An infant formula with large, milk phospholipid–coated lipid droplets containing a mixture of dairy and vegetable lipids supports adequate growth and is well tolerated in healthy, term infants

ABSTRACT Background Lipid droplets in human milk have a mode diameter of ∼4 μm and are surrounded by a native phospholipid-rich membrane. Current infant milk formulas (IMFs) contain small lipid droplets (mode diameter ∼0.5 μm) primarily coated by proteins. A concept IMF was developed mimicking more closely the structure and composition of human milk lipid droplets. Objectives This randomized, controlled, double-blind equivalence trial evaluates the safety and tolerance of a concept IMF with large, milk phospholipid–coated lipid droplets (mode diameter 3–5 μm) containing vegetable and dairy lipids in healthy, term infants. Methods Fully formula-fed infants were enrolled up to 35 d of age and randomly assigned to 1 of 2 formulas until 17 wk of age: 1) Control IMF with small lipid droplets containing vegetable oils (n = 108); or 2) Concept IMF with large, milk phospholipid–coated lipid droplets comprised of 48% dairy lipids (n = 115). A group of 88 breastfed infants served as reference. Primary outcome was daily weight gain during intervention. Additionally, number and type of adverse events, growth, and tolerance parameters were monitored. Results Equivalence of daily weight gain was demonstrated (Concept compared with Control IMF: −1.37 g/d; 90% CI: −2.71, −0.02; equivalence margin ± 3 g/d). No relevant group differences were observed in growth, tolerance and number, severity, or relatedness of adverse events. We did observe a higher prevalence of watery stools in the Concept than in the Control IMF group between 5 and 12 wk of age (P < 0.001), closer to the stool characteristics observed in the breastfed group. Conclusions An infant formula with large, milk phospholipid–coated lipid droplets containing dairy lipids is safe, well tolerated, and supports an adequate growth in healthy infants. This trial was registered in the Dutch Trial Register (www.trialregister.nl) as NTR3683.

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An Infant Formula with Partially Hydrolyzed Whey Protein Supports Adequate Growth and Is Safe and Well-Tolerated in Healthy, Term Infants: A Randomized, Double-Blind, Equivalence Trial

Nutrients ◽

10.3390/nu12072072 ◽

2020 ◽

Vol 12 (7) ◽

pp. 2072 ◽

Cited By ~ 1

Author(s):

Jean-Charles Picaud ◽

Barbara Pajek ◽

Malgorzata Arciszewska ◽

Izabela Tarczón ◽

Joaquin Escribano ◽

...

Keyword(s):

Weight Gain ◽

Adverse Events ◽

Whey Protein ◽

Infant Formula ◽

Reference Group ◽

Daily Weight Gain ◽

Intact Protein ◽

Controlled Clinical Trial ◽

Serious Adverse Events ◽

Term Infants

The current study evaluates the safety and tolerance of a partially hydrolyzed whey protein-based infant formula (PHF) versus an in intact cow’s milk protein formula (IPF). Breastfed infants were included as a reference group. In a multi-country, multicenter, randomized, double-blinded, controlled clinical trial, infants whose mothers intended to fully formula feed were randomized to PHF (n = 134) or IPF (n = 134) from ≤14 days to 17 weeks of age. The equivalence analysis of weight gain per day within margins of +/−3 g/d (primary outcome), the recorded adverse events, growth and gastro-intestinal tolerance parameters were considered for the safety evaluation. Equivalence of weight gain per day from enrolment until 17 weeks of age was demonstrated in the PHF group compared to the IPF group (difference in means −1.2 g/d; 90% CI (−2.42; 0.02)), with estimated means (SE) of 30.2 (0.5) g/d and 31.4 (0.5) g/d, respectively. No significant differences in growth outcomes, the number, severity or type of (serious) adverse events and tolerance outcomes, were observed between the two formula groups. A partially hydrolyzed whey protein-based infant formula supports adequate infant growth, with a daily weight gain equivalent to a standard intact protein-based formula; it is also safe for use and well-tolerated in healthy term infants.

