IMPROVED TOLERANCE IN A LOW CALORIE
INFANT FORMULA
CROSS REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. Provisional Application No.
61/428,833 filed December 30, 2010, which disclosure is incorporated by reference in its
entirety.
FIELD OF THE DISCLOSURE
[0002] The present disclosure is directed to low calorie infant formulas, and in
particular, low calorie infant formulas that have a low buffering capacity, exhibit an
increased rate of protein hydrolysis and digestion, and have improved tolerance, as
compared to full calorie infant formulas. Also disclosed are low calorie liquid infant
formulas that have a reduced (i.e., "low") micronutrient content on a per volume basis, and
exhibit an overall improvement in the physical appearance of the formula, including a
lighter color and improved stability, as compared to low calorie liquid infant formulas
having a higher micronutrient content.
BACKGROUND OF THE DISCLOSURE
[0003] There are numerous types of infant nutritional formulas that are well
known and widely available. These infant formulas comprise a range of nutrients designed
to meet the nutritional needs of the growing infant, and typically include fats,
carbohydrates, proteins, vitamins, minerals, and other nutrients helpful for optimal infant
growth and development.
[0004] Breast milk, however, is generally recognized as the best nutritional source
for newborn infants. It is known that human breast milk provides good immunological
benefits to the breastfed infant. Consequently, most infant formulas are designed to be
closer to breast milk in terms of composition and function.
[0005] It is also known that the composition of human breast milk changes over
the first few weeks following delivery of an infant. Human breast milk is referred to as
colostrum during the first five days after birth, transition milk during days 6-14 after birth,
and mature milk thereafter. During each stage of lactation, the corresponding human breast
milk composition differs considerably. For instance, colostrum and transition milk have
lower caloric densities than mature milk, as well as higher protein and lower carbohydrate
concentrations. Vitamin and mineral concentrations also vary in the three defined human
milk groups.
[0006] Some commercial infant formulas are similar in composition, although not
identical, to mature human breast milk, and are used for both newborns as well as older
infants. It has previously been generally accepted that the feeding of newborn infants
should be conducted with an emphasis on encouraging infant growth, and that such growth
is best accomplished by feeding the infant commercial infant formulas having a similar
nutrient and energy content to mature milk.
[0007] Recently, attempts have been made to formulate infant formulas for
newborns that have a lower energy content, and thus provide fewer calories during the
initial weeks or months of life, than would otherwise be provided from feeding with a
conventional full calorie infant formula. Previous attempts at formulating infant formulas
having a low energy content have involved reducing the levels of one or more
macronutrient (e.g., protein, fat, carbohydrate), while maintaining the micronutrient levels
at approximately the level found in full calorie infant formulas on a per volume basis.
However, the combination of reduced macronutrients and high micronutrients can result in
a formula with poor physical attributes. For instance, such formulas are typically darker in
color, have increased problems with sedimentation, and are more prone to separation over
the shelf life of the product than are full calorie formulas.
[0008] Furthermore, some infant formula fed newborns can experience
gastrointestinal (GI) intolerance problems, including loose stools, gas, and spit-up. The GI
intolerance issues may be at least in part due to incomplete nutrient (e.g., protein) digestion
and absorption by the infant. To address this intolerance problem, some infant formulas
exclude lactose as an ingredient, while others replace intact milk protein with hydrolyzed
protein to lessen the burden on the infant's digestive system.
[0009] Some formula fed infants may also experience more episodes of GI tract
infection than do breast fed infants. One explanation for this phenomenon may be the low
buffering capacity of human breast milk. Human breast milk is known to have lower acid
buffering properties than both cow milk and cow milk-based infant formulas. The low
buffering capacity of human breast milk may allow the natural level of gastric acidity in
infants to be more effective in inactivating orally ingested pathogens.
[0010] It would therefore be desirable to provide a low calorie liquid infant
formula that has improved physical attributes, such as a lighter color and improved
stability, as compared to previously known low calorie infant formulas. It would also be
desirable to provide an infant formula that has a low buffering capacity, similar to breast
milk, and that also has an increased rate of protein hydrolysis and digestion and good
tolerance so as to provide additional benefits to the infant.
SUMMARY OF THE DISCLOSURE
[001 1] The present disclosure is directed to low calorie liquid infant formulas
having improved physical attributes. These formulas have a reduced (i.e., "low")
micronutrient content on a per volume basis, and exhibit an overall improvement in the
physical appearance of the product, including a lighter color and improved stability, as
compared to low calorie liquid infant formulas having a higher micronutrient content. Also
disclosed are low calorie liquid and powder infant formulas that have a low buffering
capacity, exhibit an increased rate of protein hydrolysis and digestion, and/or have an
improved formula tolerance, as compared to conventional full calorie infant formulas. The
low calorie formulas of the present disclosure, when administered to newborn infants
during the first few weeks of life, provide adequate nutrition for the growth and
development of the newborn.
[0012] Thus, in one embodiment, the present disclosure is directed to a method of
improving infant formula tolerance of an infant. The method comprises administering to
the infant an infant formula having an energy content of from about 200 to less than 600
kilocalories per liter of formula.
[0013] In another embodiment, the present disclosure is directed to a method of
improving infant formula tolerance of an infant. The method comprises administering to
the infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 200 to less than 600
kilocalories per liter of formula. At least 65% of the micronutrients are included in the
infant formula in an amount that is from about 30% to about 80% of conventional amounts
of corresponding micronutrients on a per volume basis.
[0014] In another embodiment, the present disclosure is directed to a method of
improving infant formula tolerance of an infant. The method comprises administering to
the infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 200 to about 360
kilocalories per liter of formula. At least 45% of the micronutrients are included in the
infant formula in an amount that is from about 30% to about 65% of conventional amounts
of corresponding micronutrients, on a per volume basis.
[0015] In another embodiment, the present disclosure is directed to a method of
improving infant formula tolerance of an infant. The method comprises administering to
the infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 360 to less than 600
kilocalories per liter of formula. At least 30% of the micronutrients are included in the
infant formula in an amount that is from about 55% to about 80% of conventional amounts
of corresponding micronutrients, on a per volume basis.
[0016] In another embodiment, the present disclosure is directed to a method for
inhibiting gastroesophageal reflux in an infant. The method comprises administering to the
infant an infant formula having an energy content of from about 200 to less than 600
kilocalories per liter of formula.
[0017] In another embodiment, the present disclosure is directed to a method for
inhibiting gastroesophageal reflux in an infant. The method comprises administering to the
infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 200 to less than 600
kilocalories per liter of formula. At least 65% of the micronutrients are included in the
infant formula in an amount that is from about 30% to about 80% of conventional amounts
of corresponding micronutrients on a per volume basis.
[0018] In another embodiment, the present disclosure is directed to a method for
inhibiting gastroesophageal reflux in an infant. The method comprises administering to the
infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 200 to about 360
kilocalories per liter of formula. At least 45% of the micronutrients are included in the
infant formula in an amount that is from about 30% to about 65% of conventional amounts
of corresponding micronutrients, on a per volume basis.
[0019] In another embodiment, the present disclosure is directed to a method for
inhibiting gastroesophageal reflux in an infant. The method comprises administering to the
infant a low micronutrient infant formula comprising micronutrients and at least one
macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof, and having an energy content of from about 360 to less than 600
kilocalories per liter of formula. At least 30% of the micronutrients are included in the
infant formula in an amount that is from about 55% to about 80% of conventional amounts
of corresponding micronutrients, on a per volume basis.
[0020] It has now surprisingly been discovered that low calorie liquid infant
formulas having improved physical attributes can be formulated if a sufficient amount of
one or more micronutrients in the low calorie formula is generally matched to that of full
calorie formulas on a per kilocalorie (kcal) basis, rather than on a per volume basis. These
formulas thus have a reduced (i.e., "low") micronutrient content on a per volume basis, and
exhibit an overall improvement in the physical appearance of the product, including a
lighter color and improved stability, than do low calorie liquid infant formulas having a
higher micronutrient content.
[0021] It has also been discovered that the low calorie liquid or powder infant
formulas have a lower buffering capacity than conventional full calorie infant formulas,
and in some embodiments, have a lower buffering capacity than that of human milk. The
low calorie infant formulas of the present disclosure can thus be used to regulate gastric
acidity in infants, reduce the growth of pathogenic microorganisms in the infant GI tract,
and promote the growth of beneficial microorganisms. The low calorie infant formulas of
the present disclosure have also been found to exhibit an increased rate of protein
hydrolysis and digestion, and thus have an improved formula tolerance, as compared to
conventional, full calorie infant formulas.
BRIEF DESCRIPTION OF THE DRAWINGS
[0022] Figure 1 is a chart showing the buffering strength of various low calorie
days 1-2 and days 3-9 infant formulas, as compared to control full calorie formulas and to
human milk, as discussed in Example 16.
[0023] Figure 2 is a chart showing the buffering capacity of various low calorie
days 1-2 and days 3-9 infant formulas, as compared to control full calorie formulas and to
human milk, as discussed in Example 16.
[0024] Figure 3 is a chart showing the effect of HC1 addition on the pH of low
calorie days 1-2 and days 3-9 reconstituted powder infant formulas, as compared to a
control full calorie formula, as discussed in Example 17.
[0025] Figure 4 is a chart showing the buffering strength of low calorie days 1-2
and days 3-9 reconstituted powder infant formulas, as compared to a control full calorie
formula, as discussed in Example 17.
[0026] Figure 5 is a chart showing the buffering capacity, as measured by pH
decrease following addition of 5.50 mmoles of HC1 to 100 mL of formula, of low calorie
days 1-2 and days 3-9 reconstituted powder infant formulas, as compared to a control full
calorie formula, as discussed in Example 17.
[0027] Figure 6 is a chart showing the buffering capacity, as measured by
increase in [H+] following addition of 5.50 mmoles of HC1 to 100 mL of formula, of low
calorie days 1-2 and days 3-9 reconstituted powder infant formulas, as compared to a
control full calorie formula, as discussed in Example 17.
[0028] Figure 7 is a chart showing the protein molecular weight (MW) median for
low calorie days 1-2 and days 3-9 reconstituted powder infant formulas following in vitro
gastrointestinal digestion, as compared to a control full calorie formula, as discussed in
Example 20.
[0029] Figure 8 is a chart showing the percent total protein having a MW greater
than 5000 Da for low calorie days 1-2 and days 3-9 reconstituted powder infant formulas
following in vitro gastrointestinal digestion, as compared to a control full calorie formula,
as discussed in Example 20.
[0030] Figure 9 is a chart showing the amount of insoluble (indigestible) protein
in the protein pellet following high speed centrifugation of low calorie days 1-2 and days 3-
9 reconstituted powder infant formulas following in vitro gastrointestinal digestion, as
compared to a control full calorie formula, as discussed in Example 20.
[003 1] Figure 10 is a chart showing the protein MW median for low calorie days
1-2 and days 3-9 reconstituted powder infant formulas following pancreatin digestion for
7 1 minutes, as compared to a control full calorie formula, as discussed in Example 23.
[0032] Figure 11 is a chart showing the percent total protein having a MW greater
than 5000 Da for low calorie days 1-2 and days 3-9 reconstituted powder infant formulas
following pancreatin digestion for 7 1 minutes, as compared to a control full calorie
formula, as discussed in Example 23.
[0033] Figure 12 is a chart showing the particle size distribution for retort
sterilized days 1-2 formulas having either a high micronutrient content (Formula 3) or a
low micronutrient content (Formula 1), as discussed in Example 29.
DETAILED DESCRIPTION OF THE DISCLOSURE
[0034] The low calorie liquid infant formulas disclosed herein may have a low
micronutrient content, on a per volume basis, and improved physical attributes as compared
to conventional infant formulas that have a higher micronutrient content. Further, the
methods of the present disclosure utilize low calorie liquid and powder infant formulas to
regulate gastric acidity in infants, reduce the growth of pathogenic microorganisms and
promote the growth of beneficial microorganisms in the infant GI tract, increase the rate of
protein hydrolysis and digestion, and improve formula tolerance. These and other and
optional features of the infant formulas and methods of the present disclosure, as well as
some of the many other optional variations and additions, are described in detail hereafter.
[0035] The terms "retort" and "retort sterilized" are used interchangeably herein,
and unless otherwise specified, refer to the common practice of filling a container, most
typically a metal can or other similar package, with a nutritional liquid, such as a liquid
infant formula, and then subjecting the liquid- filled package to the necessary heat
sterilization step, to form a retort sterilized nutritional liquid product.
