100 ml, more ably 3.5 to 4.5
g per 100 ml. In case the t nutritional composition is a paediatric formula for catch-up
growth, it is preferred that the composition comprises 4.0 to 6.0 g lipid per 100 ml, more
preferably 4.5 to 5.5 g per 100 ml. Based on dry weight the nutritional composition preferably
comprises 10 to 50 wt.%, more preferably 12.5 to 40 wt.% lipid, even more preferably 19 to 32
wt.% lipid.
Lipids include polar lipids (such as phospholipids, glycolipids, sphingomyelin, and cholesterol),
monoglycerides, diglycerides, triglycerides and free fatty acids. ably the nutritional
composition comprises at least 75 wt.%, more preferably at least 85 wt.% triglycerides based on
total lipids.
The lipid that is present in nutritional composition ing to the invention preferably
comprises vegetable . The presence of vegetable lipids advantageously s an optimal
fatty acid profile, high in (poly)unsaturated fatty acids and/or more reminiscent to human milk
fat. Using lipids from cow’s milk alone, or other domestic mammals, does not provide an
optimal fatty acid profile. This less l fatty acid profile, such as a large amount of saturated
fatty acids, is known to result in increased risk of developing y. Preferably the present
composition comprises at least one, preferably at least two lipid sources selected from the group
consisting of linseed oil (flaxseed oil), rape seed oil (such as colza oil, low erucic acid rape seed
oil and canola oil), salvia oil, perilla oil, purslane oil, lingonberry oil, sea buckthorn oil, hemp
oil, sunflower oil, high oleic sunflower oil, safflower oil, high oleic safflower oil, olive oil, black
currant seed oil, echium oil, coconut oil, palm oil and palm kernel oil. ably the present
composition comprises at least one, preferably at least two lipid sources selected from the group
consisting of linseed oil, canola oil, coconut oil, sunflower oil and high oleic er oil.
Commercially available ble lipids are typically d in the form of a continuous oil
phase. When in liquid form, e.g. as a ready-to-feed liquid, the composition preferably ses
2.1 to 6.5 g vegetable lipid per 100 ml, more preferably 3.0 to 4.0 g per 100 ml. Based on dry
weight the present composition preferably comprises 10 to 50 wt.%, more preferably 12.5 to 40
wt.% vegetable lipid, even more preferably 19 to 30 wt.%. Preferably the composition comprises
50 to 100 wt.% vegetable lipids based on total lipids, more preferably 70 to 100 wt.%, even more
preferably 75 to 97 wt.%. It is noted therefore that the present composition also may comprise
non-vegetable lipids. Suitable and preferred non-vegetable lipids are further specified below.
LiQid globule size
According to the present invention, lipid is present in the composition in the form of lipid
globules, emulsified in the aqueous phase. The lipid globules according to a preferred
embodiment of the present ion have a volume-weighted mode diameter of at least 1.0 pm,
ably at least 3.0 pm, more preferably at least 4.0 pm, preferably a volume-weighted mode
diameter of 1.0 to 10 pm, more preferably 2.0 to 8.0 pm, even more preferably 3.0 to 8.0 pm,
most preferably 4.0 to 8.0 pm. More preferably, the lipid globules also have a size distribution in
such a way that at least 45 vol.%, preferably at least 55 vol.%, even more preferably at least 65
vol.%, even more ably at least 75 vol.% of the lipid globules has a diameter of 2 to 12 pm.
More preferably at least 45 vol.%, preferably at least 55 vol.%, even more preferably at least 65
vol.%, even more preferably at least 75 vol.% of the lipid es has a volume-weighted mode
diameter of 2 to 10 um. Even more preferably at least 45 vol.%, preferably at least 55 vol.%,
even more preferably at least 65 vol.%, even more preferably at least 75 vol.% of the lipid
globules has a volume-weighted mode er of 4 to 10 pm.
The volume percentage (volume % or vol.%) of lipid globules is based on the volume of total
lipid in the nutritional composition. The volume-weighted mode diameter s to the lipid
globule diameter which is the most present, based on the bution to the volume of total lipid,
or — in other words — the peak value in a graphic representation, having on the X-as the er
and on the Y-as the volume %. The volume of the lipid globule and its size distribution can
suitably be determined using a particle size analyzer such as a Mastersizer (Malvern Instruments,
Malvern, UK), for example by the method described in ski et al, 2001, Lait 81: 787-796.
Polar ligids
The present nutritional composition preferably comprises phospholipids (PL) and more
ably PL and other polar . Polar lipids are amphipathic of nature and include
glycerophospholipids, glycosphingolipids, sphingomyelin and/or cholesterol. Phospholipids are
the sum of glycerophospholipids and sphingomyelin. Polar lipids in the present invention relate
to the sum of glycerophospholipids, glycosphingolipids, sphingomyelin and cholesterol.
Preferably the polar lipids are present as a coating or outer layer of the lipid globules. The
presence of polar lipids as a coating or outer layer of the lipid globules was found to
advantageously further decrease adipose , in particular visceral adipose tissue. The
presence of polar lipids helps to maintain the lipid globules emulsified in the aqueous
ition. This is especially important when the lipid globule size is large.
Thus, in one embodiment according to the present invention the lipid globules are coated with a
layer of polar , preferably at least with phospholipids, wherein the nutritional composition
comprises at least 0.5 wt% phospholipids based on total lipid.. Such globules may be referred to
as “PL-coated es”. Thus preferably the lipid globules comprise a core and a coating. In this
embodiment, it is preferred that the core comprises vegetable lipid and preferably comprises at
least 90 wt.% triglycerides and more preferably essentially consists of triglycerides. The coating
preferably comprises phospholipids and optionally other polar lipids. Not all polar lipids that are
preferably present in the composition need arily be comprised in the coating, but
preferably a major part is. Preferably more than 50 wt.%, more preferably more than 70 wt,%,
even more preferably more than 85 wt.%, most preferably more than 95 wt.% of the polar lipids
that are present in the composition are comprised in the coating of lipid globules. Not all
vegetable lipids that are preferably present in the composition need necessarily be sed in
the core of lipid globules, but preferably a major part is, preferably more than 50 wt.%, more
preferably more than 70 wt.%, even more ably more than 85 wt.%, even more preferably
more than 95 wt.%, most preferably more than 98 wt.% of the ble lipids that are present in
the composition are comprised in the core of lipid es.
The present nutritional composition preferably comprises glycerophospholipids.
Glycerophospholipids are a class of lipids formed from fatty acids esterified at the hydroxyl
groups on carbon-l and carbon-2 of the backbone glycerol moiety and a negatively-charged
1O phosphate group attached to carbon-3 of the glycerol via an ester bond, and optionally a choline
group (in case of atidylcholine, PC), a serine group (in case of phosphatidylserine, PS), an
ethanolamine group (in case of phosphatidylethanolamine, PE), an inositol group (in case of
phosphatidylinositol, P1) or a glycerol group (in case of phosphatidylglycerol, PG) attached to
the ate group. Lysophospholipids are a class of phospholipids With one fatty acyl chain.