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Infant formula containing galacto-and fructo-oligosaccharides and Bifidobacterium breve M-16V supports adequate growth and tolerance in healthy infants in a randomised, controlled, double-blind, prospective, multicentre study

Journal of Nutritional Science ◽

10.1017/jns.2016.35 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 11

Author(s):

M. Abrahamse-Berkeveld ◽

M. Alles ◽

E. Franke-Beckmann ◽

K. Helm ◽

R. Knecht ◽

...

Keyword(s):

Weight Gain ◽

Adverse Events ◽

Blood Parameters ◽

Daily Weight Gain ◽

Control Group ◽

Double Blind ◽

Term Infants ◽

Bifidobacterium Breve ◽

Randomised Controlled ◽

Hydrolysed Formula

AbstractThe objective of the present study was to evaluate the growth and tolerance in healthy, term infants consuming a synbiotic formula with daily weight gain as the primary outcome. In a randomised, controlled, double-blind, multicentre, intervention study infants were assigned to an extensively hydrolysed formula containing a specific combination of Bifidobacterium breve M-16V and a prebiotic mixture (short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides in a 9:1 ratio; scGOS/lcFOS; synbiotic group), or the same formula without this synbiotic concept for 13 weeks (control group). Anthropometry, formula intake, tolerance, stool characteristics, blood parameters, faecal microbiota and metabolic faecal profile were assessed. Medically confirmed adverse events were recorded throughout the study. Equivalence in daily weight gain was demonstrated for the intention-to-treat (ITT) population (n 211). In the per-protocol (PP) population (n 102), the 90 % CI of the difference in daily weight gain slightly crossed the lower equivalence margin. During the intervention period, the mean weight-for-age and length-for-age values were close to the median of the WHO growth standards in both groups, indicating adequate growth. The number of adverse events was not different between both groups. No relevant differences were observed in blood parameters indicative for liver and renal function. At 13 weeks, an increased percentage of faecal bifidobacteria (60 v. 48 %) and a reduced percentage of Clostridium lituseburense/C. histolyticum (0·2 v. 2·6 %) were observed in the synbiotic group (n 19) compared with the control group (n 27). In conclusion, this study demonstrates that an extensively hydrolysed formula with B. breve M-16V and the prebiotic mixture scGOS/lcFOS (9:1) supports an adequate infant growth.

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Gastrointestinal Tolerance, Growth and Safety of a Partly Fermented Formula with Specific Prebiotics in Healthy Infants: A Double-Blind, Randomized, Controlled Trial

Nutrients ◽

10.3390/nu11071530 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1530 ◽

Cited By ~ 2

Author(s):

Alfonso Rodriguez-Herrera ◽

Kelly Mulder ◽

Hetty Bouritius ◽

Rocio Rubio ◽

Antonio Muñoz ◽

...

Keyword(s):

Infant Formula ◽

Reference Group ◽

Controlled Trial ◽

Gastrointestinal Symptoms ◽

Daily Weight Gain ◽

Control Group ◽

Double Blind ◽

Control Infant ◽

Breastfed Infants ◽

Experimental Versus

This study evaluated the effect of a partly fermented infant formula (using the bacterial strains Bifidobacterium breve C50 and Streptococcus thermophilus 065) with a specific prebiotic mixture (short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS; 9:1)) on the incidence of gastrointestinal symptoms, stool characteristics, sleeping and crying behaviour, growth adequacy and safety. Two-hundred infants ≤28 days of age were assigned either to experimental infant formula containing 30% fermented formula and 0.8 g/100 mL scGOS/lcFOS or to non-fermented control infant formula without scGOS/lcFOS. A group of breastfed infants served as a reference. No relevant differences in parent-reported gastrointestinal symptoms were observed. Stool consistency was softer in the experimental versus control group with values closer to the breastfed reference group. Daily weight gain was equivalent for both formula groups (0.5 SD margins) with growth outcomes close to breastfed infants. No clinically relevant differences in adverse events were observed, apart from a lower investigator-reported prevalence of infantile colic in the experimental versus control group (1.1% vs. 8.7%; p < 0.02). Both study formulae are well-tolerated, support an adequate infant growth and are safe for use in healthy term infants. Compared to the control formula, the partly fermented formula with prebiotics induces stool consistencies closer to breastfed infants.

