Breast-fed Group Research Articles

Serum, plasma and erythrocyte membrane lipidomes in infants fed formula supplemented with bovine milk fat globule membranes.

Supplementation of formula with bovine milk fat globule membranes has been shown to narrow the gap in immunological and cognitive development between breast-fed and formula-fed infants. In a double-blinded randomized controlled trial 160 formula-fed infants received an experimental formula (EF), supplemented with bovine milk fat globule membranes, or standard formula until 6 months of age. A breast-fed reference group was recruited. Lipidomic analyses were performed on plasma and erythrocyte membranes at 6 months and on serum at 4 and 12 months of age. At 6 months of age, we observed a significant separation in the plasma lipidome between the two formula groups, mostly due to differences in concentrations of sphingomyelins (SM), phosphatidylcholines (PC), and ceramides, and in the erythrocyte membrane lipidome, mostly due to SMs, PEs and PCs. Already at 4 months, a separation in the serum lipidome was evident where SMs and PCs contributed. The separation was not detected at 12 months. The effect of MFGM supplementation on the lipidome is likely part of the mechanisms behind the positive cognitive and immunological effects of feeding the EF previously reported in the same study population.

Effects of breast milk on pain severity during muscular injection of hepatitis B vaccine in neonates in a teaching hospital in Iran

Introduction and aimsHuman breast milk is a natural pain reliever that contains endorphins. The aim of this study was to compare the effects of breast milk and powdered milk on pain severity after a muscular injection in 1-day-old neonates. Materials and methodsOne hundred neonates admitted to a teaching hospital in Ilam city, Iran, participated in a randomized clinical trial in 2016. One-day-old neonates were divided into four equal groups including: the control group (no feeding); the breastfed group; the bottle-fed mother's milk group and the powdered formula group. All infants received the hepatitis B vaccine by muscle injection in the same position of the thigh. The severity and duration of pain were compared among all groups during and after injection using the DAN scoring method (evaluation behavioral scale of acute pain in newborn infant). ResultsOne hundred neonates (57% boys) participated in this study. The mean±SD age and weight for participants were 39.15±0.05 weeks and 3016±28g, respectively. Crying duration either during or after the injection in breastfed infants was significantly shorter compared to the control and powdered formula groups (9.2±3.9 and 16±4.6s vs. 38.2±8.9 and 30.0±4.4s, respectively, during injection, P<0.003); (11.8±3.4 and 20.6±5.1s vs. 56.2±6.5 and 49.8±9.6s, respectively, after injection, P<0.006). There was also a significant relationship between behavioral variations and pain during injection (P<0.0001). ConclusionsThe results of this study showed that breastfeeding decreases pain severity during painful experiences in neonates, which is in accordance with other reports. Based on this finding, neonates are advised to be breastfed if a painful intervention such as vaccination is needed. The pain-relieving effect of breast milk could also be added to its other suitable effects.

High Urinary Iodine Concentration Among Breastfed Infants and the Factors Associated with Iodine Content in Breast Milk

Iodine deficiency in infants leads to delayed growth and development. Some studies have reported iodine deficiency among infants and lactating women. We assessed iodine status in infants and lactating women, as well as the iodine content in breast milk. A cross-sectional study enrolled mother-infant pairs (infants aged 4-6months), who visited Well Child Clinic at Ramathibodi Hospital, Bangkok, Thailand. Infants were classified by feeding type as breastfed (BF), mixed breastfed and formula-fed (MF), and formula-fed (FF). Demographic and perinatal data were collected. The urinary iodine concentration (UIC) of infants and lactating women, and breast milk iodine concentration (BMIC) were analyzed. Seventy-one infants were enrolled. The median UIC of infants was 282mcg/L. Breastfed infants had higher median UIC than formula-fed infants (553 vs. 192mcg/L; p = 0.002). Forty-eight percent of infants had a UIC more than 300mcg/L. The median UIC and BMIC of lactating women were 149 and 255mcg/L, respectively. Among the BF group, the infant UIC was correlated with maternal UIC (rs = 0.857, p = 0.014). Multiple linear regression showed the BMIC to be associated with maternal UIC (β = 4.03, 95% CI [1.34, 6.71]) and maternal weight (β = 8.26, 95%CI [2.76, 13.77]). Iodine nutrition among our study population was adequate. The median UIC of infants and lactating mothers were 282 and 149mcg/L, respectively. Breastfed infants had a significantly higher median UIC than formula-fed infants. The BMIC was associated with maternal UIC and maternal weight.