Preferably the present composition ns PC, PS, PI and/or PE, more preferably at least PC.
Preferably the glycerophospholipids comprise negatively charged phospholipids in particular PS
and/or PI. Negatively charged glycerophospholipids advantageously improve the stability of the
oil in water emulsion.
The present nutritional composition preferably comprises glycosphingolipids. The term
2O phingolipids as in the present invention particularly refers to glycolipids With an amino
alcohol sphingosine. The sphingosine backbone is O-linked to a charged headgroup such as
ethanolamine, serine or choline backbone. The backbone is also amide linked to a fatty acyl
group. Glycosphingolipids are ceramides With one or more sugar residues joined in a B-
glycosidic linkage at the l-hydroxyl position. Preferably the present composition contains
gangliosides, more preferably at least one ganglioside selected from the group consisting of GM3
and GD3.
The t nutritional composition preferably comprises sphingomyelin. Sphingomyelins have a
orylcholine or phosphorylethanolamine molecule fied to the oxy group of a
ceramide. They are classified as phospholipid as well as sphingolipid, but are not classified as a
glycerophospholipid nor as a glycosphingolipid. Sphingolipids are in the context of the present
invention defined as the sum of omyelin and glycosphingolipids, and phospholipids as the
sum of omyelin and glycerophospholipids. Preferably, the phospholipids are d from
milk lipids. ably the weight ratio of phospholipids : glycosphingolipids is from 2:1 to 1021,
more ably 221 to 5:1.
Preferably, the present nutritional ition comprises at least 0.5 wt.% phospholipids, based
on total lipid. Preferably, the nutritional composition comprises 0.5 to 20 wt.% phospholipids
based on total lipid, more preferably 0.6 to 20 wt.% phospholipids based on total lipid, more
preferably 0.75 to 10 wt.%, more preferably 1 to 10 wt.%, even more preferably 3 to 8 wt.%.
Preferably, the ional composition comprises 0.1 to 10 wt.% glycosphingolipids based on
total lipid, more preferably 0.5 to 5 wt.%, even more preferably 2 to 4 wt.%. Preferably, the
nutritional composition comprises 0.3 to 20 wt.% (glycosphingolipids plus phospholipids) based
on total lipid, more preferably 0.5 to 20 wt.% (glycosphingolipids plus phospholipids) based on
total lipid, more preferably 1 to 10 wt.%.
The present nutritional composition preferably comprises cholesterol. The present composition
preferably comprises at least 0.005 wt.% cholesterol based on total lipid, more preferably at least
0.02 wt.%, more preferably at least 0.05 wt.%, even more preferably at least 0.1 wt.%. Preferably
the amount of terol does not exceed 10 wt.% based on total lipid, more preferably does not
exceed 5 wt.%, even more ably does not exceed 1 wt.% of total lipid.
Preferably, the present ition comprises 0.5 to 25 wt.% polar lipids based on total lipid,
wherein the polar lipids are the sum of phospholipids, glycosphingolipids, and cholesterol, more
preferably 0.6 to 25 wt.% polar lipids based on total lipid, more preferably 0.6 to 12 wt.%, more
preferably 1 to 10 wt.%, even more preferably 3 to 10 wt.%.
Preferably, the present nutritional composition comprises a lipid source selected from egg lipids,
soy lecithin, sunflower lecithin, milk fat, buttermilk fat and butter serum fat (such as beta serum
fat), more ably at least egg lipid, as those are sources of olipids, glycosphingolipids
and/or cholesterol. A preferred source for phospholipids, particularly PC, is soy lecithin and/or
sunflower lecithin. The present composition preferably comprises phospholipids derived from
milk. Preferably the present composition comprises phospholipids and glycosphingolipids
derived from milk. Preferably also cholesterol is obtained from milk. Preferably the polar lipids
are derived from milk. Polar lipids derived from milk include the polar lipids isolated from milk
lipid, cream lipid, butter serum lipid (beta serum lipid), whey lipid, cheese lipid and/or
buttermilk lipid. The milk lipid is typically ed during the manufacture of buttermilk.
The butter serum lipid or beta serum lipid is typically obtained during the manufacture of
anhydrous milk fat from butter. Preferably the phospholipids, glycosphingolipids and/or
cholesterol are obtained from milk cream. The composition preferably comprises phospholipids,
phingolipids and/or cholesterol from milk of cows, mares, sheep, goats, buffalos, horses
and camels. It is most preferred to use a lipid extract isolated from cow’s milk. Polar lipids
derived from fat milk advantageously decrease adipose tissue mass to a larger extent than polar
lipids from other sources. Preferably the polar lipids are located on the surface of the lipid
globule, i.e. as a coating or outer layer. A suitable way to determine r the polar lipids are
located on the surface of the lipid globules is laser ng microscopy. The concomitant use of
polar lipids d from domestic animals milk and trigycerides derived from vegetable lipids
therefore enables to cture lipid globules with an architecture more similar to human milk,
while at the same time providing an optimal fatty acid profile. Suitable commercially available
s for milk polar lipids are BAEF, SM2, SM3 and SM4 powder of Corman, Salibra of
Glanbia, and LacProdan MFGM-lO or PL20 from Arla. Preferably the source of milk polar lipids
comprises at least 4 wt.% phospholipids based on total lipid, more preferably 7 to 75 wt.%, most
preferably 20 to 70 wt.% phospholipids based on total lipid.
Preferably the weight ratio phospholipids to protein is above 0.10, more preferably above 0.20,
even more preferably above 0.3. Preferably at least 25 wt.%, more preferably at least 40 wt.%,
most preferably at least 75 wt.% of the polar lipids is derived from milk polar lipids.
Fatty acid ition
Herein LA refers to linoleic acid and/or acyl chain (18:2 n6); ALA refers to 0t-linolenic acid
and/or acyl chain (18:3 n3); PUFA refers to polyunsaturated fatty acids and/or acyl chains;
MUFA refers to monounsaturated fatty acids and/or acyl chains; LC-PUFA refers to long chain
polyunsaturated fatty acids and/or acyl chains comprising at least 20 carbon atoms in the fatty
acyl chain and with 2 or more rated bonds; DHA refers to docosahexaenoic acid and/or
acyl chain (22:6, n3); EPA refers to eicosapentaenoic acid and/or acyl chain (20:5 n3); ARA
refers to arachidonic acid and/or acyl chain (20:4 n6); DPA refers to docosapentaenoic acid
and/or acyl chain (22:5 n3). Medium chain fatty acids (MCFAs) refer to fatty acids and/or acyl
2014/050761
chains with a chain length of 6, 8 or 10 carbon atoms.
The lipid that is present in the nutritional composition according to the invention ably
comprises PUFAs, more preferably LC-PUFAs, as LC-PUFAs further improve the growth
patterns and body composition during catch-up growth, as well as brain and retina development.