[0036] The terms "aseptic" and "aseptic sterilized" are used interchangeably
herein, and unless otherwise specified, refer to the manufacture of a packaged product
without reliance upon the above-described retort packaging step, wherein the nutritional
liquid and package are sterilized separately prior to filling, and then are combined under
sterilized or aseptic processing conditions to form a sterilized, aseptically packaged,
nutritional liquid product.
[0037] The terms "nutritional formula" or "nutritional product" or "nutritional
composition," as used herein, are used interchangeably and, unless otherwise specified,
refer to nutritional liquids, nutritional semi-liquids, nutritional solids, nutritional semi
solids, nutritional powders, nutritional supplements, and any other nutritional food product
as known in the art. The nutritional solids and powders may be reconstituted to form a
nutritional liquid, all of which comprise one or more of fat, protein and carbohydrate, and
are suitable for oral consumption by a human. Nutritional formulas may include infant
formulas.
[0038] The term "nutritional liquid," as used herein, unless otherwise specified,
refers to nutritional products in ready-to-drink liquid form, concentrated form, and
nutritional liquids made by reconstituting the nutritional powders described herein prior to
use.
[0039] The term "nutritional powder," as used herein, unless otherwise specified,
refers to nutritional products in flowable or scoopable form that can be reconstituted with
water or another aqueous liquid prior to consumption and includes both spray dried and
drymixed/dryblended powders.
[0040] The term "nutritional semi-liquid," as used herein, unless otherwise
specified, refers to those forms that are intermediate in properties, such as flow properties,
between liquids and solids, examples of which include thick shakes and liquid gels.
[0041] The term "nutritional semi-solid," as used herein, unless otherwise
specified, refers to those forms that are intermediate in properties, such as rigidity, between
solids and liquids, examples of which include puddings, gelatins, and doughs.
[0042] The term "infant," as used herein, unless otherwise specified, refers to a
child 1 months or younger. The term "preterm infant," as used herein, refers to an infant
born prior to 36 weeks of gestation. The term "term infant," as used herein, refers to an
infant born at or after 36 weeks of gestation.
[0043] The term "newborn infant," as used herein, unless otherwise specified,
refers to infants less than about 3 months of age, including infants from zero to about 2
weeks of age. The newborn infant may be a term or preterm infant.
[0044] The term "infant formula," as used herein, unless otherwise specified,
refers to liquid and solid nutritional products suitable for consumption by an infant. Unless
otherwise specified herein, the term "infant formula" is intended to encompass both term
and preterm infant formulas.
[0045] The term "preterm infant formula," as used herein, unless otherwise
specified, refers to liquid and solid nutritional products suitable for consumption by a
preterm infant.
[0046] The term "micronutrient," as used herein, refers to essential substances
needed by organisms in small quantities. Non-limiting examples include vitamins,
minerals, and the like.
[0047] The term "full calorie infant formula," as used herein, refers to an infant
formula in which the caloric density or energy content of the formula has not been reduced
from that conventionally included in infant formula. Typically, a full calorie infant
formula will have an energy content of at least 600 kcal/L, or even at least 660 kcal/L, and
more typically at least 676 kcal/L, including 600 kcal/L to 800 kcal/L.
[0048] The term "low calorie infant formula," as used herein, refers to an infant
formula that has a lower energy content, on a per volume basis, than a full calorie infant
formula.
[0049] The terms "high micronutrient" or "high micronutrient content," when
referring to the micronutrient content of an infant formula, means at least 80% of the
micronutrients in the infant formula are present in amounts approximately the same as
(typically within about 82% for most micronutrients) the amount of the micronutrients
conventionally included in infant formulas.
[0050] All percentages, parts and ratios as used herein, are by weight of the total
composition, unless otherwise specified. All such weights, as they pertain to listed
ingredients, are based on the active level and, therefore, do not include solvents or by
products that may be included in commercially available materials, unless otherwise
specified.
[005 1] Numerical ranges as used herein are intended to include every number and
subset of numbers within that range, whether specifically disclosed or not. Further, these
numerical ranges should be construed as providing support for a claim directed to any
number or subset of numbers in that range. For example, a disclosure of from 1 to 10
should be construed as supporting a range of from 2 to 8, from 3 to 7, from 5 to 6, from 1
to 9, from 3.6 to 4.6, from 3.5 to 9.9, and so forth.
[0052] All references to singular characteristics or limitations of the present
disclosure shall include the corresponding plural characteristic or limitation, and vice versa,
unless otherwise specified or clearly implied to the contrary by the context in which the
reference is made.
[0053] All combinations of method or process steps as used herein can be
performed in any order, unless otherwise specified or clearly implied to the contrary by the
context in which the referenced combination is made.
[0054] The various embodiments of the infant formulas of the present disclosure
may also be substantially free of any optional or selected ingredient or feature described
herein, provided that the remaining infant formulas still contains all of the required
ingredients or features as described herein. In this context, and unless otherwise specified,
the term "substantially free" means that the selected infant formulas contains less than a
functional amount of the optional ingredient, typically less than 1%, including less than
0.5%, including less than 0.1%, and also including zero percent, by weight of such optional
or selected ingredient.
[0055] The infant formulas and methods of the present disclosure may comprise,
consist of, or consist essentially of the elements of the products and methods as described
herein, as well as any additional or optional element described herein or otherwise useful in
nutritional infant formula applications.
Product Form
[0056] The infant formulas of the present disclosure may be formulated and
administered in any known or otherwise suitable oral product form. Any solid, semi-solid,
liquid, semi-liquid or powder form, including combinations or variations thereof, are
suitable for use herein, provided that such forms allow for safe and effective oral delivery
to the individual of the essential ingredients as also defined herein.
[0057] Specific non-limiting examples of product forms suitable for use with
products and methods disclosed herein include, for example, liquid and powder preterm
infant formulas, liquid and powder term infant formulas, and liquid and powder elemental
and semi-elemental formulas.
[0058] The infant formulas of the present disclosure are preferably formulated as
dietary product forms, which are defined herein as those embodiments comprising the
essential ingredients of the present disclosure in a product form that then contains at least
one of fat, protein, and carbohydrate.
[0059] The infant formulas may be formulated with sufficient kinds and amounts
of nutrients to provide a sole, primary, or supplemental source of nutrition, or to provide a
specialized nutritional product for use in infants afflicted with specific diseases or
conditions or with a targeted nutritional benefit.
[0060] Desirably, the infant formulas of the present disclosure are formulated for
newborn infants, including both term and preterm newborn infants. Preferably, the infant
formula is formulated for feeding to newborn infants within the first few weeks following
birth, and more preferably for feeding to newborn infants from age zero to two weeks. In
one embodiment, the infant formula is formulated for feeding to newborn infants in the
first two days following birth. Such a formula is referred to herein as a "days 1-2 formula"
or a "days 1-2 infant formula." In other embodiments, the infant formula is formulated for
feeding to newborn infants during days 3-9 following birth. Such a formula is referred to
herein a "days 3-9 formula" or a "days 3-9 infant formula." It is to be understood that the
administration of a days 1-2 infant formula of the present disclosure is not limited to
administration during only the first two days following birth, but may be administered to
older infants as well in some embodiments. Similarly, the administration of a days 3-9
infant formula is not limited to administration during only days 3-9 following birth, but
may be administered to infants of other ages as well in some embodiments.
Nutritional Liquids
[0061] Nutritional liquids include both concentrated and ready-to-feed nutritional
liquids. These nutritional liquids are most typically formulated as suspensions, emulsions
or clear or substantially clear liquids.
[0062] Nutritional emulsions suitable for use may be aqueous emulsions
comprising proteins, fats, and carbohydrates. These emulsions are generally flowable or
drinkable liquids at from about 1°C to about 25°C and are typically in the form of oil-inwater,
water-in-oil, or complex aqueous emulsions, although such emulsions are most
typically in the form of oil-in-water emulsions having a continuous aqueous phase and a
discontinuous oil phase.
[0063] The nutritional liquids may be and typically are shelf stable. The
nutritional liquids typically contain up to about 95% by weight of water, including from
about 50% to about 95%, also including from about 60%> to about 90%>, and also including
from about 70% to about 85%, of water by weight of the nutritional liquid. The nutritional
liquids may have a variety of product densities, but most typically have a density greater
than about 1.03 g/mL, including greater than about 1.04 g/mL, including greater than about
1.055 g/mL, including from about 1.06 g/mL to about 1.12 g/mL, and also including from
about 1.085 g/mL to about 1.10 g/mL.
[0064] The nutritional liquid may have a pH ranging from about 3.5 to about 8,
but are most advantageously in a range of from about 4.5 to about 7.5, including from
about 5.5 to about 7.3, including from about 6.2 to about 7.2.
[0065] Although the serving size for the nutritional liquid can vary depending
upon a number of variables, a typical serving size is generally at least about 2 mL, or even
at least about 5 mL, or even at least about 10 mL, or even at least about 25 mL, including
ranges from about 2 mL to about 300 mL, including from about 100 mL to about 300 mL,
from about 4 mL to about 250 mL, from about 150 mL to about 250 mL, from about 10 mL
to about 240 mL, and from about 190 mL to about 240 mL.
Nutritional Powders
[0066] The nutritional powders are in the form of flowable or substantially
flowable particulate compositions, or at least particulate compositions. Particularly
suitable nutritional powder forms include spray dried, agglomerated or dryblended powder
compositions, or combinations thereof, or powders prepared by other suitable methods.
The compositions can easily be scooped and measured with a spoon or similar other
device, wherein the compositions can easily be reconstituted with a suitable aqueous liquid,
typically water, to form a nutritional liquid, such as an infant formula, for immediate oral
or enteral use. In this context, "immediate" use generally means within about 48 hours,
most typically within about 24 hours, preferably right after or within 20 minutes of
reconstitution.
Energy Content
[0067] The infant formulas of the present disclosure have low energy content
(used herein interchangeably with the term "caloric density") relative to conventional term
and preterm infant formulas. Specifically, the infant formulas of the present disclosure
provide a caloric density or energy content of from about 200 kcal/L to less than 600
kcal/L, including from about 200 kcal/L to about 500 kcal/L, and more particularly from
about 250 kcal/L to about 500 kcal/L. The days 1-2 infant formulas of the present
disclosure provide a caloric density or energy content of from about 200 kcal/L to about
360 kcal/L, including from about 200 kcal/L to about 350 kcal/L, also including from about
250 kcal/L to about 350 kcal/L, from about 250 kcal/L to about 310 kcal/L, and more
particularly about 250 kcal/L or about 270 kcal/L. The days 3-9 infant formulas of the
present disclosure provide a caloric density or energy content of from about 360 kcal/L to
less than 600 kcal/L, including from about 370 kcal/L to less than 600 kcal/L, also
including from about 360 kcal/L to about 500 kcal/L, from about 390 kcal/L to about 470
kcal/L, and in particular about 406 kcal/L or about 410 kcal/L. In contrast to the infant
formulas of the present disclosure, the caloric density or energy content of conventional
term and preterm infant formulas, which are also referred to herein as "full calorie infant
formulas," is significantly higher, typically ranging from 600 kcal/L to 880 kcal/L.
[0068] When the infant formulas of the present disclosure are in powder form,
then the powder is intended for reconstitution prior to use to obtain the above-noted caloric
densities and other nutrient requirements as described herein. Likewise, when the infant
formulas of the present disclosure are in a concentrated liquid form, then the concentrate is
intended for dilution prior to use to obtain the requisite caloric densities and nutrient
requirements. The infant formulas can also be formulated as ready-to-feed liquids already
having the requisite caloric densities and nutrient requirements.
[0069] The infant formulas of the present disclosure are desirably administered to
infants, and in particular newborn infants, in accordance with the methods described in
detail herein. Such methods may include feedings with the infant formulas in accordance
with the daily formula intake volumes described herein.
[0070] The energy component of the infant formula is most typically provided by
a combination of fat, protein, and carbohydrate nutrients. The protein may comprise from
about 4% to about 40% of the total calories, including from about 10% to about 30%, also
including from about 15% to about 25%; the carbohydrate may comprise less than 40% of
the total calories, including from about 5% to about 37%, also including less than about
36%, and also including from about 20% to about 33%; and the fat may comprise the
remainder of the formula calories, most typically less than about 60% of the calories,
including from about 30% to about 60%. Other exemplary amounts are set forth
hereinafter.
Micronutrients
[0071] In addition to a low energy content, in some embodiments, the infant
formulas of the present disclosure are also characterized by a low micronutrient content, on
a per volume basis.