Lutein Is Differentially Deposited across Brain Regions following Formula or Breast Feeding of Infant Rhesus Macaques

BackgroundLutein, a yellow xanthophyll, selectively accumulates in primate retina and brain. Lutein may play a critical role in neural and retinal development, but few studies have investigated the impact of dietary source on its bioaccumulation in infants. ObjectiveWe explored the bioaccumulation of lutein in infant rhesus macaques following breastfeeding or formula-feeding. MethodsFrom birth to 6 mo of age, male and female rhesus macaques (Macaca mulatta) were either breastfed (BF) (n = 8), fed a formula supplemented with lutein, zeaxanthin, β-carotene, and lycopene (237, 19.0, 74.2, and 338 nmol/kg, supplemented formula-fed; SF) (n = 8), or fed a formula with low amounts of these carotenoids (38.6, 2.3, 21.5, and 0 nmol/kg, unsupplemented formula-fed; UF) (n = 7). The concentrations of carotenoids in serum and tissues were analyzed by HPLC. ResultsAt 6 mo of age, the BF group exhibited significantly higher lutein concentrations in serum, all brain regions, macular and peripheral retina, adipose tissue, liver, and other tissues compared to both formula-fed groups (P < 0.001). Lutein concentrations were higher in the SF group than in the UF group in serum and all tissues, with the exception of macular retina. Lutein was differentially distributed across brain areas, with the highest concentrations in the occipital cortex, regardless of the diet. Zeaxanthin was present in all brain regions but only in the BF infants; it was present in both retinal regions in all groups but was significantly enhanced in BF infants compared to either formula group (P < 0.001). β-Carotene accumulated across brain regions in all groups, but was not detected in retina. Although lycopene was found in many tissues of the SF group, it was not detected in the brain or retina. ConclusionsAlthough carotenoid supplementation of infant formula significantly increased serum and tissue lutein concentrations compared to unsupplemented formula, concentrations were still well below those in BF infants. Regardless of diet, occipital cortex showed selectively higher lutein deposition than other brain regions, suggesting lutein's role in visual processing in early life.

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.

Urinary prostaglandin D2 metabolite excretion during the first six months of life was significantly lower in breast-fed than formula-fed infants.

The metabolic changes that occur during the postnatal weaning period appear to be particularly important for future health, and breast milk is considered to provide the optimal source of infant nutrition. This pilot study from September 2013 to May 2015 examined the effect of breastfeeding on prostaglandin metabolism in healthy term infants. Urine samples were collected from 19 infants at one month of age in the Juntendo University Hospital, Tokyo, Japan. The 13 infants in the breast-fed group received less than 540 mL/week of their intake from formula, and the other six were exclusively fed on formula. At six months, we sampled 14 infants: nine breast-fed and five receiving formula. The infants were from normal single pregnancies and free from perinatal complications. We analysed urinary prostaglandin metabolites-tetranor prostaglandin E2 metabolite (t-PGEM) and tetranor prostaglandin D2 metabolite (t-PGDM)-using liquid chromatography tandem-mass spectrometry. Urinary t-PGDM excretion at one and six months was significantly lower in breast-fed infants than formula-fed infants. However, urinary t-PGEM excretion at one and six months was not significantly different between the groups. Our study showed that the type of feeding in early infancy affected prostaglandin metabolism in healthy term infants.

Effects of osteopontin-enriched formula on lymphocyte subsets in the first 6 months of life: a randomized controlled trial.