The nutritional ition preferably comprises 5 to 35 wt.% PUFA, more preferably 10 — 30
wt.% PUFA, most ably 15 — 20 wt.% PUFA, based on total lipid. It is also preferred that
the present ional composition comprises MUFAs, preferably 10 to 80 wt.% MUFA, more
preferably 20 — 70 wt.% MUFA, most preferably 35 — 55 wt.% MUFA, based on total lipid.
LA preferably is present in a sufficient amount in order to promote a healthy -up) growth
and development, yet in an amount as low as possible to prevent occurrence of obesity later in
life. The nutritional composition therefore preferably comprises less than 20 wt.% LA based on
total lipid, preferably 5 to 16 wt.%, more preferably 10 to 14.5 wt.%. Preferably, the nutritional
composition comprises at least 5 wt.% LA based on total lipid. Per 100 kcal, the nutritional
composition preferably comprises 350 — 1400 mg LA. Preferably, ALA is present in a sufficient
amount to promote a (catch-up) healthy growth and pment of the infant. The present
composition therefore preferably comprises at least 1.0 wt.% ALA based on total lipid.
Preferably the composition comprises at least 1.5 wt.% ALA based on total lipid, more
preferably at least 2.0 wt.%. Preferably the ition comprises less than 12.5 wt.% ALA,
more preferably less than 10.0 wt.%, most preferably less than 5.0 wt.%. In case the present
nutritional composition is a preterm formula or a low birthweight formula, it is preferred that the
nutritional composition comprises less than 120 mg ALA, more preferably 60 to 100 mg per 100
kcal. In case the present nutritional composition is a paediatric formula for up growth, it is
red that the nutritional composition comprises less than 200 mg ALA, more preferably 100
to 150 mg per 100 kcal. In case the t nutritional composition is a preterm formula or a low
birthweight formula, it is preferred that the nutritional composition comprises less than 100 mg
ALA, more ably 60 to 80 mg per 100 ml. In case the present nutritional composition is a
paediatric formula for catch-up growth, it is preferred that the nutritional composition comprises
less than 200 mg ALA, more preferably 130 to 150 mg per 100 ml. The weight ratio LA/ALA
should be well balanced in order to prevent obesity, while at the same time ensuring a normal
growth and pment. Therefore, the present composition preferably comprises a weight ratio
of LA/ALA between 2 and 15, more preferably between 4 and 13, even more preferably between
and 8. In case the present nutritional composition is a paediatric formula for catch-up , it
is preferred that the weight ratio of LA/ALA is between 4 and 10, more preferably between 5.5
and 8.0. In case the present nutritional composition is a preterm formula or a low eight
formula, it is preferred that the weight ratio of LA/ALA is between 4 and 10, more preferably
n 5 and 8, even more preferably between 6 and 7.5, even more preferably n 6.5 and
7.5.
Since MCFA may contribute to a reduced risk of developing obesity when administered to an
infant, the present composition preferably comprises at least 3 wt.% MCFA based on total lipid,
more preferably at least 9 wt.%, even more preferably 15 wt.%. Since MCFA reduces adipose
tissue deposition with no preference for visceral adipose tissue mass, and since MCFA does not
se the number of ytes, the t composition ageously comprises less than
50 wt.% MCFA based on total lipid, more preferably less than 40 wt.%, even more preferably
less than 25 wt.%.
Preferably the present nutritional composition comprises n-3 A, since n-3 LC—PUFA
reduce the risk of developing obesity later in life, more preferably central obesity. More
preferably, the present nutritional composition comprises EPA, DPA and/or DHA, even more
preferably at least DHA. Since a low concentration of DHA, DPA and/or EPA is already
effective and normal growth and development are important, the content of n-3 LC-PUFA in the
nutritional composition, preferably does not exceed 15 wt.% of total lipid, preferably does not
exceed 10 wt.%, even more preferably does not exceed 5 wt.%. Preferably, the nutritional
composition comprises at least 0.2 wt.%, preferably at least 0.5 wt.%, more preferably at least
0.75 wt.%, n-3 LC—PUFA of total lipid. The nutritional composition preferably comprises 0.05 —
0.7 wt.%, more preferably 0.15 — 0.6 wt.%, even more preferably 0.25 — 0.5 wt.%, even more
preferably 0.3 — 0.5 wt.%, most preferably 0.3 — 0.4 wt.% DHA based on total lipid. Per 100
kcal, the ional composition preferably ses 5 — 27 mg DHA, more preferably 10 — 20
mg DHA. Per 100 ml, the nutritional composition preferably comprises 8 — 30 mg DHA, more
preferably 10 — 22 mg DHA, most preferably 12 — 19 mg DHA. The weight ratio of EPA to
DHA is preferably at most 0.3, more preferably between 0.01 and 0.25.
2014/050761
The n-6 LC-PUFA content preferably does not exceed 5 wt.%, more preferably does not exceed
2.0 wt.%, more preferably does not exceed 0.75 wt.%, based on total lipid. Since ARA is
important in infants for optimal functional membranes, especially membranes of neurological
tissues, the amount of n-6 LC—PUFA is preferably at least 0.02 wt.% more preferably at least
0.05 wt.%, more ably at least 0.1 wt.% based on total lipid, more preferably at least 0.2
wt.%. The presence of ARA is beneficial in nutrition to be administered to infants below the age
of 6 months, since for these infants the infant formulae is lly the only source of nutrition.
The nutritional composition preferably comprises 0.05 — 1.0 wt.%, more preferably 0.2 — 0.7
wt.%, even more preferably 0.3 — 0.7 wt.%, most ably 0.3 — 0.5 wt.% ARA based on lipid.
Per 100 kcal, the nutritional composition preferably comprises 14 — 27 mg ARA, more
preferably 16 — 24 mg ARA. The weight ratio of DHA 2 ARA is preferably from 120.9 to 122.5,
more preferably 121 to 121.9, most preferably 121 to 121.4. Per 100 ml, the nutritional
composition ably comprises 8 — 30 mg ARA, more preferably 12 — 22 mg ARA, most
preferably 16 — 19 mg ARA. The weight ratio of DHA 2 ARA is preferably from 120.9 to 122.5,
more preferably 121 to 121.9, most ably 121 to 121.4.
Preferably, the nutritional composition comprises at least one source of vegetable lipid selected
from sunflower oil, rapeseed oil, coconut oil and palm oil. Furthermore, it is preferred that in
addition to the vegetable lipid, at least one lipid source selected from fish oil (preferably tuna
fish oil), single cell oil (such as algal, microbial oil and fungal oil), MCT oil and egg lipid is
present. These sources of oil are le as LC-PUFA sources. Preferably as a source of n-3 LC-
PUFA single cell oil, including algal oil and microbial oil, is used. In a preferred embodiment the
nutritional composition comprises at least one lipid ed from the group consisting of
sunflower oil, rapeseed oil, coconut oil, palm oil, MCT oil, egg lipid, soy lecithin, sunflower
lecithin, milk fat, buttermilk fat, butter serum fat, fish oil, marine oil, algal oil, fungal oil and
microbial oil.