[0072] As described herein, previous attempts at formulating infant formulas
having a low energy content have involved reducing the levels of one or more
macronutrients (e.g., protein, fat, carbohydrate), while maintaining the micronutrient level
at approximately the level found in full calorie infant formulas on a per volume basis. For
example, one liter of such a low calorie formula would have reduced amounts of one or
more macronutrient, as compared to one liter of the full calorie formula, but approximately
the same amount (typically within at least about 82% for most micronutrients) of
micronutrients as are found in one liter of the full calorie formula. However, the
combination of reduced macronutrients and high micronutrients results in a formula with
poor physical attributes. For instance, such formulas are typically darker in color, have
increased problems with sedimentation, and are more prone to separation over the shelf life
of the product than are full calorie formulas.
[0073] It has now surprisingly been discovered that low calorie liquid infant
formulas having improved physical attributes can be formulated if the amount of
micronutrients in the low calorie formula is generally matched to that of full calorie
formulas on a per kilocalorie (kcal) basis, rather than on a per volume basis. For example,
100 kcal of the low calorie formula would comprise approximately the same amount
(typically within about 80% for most micronutrients) of micronutrients as are found in 100
kcal of the full calorie formula. In this example, the micronutrient content of the low
calorie formula would be formulated on a 100 kcal basis. Low calorie liquid infant
formulas that are formulated on a per kcal basis have a reduced (i.e., "low") micronutrient
content on a per volume basis (i.e., as compared to the same volume of a full calorie
formula), and exhibit an overall improvement in the physical appearance of the formula,
including a lighter color and improved stability.
[0074] Thus, in some embodiments, the present disclosure is directed to low
calorie, low micronutrient infant formulas. As used herein, the term "low micronutrient" or
"low micronutrient content," when referring to infant formula, means the amount of at least
a portion of the micronutrients included in the infant formula is lower than the amount of
the corresponding micronutrients conventionally included in infant formula, on a per
volume basis. It should be understood that it is not necessary for the amount of all
micronutrients included in an infant formula to be lower than the conventional amounts of
corresponding micronutrients, on a per volume basis, in order for the infant formula to be
considered a low micronutrient infant formula. Reduction of a portion of the
micronutrients in the infant formula, as compared to conventional amounts on a per volume
basis, is sufficient.
[0075] The amount of micronutrients "conventionally included in infant formula"
or "conventional amounts" of micronutrients refers to industry recognized standard
amounts of micronutrients, on a per volume basis, for inclusion in infant formula in order
to achieve adequate growth and development of infants. Conventional amounts of select
micronutrients that may be included in infant formula, on a per volume basis, are set forth
in Table A (ready-to-feed formulas) and Table B (reconstituted powder formulas) below.
Table A: Ready-to-Feed Formulas
Table B: Reconstituted Powder Formulas
[0076] Exemplary non-limiting micronutrients that may be included in
conventional infant formulas include vitamin A, vitamin D, vitamin E, vitamin K, thiamin,
riboflavin, vitamin B6, vitamin B12, niacin, folic acid, pantothenic acid, biotin, vitamin C,
choline, inositol, calcium, phosphorus, magnesium iron, zinc, manganese, copper, iodine,
sodium, potassium, chloride, fluoride, selenium, and combinations thereof. Some
exemplary conventional infant formula may include a combination of copper, phosphorus,
iron, calcium, and zinc. Some other exemplary conventional infant formulas may include a
combination of copper, iron and phosphorus.
[0077] In one specific embodiment, at least two of copper, phosphorus, iron,
calcium, and zinc are present in the low micronutrient formulas in amount of about 5%
less, or even 10% less, or even 20%> less, or even 30%> less, or even 50%> less, or even 75%
less, or even 80%> less, or even 90%> less than the amounts set forth in Tables A and B
above. In another specific embodiment, iron and copper are present in the low
micronutrient formulas in amount of about 5% less, or even 10% less, or even 20%> less, or
even 30%> less, or even 50%> less, or even 75% less, or even 80%> less, or even 90%> less
than the amounts set forth in Tables A and B above.
[0078] It should be understood that Tables A and B do not contain an exhaustive
list of suitable micronutrients that can be included in the infant formulas of the present
disclosure. Further, the low micronutrient infant formulas of the present disclosure need
not comprise every micronutrient listed in Tables A and B. The present disclosure
contemplates infant formulas comprising any combination of one or more of the
micronutrients listed in Tables A and B and/or other micronutrients known in the art as
suitable for inclusion in infant formula. Standard or conventional amounts of these and
other micronutrients (on a per 100 kcal basis) can readily be determined with reference to
European and/or United States infant formula regulations and standards.
[0079] When determining whether the micronutrient content in an infant formula
is low, on a per volume basis, as compared to conventional amounts, the amounts of
"corresponding micronutrients" should be compared. In this instance, "corresponding
micronutrients" refers to the same micronutrients as are present in the infant formula being
evaluated. For example, if the infant formula comprises the micronutrients calcium,
phosphorus, and magnesium, the amounts of these micronutrients in the infant formula
should be compared to the amounts of calcium, phosphorus, and magnesium, respectively,
that are conventionally included in infant formula, to determine if the amount of these
micronutrients in the infant formula is "low."
[0080] The amount of micronutrients included in the low micronutrient infant
formulas of the present disclosure can be expressed as a percentage of the conventional
amounts of corresponding micronutrients, on a per volume basis. For instance, in some
embodiments of the present disclosure, low micronutrient infant formulas are provided
wherein the micronutrients are included in the infant formula in an amount that is from
about 30% to about 80% of conventional amounts of corresponding micronutrients, on a
per volume basis, including from about 30%> to about 65%, from about 55% to about 80%>,
from about 40% to about 70%, from about 40% to about 50%, and from about 60% to
about 70% of conventional amounts of corresponding micronutrients, all on a per volume
basis. Typically, at least 65% of the micronutrients, including at least 75%, at least 80%>, at
least 90%, and 100% of the micronutrients in the low micronutrient infant formulas of the
present disclosure are included in the infant formula in amounts that are from about 30% to
about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis.
[0081] In some embodiments, low micronutrient infant formulas are provided
wherein the micronutrients are included in the infant formula in an amount that is from
about 30% to about 65% of conventional amounts of corresponding micronutrients, on a
per volume basis, including from about 35% to about 60%>, from about 40%> to about 50%>,
from about 40% to about 45%, and in particular about 40% of conventional amounts of
corresponding micronutrients, all on a per volume basis. In such embodiments, typically at
least 45% of the micronutrients, including at least 50%, at least 60% at least 75%, at least
80%, at least 90%, and 100% of the micronutrients in the low micronutrient infant formula
are included in the infant formula in amounts that are from about 35% to about 60% of
conventional amounts of corresponding micronutrients, on a per volume basis. In other
embodiments, at least 10% of the micronutrients, including at least 25%, at least 50%, at
least 60%, at least 75%, and at least 80% of the micronutrients in the low micronutrient
infant formula are included in the infant formula in amounts that are from about 40% to
about 50% of conventional amounts of corresponding micronutrients, on a per volume
basis. Such low micronutrient infant formulas may include, for example, days 1-2 infant
formulas.
[0082] In other embodiments, low micronutrient infant formulas are provided
wherein the micronutrients are included in the infant formula in an amount that is from
about 55% to about 80% of conventional amounts of corresponding micronutrients, on a
per volume basis, including from about 60%> to about 75%, from about 60%> to about 70%>,
from about 60% to about 65%, and in particular about 60% of conventional amounts of
corresponding micronutrients, all on a per volume basis. In such embodiments, typically at
least 30% of the micronutrients, including at least 50%>, at least 60%>, at least 75%, at least
80%, at least 90%, and 100% of the micronutrients in the low micronutrient infant formula
are included in the infant formula in amounts that are from about 55% to about 80% of
conventional amounts of corresponding micronutrients, on a per volume basis. In other
embodiments, at least 10%, including at least 25%, at least 50%, at least 60%, at least 75%,
and at least 80%, of the micronutrients in the low micronutrient infant formula are included
in the infant formula in amounts that are from about 60% to about 70% of conventional
amounts of corresponding micronutrients, on a per volume basis. Such low micronutrient
infant formulas may include, for example, days 3-9 infant formulas.
[0083] In some embodiments where the micronutrient includes minerals, the
minerals are included in the low micronutrient infant formula in an amount that is from
about 30% to about 80% of conventional amounts of corresponding minerals, on a per
volume basis, including from about 30%> to about 65%, from about 55% to about 80%>,
from about 40% to about 70%, from about 40% to about 50%, and from about 60% to
about 70% of conventional amounts of corresponding minerals, all on a per volume basis.
Typically, at least 10%>, including at least 45%, at least 50%>, at least 60%>, at least 70%>, at
least 75%, at least 80%, at least 90%, and 100%, of the minerals in the low micronutrient
infant formulas of the present disclosure are included in the infant formula in amounts that
are from about 30% to about 80% of conventional amounts of corresponding minerals, on a
per volume basis.
[0084] In still other embodiments, the minerals are included in the low
micronutrient infant formula in an amount that is from about 30% to about 65% of
conventional amounts of corresponding minerals, on a per volume basis, including from
about 35% to about 60%, from about 40% to about 50%, from about 40% to about 45%,
and in particular about 40% of conventional amounts of corresponding minerals, all on a
per volume basis. In such embodiments, typically at least 10%>, including at least 25%, at
least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100%, of the minerals
in the low micronutrient infant formula are included in the infant formula in amounts that
are from about 30% to about 65% of conventional amounts of corresponding minerals, on a
per volume basis. In other embodiments, at least 10%, including at least 25%, at least
50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100%, of the minerals in
the low micronutrient infant formula are included in the infant formula in amounts that are
from about 40% to about 50% of conventional amounts of corresponding minerals, on a per
volume basis. Such low micronutrient infant formulas may include, for example, days 1-2
infant formulas.
[0085] In still other embodiments, the minerals are included in the low
micronutrient infant formula in an amount that is from about 55% to about 80% of
conventional amounts of corresponding minerals, on a per volume basis, including from
about 60% to about 75%, from about 60%> to about 70%>, from about 60%> to about 65%,
and in particular about 60% of conventional amounts of corresponding minerals, all on a
per volume basis. In such embodiments, typically at least 10%>, including at least 25%, at
least 50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100%, of the minerals
in the low micronutrient infant formula are included in the infant formula in amounts that
are from about 55% to about 80% of conventional amounts of corresponding minerals, on a
per volume basis. In other embodiments, at least 10%>, including at least 25%, at least
50%, at least 60%, at least 75%, at least 80%, at least 90%, and 100%, of the minerals in
the low micronutrient infant formula are included in the infant formula in amounts that are
from about 60% to about 70% of conventional amounts of corresponding minerals, on a per
volume basis. Such low micronutrient infant formulas may include, for example, days 3-9
infant formulas.
[0086] In some embodiments where the micronutrient includes vitamins, the
vitamins are included in the low micronutrient infant formula in an amount that is from
about 30% to about 80% of conventional amounts of corresponding vitamins, on a per
volume basis, including from about 30% to about 65%, from about 55% to about 80%,
from about 40% to about 70%, from about 40% to about 50%, and from about 60% to
about 70% of conventional amounts of corresponding vitamins, all on a per volume basis.
Typically, at least 45%, including at least 50%, at least 60%, at least 70%, at least 80%, at
least 85%, at least 90%, and 100%, of the vitamins in the low micronutrient infant formulas
of the present disclosure are included in the infant formula in amounts that are from about
30% to about 80% of conventional amounts of corresponding vitamins, on a per volume
basis.
[0087] In still other embodiments, the vitamins are included in the low
micronutrient infant formula in an amount that is from about 30% to about 65% of
conventional amounts of corresponding vitamins, on a per volume basis, including from
about 35% to about 60%, from about 40% to about 50%, from about 40% to about 45%,
and in particular about 40% of conventional amounts of corresponding vitamins, all on a
per volume basis. In such embodiments, typically at least 10%, including at least 25%, at
least 50%, at least 60%>, at least 75%, at least 80%>, at least 90%>, and 100%, of the vitamins
in the low micronutrient infant formula are included in the infant formula in amounts that
are from about 30% to about 65% of conventional amounts of corresponding vitamins, on a
per volume basis. In other embodiments, at least 10%, including at least 25%, at least
50%, at least 60%, at least 75%, and at least 80%, of the vitamins in the low micronutrient
infant formula are included in the infant formula in amounts that are from about 40% to
about 50% of conventional amounts of corresponding vitamins, on a per volume basis.
Such low micronutrient infant formulas may include, for example, days 1-2 infant
formulas.