BackgroundHuman milk is rich in osteopontin (OPN), which has immunomodulatory functions.MethodsIn a randomized controlled trial, standard formula (SF) and the same formula with 65 mg of OPN/L (F65) or 130 mg of OPN/L (F130), representing ~50 and 100% of the OPN concentration in human milk, were compared. We examined frequencies and composition of peripheral blood immune cells by four-color immunoflow cytometry of formula-fed infants at ages 1, 4, and 6 months, and compared them with a breastfed (BF) reference group.ResultsThe F130 group had increased T-cell proportions compared with the SF (P=0.036, average effect size 0.51) and F65 groups (P=0.008, average effect size 0.65). Compared with the BF group, the monocyte proportions were increased in the F65 (P=0.001, average effect size 0.59) and F130 (P=0.006, average effect size 0.50) groups, but were comparable among the formula groups.ConclusionOPN in an infant formula at a concentration close to that of human milk increased the proportion of circulating T cells compared with both SF and formula with added OPN at ~50% of the concentration in human milk. This suggests that OPN may favorably influence immune ontogeny in infancy and that the effects appear to be dose-dependent.

A pilot study of the effect of human breast milk on urinary metabolome analysis in infants.

This study aimed to examine the nutritional effect of breast feeding on healthy term infants by using urinary metabolome analysis. Urine samples were collected from 19 and 14 infants at 1 and 6 months, respectively. Infants were separated into two groups: the breast-fed group receiving <540 mL/week of their intake from formula (n=13 at 1 month; n=9 at 6 months); and the formula-fed group receiving no breast milk (BM) (n=6 at 1 month; n=5 at 6 months). Urinary metabolome analysis was performed using capillary electrophoresis-time-of-flight mass spectrometry (CE-TOF/MS). A total of 29 metabolites were detected by CE-TOF/MS metabolome analysis in all samples. Urinary excretion of choline metabolites (choline base solution, N,N-dimethylglycine, sarcosine, and betaine) at 1 month were significantly (p<0.05) higher in breast-fed infants than in formula-fed infants. However, choline metabolites were not significantly different between the groups at 6 months. Urinary excretion of lactic acid in breast-fed infants at 1 and 6 months was significantly lower than that in formula-fed infants. Urinary l(-)-threonine and l-carnosine excretion at 1 month was significantly lower in breast-fed infants than in formula-fed infants, but it was not significantly different between the groups at 6 months. The type of feeding in early infancy affects choline metabolism, as well as lactate, threonine, and carnosine levels, in healthy term infants. Urinary metabolome analysis by the CE-TOF/MS method is useful for assessing nutritional metabolism in infants.

The ingestion of cow's milk formula in the first 3 months of life prevents the development of cow's milk allergy.

BackgroundIgE-mediated cow's milk allergy (CMA) is one of the most common food allergies in infants. It is still controversial whether the early introduction of cow's milk formula (CMF) prevents the development of CMA.ObjectiveWe aimed to evaluate the duration and frequency of CMF ingestion as compere with exclusive breast-fed for preventing CMA in high-risk infants.MethodsWe enrolled the patients diagnosed with hen's egg allergy by an oral food challenge. A questionnaire was completed by the caregivers of the patients regarding the timing of introduction and discontinuation of CMF, and the frequency of CMF ingestion. Based on the information, we analyzed the relationship between the duration and frequency of CMF ingestion and the development of CMA at 3–24 months of age.ResultsThree hundred seventy-four patients were analyzed; 171 were diagnosed with CMA (45.7%). The analyzed patients (n = 374) were categorized into the following subgroups: exclusively breast-fed (breast-fed group, n = 75); discontinued ingestion of CMF before 3 months of age (temporary group, n = 177); continuous ingestion of CMF, but not daily, up to 3 months of age (nondaily group, n = 47); continuous ingestion of CMF at least once daily (daily group, n = 75). The incidence of developing CMA between the breast-fed group and temporary group did not show any statistical difference. Nondaily group and daily group had significantly lower incidence of developing CMA in comparison to the breast-fed group (nondaily group odds ratio 0.43; p = 0.02, daily group odds ratio 0.11; p < 0.001).ConclusionIngestion of CMF during the first 3 months of life might prevent the development of CMA in high-risk infants.

