Growth Of Healthy Term Infants Research Articles

Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial.

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.

Neurodevelopmental outcomes of healthy Chinese term infants fed infant formula enriched in bovine milk fat globule membrane for 12 months - A randomized controlled trial.

Human milk fat globule membrane (MFGM) has multifunctional health benefits. We evaluated neurodevelopment and growth of healthy term infants fed bovine milk-derived MFGM-enriched formula (MF) over 12 months. A prospective, multi-center, double-blind, randomized trial was conducted in Fuzhou, China. Healthy term infants (n=212), aged <14 days, were assigned randomly to be fed MF or a standard formula (SF) for 6 months and then switched to stage 2 MF and SF formula until 12 months. A reference group (n=206) contained healthy breastfed infants (BFR). Neurodevelopment was assessed with Bayley-III Scales. At 12 months, the composite social emotional (+3.5) and general adaptive behaviour (+5.62) scores were significantly higher in MF than SF (95% CIs 0.03 to 6.79 and 1.78 to 9.38; p=0.048 and 0.004, respectively). Mean cognitive (+2.86, 95% CIs -1.10 to 6.80, p=0.08), language (+0.39, 95% CIs -2.53 to 3.30, p=0.87) and motor (+0.90, 95% CIs -2.32 to 4.13, p=0.49) scores tended to be higher in MF than SF, but the differences between the two groups were not significant. BFR scored higher on Bayley-III than either MF or SF at 6 and 12 months. Cognitive scores were significantly higher in BFR than SF (95% CI 0.05 to 7.20; p=0.045), but not MF (p=0.74) at 6 months. Short-term memory was significantly higher in MF than SF at 12 months (95% CI 1.40 to 12.33; p=0.002). At 4 months, serum gangliosides were significantly higher in MF and BFR than SF (95% CI 0.64 to 13.02; p=0.025). Milk intake, linear growth, body mass and head circumference were not significantly different between formula-fed groups. MFGM supplementation in early life supports adequate growth, increased serum gangliosides concentration and improves some measures of cognitive development in Chinese infants.

Growth and tolerance of healthy, term infants fed lower protein extensively hydrolyzed or amino acid-based formula: double-blind, randomized, controlled trial

BackgroundOptimal protein level in hypoallergenic infant formulas is an area of ongoing investigation. The aim was to evaluate growth of healthy term infants who received extensively hydrolyzed (EH) or amino acid (AA)-based formulas with reduced protein.MethodsIn this prospective, multi-center, double-blind, controlled, parallel group study, infants were randomized to receive a marketed EH casein infant formula at 2.8 g protein/100 kcal (Control) or one of two investigational formulas: EH casein formula at 2.4 g protein/100 kcal (EHF) or AA-based formula at 2.4 g total protein equivalents/100 kcal (AAF). Control and EHF each had 2 × 107 CFU Lactobacillus rhamnosus GG/100 kcal. Anthropometrics were measured and recall of formula intake, tolerance, and stool characteristics was collected at 14, 30, 60, 90, 120 days of age. Primary outcome was weight growth rate (g/day) between 14 and 120 days of age (analyzed by ANOVA). Medically confirmed adverse events were recorded throughout the study.ResultsNo group differences in weight or length growth rate from 14 to 120 days were detected. With the exception of significant differences at several study time points for males, no group differences were detected in mean head circumference growth rates. However, mean achieved weight, length, and head circumference demonstrated normal growth throughout the study period. No group differences in achieved weight or length (males and females) and head circumference (females) were detected and means were within the WHO growth 25th and 75th percentiles from 14 to 120 days of age. With the exception of Day 90, there were no statistically significant group differences in achieved head circumference for males; means remained between the WHO 50th and 75th percentiles for growth at Days 14, 30, and 60 and continued along the 75th percentile through Day 120. No differences in study discontinuation due to formula were detected. The number of participants for whom at least one adverse event was reported was similar among groups.ConclusionsThis study demonstrated hypoallergenic infant formulas at 2.4 g protein/100 kcal were safe, well-tolerated, and associated with appropriate growth in healthy term infants from 14 to 120 days of age.Trial registrationClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT01354366. Registered 13 May 2011.

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

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.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Comparison of Growth of Healthy Term Infants Fed Extensively Hydrolyzed Protein- and Amino Acid-Based Infant Formulas.