In an especially preferred embodiment, the nutritional composition ses lipid in the form of
lipid globules, wherein the lipid comprises, based on total lipid:
- 0.5 to 25 wt.% polar lipids, preferably 0.6 to 25 wt.%, more preferably 0.6 to 12 wt.%,
more preferably 1 to 10 wt.%, even more preferably 3 to 10 wt.% polar lipids,
wherein the polar lipids comprise, based on total lipid:
- 0.5 to 20 wt.% phospholipids, preferably 0.6 to 20 wt.%, more ably 0.75 to 10
wt.%, even more preferably 1 to 10 wt.%, most preferably 3 to 8 wt.%
phospholipids;
- 0.1 to 10 wt.% glycosphingolipids, preferably 0.5 to 5 wt.%, more preferably 2 to 4
wt.% glycosphingolipids;
- at least 0.005 wt.% cholesterol, preferably 0.02 to 10 wt.%, more preferably 0.05 to 5
wt.%, most preferably 0.1 to 1 wt.% cholesterol;
- 10 to 80 wt.% MUFA, preferably 20 to 70 wt.%, more preferably 35 to 55 wt.%;
- 5 to 35 wt.% PUFA, preferably 10 to 30 wt.%, more preferably 15 to 20 wt.%;
- 3 to 50 wt.% MCFA, preferably 9 to 40 wt.%, more preferably 15 to 25 wt.%;
- less than 20 wt.% LA, preferably 5 to 16 wt.%, more ably 10 to 14.5 wt.%;
- 1.0 to 12.5 wt.% ALA, preferably 1.5 to 10.0 wt.%, more preferably 2.0 to 5.0 wt%;
- 0.05 to 0.7 wt.% DHA, preferably 0.15 to 0.6 wt.%, more preferably 0.3 to 0.5 wt%, even
more preferably 0.25 to 0.5 wt%, most preferably 0.3 to 0.4 wt%;
- 0.05 to 1.0 wt.% ARA, preferably 0.2 to 0.7 wt.%, more preferably 0.3 to 0.7 wt%, most
preferably 0.3 to 0.5 wt%.
Preferably, the lipid globules have a coating comprising the major part of the polar lipids and a
core comprising the major part of the other lipid components.
Process for obtaining liQid es
The present nutritional composition comprises lipid globules. The lipid e size can be
manipulated by adjusting the process steps by which the composition is manufactured. A suitable
and preferred way to obtain larger lipid globule sizes is to adapt the process of homogenization
such as bed in . In particular aqueous and lipid phases are mixed in a
batch mixer after which homogenization at a lower pressure than usually applied in the
ation of infant formula is carried out.
atively, nutritional itions having the desired lipid globule size can be prepared by
the method as described in WC 2013/135738, 1'. e. by admixing lipid employing an inline mixer
to obtain lipid globules, preferably followed by spray drying with an atomization system
employing a two-fluid nozzle.
Nutritional comgosition
The present nutritional composition comprises lipid and preferably further ses protein
and carbohydrates, wherein the lipids are present in lipid es. ably, the ional
composition is an infant a, more preferably a preterm or low birthweight infant formula or
paediatric a for catch-up growth, which is intended for providing nutrition to an infant
selected from the group consisting of preterm infants, small for gestational age infants and
infants with retarded growth due to al or mental stress after birth.
In view of this target group, the present ional composition preferably has a increased
caloric density, compared to regular infant formulae, which supports growth and development of
preterm infants, small for gestational age infants and infants with retarded growth due to physical
or mental stress after birth. Preterm infants and small for gestational age infants usually have a
little stomach and cannot e a large amount of nutrition. Preferably, the nutritional
composition contains 50 to 200 kcal/100 ml liquid, more preferably 70 to 120 kcal per 100 ml,
more preferably 70 to 100 kcal per 100 ml, even more preferably 74 to 90 kcal per 100 ml, most
preferably 77 to 87 kcal per 100ml. These caloric densities are especially red for m
formulae and low birthweigth formulae. For a paediatric formula for catch-up growth, the caloric
density may be even higher, such as 75 to 150 kcal per 100 ml, preferably 85 to 150 kcal per 100
ml, more preferably 93 to 125 kcal per 100 ml, most preferably 95 to 115 kcal per 100 ml. The
osmolarity of the nutritional composition is preferably between 150 and 420 mOsmol/l, more
preferably 260 to 380 mOsm/l, even more preferably 280 to 350 mOsm/l. Such an osmolarity is
beneficial in the prevention of gastrointestinal stress and ensures proper hydration, which is of
importance especially for preterm and SGA infants.
Apart from the lipid, as bed above, the nutritional composition according to the invention
preferably comprises protein and carbohydrate.
Preferably, the protein provides 5 to 20 % of the total calories of the nutritional composition,
preferably 8 to 16 %, more preferably 9 to 14 %, more preferably 9.5 to 11.5 %. In case the
nutritional composition is especially designed for infants with a body weight below 1000 g, the
protein content is preferably 12.5 to 14 % based on total calories. It is preferred that the
nutritional composition comprises 2.1 to 4.1 g protein based on 100 kcal, more preferably 2.4 to
3.4 g per 100 kcal. In case the present nutritional composition is a preterm a or a low
birthweight formula, it is red that the composition comprises 2.6 to 3.4 g protein based on
100 kcal. In case the nutritional composition is especially ed for infants with a body
weight below 1000 g, the protein content is preferably 3.0 to 3.4 g per 100 kcal. In case the
ional ition is especially designed for infants with a body weight above 1000 g, the
protein content is preferably 2.6 to 3.0 g per 100 kcal. In case the present nutritional composition
is a paediatric formula for catch-up growth, it is preferred that the composition comprises 2.4 to
2.8 g protein based on 100 kcal. Based on dry weight of the nutritional composition, the amount
of protein is preferably 8 to 27 wt.%, more preferably 10 to 25 wt.%, even more preferably 13 —
22 wt.%. In case the present nutritional composition is a preterm formula or a low birthweight
formula, it is preferred that the composition comprises 12.5 to 20 wt.% protein, more preferably
13 to 17 wt.%. In case the present nutritional composition is a paediatric formula for catch-up
growth, it is red that the ition comprises 12.5 to 18 wt.% protein, more preferably
13 to 15 wt.%. Based on 100 ml composition, the amount of protein is preferably 1.5 to 3.3 g,
more preferably 1.7 to 3.1 g, most preferably 1.9 to 2.7 g.