Gut wall integrity in exclusively breastfed vs. formula-fed infants

Background Breast milk has bioactive substances that modulate gastrointestinal maturation and maintain mucosal integrity of the gut in infants. Markers that are both non-invasive and reliable, such as fecal alpha-1 antitrypsin (AAT), calprotectin, and secretory immunoglobulin A (sIgA) have been used to assess gut integrity in adults. Higher AAT levels may imply greater enteric protein loss due to increase intestinal permeability of immaturity gut.Objective To assess and compare gut integrity of exclusively breastfed (BF) and exclusively formula fed (FF) infants aged 4-6 months.Methods Subjects were 80 healthy infants (BF=40; FF=40), aged 4-6 months who visited the Pediatric Polyclinic at St. Carolus Hospital, and lived in Pasar Minggu or Cempaka Putih Districts, Jakarta. The fecal AAT was analyzed by an ELISA method. Mann-Whitney and unpaired T-test were used to analyze possible correlations between feeding type and gut integrity.Results The BF group had significantly higher mean fecal AAT than the FF group (P=0.02). Median sIgA levels were not significantly different between groups (P=0.104). The FF group had a higher mean fecal calprotectin level but this difference was also not significant (P=0.443). There was a significant correlation between breastfeeding and mean fecal AAT level (P=0.02), but no significant correlation with calprotectin (P=0.65) or sIgA (P=0.26).Conclusion The breastfed group shows better mucosal integrity compared to the formula fed group. Higher mean fecal AAT level in the BF group is related to the AAT content of breast milk. Therefore AAT content of BF group is actually lower than formula fed group which shows greater mucosal integrity in BF group.

Infant feeding and health-related quality of life in healthy Chinese infants: results from a prospective, observational cohort study.

BackgroundInfant feeding regimens, including breastfeeding, formula-feeding, or a combination of the two, may influence infant health-related quality of life (HRQOL). However, few studies have examined this association.MethodsThis prospective cohort study assessed HRQOL in relation to three parent-selected feeding regimens: exclusively breastfed (n = 136), exclusively study formula-fed (n = 140), and mixed-fed with study formula and breast milk (n = 151). Healthy Chinese infants were enrolled at their first normally scheduled well infant clinic visit at age 42 days (study day 1). Parents independently chose their infants’ feeding regimens prior to recruitment into the study, with infants in the formula and mixed-fed groups already consuming an infant formula enriched with α-lactalbumin and increased sn-2 palmitate and oligofructose. The Infant and Toddler Quality of Life Questionnaire, which includes six infant-focused and three parent-focused concepts, was used to assess HRQOL at day 1 and at a follow-up visit 48 days later. Scores for each concept ranged from 0 to 100. Parent quality of life (assessed using the Mental Component Summary score of the SF-12v2 Health Survey) was included in the ANCOVA model to adjust for its potential effect on parent’s perception of infant HRQOL.ResultsHRQOL concept scores were high in all three study groups at both visits (mean scores 71–95). Day 1 HRQOL scores were not significantly different between groups. At day 48, 5 of 9 HRQOL scores were not significantly different between groups. However, scores for Temperament and Moods, General Health Perceptions and Parent Impact–Time were slightly but statistically significantly lower in the formula-fed group (mean scores 75–86; all p ≤ 0.01) compared to the breastfed (78–90) and mixed-fed (77–91) groups. Day 48 Parent Impact–Emotional scores were also significantly lower by a small margin (4 points; p = 0.003) in the formula-fed group compared with the breastfed group.ConclusionsHRQOL was high in this population of healthy infants, with only a few small differences in HRQOL concept scores observed between breastfed, formula-fed and mixed-fed infants. These results indicate favorable physical, mental, and social well-being in these infants and parents. Assessment of infant HRQOL is therefore feasible and provides valuable insight into parental perceptions of their child’s health and well-being.Trial registrationClinicalTrials.gov, NCT01370967.