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Normal Growth of Healthy Infants Born from HIV+ Mothers Fed a Reduced Protein Infant Formula Containing the Prebiotics Galacto-Oligosaccharides and Fructo-Oligosaccharides: A Randomized Controlled Trial

Clinical Medicine Insights Pediatrics ◽

10.4137/cmped.s17841 ◽

2015 ◽

Vol 9 ◽

pp. CMPed.S17841

Author(s):

Hugo Da Costa Ribeiro Júnior ◽

Tereza Cristina Medrado Ribeiro ◽

Angela Peixoto De Mattos ◽

Mariana Pontes ◽

Roseli Oselka Saccardo Sarni ◽

...

Keyword(s):

Weight Gain ◽

Infant Formula ◽

Controlled Trial ◽

Normal Growth ◽

Daily Weight Gain ◽

Term Infants ◽

Intention To Treat ◽

Formula Group ◽

The Difference ◽

Breast Fed

Objective The aim of the current study was to evaluate the safety of a new reduced protein (2.1 g/100 kcal) infant formula containing 4 g/L of 90% galacto-oligosaccharides (GOS) and 10% fructo-oligosaccharides (FOS). Methods Healthy term infants from Brazil were enrolled. Those born to human immunodeficiency virus (HIV)-positive mothers were randomized to a test ( n = 65) or control ( n = 63) formula group. Infants born to HIV-negative mothers were either exclusively breast-fed ( n = 79) or received a mixed diet (breast milk and test formula, n = 65). Between 2 weeks and 4 months of age, infants were exclusively fed according to their assigned group. Anthropometric measurements were taken at baseline, 1, 2, 3, 4, 6, 8, 10, and 12 months. Digestive tolerance was evaluated during the first 4 months. The primary outcome was mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups. Results Data from all infants ( N = 272) were used in the intention-to-treat (ITT) analysis and data from 230 infants were used in the per-protocol (PP) analysis. The difference in mean daily weight gain between 2 weeks and 4 months in the test formula and breast-fed groups was 1.257 g/day (onesided 95% confidence interval [CI]: -0.705 to inf, P < 0.001) in the PP analysis, showing that the lower bound of the 95% CI was above the -3.0 g/day non-inferiority margin. Results were similar in the ITT analysis. Symptoms of digestive tolerance and frequency of adverse events were similar in the two groups. Conclusions The formula containing 2.1 g/100 kcal protein and GOS and FOS was safe and tolerated well.

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A Partly Fermented Infant Formula with Postbiotics Including 3′-GL, Specific Oligosaccharides, 2′-FL, and Milk Fat Supports Adequate Growth, Is Safe and Well-Tolerated in Healthy Term Infants: A Double-Blind, Randomised, Controlled, Multi-Country Trial

Nutrients ◽

10.3390/nu12113560 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3560

Author(s):

Yvan Vandenplas ◽

Virginie de Halleux ◽

Małgorzata Arciszewska ◽

Piotr Lach ◽

Valeriy Pokhylko ◽

...