The aim of this narrative review was to assess published growth data for healthy, term, infants consuming extensively hydrolyzed protein-based (EHF), or amino acid-based formulas (AAF). These data may be of use to clinicians managing infants with medical conditions consuming these products. A search was conducted using key terms: amino acid-based, hydrolysate, hydrolyzed, hydrolysed, infant formula, infant formulae or formulas, baby formula, or formulae or formulas, infant, infants, infantile, and growth. Seven controlled, randomized, prospective growth trials of healthy term infants fed EHFs or AAFs at similar time points during the first four months of age met these and other criteria, including that the trial was published in a peer-reviewed journal, subjects were enrolled by ≤14 days of age and were exclusively formula-fed at entry and throughout the duration of the trial, and infants were assessed at regular intervals with weight measures available ideally at 14 days, one, two, three, and four months of age. Results suggested that healthy infants receiving commonly available EHFs and AAFs do not appear to experience accelerated growth as reported for infants fed many standard formulas. Differences in growth patterns were observed with some formulas supporting normative growth patterns during the first four months but others appearing to support markedly lower growth patterns. These observations should be confirmed in well-designed prospective randomized trials. Until that time, it is recommended that EHFs and AAFs be chosen carefully with individual patient needs considered.

Growth, Gastrointestinal Tolerance and Stool Characteristics of Healthy Term Infants Fed an Infant Formula Containing Hydrolyzed Whey Protein (63%) and Intact Casein (37%): A Randomized Clinical Trial.

To investigate whether healthy term infants, fed an infant formula containing hydrolyzed whey protein (HWP-F, hydrolyzed whey/intact casein =63/37), differ in growth, gastrointestinal tolerance and stool characteristics from those fed an infant formula containing intact whey protein (IWP-F, intact whey/intact casein =61/39) or breast milk. Healthy term infants, born within 14 days of the study’s commencement, were randomly assigned to be fed IWP-F or HWP-F until 13 weeks of age, and breast-fed (BF) infants were enrolled as a reference group. Anthropometric measurements, gastrointestinal tolerance indexes and stool characteristics were assessed at baseline, and 7 and 13 weeks of age. There were no significant differences in any growth measurements and the occurrence of crying, spit-up and difficult defecation among the three feeding groups during the study period. However, daily feeding frequency was consistently lower in the formula-fed infants than in the BF group throughout the study (p < 0.05), and infants in the HWP-F group consumed more formula than those in the IWP-F group at 7 and 13 weeks of age (p ≤ 0.002). The HWP-F-fed infants had more similar stool characteristics to the breast-fed infants than infants in the IWP-F group at 13 weeks of age, regardless of frequency, volume, color or consistency of stool. This study demonstrates that the HWP-F could support the normal growth of healthy term infants, to a comparable extent to that of breast-fed infants during the first three months of life. Moreover, stool characteristics of HWP-F-fed infants are much closer to breast-fed infants than IWP-F-fed infants, but no significant gastrointestinal tolerance improvement was observed in HWP-F group.

Long-term safety assessment in children who received hydrolyzed protein formulas with Lactobacillus rhamnosus GG: a 5-year follow-up

Extensively hydrolyzed (EH) formula with Lactobacillus rhamnosus GG (LGG) was demonstrated to alleviate cow’s milk allergy (CMA) symptoms and promote faster acquisition of tolerance to cow’s milk protein. We previously demonstrated that partially hydrolyzed (PH) and EH formulas with LGG supported normal growth in healthy-term infants through 120 days of age. The objective of the current study was to evaluate growth, development, and specific adverse events through 5 years of age in participants from that cohort who continued receiving study formula. Infants who completed a double-blind, randomized growth and tolerance study were eligible to continue receiving the assigned study formula through 1 year of age (control: EH casein formula, EHF, or one of two investigational formulas: EH casein formula with LGG (EHF-LGG) or a PH formula with LGG (PHF-LGG)) and participate in follow-up through 5 years of age. Anthropometric measures, behavior development, and specific adverse events were recorded. No significant differences in achieved weight and height or behavioral development outcomes at 3 or 5 years of age were observed among study groups. Few statistically significant differences in the incidence of specific infection-related events through years 3 or 5 were observed among study groups, none of which were considered clinically relevant.Conclusion: Extensively and partially hydrolyzed formulas with LGG were associated with normal growth and development and long-term safety through 5 years of age.What is Known:• Infants with cow’s milk allergy often experience allergic manifestations that can lead to poor nutrition status and poor growth.• Providing partially hydrolyzed (PH) and EH formulas with or without LGG in infants can support normal growth in healthy-term infants.What is New:• This study provides long-term safety data for the first 5 years of life on the use of extensively and partially hydrolyzed formulas with LGG when fed through 1 year of age.• Extensively and partially hydrolyzed formulas with LGG are associated with normal growth, development, and long-term safety through 5 years of age.

Growth and safety evaluation of infant formulae containing oligosaccharides derived from bovine milk: a randomized, double-blind, noninferiority trial.