[0088] In still other embodiments, the vitamins are included in the low
micronutrient infant formula in an amount that is from about 55% to about 80% of
conventional amounts of corresponding vitamins, on a per volume basis, including from
about 60% to about 75%, from about 60%> to about 70%>, from about 60%> to about 65%,
and in particular about 60% of conventional amounts of corresponding vitamins, all on a
per volume basis. In such embodiments, typically at least 10%>, including at least 25%, at
least 50%o, at least 60%, at least 75%, at least 80%, at least 90%, and 100%, of the vitamins
in the low micronutrient infant formula are included in the infant formula in amounts that
are from about 55% to about 80% of conventional amounts of corresponding vitamins, on a
per volume basis. In other embodiments, at least 10%, including at least 25%, at least
50%, at least 60%, at least 75%, at least 80%, and at least 90%, of the vitamins in the low
micronutrient infant formula are included in the infant formula in amounts that are from
about 60% to about 70% of conventional amounts of corresponding vitamins, on a per
volume basis. Such low micronutrient infant formulas may include, for example, days 3-9
infant formulas.
[0089] Suitable micronutrients for inclusion in the infant formulas of the present
disclosure include vitamins or related nutrients, minerals, and combinations thereof. Nonlimiting
examples of suitable vitamins include vitamin A, vitamin D, vitamin E, vitamin K,
thiamine, riboflavin, pyridoxine, vitamin B5, vitamin B6, vitamin B12, niacin, folic acid,
pantothenic acid, biotin, vitamin C, choline, inositol, ascorbic acid, salts and derivatives
thereof, and combinations thereof.
[0090] Non-limiting examples of suitable minerals that may be included in the
infant formulas of the present disclosure include calcium, phosphorus, magnesium, iron,
zinc, manganese, copper, iodine, sodium, potassium, molybdenum, chromium, chloride,
fluoride, selenium, and combinations thereof.
[0091] Any infant formula may be formulated with a low micronutrient content as
disclosed herein, including both retort and aseptic ready-to-feed nutritional liquids,
concentrated nutritional liquids, and nutritional powders.
Macronutrients
[0092] The infant formulas of the present disclosure may further comprise one or
more macronutrient, in addition to the micronutrients described herein. The macronutrients
include protein, fat, carbohydrate, and combinations thereof. Macronutrients suitable for
use herein include any protein, fat, carbohydrate, or source thereof that is known for or
otherwise suitable for use in an oral nutritional product, provided that the macronutrient is
safe and effective for oral administration to infants and is otherwise compatible with the
other ingredients in the infant formula.
[0093] Although total concentrations or amounts of the protein, fat, and
carbohydrate may vary depending upon the product form (e.g., powder or ready-to-feed
liquid) and targeted dietary needs of the intended user, such concentrations or amounts
most typically fall within one of the embodied ranges described in the following table (each
numerical value is preceded by the term "about"), inclusive of any other essential fat,
protein, and/or carbohydrate ingredients as described herein. For powder embodiments, the
amounts in the following table are amounts following reconstitution of the powder.
Table C
[0094] The total concentrations or amounts of the protein, fat, and carbohydrate
may also vary depending upon whether the infant formula is a days 1-2 formula or a days
3-9 formula. The concentration of protein, fat, and carbohydrate for the days 1-2 and the
days 3-9 formulas are most typically formulated within any of the embodied ranges
described in the following table (each numerical value is preceded by the term "about"),
inclusive of any other essential fat, protein, and/or carbohydrate ingredients as described
herein. For powder embodiments, the amounts in the following table are amounts
following reconstitution.
Table D
[0095] The level or amount of carbohydrate, fat, and protein in the infant formula
(whether a powder formula or a liquid ready-to-feed or concentrated liquid) may also be
characterized in addition to or in the alternative as a percentage of total calories in the
infant formulas. These macronutrients for infant formulas of the present disclosure are
most typically formulated within any of the caloric ranges described in the following table
(each numerical value is preceded by the term "about").
Table E
Protein
[0096] The infant formulas of the present disclosure may comprise protein in
addition to the micronutrients described herein. Any known or otherwise suitable protein
or protein source may be included in the infant formulas of the present disclosure, provided
that such proteins are suitable for feeding to infants, and in particular, newborn infants.
[0097] Non-limiting examples of suitable protein or sources thereof for use in the
infant formulas include hydrolyzed, partially hydrolyzed or non-hydrolyzed proteins or
protein sources, which may be derived from any known or otherwise suitable source such
as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn), vegetable
(e.g., soy), or combinations thereof. Non-limiting examples of such proteins include milk
protein isolates, milk protein concentrates as described herein, casein protein isolates,
extensively hydrolyzed casein, whey protein, sodium or calcium casemates, whole cow
milk, partially or completely defatted milk, soy protein isolates, soy protein concentrates,
and so forth. The proteins for use herein can also include, or be entirely or partially
replaced by, free amino acids known for use in nutritional products, non-limiting examples
of which include L-alanine, L-aspartic acid, L-glutamic acid, glycine, L-histidine, Lisoleucine,
L-leucine, L-phenylalanine, L-proline, L-serine, L-threonine, L-valine, Ltryptophan,
L-glutamine, L-tyrosine, L-methionine, L-cysteine, taurine, L-arginine, Lcarnitine,
and combinations thereof.
Fat
[0098] The infant formulas of the present disclosure may comprise a source or
sources of fat in addition to micronutrients described herein. Suitable sources of fat for use
in the infant formulas disclosed herein include any fat or fat source that is suitable for use
in an oral nutritional product and is compatible with the essential elements and features of
such products, provided that such fats are suitable for feeding to infants.
[0099] Non-limiting examples of suitable fats or sources thereof for use in the
infant formulas described herein include coconut oil, fractionated coconut oil, soybean oil,
corn oil, olive oil, safflower oil, high oleic safflower oil, high GLA-safflower oil, oleic
acids, MCT oil (medium chain triglycerides), sunflower oil, high oleic sunflower oil,
structured triglycerides, palm and palm kernel oils, palm olein, canola oil, flaxseed oil,
borage oil, evening primrose oil, blackcurrant seed oil, transgenic oil sources, marine oils
(e.g., tuna, sardine), fish oils, fungal oils, algae oils, cottonseed oils, and combinations
thereof. In one embodiment, suitable fats or sources thereof include oils and oil blends
including long chain polyunsaturated fatty acids (LC-PUFAs). Some non-limiting specific
polyunsaturated acids for inclusion include, for example, docosahexaenoic acid (DHA),
arachidonic acid (ARA), eicosapentaenoic acid (EPA), linoleic acid (LA), and the like.
Non-limiting sources of arachidonic acid and docosahexaenoic acid include marine oil, egg
derived oils, fungal oil, algal oil, and combinations thereof.
Carbohydrate
[00100] The infant formulas of the present disclosure may comprise any
carbohydrates that are suitable for use in an oral nutritional product, such as infant formula,
and are compatible with the essential elements and features of such product.
[00101] Non-limiting examples of suitable carbohydrates or sources thereof for
use in the infant formulas described herein may include maltodextrin, hydrolyzed, intact, or
modified starch or cornstarch, glucose polymers, corn syrup, corn syrup solids, rice-derived
carbohydrates, rice syrup, pea-derived carbohydrates, potato-derived carbohydrates,
tapioca, sucrose, glucose, fructose, lactose, high fructose corn syrup, honey, sugar alcohols
(e.g., maltitol, erythritol, sorbitol), artificial sweeteners (e.g., sucralose, acesulfame
potassium, stevia), indigestible oligosaccharides such as fructooligosaccharides (FOS), and
combinations thereof. In one embodiment, the carbohydrate may include a maltodextrin
having a DE value of less than 20.
Other Optional Ingredients
[00102] The infant formulas of the present disclosure may further comprise other
optional ingredients that may modify the physical, chemical, aesthetic or processing
characteristics of the products or serve as pharmaceutical or additional nutritional
components when used in the targeted population. Many such optional ingredients are
known or otherwise suitable for use in medical food or other nutritional products or
pharmaceutical dosage forms and may also be used in the compositions herein, provided
that such optional ingredients are safe for oral administration and are compatible with the
essential and other ingredients in the selected product form.
[00103] Non-limiting examples of such optional ingredients include
preservatives, anti-oxidants, emulsifying agents, buffers, fructooligosaccharides,
galactooligosaccharides, human milk oligosaccharides and other prebiotics, pharmaceutical
actives, additional nutrients as described herein, colorants, flavors, thickening agents and
stabilizers, emulsifying agents, lubricants, carotenoids (e.g., beta-carotene, zeaxanthin,
lutein, lycopene), and so forth, and combinations thereof.
[00104] A flowing agent or anti-caking agent may be included in the powder
infant formulas as described herein to retard clumping or caking of the powder over time
and to make a powder embodiment flow easily from its container. Any known flowing or
anti-caking agents that are known or otherwise suitable for use in a nutritional powder or
product form are suitable for use herein, non limiting examples of which include tricalcium
phosphate, silicates, and combinations thereof. The concentration of the flowing agent or
anti-caking agent in the nutritional product varies depending upon the product form, the
other selected ingredients, the desired flow properties, and so forth, but most typically
range from about 0.1% to about 4%, including from about 0.5%> to about 2%, by weight of
the nutritional product.
[0105] A stabilizer may also be included in the infant formulas. Any stabilizer
that is known or otherwise suitable for use in a nutritional product is also suitable for use
herein, some non-limiting examples of which include gums such as xanthan gum. The
stabilizer may represent from about 0.1% to about 5.0%, including from about 0.5% to
about 3%, including from about 0.7% to about 1.5%, by weight of the infant formula.
Stability
[0106] The low calorie, low micronutrient liquid infant formulas of the present
disclosure advantageously exhibit improved physical attributes, including improved
stability, as compared to low calorie, high micronutrient formulas. Physical stability issues
in liquid infant formulas often arise when the formulas are stored for extended periods of
time prior to use. During this time, components of the formulas, fats for example, often
separate from the aqueous components. Components of the infant formula may also fall
out of suspension, forming sediment at the bottom of the formula container. Although this
phase separation and sedimentation may be rectified by shaking the formula to remix
formula components, such phase separation and sedimentation often results in greatly
diminished consumer acceptance of the product.
[0 107] It has now been discovered that the micronutrient content of low calorie
liquid infant formulas may affect the stability of the infant formulas. In particular, the low
calorie, low micronutrient liquid infant formulas of the present disclosure advantageously
exhibit less sedimentation and less separation over the shelf life of the formulas, than do
low calorie, high micronutrient formulas.
Protein Loading
[0108] A variety of measures may be used to demonstrate the stability of liquid
infant formulas. For instance, one way the stability of liquid infant formulas can be
determined is by measuring the protein loading levels. Protein loading levels are expressed
as the protein percent of a cream layer formed following high speed centrifugation of the
infant formula (the number of grams of protein per 100 grams of cream layer). Suitable
techniques for determining protein loading levels are described in detail in the examples of
the current disclosure.
[0109] The stability of a liquid infant formula emulsion generally increases with
increasing protein loading levels. It has now been discovered that low calorie, low
micronutrient retort sterilized liquid infant formulas have higher levels of protein loading
than low calorie, high micronutrient retort sterilized liquid infant formulas. This was found
to be the case for both days 1-2 retort infant formulas and days 3-9 retort infant formulas.
[01 10] Thus, in one aspect, the present disclosure is directed to a low calorie, low
micronutrient liquid infant formula having an increased protein loading level, as compared
to a low calorie, high micronutrient infant formula. Preferably, the low calorie, low
micronutrient liquid infant formula is a retort sterilized, ready-to-feed (RTF) formula. In
embodiments where the low calorie, low micronutrient liquid infant formula is a days 1-2
infant formula, the infant formula will typically have a protein loading level of at least
about 5.0%, including from about 5.0% to about 7.0%, from about 5.5% to about 6.5%,
from about 5.7% to about 6.1%, and in particular about 5.9%.
[01 11] In embodiments where the low calorie, low micronutrient liquid infant
formula is a days 3-9 infant formula, the infant formula will typically have a protein
loading value of at least about 6.0%, including from about 6.0%> to about 8.0%>, from about
6 .5% to about 7.5%, from about 6.7% to about 7.1%>, and in particular about 6.9%.
Preferably, the low calorie, low micronutrient liquid infant formula is retort sterilized.
Particle Size
[01 12] Another measure that may be used to demonstrate the stability of liquid
infant formulas is particle size distribution and the average size of particles present in the
infant formula. Particle size distribution and average particle size may be determined using
any technique known in the art. One technique, described in the examples of the current
disclosure, involves the use of a light scattering machine (e.g., Beckman Coulter LS 13
320), which measures the size distribution of particles suspended in a sample of the liquid
infant formula using multiple wavelength light sources. Other suitable techniques may also
be used.
[01 13] Stability of a liquid infant formula emulsion generally increases with
reducing particle size. It has now been discovered that the low calorie, low micronutrient
days 1-2 retort sterilized liquid infant formulas of the present disclosure have a larger
number of small particles, and a smaller average particle size for particles present in the
formulas, than do low calorie, high micronutrient days 1-2 retort sterilized liquid infant
formulas.