Keyword(s):

Weight Gain ◽

Infant Formula ◽

Milk Fat ◽

Controlled Trial ◽

Gastrointestinal Symptoms ◽

Test Group ◽

Control Group ◽

Anthropometric Measures ◽

Double Blind ◽

Term Infants

This study investigated growth, safety, and tolerance in healthy infants consuming a partly fermented infant formula (IF) with postbiotics, 2′-linked fucosyllactose (2′-FL), a specific prebiotic mixture of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS), and milk fat. This double-blind, controlled trial randomised 215 fully IF-fed infants ≤ 14 days of age to either: Test Group (IF) containing 26% fermented formula with postbiotics derived from Lactofidus fermentation process (including 3′-Galactosyllactose; 3′-GL), 0.8 g/100 mL scGOS/lcFOS (9:1), 0.1 g/100 mL 2′-FL, and milk fat), or Control group (IF with 0.8 g/100 mL scGOS/lcFOS (9:1)) until 17 weeks of age. Fully breastfed infants were included as a reference. Anthropometric measures, gastrointestinal symptoms, and safety were assessed monthly. Equivalence in weight gain (primary outcome) between the Test and Control groups was confirmed (difference in means −0.08 g/day; 90% CI (−1.47;1.31)) with estimated mean weight gain (SE) of 31.00 (0.59) g/day and 31.08 (0.60) g/day, respectively, (PP population, n = 196). Equivalence in length and head circumference gain between the randomised groups was also confirmed. No statistically significant differences were observed in adverse events or gastrointestinal tolerance between randomised IF groups. A partly fermented IF with postbiotics, specific oligosaccharides, 2′-FL, and milk fat supports adequate infant growth and is safe and well-tolerated in healthy term infants.

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A Partially Hydrolyzed Whey Infant Formula Supports Appropriate Growth: A Randomized Controlled Non-Inferiority Trial

Nutrients ◽

10.3390/nu12103056 ◽

2020 ◽

Vol 12 (10) ◽

pp. 3056

Author(s):

Eva Karaglani ◽

Inge Thijs-Verhoeven ◽

Marjan Gros ◽

Christina Chairistanidou ◽

Giorgos Zervas ◽

...

Keyword(s):

Weight Gain ◽

Infant Formula ◽

Controlled Trial ◽

Daily Weight Gain ◽

Intact Protein ◽

Control Group ◽

Intervention Period ◽

Term Infants ◽

Randomized Controlled ◽

Secondary Outcomes

The aim of the current study was to investigate the effects of a partially hydrolyzed whey infant formula (PHF) on growth in healthy term infants as compared to a standard infant formula with intact protein (IPF). In a double-blind, non-inferiority, randomized controlled trial, a total of 163 healthy formula-fed infants, 55–80 days old, were recruited and randomly allocated to either the PHF (test) or the IPF (control) group. They were followed up for three months during which they were evaluated monthly on growth and development. In total, 21 infants discontinued the study, while 142 infants completed the study (test n = 72, control n = 70). The primary outcome was daily weight gain during the three months. Secondary outcomes included additional anthropometric indices at every timepoint over the intervention period. Daily weight gain during the three-month intervention period was similar in both groups with the lower bound of 95% confidence interval (CI) above the non-inferiority margin of −3 g/day [mean difference (95% CI) test vs. control: −0.474 (−2.460, 1.512) g/day]. Regarding secondary outcomes, i.e., infants’ weight, length, head circumference, body mass index (BMI), and their Z-scores, no differences were observed between the two groups at any time point. The PHF resulted in similar infant growth outcomes as the standard IPF. Based on these results, it can be concluded that the partially hydrolyzed whey infant formula supports adequate growth in healthy term infants.

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Safety of supplementing infant formula with long-chain polyunsaturated fatty acids and Bifidobacterium lactis in term infants: a randomised controlled trial

British Journal Of Nutrition ◽

10.1017/s0007114508084080 ◽

2009 ◽

Vol 101 (11) ◽

pp. 1706-1713 ◽

Cited By ~ 26

Author(s):

Robert A. Gibson ◽

Denis Barclay ◽

Helen Marshall ◽

Julie Moulin ◽

Jean-Claude Maire ◽

...