The source of the protein is preferably selected in such a way that the minimum requirements for
essential amino acid content are met and satisfactory growth is d. Hence, the source of
protein is preferably from bovine milk protein. Preferably, the protein component comprises
whey protein and/or casein, more preferably ts of whey protein and/or casein, most
ably is a mixture of whey protein and casein. Preferably, the weight ratio of whey protein :
casein is 70 : 30 to 40 : 60, more preferably 65 : 35 to 50 : 50, most preferably about 60 : 40. As
such, an optimal amino acid profile is obtained, closely resembling that of human milk, which is
beneficial for optimal up growth.
The protein component may contain intact protein, partially yzed protein or free amino
acids (i.e. fully yzed), preferably the protein is partially or fully hydrolyzed, as this
improves the digestion of protein in SGA and premature infants.
Preferably, the carbohydrate comprises digestible ydrates. The digestible carbohydrates
preferably provide 30 to 80 % of the total calories of the ional composition, preferably 35
to 50 %, more preferably 38 to 45 %. It is preferred that the ional composition comprises 10
to 12 g digestible carbohydrates based on 100 kcal, preferably 10.2 to 11 g. Based on dry weight
of the ional composition, the amount of digestible carbohydrates is preferably 20 to 80
wt.%, more preferably 40 to 65 wt.%. Based on 100 ml ition, the amount of digestible
carbohydrates is preferably 3.0 to 30 g, more preferably 6.0 to 20 g, even more preferably 7.0 to
11 g per 100 ml. In case the present nutritional composition is a preterm formula or a low
birthweight formula, it is preferred that the composition comprises 7.0 to 9.0 g digestible
carbohydrates per 100 ml. In case the t nutritional composition is a paediatric formula for
catch-up growth, it is preferred that the composition comprises 9.0 to 11 g digestible
carbohydrates per 100 ml.
Preferred digestible carbohydrate sources are lactose, e, sucrose, fructose, galactose,
maltose, starch and maltodextrin, more ably at least lactose is present, most preferably at
least lactose and starch are present. Lactose is the main digestible carbohydrate present in human
milk, thus the nutritional composition ably comprises e. The nutritional composition
preferably comprises digestible carbohydrate, wherein at least 35 wt.%, more preferably at least
50 wt.% of the digestible carbohydrate is lactose. Based on dry weight the present composition
ably comprises at least 25 wt.% lactose.
Preferably, the carbohydrate also ses non-digestible carbohydrates, also referred to as
non-digestible oligosaccharides in the context of the t ion. Preferably the present
composition comprises non-digestible oligosaccharides with a degree of polymerization (DP) of
2 to 250, more preferably 3 to 60. The non-digestible oligosaccharides advantageously prevent
the onset of insulin resistance, which also may result in a reduced adipose tissue mass.
Preferably the non-digestible oligosaccharide comprises at least one oligosaccharide selected
from the group of fructo-oligosaccharides (such as inulin), galacto-oligosaccharides (such as
transgalacto-oligosaccharides or beta-galacto-oligisaccharides), gluco-oligosaccharides (such as
-, nigero- and cyclodextrin-oligosaccharides), o-oligosaccharides, mannan-
oligosaccharides, xylo-oligosaccharides, fuco-oligosaccharides, arabinogalacto-oligosaccharides,
glucomanno-oligosaccharides, galactomanno-oligosaccharides, sialic acid oligosaccharides and
uronic acid oligosaccharides, more preferably selected from the group of fructo-oligosaccharides,
galacto-oligosaccharides and uronic acid oligosaccharides, most preferably selected from the
group of fructo-oligosaccharides, o-oligosaccharides. ably, the nutritional
composition comprises galacto-oligosaccharides, more preferably transgalacto-oligosaccharides.
In a preferred embodiment the composition comprises a mixture of galacto-oligosaccharides and
-oligosaccharides.
The galacto-oligosaccharides preferably have a DP of 2 to 10. Preferably the galactooligosaccharides
have an average DP of below 6. The galacto-oligosaccharide is preferably
selected from the group consisting of transgalacto-oligosaccharides, lacto-N—tetraose (LNT),
lacto-N—neotetraose (neo-LNT), fucosyl-lactose, fucosylated LNT and fucosylated neo-LNT.
Transgalacto-oligosaccharides (TOS) are for example sold under the trademark VivinalTM
(Borculo Domo Ingredients, Netherlands). Preferably the saccharides of the alacto-
oligosaccharides are B-linked. The fructo-oligosaccharide preferably have a DP of 2 to 250, more
preferably 2 to 100, most preferably 5 to 60. Preferably the fructo-oligosaccharides have an
average DP of above 10. Fructo-oligosaccharides include inulin, levan and/or a mixed type of
polyfructan. An ally preferred fructo-oligosaccharide is inulin. Fructo-oligosaccharide
suitable for use in the compositions is commercially available, e.g. as Raftiline®HP i).
Preferably, the present nutritional composition comprises galacto-oligosaccharides and fructo-
oligosaccharides in a weight ratio galacto-oligosaccharides : fructo-oligosaccharides of 99 : l to
l : 99, more preferably 20 : l to l : 1, most preferably 12 : l to 7 : l.
Preferably, the composition comprises of 80 mg to 2 g gestible oligosaccharides per 100
ml, more ably 150 mg to 1.50 g, even more preferably 300 mg to l g per 100 ml. Based on
dry weight, the composition preferably comprises 0.25 wt.% to 20 wt.% gestible
accharides, more preferably 0.5 wt.% to 10 wt.%, even more preferably 1.5 wt.% to 7.5
wt.% non-digestible oligosaccharides. The ce of non-digestible oligosaccharides gives rise
to reduced stool viscosity and thus prevents constipation, which is particularly important in the
group of vulnerable infants, such as preterm infants, SGA infants and convalescent infants.
The present nutritional composition is not human breast milk. The nutritional composition
according to the ion preferably comprises other ingredients, such as minerals, trace
elements, vitamins and other micronutrients as recommended and known in the art.
The nutritional composition is preferably in the form of a powder or a liquid. In one
ment, the nutritional composition is in the form of a powder suitable for making a liquid
composition after reconstitution with an s solution, preferably with water. ably, the
composition is a powder to be tituted with water. It was surprisingly found that the size
and the coating with polar lipids of the lipid globules remained the same after the drying step and
subsequent titution. The presence of larger lipid globules may have a slightly negative
effect on the long term stability of the liquid composition. However, separation of the lipid and
aqueous layers was not observed within 48 h, which is much longer than the time between
reconstituting the powder to a ready to drink liquid and the consumption of it, which will be less
1O than 24 h and typically within 1 h. The composition being in a powder form has therefore an
additional advantage in the present invention.
In case the nutritional composition is administered to an infant, it is highly preferred that the
composition is in the liquid form. The preferred mode of administration is orally, e.g. bottle
feeding, but other modes of stration such as tube feeding are also possible.
Preferably, the nutritional composition is in a liquid form, with a viscosity below 35 mPa‘s, more
preferably below 6 mPa‘s, most preferably 1 to 6 mPa‘s, as measured in a Brookfield eter
at 20 °C at a shear rate of 100 s'l. Suitably, the composition is in a powdered from, which can be
2O reconstituted with water to form a liquid, or in a liquid concentrate form, which could be diluted
with water.