[01 14] Thus, in one aspect, the present disclosure is directed to a low calorie, low
micronutrient liquid infant formula having a smaller average particle size for particles
present in the formula, as compared to a low calorie, high micronutrient liquid infant
formula. Preferably, the low calorie, low micronutrient liquid infant formula is a retort
sterilized RTF formula, and more preferably is a days 1-2 retort sterilized liquid infant
formula. In embodiments where the low calorie, low micronutrient liquid infant formula is
a days 1-2 infant formula, particles present in the infant formula will typically have an
average particle size of from about 0.1 mih to about 1.0 m h, including from about 0.15 mih
to about 0.8 mih, and from about 0.15 mih to about 0.7 mih.
[01 15] Typically, for the low calorie, low micronutrient days 1-2 liquid infant
formulas of the present disclosure, at least about 50%, including from about 50% to about
100%, and from about 50% to about 70% of the particles present in the infant formula will
have a particle size (diameter) of from about 0.15 mih to about 0.8 mih.
Creaming Velocity
[01 16] Another measure that may be used to demonstrate the stability of liquid
infant formulas is creaming velocity. Creaming velocity measures the rate of movement of
particles through a liquid sample, in this instance, an infant formula, and is predictive of the
capacity of the infant formula to form a cream layer upon standing for extended periods of
time or upon centrifugation. Creaming velocity can be calculated using the following
equation:
2 Pfluid Pparticle 2
V cream = g R
9 h
wherein:
Vcream is the creaming velocity
Pfiuid is the density of the formula
Pparticie is the density of the particles
h is the viscosity of the formula
R is the average particle size
g is the gravitational acceleration
[01 17] Stability of a liquid infant formula emulsion generally increases with
decreasing creaming velocity. It has now been discovered that the low calorie, low
micronutrient days 1-2 retort sterilized liquid infant formulas of the present disclosure have
a lower creaming velocity, than do low calorie, high micronutrient days 1-2 retort sterilized
liquid infant formulas.
[01 18] Thus, in one aspect, the present disclosure is directed to a low calorie, low
micronutrient liquid infant formula having a low creaming velocity, as compared to a low
calorie, high micronutrient infant formula. Preferably, the low calorie, low micronutrient
liquid infant formula is a retort sterilized RTF formula, and more preferably is a days 1-2
retort sterilized liquid infant formula. In embodiments where the low calorie, low
micronutrient liquid infant formula is a days 1-2 infant formula, the infant formula will
typically have a creaming velocity about 5.0 cm/day or less, including from about 1.0
cm/day to about 5.0 cm/day, from about 3.0 cm/day to about 3.5 cm/day, and in particular
about 3.2 cm/day.
Color
[01 19] The low calorie, low micronutrient liquid infant formulas of the present
disclosure also advantageously exhibit improved color, as compared to low calorie, high
micronutrient formulas.
[0120] Liquid infant formulas contain a variety of nutrients that potentially
interact during formulation, processing, and storage. Such interactions can distort the color
of the formula with gray, beige, or similar other discolorations. Such discolorations often
result in greatly diminished acceptance of the product by consumers, who typically prefer a
bright, whitish colored product.
[0121] One technique that can be used to evaluate the color characteristics of an
infant formula is Agtron color scores. Agtron scores as used herein are measured by
conventional techniques using an Agtron 45 Spectrophotometer (available from Agtron
Inc., Reno, Nevada). The Agtron scores are a measure of the percentage of reflected
energy (light) from the surface of each infant formula. The more reflective or brighter in
color the formula surface, the higher the Agtron score. These scores range from zero
(black) to 100 (white).
[0 122] It has now been discovered that the micronutrient content of low calorie
liquid infant formulas affects the color of the formulas. In particular, the low calorie, low
micronutrient liquid infant formulas of the present disclosure advantageously have a
brighter, whiter color, as defined by Agtron score, than do low calorie, high micronutrient
formulas. This was found to be the case for both retort and aseptic low calorie, low
micronutrient liquid formulas. The improved color of the low calorie, low micronutrient
liquid infant formulas was also observed not just upon formulation, but also after extended
periods of time, in some cases at least 9 months following product formulation.
[0123] Thus, in one aspect, the present disclosure is directed to a low calorie, low
micronutrient days 1-2 liquid infant formula that has an Agtron score following
formulation (within a day of formulation) of at least about 45, including from about 45 to
about 60, and from about 47 to about 55. Preferably, the formula is a retort sterilized RTF
formula. In other embodiments, the formula has an Agtron score two months after
formulation of at least about 40, including from about 40 to about 50; has an Agtron score
four months after formulation of at least about 37, including from about 40 to about 50; has
an Agtron score six months after formulation of at least about 37, including from about 37
to about 50; and has an Agtron score nine months after formulation of at least about 35,
including from about 35 to about 45.
[0124] In another aspect, the present disclosure is directed to a low calorie, low
micronutrient days 3-9 liquid retort sterilized infant formula that has an Agtron score
following formulation of at least about 42, including from about 42 to about 55, and from
about 45 to about 52. In other embodiments, the formula has an Agtron score three months
after formulation of at least about 40, including from about 40 to about 50; and has an
Agtron score six months after formulation of at least about 40, including from about 40 to
about 50.
[0125] In another aspect, the present disclosure is directed to a low calorie, low
micronutrient days 3-9 liquid aseptic sterilized infant formula that has an Agtron score
following formulation of at least about 58, including from about 58 to about 65, and from
about 60 to about 62. In other embodiments, the formula has an Agtron score two months
after formulation of at least about 55, including from about 55 to about 62; has an Agtron
score six months after formulation of at least about 55, including from about 55 to about
60; and has an Agtron score nine months after formulation of at least about 52, including
from about 52 to about 55.
Buffering Capacity
[0126] The low calorie infant formulas of the present disclosure (having either a
high or a low micronutrient content) also advantageously exhibit improved buffering
capacity, as compared to full calorie formulas.
[0127] Human breast milk is believed to contain certain factors which promote
the development of a favorable intestinal bacterial flora, specifically, Bifidobacterium,
which discourage the proliferation of pathogenic microbes. The growth of Bifidobacterium
in the intestine of an infant is believed to be promoted by the physicochemical properties of
human breast milk, particularly its high lactose content, which is a substrate for
Bifidobacterium, its low protein content, and its low buffering capacity. Further, the low
buffering capacity of human milk may allow the natural level of acidity in gastrointestinal
(GI) tract of infants to be more effective in inactivating orally ingested pathogens. In some
cases, infant formula may have a relatively high buffering capacity, which may not be
completely favorable for the growth of Bifidobacterium, and may potentially impact the
natural acidity of an infant's GI tract. Consequently, some formula fed infants may
experience more episodes of GI tract infection as compared to breast fed infants.
[0128] It has now been discovered that the buffering capacity of infant formula is
correlated to the energy content of the formula. Specifically, it has been discovered that
the buffering capacity of infant formula decreases with decreasing energy content. The low
calorie infant formulas of the present disclosure thus advantageously have an improved
(i.e., lower) buffering capacity than full calorie infant formulas, and in some embodiments,
have a lower buffering capacity than that of human milk. The low calorie infant formulas
of the present disclosure can thus be used to regulate gastric acidity in infants, and in
particular newborns, reduce the growth of pathogenic microorganisms in the infant GI
tract, promote the growth of beneficial microorganisms, such as Bifidobacterium, and
increase the effectiveness of the inactivation of orally ingested pathogens.
[0129] Buffering capacity refers generally to the ability of a liquid to resist
changes in pH. There are several measures that can be used to express buffering capacity
of the infant formulas of the present disclosure. For instance, buffering capacity of the
infant formulas can be expressed as the increase in hydrogen ion concentration ([H+])
following addition of hydrochloric acid (HC1) to the infant formula (or to reconstituted
formula for powder infant formula embodiments). Specifically, buffering capacity can be
expressed as the increase in [H+] following addition of 5 mmoles of HC1 to 100 mL of
formula, or alternately, as the increase in [H+] following the addition of 5.50 mmoles of
HC1 to 100 mL of formula (or the addition of 2.75 mmoles of HC1 to 50 mL of formula).
[0130] The low calorie infant formulas of the present disclosure may have a
buffering capacity, expressed as the [H+] following addition of 5 mmoles of HC1 to 100
mL of formula, of at least about 2.0 mM, including at least about 5.0 mM, at least about 7.0
mM, at least about 10.0 mM, at least about 13.0 mM, and at least about 17.0 mM, and/or
from about 2.0 mM to about 25.0 mM, including from about 5.0 mM to about 2 1.0 mM,
and from about 10.0 mM to about 21.0 mM. The infant formulas may be reconstituted
powder formulas, retort sterilized, or aseptic sterilized, and may be a days 1-2 or a days 3-9
formula. In one embodiment, the low calorie infant formula is a days 3-9 formula, and has
a buffering capacity, expressed as the [H+] following addition of 5 mmoles of HCl to 100
mL of formula at least about 2.0 mM, including at least about 5.0 mM, at least about 7.0
mM, and at least about 9.0 mM, and/or from about 2.0 mM to about 13.0 mM, including
from about 8.0 mM to about 11.0 mM. In another embodiment, the low calorie infant
formula is a days 1-2 formula and has a buffering capacity, expressed as the [H+] following
addition of 5 mmoles of HCl to 100 mL of formula, of at least about 8.0 mM, including at
least about 10.0 mM, at least about 13.0 mM, at least about 17.0 mM, and at least about
20.0 mM, and/or from about 8.0 mM to about 25.0 mM, including from about 8.0 mM to
about 21.0 mM, from about 13.0 mM to about 20.0 mM, and from about 17.0 mM to about
20.0 mM.
[0131] Alternately, the buffering capacity of the infant formula can be expressed
as the decrease in pH of the formula following addition of HCl to the infant formula (or to
reconstituted formula for powder infant formula embodiments). Specifically, buffering
capacity can be expressed as the decrease in pH following addition of 5.50 mmoles of HCl
to 100 mL of formula (or the addition of 2.75 mmoles of HCl to 50 mL of formula).
[0132] Thus, in one embodiment, the low calorie infant formulas of the present
disclosure is a powder infant formula, and may have a buffering capacity following
reconstitution, expressed as the decrease in pH of the formula following addition of 5.50
mmoles of HCl to 100 mL of reconstituted formula, of at least about 4.20, including at least
about 4.50, and at least about 4.80. In another embodiment where the low calorie infant
formula is a retort sterilized RTF formula, the buffering capacity, expressed as the decrease
in pH of the formula following addition of 2.75 mmoles of HCl to 50 mL of formula, is at
least about 4.20, including at least about 4.30. In still another embodiment wherein the low
calorie infant formula is an aseptic sterilized RTF formula, the buffering capacity,
expressed as the decrease in pH of the formula following addition of 5.50 mmoles of HCl
to 100 mL of formula, is at least about 4.60, including at least about 4.70.
[0133] Another measure of buffering capacity is buffering strength. Unless
otherwise indicated, the buffering strength of the infant formulas of the present disclosure
is expressed as the volume of 0.1 M HCl needed to decrease the pH of 50 mL of formula
(or reconstituted formula for powder infant formula embodiments) from the starting pH
(e.g., 6.0) to a pH of 3.0. As used herein, the term "low buffering strength" refers to a
buffering strength of about 18 mL or less. Buffering strength is also expressed herein
(where indicated) as mmoles of HCl required to lower the pH of 100 mL of formula from
6.0 to 3.0 and as mmoles of HCl required to lower the pH of 50 mL of formula from 6.0 to
3.0.
[0134] The low calorie infant formulas of the present disclosure may have a
buffering strength, expressed as the mL of 0.1 M HCl needed to decrease the pH of 50 mL
of formula (or reconstituted formula for powder infant formula embodiments) from the
starting pH to a pH of 3.0, of about 18 mL or less, including about 14 mL or less, and/or
including from about 9 mL to about 18 mL, including from about 10 mL to about 14 mL,
and from about 14 mL to about 18 mL. In one embodiment, the low calorie infant formula
is a days 3-9 formula, and has a buffering strength of about 18 mL or less, including from
about 14 mL to about 18 mL, and from about 16 mL to about 1 mL. In another
embodiment, the low calorie infant formula is a days 1-2 formula, and has a buffering
strength of about 14 mL or less, including from about 9 mL to about 14 mL, and from
about 10 mL to about 11 mL. The buffering strength of human milk typically ranges from
9 mL to 18 mL. The low calorie infant formulas of the present disclosure advantageously
have a buffering strength comparable to or lower than that of human milk.