Keyword(s):

Weight Gain ◽

Infant Formula ◽

Head Circumference ◽

Controlled Trial ◽

Double Blind ◽

Term Infants ◽

Bifidobacterium Lactis ◽

Significant Difference ◽

Formula Group ◽

Long Chain

Probiotics and long-chain PUFA (LC-PUFA) may be beneficial supplements for infants who are not breast-fed. The aim of the present study is to evaluate the safety of an infant formula containing the LC-PUFA DHA and arachidonic acid (AA) and the probiotic Bifidobacterium lactis by comparing the growth rate of infants fed the supplemented and unsupplemented formulas. One hundred and forty-two healthy, term infants were enrolled in a single-centre, randomised, double-blind, controlled, parallel-group trial, and allocated to receive either standard or probiotic and LC-PUFA-containing experimental formulas. The infants were fed with their assigned formulas for 7 months. The primary outcome (weight gain) and the secondary outcomes (length, head circumference and formula tolerance) were measured throughout the study. LC-PUFA status was assessed at 4 months of age and immune response to childhood vaccines was measured at 7 months of age. There was no significant difference in growth between the two groups. The 90 % CI for the difference in mean weight gain was − 0·08, 3·1 g in the intention-to-treat population and 0·1–3·8 g in the per protocol population, which lay within the predefined boundaries of equivalence, − 3·9–3·9. There were no significant differences in mean length and head circumference. DHA and AA concentrations were higher in infants in the experimental formula group compared with the control formula group. No influence of the supplements on the response to vaccines was observed. Growth characteristics of term infants fed the starter formula containing a probiotic and LC-PUFA were similar to standard formula-fed infants.

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Infant formula with galacto-oligosaccharides (OM55N) stimulates the growth of indigenous bifidobacteria in healthy term infants

Beneficial Microbes ◽

10.3920/bm2015.0168 ◽

2016 ◽

Vol 7 (4) ◽

pp. 453-461 ◽

Cited By ~ 19

Author(s):

T. Matsuki ◽

S. Tajima ◽

T. Hara ◽

K. Yahagi ◽

E. Ogawa ◽

...

Keyword(s):

Infant Formula ◽

Controlled Trial ◽

Shannon Index ◽

Present Species ◽

Double Blind ◽

Term Infants ◽

Breastfed Infants ◽

Trial Onset ◽

Α Diversity ◽

Faecal Samples

The objective of the study was to investigate whether an infant formula supplemented with galacto-oligosaccharides (GOS; OM55N) was able to stimulate the growth of indigenous bifidobacteria and to establish microbiota similar to that of breastfed infants. A randomised, double-blind, placebo-controlled trial was performed using 35 healthy term infants (31-54 days of age; 42±6 days) to determine whether infant formula with 0.3 g/dl GOS (OM55N) stimulated the growth of bifidobacteria in the infants’ guts. At the trial onset and 2 weeks after, the infants’ faecal samples were examined for microbiota composition (bacterial abundance and α-diversity) and faecal characteristics. Among the 35 infants, 5 were withdrawn and 8 were excluded from the final evaluation before breaking the blinding since the indigenous bifidobacteria were not detected at the trial onset. After 2 weeks, the abundance of Bifidobacteriaceae was significantly increased in the GOS feeding group compared to the control (+11.6±24.1% vs -3.9±13.0%; P=0.043). The Shannon index, which accounts for both abundance and evenness of the present species, was significantly decreased with GOS supplementation (-0.1±0.4 vs +0.4±0.4; P=0.014). Faecal characteristics such as pH and organic acids were similar in both groups, with no statistical differences. No adverse side effects related to the formula consumption were reported. Although the concentration of GOS was relatively low, the infant formula with GOS increased the abundance of bifidobacteria and resulted in a reduced α-diversity of the microbiota.

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Long-Term Safety and Efficacy of Prebiotic Enriched Infant Formula—A Randomized Controlled Trial

Nutrients ◽

10.3390/nu13041276 ◽

2021 ◽

Vol 13 (4) ◽

pp. 1276

Author(s):

Franka Neumer ◽

Orenci Urraca ◽

Joaquin Alonso ◽

Jesús Palencia ◽

Vicente Varea ◽

...