In one aspect the invention relates to a nutritional ition, comprising protein,
carbohydrates and lipid, wherein:
(i) the caloric density is 50 to 200 kcal per 100 ml;
(ii) lipid is present in 4.4 to 6.0 g per 100 kcal;
(iii) n is present in 2.1 to 4.1 g per100 kcal and in 1.5 to 3.3 g per 100 ml;
(iv) carbohydrates are present in 10 to 12 g per100 kcal,
(v) the lipid is present in lipid globules, having:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the composition comprises at least 0.5 wt.%
phospholipids based on total lipid.
In one aspect the invention s to a preterm formula, a low birthweight formula, comprising
protein, carbohydrates and lipid, wherein:
(i) the caloric density is 77 to 87 kcal per 100 ml;
(ii) lipid is present in 4.4 to 6.0 g per 100 kcal;
(iii) protein is present in 2.6 to 3.4 g per100 kcal and in 1.7 to 3.1 g per 100 ml;
(iV) carbohydrates are present in 10 to 12 g per100 kcal,
(V) the lipid is t in lipid globules, haVing:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the composition comprises at least 0.5 wt.%
phospholipids based on total lipid.
In one aspect the invention relates to a tric formula for catch-up growth, comprising
protein, carbohydrates and lipid, wherein:
(i) the caloric density is 93 to 125 kcal per 100 ml;
(ii) lipid is t in 4.4 to 6.0 g per 100 kcal;
(iii) protein is t in 2.4 to 2.8 g per100 kcal and in 1.7 to 3.1 g per 100 ml;
(iV) carbohydrates are present in 10 to 12 g per100 kcal,
(V) the lipid is present in lipid globules, haVing:
(a) a volume-weighted mode diameter of at least 1.0 um; and/or
(b) a phospholipid coating, wherein the composition comprises at least 0.5 wt.%
olipids based on total lipid.
In one embodiment, the preterm formula, low birthweight formula or paediatric formula for
catch-up growth comprises 0.3 to 0.7 wt.% arachidonic acid, based on total lipid, preferably 0.4
to 0.6 wt.% arachidonic acid, based on total lipid.
In yet a further embodiment, the preterm a, low birthweight formula or tric formula
for catch-up growth comprises 0.3 to 0.5 wt.% docosahexaenoic acid, based on total lipid.
AQQlication
The present composition is preferably administered orally to the infant. The present invention
aims to promote controlled catch-up growth in an infant selected from the group of preterm
infants, small for gestational age s and escent infants. In the context of the present
ion, ‘controlled catch-up growth’ can also be referred to as ced catch up growth’ or
‘proportional weight for length catch up growth’. In the context of the present invention,
‘uncontrolled catch-up growth or ‘unbalanced catch-upgrowth or ‘accelarated catch-up growth’,
also referred to as ‘excessive weight gain’, is defined as an increase in weight adjusted for length
of > 0.5 SD score in the first three months of life, see for e Kerkhof & Hokken-Koelega,
1O Nat. Rev. Endocrinol. 8, 689—692 (2012); Kerkhof et al. J Clin inol Metab 97: 4498—
4506, (2012). In this context, the first three months of life for preterm infants start at term age
and for SGA s at birth. For convalescent infants ‘uncontrolled catch-up growth’ or
‘unbalanced catch-up growth’ or ‘accelarated catch-up growth’ or ‘excessive weight gain’, is
defined as an increase in weight ed for length of > 0.5 SD score in the first three months
from the start of recovery of the convalescent infant. uently, controlled catch up in the
present context is defined as a weight gain adjusted for length of g 0.5 SD score within three
months, wherein the three months are the first three months after term age for preterms and after
birth for the SGA infants., and is defined as a weight gain adjusted for length of g 0.5 SD score
within three months after start of recovery for convalescent infants, e.g. the first three months
2O after the growth retardation due to mental or physical stress has stopped.
The present invention also aims to (i) improve body composition, (ii) e adipose tissue
distribution, (iii) decrease visceral adipose tissue based on body weight and/or on total adipose
tissue, and/or (iv) decrease the ratio visceral adipose tissue to subcutaneous adipose tissue, in an
infant selected from the group consisting of preterm infants, small for ional age infants and
convalescent infants, preferably during or directly after catch-up growth. In one embodiment the
present method is for preventing visceral adiposity. ‘
In one embodiment, the present nutritional composition is for feeding an infant selected from the
group consisting of preterm infants, small for gestational age infants and convalescent infants.
Such feeding preferably promotes controlled catch-up growth. Such g preferably (i)
improves body ition, (ii) improves e tissue distribution, (iii) decreases visceral
adipose tissue based on body weight and/or on total adipose tissue, and/or (iv) decreases the ratio
visceral adipose tissue to subcutaneous adipose . Preferably, these effects are observed
during or directly after catch-up growth, more preferably before the infant reaches an age of 36
months, most preferably before the infant reaches an age of 12 months. This does not mean that
effects cease to be observable after the infant has reached the age of 12 months or 36 months, as
the beneficial effect of the t nutritional composition may prolong to later in life.
In this document and in its claims, the verb ”to comprise" and its conjugations is used in its non-
ng sense to mean that items following the word are ed, but items not specifically
1O mentioned are not excluded. In addition, reference to an element by the indefinite article ”a" or
"an" does not exclude the possibility that more than one of the element is present, unless the
context clearly es that there be one and only one of the elements. The indefinite article ”a"
or "an" thus usually means ”at least one”.
ES
Exam le 1: Process or re arin an IMF with lar er li id lobule size
An infant a was ed as described in example 1 of WC 2013/135738. In particular, an
infant formula in the form of a powder was prepared comprising per kg final product about 4800
2O kcal, about 247 g lipid, about 540 g digestible carbohydrates, about 41 g non-digestible
oligosaccharides and about 97 g protein. The composition was prepared using butter milk serum
powder enriched in milk phospholipids, a vegetable oil blend (lipid), demineralised whey powder
(protein), lactose, and non- digestible oligosaccharides. Also vitamins, minerals, trace elements
as known in the art were used.
The amount of butter milk serum powder was such that 1.62 wt.% phospholipids based on total
lipids were present in the final ition. An aqueous phase, comprising the butter milk
powder, protein and ible carbohydrates and the other ingredients, except the lipid and lipid
soluble vitamins, was prepared as known in the art and heat treated to t bacterial
contamination, namely by an Ultra High Temperature (UHT) treatment, as known in the art, after
which an evaporation step was applied. The dry matter content of the aqueous phase was
between 30 to 48 wt.% after the evaporation step. The mixture was heated to 50 °C.