Protein Hydrolysis and Digestion
[0135] The low calorie infant formulas of the present disclosure (having either a
high or a low micronutrient content) also advantageously exhibit a faster rate of protein
hydrolysis and digestion, as compared to full calorie formulas.
[0136] Two factors in determining the nutritional quality of food proteins are
digestibility and bioavailability. Typically, infant formulas contain a higher level of
protein than the level found in breast milk. Infant formulas are typically manufactured
with higher levels of proteins to account for the assumed lower digestibility of the proteins.
[0137] Further, in some cases, the processes used during the manufacture of
infant formulas may potentially have some nutritional consequences, such as lowered
solubility and/or digestibility of the proteins in the formula. For example, some heat
treatments over extended periods of time that are used to produce concentrated liquid and
ready-to-feed infant formulas may possibly decrease digestibility of proteins in some cases.
As a result of exposure to heat, proteins denature or aggregate, possibly altering their
digestibility in some cases. The treatment of milk at high temperatures may also increase
reactions of amino acids with sugars known as Maillard reactions. These reactions may
decrease the bioavailability of amino acids by limiting the accessibility of proteolytic
enzymes in some cases. As a result, some formula fed infants may potentially experience
some incomplete nutrient (and in particular protein) absorption. Consequently, an infant
formula having improved protein digestion would be beneficial, especially for newborn
infants who are known to have lower amounts of digestive enzymes, such a gastric pepsin
and intestinal pancreatin, than do older infants and adults.
[0138] It has now been discovered that the extent (used interchangeably herein
with the term "rate") of digestion (used interchangeably herein with the term "hydrolysis")
of protein in infant formula is correlated to the energy content of the formula. Specifically,
it has been discovered that the rate of digestion of protein present in the infant formula
increases with decreasing energy content of the formula. The low calorie infant formulas
of the present disclosure thus advantageously have an improved (e.g., faster) rate of protein
digestion than do full calorie infant formulas. This may result in improved infant formula
tolerance and improved nutrient (and in particular protein) absorption by the infant.
[0139] There are several measures that can be used to express the rate or extent of
protein digestion. For instance, the rate or extent of digestion of the proteins in the infant
formulas of the present disclosure can be expressed as the median molecular weight (MW)
of the proteins following an in vitro gastrointestinal digestion using pepsin and pancreatin
(amylase/protease/lipase) or an in vitro pancreatin digestion. A decreasing protein MW
median is indicative of a faster rate and increased extent of digestion. The procedures for
these digestions are set forth in the examples.
[0140] In some embodiments, the low calorie infant formulas of the present
disclosure may have a rate or extent of protein digestion, expressed as the protein MW
median following in vitro gastrointestinal digestion, performed as described herein, of
about 950 Daltons (Da) or less, including about 925 Da or less, about 850 Da or less, about
800 Da or less, and about 790 Da or less. For days 3-9 formulas of the present disclosure,
the rate or extent of protein digestion, expressed as the protein MWmedian following in
vitro gastrointestinal digestion, performed as described herein, is typically from about 700
Da to about 950 Da. For days 1-2 formulas, the rate or extent of protein digestion,
expressed as the protein MW median following in vitro gastrointestinal digestion,
performed as described herein, is typically about 825 Da or less, including about 800 Da or
less, about 780 Da or less, about 750 Da or less and about 720 Da or less. Typically the
rate or extent of protein digestion for days 1-2 formulas is from about 700 Da to about 800
Da.
[0141] The low calorie infant formulas of the present disclosure may have a rate
or extent of protein digestion, expressed as the protein MW median following in vitro
pancreatin digestion for 7 1 minutes, performed as described herein, of about 800 Da or
less, including about 775 Da or less, and about 750 Da or less, and in particular from about
725 Da to about 775 Da for days 3-9 formulas. For days 1-2 formulas, the rate or extent of
protein digestion, expressed as the protein MW median following in vitro pancreatin
digestion for 7 1 minutes, performed as described herein, is typically about 750 Da or less,
including about 725 Da or less, about 700 Da or less, and about 690 Da or less, and in
particular from about 675 Da or less to about 700 Da or less.
[0142] The low calorie infant formulas of the present disclosure may have a rate
or extent of protein digestion, expressed as the protein MW median following in vitro
pancreatin digestion for 60 minutes, performed as described herein, of about 1000 Da or
less, including about 950 Da or less, about 900 Da or less, about 850 Da or less, about 825
Da or less, and about 810 Da or less, and in particular from about 775 Da to about 825 Da.
[0143] The rate or extent of protein digestion can also be expressed as the percent
of total proteins having a MW of greater than 5000 Da, following either the in vitro
gastrointestinal digestion or the in vitro pancreatin digestion described herein. A smaller
percentage is indicative of a faster rate and increased extent of digestion. The low calorie
infant formulas of the present disclosure may have a rate or extent of protein digestion,
expressed as the percent of total proteins having a MW of greater than 5000 Da following
in vitro gastrointestinal digestion, performed as described herein, of about 13.5% or less,
including about 12.0% or less, about 11.0% or less, about 9.0 % or less, and about 6.0% or
less, and in particular from about 5.0%> to about 13.5% for powder formulas. In
embodiments where the infant formula is retort sterilized, the rate or extent of protein
digestion, expressed as the percent of total proteins having a MW of greater than 5000 Da
following in vitro gastrointestinal digestion, performed as described herein, is about 8.0%
or less, including about 7.0%> or less, about 6.0%> or less, about 5.0%> or less, about 4.0%> or
less, and about 3.0%> or less, and further including from about 2.0%> to about 6.0%>. In
embodiments where the infant formula is aseptic sterilized, the rate or extent of protein
digestion, expressed as the percent of total proteins having a MW of greater than 5000 Da
following in vitro gastrointestinal digestion, performed as described herein, is about 9.0%>
or less, including about 7.0%> or less, about 6.0%> or less, about 5.0%> or less, about 3.0%> or
less, and further including from about 2.0%> to about 5.0%>.
[0144] The rate or extent of protein digestion can also be expressed by the amount
of insoluble protein present in the infant formula following in vitro gastrointestinal
digestion, performed as described herein. Techniques for determining the level of
insoluble protein are set forth in the examples of the present disclosure. A smaller amount
of insoluble protein is indicative of a faster rate and increased extent of digestion.
[0145] The low calorie infant formulas of the present disclosure may have a rate
or extent of protein digestion, expressed as the amount of insoluble protein in the formula
following in vitro gastrointestinal digestion, performed as described herein, of about 150
mg/L or less, including about 110 mg/L or less, about 75 mg/L or less, about 50 mg/L or
less, and about 25 mg/L or less, and in particular from about 20 mg/L to about 110 mg/L.
[0146] As discussed herein, processing of infant formulas, and in particular the
treatment of milk products at high temperatures may increase reactions of amino acids with
sugars, known as Maillard reactions. These reactions decrease the bioavailability of amino
acids by limiting the accessibility of proteolytic enzymes. It has now been discovered that
Maillard reactions proceed to a lesser extent in the low calorie infant formulas of the
present disclosure as compared to full calorie formulas. This may be illustrated by
determining the level of Maillard reaction markers in the infant formula following
digestion. Specifically, the low calorie infant formulas of the present disclosure have been
found to have lower levels of the Maillard reaction marker furosine, following in vitro
gastrointestinal digestion performed as described herein, than do full calorie formulas.
[0147] Thus, in one aspect the present disclosure provides infant formulas that
comprise, following in vitro gastrointestinal digestion performed as described herein, the
Maillard reaction marker furosine in amounts (mg/100 g product) of about 2.5 or less,
including about 1.5 or less, about 1.0 or less, and about 0.90 or less, and in particular from
about 0.7 to about 1.0.
Methods of Manufacture
[0148] The infant formulas of the present disclosure may be prepared by any
known or otherwise effective manufacturing technique for preparing the selected product
solid or liquid form. Many such techniques are known for any given product form such as
nutritional liquids or powders and can easily be applied by one of ordinary skill in the art to
the infant formulas described herein.
[0149] The infant formulas of the present disclosure can therefore be prepared by
any of a variety of known or otherwise effective formulation or manufacturing methods. In
one suitable manufacturing process, for example, at least two separate slurries are prepared,
that are later blended together, heat treated, standardized, and either terminally sterilized to
form a retort infant formula or aseptically processed and filled to form an aseptic infant
formula. Alternately, the slurries can be blended together, heat treated, standardized, heat
treated a second time, evaporated to remove water, and spray dried to form a powder infant
formula.
[0150] The slurries formed may include a carbohydrate-mineral (CHO-MIN)
slurry and a protein-in-oil (PIO) slurry. Initially, the CHO-MIN slurry is formed by
dissolving selected carbohydrates (e.g., lactose, galactooligosaccharides, etc.) in heated
water with agitation, followed by the addition of minerals (e.g., potassium citrate,
magnesium chloride, potassium chloride, sodium chloride, choline chloride, etc.). The
resulting CHO-MIN slurry is held with continued heat and moderate agitation until it is
later blended with the other prepared slurries.
[0151] The PIO slurry is formed by heating and mixing the oil (e.g., high oleic
safflower oil, soybean oil, coconut oil, monoglycerides, etc.) and emulsifier (e.g., soy
lecithin), and then adding oil soluble vitamins, mixed carotenoids, protein (e.g., milk
protein concentrate, milk protein hydrolysate, etc.), carrageenan (if any), calcium carbonate
or tricalcium phosphate (if any), and ARA oil and DHA oil (in some embodiments) with
continued heat and agitation. The resulting PIO slurry is held with continued heat and
moderate agitation until it is later blended with the other prepared slurries.
[0152] Water was heated and then combined with the CHO-MIN slurry, nonfat
milk (if any), and the PIO slurry under adequate agitation. The pH of the resulting blend
was adjusted to 6.6-7.0, and the blend was held under moderate heated agitation. ARA oil
and DHA oil is added at this stage in some embodiments.
[0153] The composition is then subjected to high-temperature short-time (HTST)
processing, during which the composition is heat treated, emulsified and homogenized, and
then cooled. Water soluble vitamins and ascorbic acid are added, the pH is adjusted to the
desired range if necessary, flavors (if any) are added, and water is added to achieve the
desired total solid level. For aseptic infant formulas, the emulsion receives a second heat
treatment through an aseptic processor, is cooled, and then aseptically packaged into
suitable containers. For retort infant formulas, the emulsion is packaged into suitable
containers and terminally sterilized. In some embodiments, the emulsions can be
optionally further diluted, heat-treated, and packaged to form a desired ready-to-feed or
concentrated liquid, or can be heat-treated and subsequently processed and packaged as a
reconstitutable powder, e.g., spray dried, dry mixed, agglomerated.
[0154] The spray dried powder infant formula or dry-mixed powder infant
formula may be prepared by any collection of known or otherwise effective techniques,
suitable for making and formulating a nutritional powder. For example, when the powder
infant formula is a spray-dried nutritional powder, the spray drying step may likewise
include any spray drying technique that is known for or otherwise suitable for use in the
production of nutritional powders. Many different spray drying methods and techniques
are known for use in the nutrition field, all of which are suitable for use in the manufacture
of the spray dried powder infant formulas herein. Following drying, the finished powder
may be packaged into suitable containers.
Methods of Use
[0155] The low calorie infant formulas of the present disclosure may be orally
administered to infants, including term, preterm, and/or newborn infants. The low calorie
infant formulas may be administered as a source of nutrition for infants and/or can be used
to address one or more of the diseases or conditions discussed herein, or can be used to
provide one or more of the benefits described herein, to preterm infants, term infants,
and/or newborn infants. Any of this group may actually have the disease or condition, or
may be at risk of getting the disease or condition (due to family history, etc.), may be
susceptible to the disease or condition, or may be in need of treatment/control/reduction of
a certain disease or condition. The infant formulas will typically be administered daily, at
intake volumes suitable for the age of the infant. As such, because some of the method
embodiments disclosed herein are directed to certain subsets or subclasses of infants (e.g.,
those infants in need of treatment or control of a disease or condition) and not generally to
the standard infant population, not all infants can benefit from all method embodiments
disclosed herein.
[0156] For instance, the methods of the present disclosure may include
administering one or more of the low calorie formulas of the present disclosure to an infant
at the average intake volumes described herein. In some embodiments, newborn infants
are provided with increasing formula volumes during the initial weeks of life. Such
volumes most typically range up to about 100 mL/day on average during the first day or so
of life; up to about 200 to about 700 mL/day, including from about 200 to about 600
mL/day, and also including from about 250 to about 500 mL/day, on average during the
remainder of the three month newborn feeding period. It is to be understood, however, that
such volumes can vary considerably depending upon the particular newborn infant and
their unique nutritional needs during the initial weeks or months of life, as well as the
specific nutrients and caloric density of the infant formula administered.