BackgroundA limited number of nondigestible oligosaccharides are available for use in infant formula. This study evaluated growth and safety in infants fed formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS). This mixture, which was generated from whey permeate, contains galactooligosaccharides and other oligosaccharides from bovine milk, such as 3′- and 6′-sialyllactose. We hypothesized that growth in infants fed BMOS-supplemented formula would be noninferior to that in infants fed standard formula.MethodsHealthy term infants ≤14 days old were randomly assigned to standard formula (control; n = 84); standard formula with BMOS (IF-BMOS; n = 99); or standard formula with BMOS and probiotics (Bifidobacterium longum, Lactobacillus rhamnosus) (IF-BMOS + Pro; n = 98). A breastfed reference group was also enrolled (n = 30). The primary outcome was mean weight gain/day from enrollment to age 4 months (noninferiority margin: −3.0 g/day).Results189 (67.3%) formula-fed infants were included in the primary analysis. Mean differences in weight gain between the control and IF-BMOS and IF-BMOS + Pro groups were <1 g/day, with 97.5% confidence intervals above −3.0 g/day, indicating noninferior weight gain in the BMOS formula groups. Compared with control, infants in the BMOS groups had more frequent (p < 0.0001) and less hard (p = 0.0003) stools. No significant differences were observed between the control and BMOS groups in caregivers’ reports of flatulence, vomiting, spitting up, crying, fussing, and colic. When based on clinical evaluation by the investigator, the incidence of colic was higher (p = 0.01) in IF-BMOS than in control; the incidence of investigator-diagnosed colic was not significantly different in control and IF-BMOS + Pro (p = 0.15). Stool bifidobacteria and lactobacilli counts were higher with IF-BMOS + Pro compared with control (p < 0.05), whereas Clostridia counts were lower (p < 0.05) in both BMOS groups compared with control.ConclusionsInfant formula containing BMOS either with or without probiotics provides adequate nutrition for normal growth in healthy term infants. Further studies are needed to fully explore the digestive tolerance of BMOS formula.Trial registrationClinicalTrials.gov NCT01886898. Registered 24 June 2013.

Growth of healthy term infants fed partially hydrolyzed whey-based infant formula: a randomized, blinded, controlled trial.

Partially hydrolyzed formulas (pHF) represent a significant percentage of the infant formula market. A new whey-based, palm olein oil (PO)-free pHF was developed and a masked, randomized, parallel growth study was conducted in infants fed this formula or a commercially available whey-based pHF with PO. Infants between 0 and 8 days were to be enrolled and studied to 119 days of age. Growth and tolerance of infants were evaluated. Mean weight gain from 14 to 119 days of age was similar between groups. There were no significant differences between groups in weight, length, head circumference (HC), or length or HC gains. Infants fed the new PO-free pHF had significantly softer stools than those fed the PO-containing formula except at 119 days of age. This study demonstrates that whereas growth of infants fed different formulas during the first 4 months of life may be similar, infants may tolerate individual formulas differently.

Growth of Healthy Term Infants Fed Ready-to-Feed and Powdered Forms of an Extensively Hydrolyzed Casein-Based Infant Formula

Extensively hydrolyzed formulas present a complex matrix subject to adverse conditions during manufacture that could influence growth and tolerance of infants fed these formulas. A masked, randomized, parallel growth study was conducted in infants fed a ready-to-feed (RTF) or powdered (PWD) form of an extensively hydrolyzed casein-based formula. Infants were enrolled between 0 and 9 days and studied to 112 days of age. Growth, formula intake, and stool patterns were assessed. There were no significant differences between groups in weight, length, head circumference, or their respective gains. Tolerance was similar between groups except that the RTF group had greater formula intakes and passed more stools/day compared to the PWD group. This study demonstrates that the PWD formulation of this RTF formula supports similar growth and tolerance in infants during the first 4 months of life.

Growth of Healthy Term Infants Fed an Extensively Hydrolyzed Casein-Based or Free Amino Acid–Based Infant Formula

A masked, randomized, parallel growth study was conducted in infants fed an amino acid-based formula (AF) or an extensively hydrolyzed casein-based formula (HF). Infants were enrolled between 0 and 9 days and studied to 112 days of age. Growth, formula intake, stool patterns, and serum albumin concentrations were assessed. There were no significant differences between groups in weight, length, or head circumference, gains in weight or length, or study formula intake. The number of stools parents rated as being formed, and the mean daily number of stools were greater in the HF than in the AF group at 14 and 28 days of age. Mean serum albumin concentrations were not significantly different between groups and were within the normal range. This study demonstrates that AF supports normal growth of infants comparable to that of infants fed HF during the critical first 4 months of life.