2014/050761
A lipid phase was prepared as known in the art. The ble oil blend was also heated to 50 °C
and added to the water phase in a w/w ratio of between 15 to 30 by injection and a fugal
booster pump. The total solid content of the lipid and aqueous phase mixture was between 40
and 60 wt.%. Accordingly, the aqueous and lipid phase were fed into the inline mixer (Ystral
280) comprising one mixing head. The rotar stator design of the inline mixer had 3 rows of teeth.
The aqueous and lipid phase were mixed with a tip speed of 20 to 50 m/s (resulting in a shear
rate from 50000 to 100000 /s) in order to emulsify the lipid phase into the aqueous phase and
thereafter pumped with a positive displacement pump, a mono pump, with a pressure of about 8
bar to the heater.
The oil in water mixture was subsequently fed via the concentrate heater to the spray dryer,
driven by the pump used downstream of the inline mixer.
The emulsion was atomized with a low shear atomization system employing a two-fluid nozzle
of Schlick (0/2-0/5 series), wherein the pressure used for spray-drying was below 8 bar, and
dried with the inlet temperature of the drying gas being 195 °C. The size of the lipid globules in
the final powder, after reconstitution with water, was measured with a Mastersizer 2000
rn Instruments, Malvern UK). The volume weighted mode diameter was 4.3 pm. About
60 % of the lipid globules based on lipid volume had a diameter between 2 and 12 um.
Exam [6 2: An earl in Ii 6 diet with lar 6 li id s and milk hos holi ids im roves catch-
uQ growth in IUGR rats.
Methods: Male offspring of Wistar dams either underwent prenatal bilateral uterine artery and
vein operation (LIG) or a sham operation (SOP) on day 19 of the first pregnancy of the dams.
Offspring of dams without ent served as controls (C). Control diet 1 or mental diet 2
was provided for 4 weeks between postnatal days 15 (P15) and 42 (P42).
Control and experimental diets were:
Diet 1 : The control diet was a standard infant milk formula (IMF) based control diet. This diet
comprised 282 g standard Nutrilon 1® per kg, having lipid es with a volume weighted
mode er of 0.4 pm, and no added polar lipids. The rest of the diet was AIN-93G protein,
carbohydrates and fibre. The volume % of lipid globules with a size between 2 and 12 m was
below 40 % based on total lipid volume. All lipid present in the diet was derived from the IMF.
Diet 2 : The experimental diet was based on the infant formula prepared according to example 1.
This experimental diet differed from diet 1 in that it comprised 282 g infant formula of e
1, i.e. comprised lipid es larger than the control coated with polar lipids derived from milk.
All lipid t in the diet was derived from the IMF.
Thus, six groups were compared: (a) et 2 (n=8); (b) SOP-diet 2 (n=lO); (c) C—diet 2
(n=20); (d) LIG-diet 1 (n=9); (e) SOP-diet l (n=lO); and (f) C—diet l (n=lO). Accumulation of
body weight was recorded weekly. Crown-rump-length and body composition were detected via
micro-CT scan on P42.
All blocks were tested for outliers using Grubbs Test. Maximally 1 value per block was removed
(in most blocks no outlier). All data were normally distributed. A 1 way ANOVA test was
1O performed with a Bonferroni correction, and in case of significant a ANOVA value, a T-test was
performed if the data showed a similar variance, otherwise a MW test was applied. Group
comparisons were made between:
- (a) LIG-diet 2 vs. (b) SOP-diet 2;
- (a) LIG-diet 2 vs. (c) C-diet 2;
- (b) SOP-diet 2 vs. (c) C—diet 2;
- (d) LIG-diet 1 vs. (e) SOP-diet l;
- (d) LIG-diet 1 vs. (f) C-diet l;
- (e) SOP-diet 1 vs. (f) C-diet l;
2O - (a) et 2 vs. (d) LIG-diet l;
- (b) SOP-diet 2 vs. (e) et l; and
- (c) C-diet 2 vs. (f) C-diet 1.
Results: No difference in food intake was observed n the different groups. In Table 2 the
body weight development over time is shown. In general, the two L1G groups showed the lowest
body weight direct after birth and over time (except for LIG-diet l at P40), and the bodyweight
of the two C groups was highest at P2, P12 and P40. So, all groups experienced a very similar
rate of (catch-up) growth, irrespective of which diet was administered.
Table 2: Body weight pment 0Ver time
Postnatal day (P) 2 40
Group sample size BW (g) SD BW (g) SD BW (g) SD
(a) LIG—diet 2 9 5.667 0.324 159.6 10.3
(b) SOP—diet 2 10 6.19 0.7156 165.4 10.19
(c) C—diet 2 20 7.225 * 0.8263 175.3 + 9.603
(d) LIG—diet 1 9 5.767 0.5148 164.3 7.07
(e) SOP—diet 1 10 6.66 0.2271 162.5 12.02
(f) C—diet 1 10 7.28 # 0.5554 174.2 13.71
BW = body weight; SD = standard deViation.
*2 p < 0.001 VS. LIG-diet 2 and VS. SOP-diet 2; #2 p < 0.001 VS. LIG-diet 1; +2 p < 0.01VS. LIG-
diet 2.
In Table 3, the body composition at P42 iS Shown. The amount of total adipose tissue maSS
(ATM) based on body weight waS highest in the LIG-diet 1 group, when ed with the
other . ThiS waS in particular the case for the al adipose tissue maSS (VTM). ThiS iS
indicatiVe for the increased catch-up growth in the LIG-diet 1 group, resulting in increased
adipose tissue deposition, in particular Visceral adipose tissue. The amount adipose tissue maSS in
the LIG-diet 2 group, which were fed with a nutritional composition according to the inVention,
waS Very Similar to the control (C) and SOP groupS. Interestingly, the amount of al tissue
maSS, both based on body weight or total adipose tissue maSS, waS decreased in the LIG-diet 2
group, when compared to all other groupS, and statistically Significant lower than in the LIG-diet
1 group. On the other hand, subcutaneouS tissue maSS (STM), based on body weight and based
on total adipose tissue maSS, waS higher in the LIG-diet 2 group than in the other two -diet 2
groupS, aS well aS compared to the LIG-diet 1 group, which indicateS that the L1G group benefitS
most from the ional composition according to the inVention.