[0157] In some embodiments, the methods of the present disclosure may be
directed to newborn infants during the initial weeks or months of life, preferably during at
least the first week of life, more preferably during at least the first two weeks of life, and
including up to about 3 months of life. Thereafter, the infant may be switched to a
conventional infant formula, alone or in combination with human milk.
[0158] The methods described herein may comprise administering two or more
different infant formulas to the infant. For instance, the infant may be administered a low
calorie days 1-2 infant formula during the first two days following birth and may then
subsequently be administered a low calorie days 3-9 infant formula on days 3 to 9
following birth. Optionally, the days 3-9 infant formula may be administered past day 9
following birth, or alternatively, a higher calorie formula (including full calorie formulas)
may be administered starting on day 10 following birth.
[0159] The infant formulas used in the methods described herein, unless
otherwise specified, are nutritional formulas and may be in any product form, including
ready-to-feed liquids, concentrated liquids, reconstituted powders, and the like. In
embodiments where the infant formulas are in powder form, the method may further
comprise reconstituting the powder with an aqueous vehicle, most typically water or
human milk, to form the desired caloric density, which is then orally or enterally fed to the
infant. The powdered formulas are reconstituted with a sufficient quantity of water or
other suitable fluid such as human milk to produce the desired caloric density, as well as
the desired feeding volume suitable for one infant feeding. The infant formulas may also
be sterilized prior to use through retort or aseptic means.
[0160] Other embodiments are described in more detail below.
Nutrition
[0161] In one aspect, the present disclosure is directed to a method of providing
nutrition to an infant. The method comprises administering to the infant any one or more
of the low calorie, low micronutrient infant formulas of the present disclosure. Such
methods may include the daily administration of the infant formulas, including
administration at the daily intake volumes as described hereinbefore. In some
embodiments, the infant is a newborn infant.
[0162] As noted above, any of the low calorie, low micronutrient infant formulas
of the present disclosure may be used in this method. Specifically, the low micronutrient
infant formula comprises micronutrients and at least one macronutrient selected from the
group consisting of protein, carbohydrate, fat, and combinations thereof. In one
embodiment, the low micronutrient infant formula has an energy content of from about 200
kcal/L to less than 600 kcal/L, wherein at least 65% of the micronutrients are included in
the infant formula in an amount that is from about 30% to about 80% of conventional
amounts of corresponding micronutrients, on a per volume basis. In another embodiment,
the low micronutrient infant formula has an energy content of from about 200 kcal/L to
about 360 kcal/L, wherein at least 45% of the micronutrients are included in the infant
formula in an amount that is from about 30% to about 65% of conventional amounts of
corresponding micronutrients, on a per volume basis. In still another embodiment, the low
micronutrient infant formula has an energy content of from about 360 kcal/L to less than
600 kcal/L, wherein at least 30% of the micronutrients are included in the infant formula in
an amount that is from about 55% to about 80% of conventional amounts of corresponding
micronutrients, on a per volume basis. The low calorie infant formula may be a days 1-2
and/or a days 3-9 formula.
[0163] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula) during the first two days following birth, and is subsequently
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 360 kcal/L to less than 600 kcal/L (e.g., a
days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
Buffering Capacity
[0164] It has been discovered that the buffering capacity of infant formula is
correlated to the energy content of the formula. Specifically, it has been discovered that
the buffering capacity of infant formula decreases with decreasing energy content. The low
calorie infant formulas of the present disclosure thus advantageously have an improved
(i.e., lower) buffering capacity than full calorie infant formulas, and in some embodiments,
have a lower buffering capacity than human breast milk. The low calorie infant formulas
of the present disclosure can thus be used to increase the level of gastric acidity in infants,
and in particular newborns, and to regulate the growth of gastrointestinal flora in infants,
including controlling (e.g., reducing) the growth of pathogenic microorganisms in the
infant GI tract, promoting the growth of beneficial microorganisms in the infant GI tract,
and increasing the effectiveness of the inactivation of orally ingested pathogens.
[0 165] Without wishing to be bound to any particular theory, it is believed that
the more acidic pH in the GI tract of breastfed infants, as compared to infants fed full
calorie formulas, helps inactivate orally ingested pathogens, and provides a more
hospitable environment for the growth of naturally occurring beneficial gastrointestinal
flora. This is believed to be due, at least in part, to the low buffering capacity of human
breast milk. Because the low calorie infant formulas of the present disclosure have a
buffering capacity comparable to or lower than that of human breast milk, infants fed the
low calorie infant formulas disclosed herein will have a level of gastric acidity more
closely resembling that found in breastfed infants.
[0166] Thus, in one aspect, the present disclosure is directed to a method for
increasing the level of gastric acidity (e.g., by lowering gastric pH) in an infant to about the
same level of a breastfed infant. The method comprises identifying an infant having a
depressed level of gastric acidity, and administering to the infant any of the low calorie
infant formulas of the present disclosure. Preferably, the infant is a newborn infant.
[0167] The term "level of gastric acidity" refers to the level of acidity in the
stomach, and can be measured using pH. For instance, as the pH of the gastric contents
decreases, the level of gastric acidity increases. As used herein, the term "depressed level
of gastric acidity" means the level of gastric acidity in the infant is lower than that typically
found in breastfeed infants. Infants having a depressed level of gastric acidity can be
identified as having a reduced or lower rate of pathogenic bacteria colonization in the gut.
Upon administration of the low calorie infant formula of the present disclosure, the level of
gastric acidity in the infant is increased to the levels typically found in breastfed infants.
[0168] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 or a days 3-9 formula. In one embodiment, the infant formula has
an energy content of from about 200 kcal/L to about 500 kcal/L.
[0169] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal/L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0170] In another aspect, the present disclosure is directed to a method for
increasing the level of gastric acidity in an infant comprising administering to the infant
any of the low micronutrient infant formulas of the present disclosure. Preferably, the
infant is a newborn infant. The low micronutrient infant formula comprises micronutrients
and at least one macronutrient selected from the group consisting of protein, carbohydrate,
fat, and combinations thereof. In one embodiment, the low micronutrient infant formula
has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least
65% of the micronutrients are included in the infant formula in an amount that is from
about 30% to about 80% of conventional amounts of corresponding micronutrients, on a
per volume basis. In another embodiment, the low micronutrient infant formula has an
energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 65% of conventional amounts of corresponding micronutrients, on a per volume
basis. In still another embodiment, the low micronutrient infant formula has an energy
content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the
micronutrients are included in the infant formula in an amount that is from about 55% to
about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis. The low calorie infant formula may be a days 1-2 and/or a days 3-9 formula.
[0171] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
[0172] In still another embodiment, the present disclosure is directed to a method
for regulating growth of beneficial gastrointestinal flora in an infant. The method
comprises identifying an infant having an imbalance in the growth of gastrointestinal flora,
and administering to the infant any of the low calorie infant formulas of the present
disclosure. Preferably, the infant is a newborn infant.
[0173] For purposes of the present disclosure, the growth of gastrointestinal flora
can be regulated by either promoting the growth of microorganisms beneficial to GI health,
and/or by controlling the growth of pathogenic microorganisms. The growth of pathogenic
microorganisms can be controlled by suppressing, inhibiting, killing, inactivating,
destroying or otherwise interfering with the growth of the pathogenic microorganisms, such
that the growth rate of these microorganisms is slowed or stopped. Infants having an
imbalance in the growth of GI flora include infants in which the levels of one or more
pathogenic microorganism in the infant's GI tract is higher than the levels typically found
in breastfed infants and/or the levels of one or more beneficial microorganism in the
infant's GI tract are lower than the levels typically found in breastfeed infants. Such
infants may be identified by a lower rate of pathogenic bacteria colonization in the gut.
Upon administration of the low calorie infant formula of the present disclosure, the level of
gastric acidity in the infant is increased to the levels similar to those typically found in
breastfed infants, resulting in a GI environment which promotes the growth of beneficial
microorganisms and controls the growth of pathogenic microorganisms.
[0174] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 or a days 3-9 formula. In one embodiment, the infant formula has
an energy content of from about 200 kcal/L to about 500 kcal/L of formula.
[0175] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0176] In another aspect, the present disclosure is directed to a method for
regulating the growth of gastrointestinal flora in an infant comprising administering to the
infant any of the low micronutrient infant formulas of the present disclosure. Preferably,
the infant is a newborn infant. The low micronutrient infant formula may be any of those
set forth above.
[0177] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
[0178] Beneficial microorganisms refer to those microorganisms that maintain the
microbial ecology of the GI tract, and show physiological, immuno-modulatory, and/or
antimicrobial effects, such that their presence has been found to prevent and treat GI
diseases and/or disorders. Non-limiting examples of beneficial microorganisms include
any one or more of the following: the genus Lactobacillus including L. acidophilus, L.
amylovorus, L. brevis, L. bulgaricus, L. casei spp. Casei, L. casei spp. Rhamnosus, L.
crispatus, L. delbrueckii ssp. Lactis, L.fermentum, L. helvaticus, L.johnsonii, L. paracasei,
L. pentosus, L. plantarum, L. reuteri, and L. sake; the genus Bifidobacterium including B.
animalis, B. bifidum, B. breve, B. infantis, and B. longum; the genus Pediococcus including
P. acidilactici; the genus Propionibacterium including P. acidipropionici, P.
freudenreichii, P.jensenii, and P. theonii; and the genus Streptococcus including S.
cremoris, S. lactis, and S. thermophilus; and combinations thereof.
[0179] Non-limiting examples of pathogenic microorganisms whose growth may
be controlled by the methods disclosed herein include any one or more of the following:
bacteria such as the genus Clostridum including C. difficile; Escherichia coli (E. coli);
Vibrio sp.; Salmonella sp.; Shigella sp.; Camphylobacter sp.; Aeromonas sp.;
Staphylococcus sp.; Pseudomonas sp.; and parasites such as Giardia sp.; and
Cryptosporidium sp.; and combinations thereof.
Protein Digestion and Hydrolysis
[0180] It has been discovered that the rate and extent of digestion of protein in
infant formula is correlated to the energy content of the formula. Specifically, it has been
discovered that the rate of digestion of proteins in infant formula increases with decreasing
energy content of the formula. The low calorie infant formulas of the present disclosure
thus advantageously have an improved (e.g., faster) rate of digestion as compared to full
calorie infant formulas. The low calorie infant formulas of the present disclosure can thus
be used to improve formula tolerance, protein digestion, and nutrient (and in particular
protein) absorption in infants, and in particular newborns.
[0181] Thus, in one aspect, the present disclosure is directed to a method for
improving protein digestion in an infant. The method comprises identifying an infant
experiencing incomplete protein digestion, and administering to the infant any of the low
calorie infant formulas of the present disclosure. Preferably, the infant is a newborn infant.
[0182] As used herein, the term "improving protein digestion" includes increasing
the rate of digestion (or hydrolysis) of protein present in the infant formula and/or
increasing the extent to which protein in the infant formula is digested when contacted with
digestive enzymes. This improvement in protein digestion can be determined using any of
the measures described herein, including, for example, the protein median weight following
digestion, the percent of total protein having a molecular weight of greater than 5000
Daltons following digestion, and/or the amount of insoluble protein present in the formula
following digestion.
[0183] As used herein, the term "incomplete protein digestion" means the amount
of protein, present in nutritional products consumed by the infant, that is actually digested
is lower than the amount typically digested by breastfed infants. Infants experiencing
incomplete protein digestion may show signs of formula intolerance, and may thus be
identified using any of the symptoms of formula intolerance described herein. Infants
experiencing incomplete protein digestion can also be identified by diarrhea, loose stools,
gas, and/or bloating. Upon administration of a low calorie infant formula of the present
disclosure, the rate and extent of protein digestion is improved.
[0184] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 and/or a days 3-9 formula. In one embodiment, the infant formula
has an energy content of from about 200 kcal/L to less than 600 kcal/L of formula.
[0185] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal/L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0186] In another aspect, the present disclosure is directed to a method for
improving protein digestion in an infant comprising administering to the infant any of the
low micronutrient infant formulas of the present disclosure. Preferably, the infant is a
newborn infant. The low micronutrient infant formula comprises micronutrients and at least
one macronutrient selected from the group consisting of protein, carbohydrate, fat, and
combinations thereof. In one embodiment, the low micronutrient infant formula has an
energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least 65% of
the micronutrients are included in the infant formula in an amount that is from about 30%
to about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis. In another embodiment, the low micronutrient infant formula has an energy content
of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the micronutrients
are included in the infant formula in an amount that is from about 30% to about 65% of
conventional amounts of corresponding micronutrients, on a per volume basis. In still
another embodiment, the low micronutrient infant formula has an energy content of from
about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the micronutrients are
included in the infant formula in an amount that is from about 55% to about 80% of
conventional amounts of corresponding micronutrients, on a per volume basis. The low
calorie infant formula may be a days 1-2 and/or a days 3-9 formula.