Effects of Term Infant Formula Supplemented with Oligofructose on Intestinal Microbiota Composition, Diversity, and Metabolic Activity

Background and AimsPrebiotic oligosaccharides in breastmilk may promote infants’ digestive health. We evaluated the effects of a term infant formula with oligofructose (OF) on infant growth, fecal microbiota and microbial metabolism.MethodsData from an 8‐week randomized controlled trial of healthy Filipino infants was used to compare growth and fecal microbiota outcomes in a subset of infants fed high sn‐2 palmitate formula (F1) or an identical formula with 5 g/L OF (F2), and a non‐randomized breastfed group (BF). Growth was measured at baseline, week 4, and week 8 (n per group 73–75). Stool samples were collected at baseline and week 8. Baseline‐adjusted group comparisons based on wet weight stool were performed in the per‐protocol population at week 8 (n per group 30–37), including fecal bacteria group counts (FISH), organic acids (HPLC) and pH as well as pathogen counts (qPCR, n per group 26–27). Fecal bacteria abundance and diversity (pyrosequencing, n per group 9–11) were assessed at week 8.ResultsWeight, length and head circumference were similar in all groups at each visit and together with z‐scores supported clinically adequate growth. From baseline to week 8, infants fed F2 (vs. F1) had a smaller increase in the Clostridia group (mean difference ± SE; 0.41 ± 0.16 vs. 0.91 ± 0.18, p=0.015) and a greater decrease in the Enterobacteriaceae group (−0.29 ± 0.13 vs. −0.06 ± 0.11, p=0.037). Infants fed F2 (vs. F1) had significantly different changes from baseline in pH (p&lt;0.0001), lactate (p&lt;0.0001), propionate (p=0.0057), butyrate (p=0.0139), and total organic acids (p=0.0148). At week 8, infants receiving F2 did not differ from BF in pH, or in concentrations of lactate, butyrate, the Lactobacilli/Enterococci group, the Clostridia group, C. perfringens species, or E. coli, EPEC species. In the pyrosequencing analysis, the F2 group had less of the Peptostreptococcaceae group vs. F1 (p=0.047) at week 8 and was not different from the BF infants, and bifidobacteria strongly dominated the microbiota of infants receiving F2 (median=92%), similar to BF infants (90%). Insufficient power limited some analyses. The F2 group (vs. F1) had a numerically smaller increase from baseline in C. difficile and E. coli, EPEC species. The average weighted UniFrac distance (a measure of phylogenetic distance between bacterial communities) was smaller between the F2 group vs. BF than between the F1 group vs. BF. Finally, bacterial communities from the F2 group had a smaller Shannon diversity index vs. F1, suggesting fewer and less evenly distributed species, and closer to the diversity index of the BF infants.ConclusionInfants grew similarly in all groups. Term infant formula supplemented with 5g/L OF inhibited growth of potentially pathogenic fecal bacteria, lowered pH and shifted the organic acid profile closer to breastfed infants vs. formula without OF. After 8 weeks of feeding, the fecal microbiota composition and microbial metabolism patterns of infants receiving 5 g/L OF were closer to those of breastfed infants.Support or Funding Information This study was sponsored by Wyeth Nutrition, a Nestlé business. The infant formula evaluated in this study was a Wyeth Nutrition product and was provided free of charge.

Human Breast Milk and Infant Formulas Differentially Modify the Intestinal Microbiota in Human Infants and Host Physiology in Rats