Table 3: Body composition at P42
Group g (SD) wt.% (SD) wt.% (SD) wt.% (SD) wt.% (SD) wt.% (SD)
159.6 2.62 1.4 & 51.94 & 1.2 48.06 33
(a) et 2
(10.3) (0.62) (0.26) (4.997) (0.4) (4.997)
165.4 2.49 1.5 61.77 1.0 38.23
(b) SOP—diet 2
(10.19) (0.58) (0.30) (8.711) (0.4) )
175.3 + 2.55 1.5 57.55 1.1 42.45
(C) C-diet 2
(9.603) (0.54) (0.31) (6.495) (0.3) (6.495)
164.3 # 3.06 1.8 56.67 1.3 43.33
(d) LIG—diet 1
(7.07) (0.53) (0.30) (1.584) (0.3) (1.584)
162.5 2.63 1.6 58.76 1.0 41.24
(e) SOP—diet 1
(12.02) (0.56) (0.31) (4.104) (0.3) (4.104)
174.2 2.63 1.6 60.81 1.0 39.19
(f) C—diet 1
(13.71) (0.38) (0.32) (7.525) (0.2) (7.525)
BW = body weight; SD = standard deviation; ATM = total adipose tissue mass; VTM = visceral
adipose tissue mass; STM = subcutaneous adipose tissue mass; * = in wt.%, based on BW; ** =
in wt.%, based on ATM.
p < 0.05: +2 vs. LIG-diet 2 and vs. SOP-diet 2; #2 vs. C-diet 1; &: vs. LIG-diet 1; $2 vs. SOP-diet
2; C—diet 2 and vs. LIG-diet 1.
These results are indicative for the beneficial effect of the experimental diet in promoting
controlled catch-up growth, as well as on improving body composition, improving adipose tissue
distribution, decreasing visceral adipose tissue based on body weight and/or on total adipose
tissue, and/or decreasing the ratio visceral adipose tissue to aneous adipose tissue, in
particular in SGA or preterm s.
Exam [6 3:111 ant ormula 0r remature or low birthwei ht in ants.
A preterm or low birth weight formula comprising per 100 ml, of which 87.4 g water and 12.6 g
dry matter:
Energy: 81 kcal
WO 65193
Protein: 2.64 g (bovine whey protein/casein 6/4 wt/wt ratio)
Digestible carbohydrates: 8.40 (2.37 g , 5.73 sugars (mainly lactose))
Lipid: 3.9 g, a mix of rapeseed oil, sunflower oil, coconut oil, palm
kernel oil, corn oil, single cell oil, milk fat (including polar
) and fish oil, with the same lipid globule architecture as
in example 1 (comprising 503 mg LA, 72 mg ALA, 17.7 mg
ARA, 13.6 mg DHA)
Non digestible oligosaccharides: 0.8 g (galacto-oligosaccharides (short chain — average DP
below 7) and fructo-oligosaccharides (long chain — average DP
above 7) in a 9/1 wt/wt ratio), representing 0.6 g fiber
according to EU regulation.
ns, minerals and other micronutrients according to guidelines.
Exam [6 4: In ant ormala 0r convalescent in ants
A paediatric formula comprising per 100 ml (15 wt% dry weight and 85 ml water):
Energy: 101 kcal
Protein: 2.6 g (bovine whey protein/casein 6/4 wt/wt ratio)
Digestible carbohydrates: 10.3 (4.4 g polysaccharides (mainly starch), the rest mainly
sugars, of which the majority (5.2 g) is lactose)
Lipid: 5.4 g, a mix of rapeseed oil, sunflower oil, coconut oil, palm
kernel oil, corn oil, single cell oil, milk fat ding polar
lipids) and fish oil, with the same lipid globule architecture as
in example 1 (comprising 799 mg LA, 139 mg ALA, 17.7 mg
ARA, 17.6 mg DHA)
Non ible oligosaccharides: 0.8 g (galacto-oligosaccharides (short chain — average DP
below 7) and fructo-oligosaccharides (long chain — average DP
above 7) in a 9/1 wt/wt ratio), enting 0.6 g fiber
according to EU regulations.
Vitamins, minerals and other micronutrients according to guidelines.
Claims (17)
1) Use of lipid for the preparation of a ional composition for improving e tissue distribution in an infant selected from the group ting of preterm infants, small for gestational age infants and infants with retarded growth due to physical or mental stress after birth, wherein the lipid is present in lipid globules, having: (a) a volume-weighted mode diameter of at least 1.0 m; and (b) a phospholipid coating, wherein the nutritional composition ses at least 0.5 wt.% phospholipids based on total lipid, and wherein the nutritional composition further comprises 2.1 to 4.1 g protein per 100 kcal and 1.7 to 3.3 g n per 100 ml.
2) The use according to claim 1, wherein improving adipose tissue distribution occurs during or directly after catch-up growth.
3) The use according to claim 1 or 2, n the lipid globules have a volume-weighted mode diameter of at least 1.0 m.
4) The use according to claim 3, wherein the lipid globules have a volume-weighted mode diameter of 3.0 to 8.0 m.
5) The use according to any one of claims 1 to 4, wherein the phospholipids are derived from milk.
6) The use according to any one of claims 1 to 5, wherein the infant is a small for ional age infant.
7) The use according to claim 6, wherein the small for gestational age infant is an intrauterine growth restricted infant.
8) The use according to any one of claims 1 to 7, wherein the nutritional composition comprises 0.3 to 0.7 wt.% arachidonic acid, based on total lipid.
9) An infant formula selected from a preterm formula, a low birthweight formula or a tric formula for catch-up growth comprising protein, carbohydrates and lipid, wherein: (i) the caloric density is 50 to 200 kcal per 100 ml; (ii) lipid is present in 4.4 to 6.0 g per 100 kcal; (iii) protein is present in 2.1 to 4.1 g per 100 kcal and in 1.7 to 3.3 g per 100 ml; (iv) carbohydrates are present in 10 to 12 g per100 kcal, (v) the lipid is present in lipid globules, having: (a) a volume-weighted mode diameter of at least 1.0 m; and (b) a phospholipid coating, wherein the composition comprises at least 0.5 wt.% phospholipids based on total lipid.
10) The infant formula ing to claim 9, which is a preterm formula or a low birthweight formula, comprising 2.6 to 3.4 g protein per 100 kcal and 1.7 to 3.1 g n per 100 ml.
11) The infant a according to claim 9, which is a paediatric formula for catch-up growth, comprising 2.4 to 2.8 g protein per 100 kcal and 1.7 to 3.1 g protein per 100 ml.
12) The infant a according to any one of claims 9 to 11, comprising 0.3 to 0.7 wt.% arachidonic acid, based on total lipid.
13) The infant formula according to any one of claims 9 to 12, comprising 0.3 to 0.5 wt.% docosahexaenoic acid, based on total lipid.
14) A erapeutic method for providing ion to an infant selected from the group consisting of m infants, small for gestational age infants and infants with retarded growth due to physical or mental stress after birth, comprising administering the nutritional composition according to any one of claims 9 to 13 to said infant.
15) A use according to claim 1, substantially as herein described or exemplified.
16) An infant formula according to claim 9, substantially as herein described or exemplified.
17) A method according to claim 14, substantially as herein described or exemplified.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP13191300 | 2013-11-01 | ||
| EP13191300.6 | 2013-11-01 | ||
| PCT/NL2014/050761 WO2015065193A1 (en) | 2013-11-01 | 2014-11-03 | Lipid composition for improving body composition during catch-up growth |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ719159A NZ719159A (en) | 2021-03-26 |
| NZ719159B2 true NZ719159B2 (en) | 2021-06-29 |
Family
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