[0187] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
[0188] In still another embodiment, the present disclosure is directed to a method
of improving protein absorption in an infant. The method comprises identifying an infant
experiencing incomplete protein absorption; and administering to the infant any of the low
calorie infant formulas of the present disclosure. Infants experiencing incomplete protein
absorption may be identified using any of the criteria described herein for identifying
infants experiencing incomplete protein digestion.
[0189] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 or a days 3-9 formula. In one embodiment, the infant formula has
an energy content of from about 200 kcal/L to less than 600 kcal/L of formula.
[0190] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal/L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0191] In another aspect, the present disclosure is directed to a method of
improving protein absorption in an infant comprising administering to the infant any of the
low micronutrient infant formulas of the present disclosure. Preferably, the infant is a
newborn infant. The low micronutrient infant formula may be any of those set forth above.
[0192] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
Tolerance
[0193] The present disclosure is also directed to a method of improving the infant
formula tolerance of an infant. Infant formula intolerance is a non-immune system
associated reaction that may be evidenced by behavior or by stool or feeding pattern
changes, such as increased spit-up or vomiting, an increased number of stools, more watery
stools, black stools, and increased fussiness. Infant formula intolerance is most often
associated with gastrointestinal symptoms (e.g., stool patterns, gas, spit-up) as well as
behavior characteristics (e.g., acceptance of formula, fussing and crying). Infants suffering
from formula intolerance may also experience gastroesophageal reflux.
[0194] It has now unexpectedly been discovered that infants have a greater
tolerance for an infant formula having a low energy content than for full calorie formulas.
Specifically, it has been discovered that low calorie infant formulas demonstrate a faster
rate of protein hydrolysis and digestion, produce less Maillard reaction products (which
cannot be broken down and absorbed) upon consumption, and have a faster rate of gastric
emptying than do full calorie formulas. The faster gastric emptying leads to decreased
gastroesophageal reflux, and improved tolerance of the formula.
[0195] The low calorie infant formulas of the present disclosure may thus be used
to decrease the incidence of gas, and/or spit up in infants. The low calorie infant formulas
of the present disclosure may also be used to increase the rate of gastric emptying in the
infant and reduce the degree of Maillard reaction products resulting from formula
consumption, as compared to full calorie infant formulas.
[0196] The low calorie infant formulas can be administered to any infant, preterm
or full term, and especially any infant that can benefit from receiving an infant formula
having a low energy content that also has high tolerance. In some embodiments, the low
calorie infant formulas of the present disclosure are administered to newborn infants.
[0197] Thus, in one aspect, the present disclosure is directed to a method of
improving the infant formula tolerance of an infant. The method comprises identifying an
infant having infant formula intolerance and administering to the infant any one or more of
the low calorie infant formulas of the present disclosure. Infants having infant formula
intolerance can include infants having any one or more of the symptoms of formula
intolerance. Such symptoms include, but are not limited to, stool or feeding pattern
changes, such as increased spit-up or vomiting, an increased number of stools, more watery
stools, black stools, increased fussiness, crying, gas, and lack of acceptance of formula.
Upon administration of a low calorie infant formula of the present disclosure, some or all
of the symptoms of formula intolerance may be reduced or eliminated.
[0198] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 or a days 3-9 formula. In one embodiment, the low calorie infant
formula has an energy content of from about 200 to about 600 kilocalories per liter of
formula.
[0199] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal/L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0200] In another aspect, the present disclosure is directed to a method for
improving the infant formula tolerance of an infant comprising administering to the infant
any of the low micronutrient infant formulas of the present disclosure. Preferably, the
infant is a newborn infant. The low micronutrient infant formula comprises micronutrients
and at least one macronutrient selected from the group consisting of protein, carbohydrate,
fat, and combinations thereof. In one embodiment, the low micronutrient infant formula
has an energy content of from about 200 kcal/L to less than 600 kcal/L, wherein at least
65% of the micronutrients are included in the infant formula in an amount that is from
about 30% to about 80% of conventional amounts of corresponding micronutrients, on a
per volume basis. In another embodiment, the low micronutrient infant formula has an
energy content of from about 200 kcal/L to about 360 kcal/L, wherein at least 45% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 65% of conventional amounts of corresponding micronutrients, on a per volume
basis. In still another embodiment, the low micronutrient infant formula has an energy
content of from about 360 kcal/L to less than 600 kcal/L, wherein at least 30% of the
micronutrients are included in the infant formula in an amount that is from about 55% to
about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis. The low calorie infant formula may be a days 1-2 or a days 3-9 formula.
[0201] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
[0202] In still another embodiment, the present disclosure is directed to a method
for inhibiting gastroesophageal reflux in an infant. The method comprises identifying an
infant having gastroesophageal reflux, and administering to the infant any one or more of
the low calorie infant formulas of the present disclosure. Preferably, the infant is a
newborn infant.
[0203] Gastroesophageal reflux (GER) occurs when stomach contents reflux into
the esophagus and out of the mouth, resulting in regurgitation, spitting up, and/or vomiting.
Symptoms of GER include spitting up, vomiting, coughing, irritability, poor feeding,
bloody stool, and combinations thereof. GER may also occur when infants cough, cry, or
strain. For purposes of the present disclosure, the term "inhibiting gastroesophageal
reflux" is intended to include treating, preventing, and/or decreasing the rate of occurrence
of GER and/or at least one of its symptoms. Without wishing to be bound to any particular
theory, it is believed that the low calorie infant formula of the present disclosure has a
faster rate of gastric emptying (i.e., the rate at which contents pass through the stomach),
which leads to decreased gastroesophageal reflux, as compared to full calorie formulas.
[0204] As noted above, any of the low calorie infant formulas of the present
disclosure may be used in this method. The low calorie infant formula may have a low
micronutrient content, or, in some embodiments, may have a high micronutrient content,
and may be a days 1-2 or a days 3-9 formula. In one embodiment, the infant formula has
an energy content of from about 200 kcal/L to less than 600 kcal/L of formula.
[0205] The method may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a days 1-2 formula having an energy content of from about 200 kcal/L to
about 360 kcal/L during the first two days following birth, and is subsequently
administered a days 3-9 formula having an energy content of from about 360 kcal/L to less
than 600 kcal/L on days 3 to 9 following birth. Optionally, the days 3-9 formula may be
administered past day 9 following birth, or alternatively, a higher calorie formula
(including full calorie formulas) may be administered starting on day 10 following birth.
The formula(s) administered to the infant will typically be administered daily at intake
volumes as described hereinbefore.
[0206] In another aspect, the present disclosure is directed to a method for
inhibiting gastroesophageal reflux in an infant comprising administering to the infant any
one or more of the low micronutrient infant formulas of the present disclosure. Preferably,
the infant is a newborn infant. The low micronutrient infant formula may be any of those
set forth above.
[0207] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) having an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. In embodiments where the low calorie infant formulas have a low micronutrient
content, the amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
[0208] In another aspect, the present disclosure is directed to a method for
increasing the rate of gastric emptying in an infant comprising administering to the infant
any one or more of the low micronutrient infant formulas of the present disclosure.
Preferably, the infant is a newborn infant. The low micronutrient infant formula may be
any of those set forth above.
[0209] These methods may also further comprise administering two or more
different infant formulas to the infant. For instance, in one embodiment, the infant is
administered a low calorie infant formula (having either a high or low micronutrient
content) that has an energy content of from about 200 kcal/L to about 360 kcal/L (e.g., a
days 1-2 formula), during the first two days following birth. The infant may then
subsequently be administered a low calorie infant formula (having either a high or low
micronutrient content) that has an energy content of from about 360 kcal/L to less than 600
kcal/L (e.g., a days 3-9 formula) on days 3 to 9 following birth. Optionally, the days 3-9
formula may be administered past day 9 following birth, or alternatively, a higher calorie
formula (including full calorie formulas) may be administered starting on day 10 following
birth. The amounts of micronutrients included in the formulas may be any of those set
forth above. The formula(s) administered to the infant will typically be administered daily
at intake volumes as described hereinbefore.
Kits
[0210] The present disclosure further provides kits comprising two or more of the
low calorie infant formulas of the present disclosure.
[021 1] For instance, in some embodiments, the kit may comprise at least one days
1-2 formula and at least one days 3-9 formula. Preferably, the kit will comprise sufficient
amounts of the days 1-2 formula to provide an infant with adequate nutrition during the
first two days following birth, and sufficient amounts of the days 3-9 formula to provide an
infant with adequate nutrition for at least days 3-9 following birth. The infant formulas
included in the kit may be in any suitable form, including, for example, a ready-to-feed
liquid, a concentrated liquid, a powder, or combinations thereof. The kit may include low
calorie, low micronutrient formulas and/or low calorie, high micronutrient formulas.

WHAT IS CLAIMED IS:
1. A method of improving infant formula tolerance of an infant, the method
comprising administering to the infant an infant formula having an energy content of from
about 200 to less than 600 kilocalories per liter of formula.
2. The method of claim 1, wherein the infant is a newborn infant.
3. The method of claim 1, wherein the infant formula is a days 1-2 infant
formula having an energy content of from about 200 to about 360 kilocalories per liter of
formula.
4. The method of claim 3, further comprising administering the days 1-2 infant
formula to the infant during the first two days following birth and administering a days 3-9
infant formula having an energy content of from about 360 to less than 600 kilocalories per
liter of formula to the infant on days 3 to 9 following birth.
5. A method of improving infant formula tolerance of an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
200 to less than 600 kilocalories per liter of formula, wherein at least 65% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 80% of conventional amounts of corresponding micronutrients on a per volume
basis.
6. The method of claim 5, wherein the infant is a newborn infant.
7. A method of improving infant formula tolerance of an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
200 to about 360 kilocalories per liter of formula, wherein at least 45% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 65% of conventional amounts of corresponding micronutrients, on a per volume
basis.
8. The method of claim 7, wherein the infant is a newborn infant.
9. The method of claim 7, wherein the infant formula is a days 1-2 infant
formula.
10. The method of claim 9, further comprising administering the days 1-2 infant
formula to the infant during the first two days following birth and administering a days 3-9
infant formula having an energy content of from about 360 to less than 600 kilocalories per
liter of formula to the infant on days 3 to 9 following birth.
11. The method of claim 10, wherein the days 3-9 infant formula is a low
micronutrient infant formula comprising micronutrients and at least one macronutrient
selected from the group consisting of protein, carbohydrate, fat, and combinations thereof,
wherein at least 30% of the micronutrients are included in the days 3-9 infant formula in an
amount that is from about 55% to about 80% of conventional amounts of corresponding
micronutrients, on a per volume basis.
12. A method of improving infant formula tolerance of an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
360 to less than 600 kilocalories per liter of formula, wherein at least 30% of the
micronutrients are included in the infant formula in an amount that is from about 55% to
about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis.
13. A method for inhibiting gastroesophageal reflux in an infant, the method
comprising administering to the infant an infant formula having an energy content of from
about 200 to less than 600 kilocalories per liter of formula.
14. A method for inhibiting gastroesophageal reflux in an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
200 to less than 600 kilocalories per liter of formula, wherein at least 65% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 80% of conventional amounts of corresponding micronutrients on a per volume
basis.
15. The method of claim 14, wherein the infant is a newborn infant.
16. A method for inhibiting gastroesophageal reflux in an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
200 to about 360 kilocalories per liter of formula, wherein at least 45% of the
micronutrients are included in the infant formula in an amount that is from about 30% to
about 65% of conventional amounts of corresponding micronutrients, on a per volume
basis.
17. A method for inhibiting gastroesophageal reflux in an infant, the method
comprising: administering to the infant a low micronutrient infant formula comprising
micronutrients and at least one macronutrient selected from the group consisting of protein,
carbohydrate, fat, and combinations thereof, and having an energy content of from about
360 to less than 600 kilocalories per liter of formula, wherein at least 30% of the
micronutrients are included in the infant formula in an amount that is from about 55% to
about 80% of conventional amounts of corresponding micronutrients, on a per volume
basis.
18. The method of claim 17, wherein the infant is a newborn infant.
19. The method of claim 17, wherein the infant formula is a days 3-9 infant
formula.
20. The method of claim 19, further comprising administering a days 1-2 infant
formula having an energy content of from about 200 to about 360 kilocalories per liter of
formula to the infant during the first two days following birth and administering the days 3-
9 infant formula to the infant on days 3 to 9 following birth.