Background: In the absence of human breast milk, infant and follow-on formulas can still promote efficient growth and development. However, infant formulas can differ in their nutritional value.Objective: The objective of this study was to compare the effects of human milk (HM) and infant formulas in human infants and a weanling rat model.Methods: In a 3 wk clinical randomized controlled trial, babies (7- to 90-d-old, male-to-female ratio 1:1) were exclusively breastfed (BF), exclusively fed Synlait Pure Canterbury Stage 1 infant formula (SPCF), or fed assorted standard formulas (SFs) purchased by their parents. We also compared feeding HM or SPCF in weanling male Sprague-Dawley rats for 28 d. We examined the effects of HM and infant formulas on fecal short chain fatty acids (SCFAs) and bacterial composition in human infants, and intestinal SCFAs, the microbiota, and host physiology in weanling rats.Results: Fecal Bifidobacterium concentrations (mean log copy number ± SEM) were higher (P = 0.003) in BF (8.17 ± 0.3) and SPCF-fed infants (8.29 ± 0.3) compared with those fed the SFs (6.94 ± 0.3). Fecal acetic acid (mean ± SEM) was also higher (P = 0.007) in the BF (5.5 ± 0.2 mg/g) and SPCF (5.3 ± 2.4 mg/g) groups compared with SF-fed babies (4.3 ± 0.2 mg/g). Colonic SCFAs did not differ between HM- and SPCF-fed rats. However, cecal acetic acid concentrations were higher (P = 0.001) in rats fed HM (42.6 ± 2.6 mg/g) than in those fed SPCF (30.6 ± 0.8 mg/g). Cecal transcriptome, proteome, and plasma metabolite analyses indicated that the growth and maturation of intestinal tissue was more highly promoted by HM than SPCF.Conclusions: Fecal bacterial composition and SCFA concentrations were similar in babies fed SPCF or HM. However, results from the rat study showed substantial differences in host physiology between rats fed HM and SPCF. This trial was registered at Shanghai Jiào tong University School of Medicine as XHEC-C-2012–024.

Evaluating the Impact of Breastfeeding on Rotavirus Antigenemia and Disease Severity in Indian Children.

ObjectivesTo evaluate the contribution of breastfeeding to Rotavirus (RV)-induced antigenemia and/or RNAemia and disease severity in Indian children (<2 yrs age).MethodsPaired stool and serum samples were collected from (a) hospitalized infants with diarrhea (n = 145) and (b) healthy control infants without diarrhea (n = 28). Stool RV-antigen was screened in both groups by commercial rapid-test and enzyme immunoassay. The disease severity was scored and real-time-PCR was used for viral-load estimation. Serum was evaluated for RV-antigenemia by EIA and RV-RNAemia by RT-PCR. Data was stratified by age-group and breastfeeding status and compared.ResultsPresence of RV-antigenemia and RV-RNAemia was positively related with presence of RV in stool. Disease severity and stool viral-load was significantly associated with RV-antigenemia[(r = 0.74; CI:0.66 to 0.84; P<0.0001,R2 = 0.59) and (r = -0.55; CI:-0.68 to -0.39; P<0.0001,R2 = 0.31) respectively], but not with RV-RNAemia. There was significant reduction in RV-antigenemiarate in the breast-fed group compared to non-breastfed infants, especially in 0–6 month age group (P<0.001). Non-breastfed infants were at risk for RV-antigenemia with severe disease manifestations in form of high Vesikari scores correlating with high fever, more vomiting episodes and dehydration.ConclusionRV-antigenemia was common in nonbreastfed children with severe RV-diarrhea and correlated with stool RV-load and disease severity.

Gut microbiota analysis reveals a marked shift to bifidobacteria by a starter infant formula containing a synbiotic of bovine milk-derived oligosaccharides and Bifidobacterium animalis subsp. lactis CNCM I-3446.

Non-digestible milk oligosaccharides were proposed as receptor decoys for pathogens and as nutrients for beneficial gut commensals like bifidobacteria. Bovine milk contains oligosaccharides, some of which are structurally identical or similar to those found in human milk. In a controlled, randomized double-blinded clinical trial we tested the effect of feeding a formula supplemented with a mixture of bovine milk-derived oligosaccharides (BMOS) generated from whey permeate, containing galacto-oligosaccharides and 3'- and 6'-sialyllactose, and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446. Breastfed infants served as reference group. Compared with a non-supplemented control formula, the test formula showed a similar tolerability and supported a similar growth in healthy newborns followed for 12 weeks. The control, but not the test group, differed from the breast-fed reference group by a higher faecal pH and a significantly higher diversity of the faecal microbiota. In the test group the probiotic B. lactis increased by 100-fold in the stool and was detected in all supplemented infants. BMOS stimulated a marked shift to a bifidobacterium-dominated faecal microbiota via increases in endogenous bifidobacteria (B. longum, B. breve, B. bifidum, B. pseudocatenulatum).