Keyword(s):

Infant Formula ◽

Controlled Trial ◽

Fecal Microbiota ◽

First Year ◽

Double Blind Study ◽

Double Blind ◽

Term Infants ◽

Intention To Treat ◽

Prebiotic Oligosaccharides ◽

First Year Of Life

The present study aims to evaluate the effects of an infant formula supplemented with a mixture of prebiotic short and long chain inulin-type oligosaccharides on health outcomes, safety and tolerance, as well as on fecal microbiota composition during the first year of life. In a prospective, multicenter, randomized, double-blind study, n = 160 healthy term infants under 4 months of age were randomized to receive either an infant formula enriched with 0.8 g/dL of Orafti®Synergy1 or an unsupplemented control formula until the age of 12 months. Growth, fever (>38 °C) and infections were regularly followed up by a pediatrician. Digestive symptoms, stool consistency as well as crying and sleeping patterns were recorded during one week each study month. Fecal microbiota and immunological biomarkers were determined from a subgroup of infants after 2, 6 and 12 months of life. The intention to treat (ITT) population consisted of n = 149 infants. Both formulae were well tolerated. Mean duration of infections was significantly lower in the prebiotic fed infants (p < 0.05). The prebiotic group showed higher Bifidobacterium counts at month 6 (p = 0.006), and higher proportions of Bifidobacterium in relation to total bacteria at month 2 and 6 (p = 0.042 and p = 0.013, respectively). Stools of infants receiving the prebiotic formula were softer (p < 0.05). Orafti®Synergy1 tended to beneficially impact total daily amount of crying (p = 0.0594). Supplementation with inulin-type prebiotic oligosaccharides during the first year of life beneficially modulates the infant gut microbiota towards higher Bifidobacterium levels at the first 6 months of life, and is associated with reduced duration of infections.

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Partially Hydrolysed Whey-Based Formulae with Reduced Protein Content Support Adequate Infant Growth and Are Well Tolerated: Results of a Randomised Controlled Trial in Healthy Term Infants

Nutrients ◽

10.3390/nu11071654 ◽

2019 ◽

Vol 11 (7) ◽

pp. 1654

Author(s):

Jacques Rigo ◽

Stefanie Schoen ◽

Marc Verghote ◽

Bart van Overmeire ◽

Wivinne Marion ◽

...

Keyword(s):

Weight Gain ◽

Protein Content ◽

G Protein ◽

Child Growth ◽

Infant Growth ◽

World Health ◽

Daily Weight Gain ◽

Term Infants ◽

Growth Standards ◽

Content Support

The current study aimed to investigate growth, safety and tolerance of partially hydrolysed infant formulae in healthy full-term infants. Fully formula-fed infants were randomised ≤14 days of age to receive a partially hydrolysed whey formula with 2.27 g protein/100 kcal (pHF2.27) or the same formula with 1.8 g or 2.0 g protein/100 kcal (pHF1.8 and pHF2.0) until 4 months of age. The primary outcome was equivalence in daily weight gain within margins of ± 3 g/day; comparison with WHO Child Growth Standards; gastrointestinal tolerance parameters and number of (serious) adverse events were secondary outcomes. A total of 207 infants were randomised, and 61 (pHF1.8), 46 (pHF2.0) and 48 (pHF2.27) infants completed the study per protocol. Equivalence in daily weight gain was demonstrated for the comparison of pHF1.8 and pHF2.27, i.e., the estimated difference was −1.12 g/day (90% CI: [−2.72; 0.47]) but was inconclusive for the comparisons of pHF2.0 and pHF2.27 with a difference of −2.52 g/day (90% CI: [−4.23; −0.81]). All groups showed adequate infant growth in comparison with the World Health Organization (WHO) Child Growth Standards. To conclude, the evaluated partially hydrolysed formulae varying in protein content support adequate growth and are safe and well tolerated in healthy infants.

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