Effect of Infant Formula Containing a Low Dose of the Probiotic Bifidobacterium lactis CNCM I-3446 on Immune and Gut Functions in C-Section Delivered Babies: A Pilot Study.

BACKGROUNDIn the absence of breast-feeding and its immunomodulatory factors, supplementation of starter infant formula (IF) with probiotics is currently used to support immune functions and gut development.AIMTo assess whether immune-related beneficial effects of regular dose (107 CFU/g of powder) of the probiotic Bifidobacterium lactis CNCM I-3446 (hereafter named B. lactis) in starter IF supplementation can be maintained with starter IF containing a low dose (104 CFU/g of powder) of B. lactis.METHODThis trial was designed as a pilot, prospective, double-blind, randomized, single-center clinical trial of two parallel groups (n = 77 infants/group) of C-section delivered infants receiving a starter IF containing either low dose or regular dose of the probiotic B. lactis from birth to six months of age. In addition, a reference group of infants breast-fed for a minimum of four months (n = 44 infants), also born by C-section, were included. All groups were then provided follow-up formula without B. lactis up to 12 months of age. Occurrence of diarrhea, immune and gut maturation, responses to vaccinations, and growth were assessed from birth to 12 months. The effect of low-dose B. lactis formula was compared to regular-dose B. lactis formula, considered as reference for IF with probiotics, and both were further compared to breast-feeding as a physiological reference.RESULTSData showed that feeding low-dose B. lactis IF provides similar effects as feeding regular-dose B. lactis IF or breast milk. No consistent statistical differences regarding early life protection against gastrointestinal infections, immune and gut maturation, microbiota establishment, and growth were observed between randomized formula-fed groups as well as with the breast-fed reference group.CONCLUSIONThis pilot study suggests that supplementing C-section born neonates with low-dose B. lactis-containing starter formula may impact immune as well as gut maturation similarly to regular-dose B. lactis, close to the breast-feeding reference.

Early Gut Colonization With Lactobacilli and Staphylococcus in Infants: The Hygiene Hypothesis Extended.

The aim of the present study was to assess the mode of delivery and type-of-feeding impact on gut microbiota. We demonstrated higher fecal bifidobacteria in infants who were breast-fed (BF) or fed formula with prebiotics polydextrose (PDX) and galactooligosaccharides (GOS) versus formula without prebiotics. Here, we tested feces of that cohort for lactobacilli and Staphylococcus aureus, 2 types of bacteria present in breast milk. In a double-blind, randomized study, 21- to 30-day-old term infants vaginally delivered and exclusively formula-fed received a cow's milk-based formula (control, n = 80) or the same formula with 4 g/L (1:1 ratio) of PDX/GOS (PDX/GOS, n = 77). A reference BF group (n = 71) was included. Stool samples were obtained at baseline and after 30 and 60 days of feeding to assess fecal bacteria by quantitative real-time polymerase chain reaction. Pairwise comparisons between baseline-adjusted means log10 colony-forming unit per gram feces of total lactobacilli counts (8.37 in control, 8.46 in PDX/GOS, and 8.42 in BF) showed a significant difference only between PDX/GOS and control at 30 and 60 days combined (P = 0.035), utilizing generalized estimating equations method. Baseline-adjusted odds ratio (OR) of colonization with S aureus was lower in control (OR 0.47, 95% confidence interval 0.22-1.00, P = 0.049) and PDX/GOS (OR 0.44, 95% confidence interval 0.21-0.94, P = 0.03) groups versus the BF group. Bacteria found in breast milk, such as lactobacilli and S aureus can also be found in infant feces. S aureus, traditionally considered harmful, may aid in educating the coevolving immune system. Modifying formula by adding prebiotics may bring gut microbiota closer to that of BF infants in terms of beneficial microbes.

Effect of dietary protein on plasma insulin-like growth factor-1, growth, and body composition in healthy term infants: a randomised, double-blind, controlled trial (Early Protein and Obesity in Childhood (EPOCH) study).

The effect of protein intake on growth velocity in infancy may be mediated by insulin-like growth factor-1 (IGF-1). This study aimed to determine the effects of formulae containing 1·8 (F1·8) or 2·7 g (F2·7) protein/418·4 kJ (100 kcal) on IGF-1 concentrations and growth. Healthy term infants were randomly assigned to receive F1·8 (n 74) or F2·7 (n 80) exclusively for the first 4 months of life. A group of breast-fed infants (n 84) was followed-up simultaneously (reference). Growth and body composition were measured at 0·5, 4, 6, 12, 36, 48 and 60 months of life. The IGF-1 concentrations at 4 months (primary outcome) were similar in the F1·8 (67·1 (sd 20·8) ng/l; n 70) and F2·7 (71·2 (sd 27·5) ng/l; n 73) groups (P=0·52). Both formula groups had higher IGF-1 concentrations than the breast-fed group at 4 and 9 months of age (P≤0·0001). During the first 60 months of life, anthropometric parameters in the F1·8 group were lower compared with the F2·7 group, and the differences were significant for head circumference from 2 to 60 months, body weight at 4 and 6 months and length at 9, 12 and 36 months of age. There were no significant differences in body composition between these two groups at any age. We conclude that, in formula-fed infants, although increased protein intake did not affect the IGF-1 concentration during the first 12 months of life, it did affect length and head circumference growth, suggesting that factors other than IGF-1 could play roles in determining growth velocity.

Adequacy of Infant Formula With Protein Content of 1.6 g/100 kcal for Infants Between 3 and 12 Months.

Infant formulas provide more protein than breast milk. High protein intakes may place infants at risk of later obesity. The present study tested whether a formula with protein content below the regulatory level supports normal growth from age 3 months. Randomized double-blind trial enrolled healthy infants less than age 3 months. At 3 months, formula-fed infants were assigned to experimental (EXPL, 1.61 g protein/100 kcal; modified bovine whey proteins with caseinoglycomacropeptide removed) or control (CTRL 2.15 g protein/100 kcal; unmodified bovine milk protein with a whey/casein ratio of 60/40) formula; breast-fed (BF) infants were enrolled in a reference group. Complementary foods were allowed in small amounts from 4 to 6 months and unrestricted after 6 months. Weight gain (g/day) from 3 to 6 months was similar in the EXPL and CTRL groups (EXPL-CTRL -0.84 g/day; 95% confidence interval -2.25 to 0.57) and faster in the EXPL and CTRL groups than in the BF group. Weight analyzed longitudinally from 4 to 12 months was lower in the EXPL group than in the CTRL group (P = 0.031) but higher than in the BF group (P < 0.0001). Longitudinal analysis of odds ratios from 4 to 12 months indicated fewer infants with weight >85th percentile in the EXPL group than in the CTRL group (P = 0.015). Length z scores were lower than, and body mass index z scores were similar to, World Health Organization Standards in all of the groups. Serum biochemical parameters in the EXPL group reflected lower protein intake and were closer to parameters in the BF infants than in the CTRL group. A formula with 1.61 g of protein/100 kcal supports normal growth of infants after age 3 months. This protein content is adequate if provided from a high-quality source.

Similar Occurrence of Febrile Episodes Reported in Non-Atopic Children at Three to Five Years of Age after Prebiotics Supplemented Infant Formula.

This is a follow up study of a multicenter randomised placebo-controlled trial in seven centres in five West European countries. The RCT assessed the effect of infant formula supplemented with a mixture of prebiotics (with neutral short-chain and long-chain oligosaccharides and pectin-derived acidic oligosaccharides) during infancy in term-born children (n=1130). In the follow-up study 672 children (60% of the study population) participated: 232 (56%) from the prebiotics group (PG), 243 (58%) from the control group (CG), and 197 (66%) from the non-randomised breast-fed group (BG). The primary outcome was the occurrence of febrile episodes at three to five years of age prospectively documented by the parents: in the PG 1.17 (interquartile range 0.50-2.08) episodes per year versus 1.20 (0.52-2.57) in the CG; and 1.48 (0.65-2.60) in the BG. This specific prebiotics mixture given during infancy in healthy non-atopic subjects does not decrease febrile episodes and therefore seems not to prevent infection between their third and fifth birthday.