Many improvements have been made to bring infant formula (IF) closer to human milk (HM) regarding its nutritional and biological properties. Nevertheless, the protein components of HM and IF are still different, which may affect their digestibility. This study aimed to evaluate and compare the protein digestibility of HM and IF using the infant INFOGEST digestion method. Pooled HM and a commercial IF were subjected to the infant INFOGEST method, which simulates the physiological digestion conditions of infants, with multiple directions, i.e. the curd state, gel images of SDS-PAGE, molecular weight distribution, free amino acid concentrations and in vitro protein digestion rate. HM underwent proteolysis before digestion and tended to have a higher protein digestion rate with finer curds during gastric digestion, than the IF. However, multifaceted analyses showed that the protein digestibility of HM and IF was not significantly different after gastrointestinal digestion. In conclusion, the infant INFOGEST method showed that the digestibility of HM and IF proteins differed to some extent before digestion and after gastric digestion, but not at the end of gastrointestinal digestion. The findings of this study will contribute to the refinement of IF with better protein digestibility in infant stomach.

This study compared the concentrations, types and distributions of sialic acid (SA) in human milk at different stages of the postnatal period with those in a range of infant formulas. Breast milk from mothers of healthy, full-term and exclusively breastfed infants was collected on the 2nd (n 246), 7th (n 135), 30th (n 85) and 90th (n 48) day after birth. The SA profiles of human milk, including their distribution, were analysed and compared with twenty-four different infant formulas. Outcome of this observational study was the result of natural exposure. Only SA of type Neu5Ac was detected in human milk. Total SA concentrations were highest in colostrum and reduced significantly over the next 3 months. Approximately 68·7–76·1 % of all SA in human milk were bound to oligosaccharides. Two types of SA, Neu5Ac and Neu5Gc, have been detected in infant formulas. Most SA was present in infant formulas combined with protein. Breastfed infants could receive more SA than formula-fed infants with the same energy intake. Overall, human milk is a preferable source of SA than infant formulas in terms of total SA content, dynamics, distribution and type. These SA profiles in the natural state are worth to be considered by the production of formulas because they may have a great effect on infant nutrition and development.

This study investigated the effects of Lacticaseibacillus rhamnosus HN001 supplementation on the architecture and gene expression in small intestinal tissues of piglets used as an animal model for infant humans. Twenty-four 10-d-old entire male piglets (4·3 (sd 0·59) kg body weight) were fed an infant formula (IF) (control) or IF supplemented with 1·3 × 105 (low dose) or 7·9 × 106 (high dose) colony-forming units HN001 per ml of reconstituted formula (n 8 piglets/treatment). After 24 d, piglets were euthanised. Samples were collected to analyse the histology and gene expression (RNAseq and qPCR) in the jejunal and ileal tissues, blood cytokine concentrations, and blood and faecal calprotectin concentrations. HN001 consumption altered (false discovery rate < 0·05) gene expression (RNAseq) in jejunal tissues but not in ileal tissues. The number of ileal goblet cells and crypt surface area increased quadratically (P < 0·05) as dietary HN001 levels increased, but no increase was observed in the jejunal tissues. Similarly, blood plasma concentrations of IL-10 and calprotectin increased linearly (P < 0·05) as dietary HN001 levels increased. In conclusion, supplementation of IF with HN001 affected the architecture and gene expression of small intestine tissue, blood cytokine concentration and frequencies, and blood calprotectin concentrations, indicating that HN001 modulated small intestinal tissue maturation and immunity in the piglet model.

During industrial processing, heat treatments applied to infant formulas may affect protein digestion. Recently, innovative processing routes have been developed to produce minimally heat-processed infant formula. Our objective was to compare the in vivo protein digestion kinetics and protein quality of a minimally processed (T−) and a heat-treated (T+++) infant formula. Sixty-eight male Wistar rats (21 d) were fed with either a diet containing 40 % T− (n 30) or T+++ (n 30), or a milk protein control diet (n 8) during 2 weeks. T− and T+++ rats were then sequentially euthanised 0, 1, 2, 3 or 6 h (n 6/time point) after ingestion of a meal containing their experimental diet. Control rats were euthanised 6 h after ingestion of a protein-free meal to determine nitrogen and amino acid endogenous losses. Nitrogen and amino acid true caecal digestibility was high for both T− and T+++ diets (> 90 %), but a tendency towards higher nitrogen digestibility was observed for the T− diet (96·6 ± 3·1 %) compared with the T+++ diet (91·9 ± 5·4 %, P = 0·0891). This slightly increased digestibility led to a greater increase in total amino acid concentration in plasma after ingestion of the T− diet (P = 0·0010). Comparable protein quality between the two infant formulas was found with a digestible indispensable amino acid score of 0·8. In conclusion, this study showed that minimal processing routes to produce native infant formula do not modify protein quality but tend to enhance its true nitrogen digestibility and increase postprandial plasma amino acid kinetics in rats.

In this study, the heavy metal (Al, Mn, Co, Cu, Zn, As, Se, Cd, Sn, Pb and Hg) concentrations were determined in a total of seventy-two infant formula samples manufactured by sixteen different brands in Türkiye. During the analyses, inductively coupled plasma MS was used in evaluating the nutritional profile and the toxicological risk associated with the consumption of these products. Given the analysis results, the highest Pb content was found in milk-based ‘beginner’ formulas (0–6 months, three samples) packed in metal containers. The highest concentration of Mn was found in powdered infant formula (Brand 3) that is suitable for 9–12-month-olds. Mn level was found to be above the limit values in nine samples (12·5 %). Cd level exceeded the limit values in two infant formula samples of Brand 3 (0·038 µg/g) and Brand 15 (0·023 µg/g). Therefore, the mean Cd concentration found here reaches the maximum limit set by the European Union commission legislation. Cu was detected in all infant formulas. The highest concentration was determined in Brand 1 (9–12 months, seven samples) and found to be 2·637 (sd 1·928) µg/g. This value is much higher than the reference values set in the national and international standards. Based on the results achieved here, the estimated daily intake (EDI) and target hazard quotient values for all the metals in infant formulas were found lower than < 1. These findings suggest that the baby foods examined would not pose any health risk. The daily intakes exceeding the baby nutrition values recommended by the WHO would pose health risk since they would exceed the EDI levels.

While breast-feeding is the recommended feeding mode in infancy, rates are low in some Western societies, and infants are widely fed formula. France, in particular, shows high rates of infant formula use, including formulas with protein hydrolysates. The degree of protein hydrolysis has previously been associated with neurodevelopmental outcomes. The present study examines the associations between the protein’s hydrolysis degree in infant formula and child neurodevelopment up to 3·5 years of age in the French nationwide Étude Longitudinale Française depuis l’Enfance (ELFE study). Parents reported on brand and name of the formula used at 2 months, and protein hydrolysis degree was derived from the ingredient list. Analyses were based on 6979 infants (92·2, 6·8 and 1 % consuming non-hydrolysed, partially and extensively hydrolysed formulas, respectively). Neurodevelopment was assessed at age 1 and 3·5 years with the Child Development Inventory (CDI), at age 2 years with the MacArthur-Bates Communicative Development Inventories and at age 3·5 years with the Picture Similarities sub-scale (British Ability Scales). Associations between protein hydrolysis degree and child neurodevelopment were assessed using linear and logistic regression for overall scores and poor CDI sub-domain scores (<25th centile), respectively. Among formula-fed infants, protein hydrolysis degree in infant formula was not associated with overall neurodevelopmental scores up to 3·5 years. Some associations were found with the motor skills CDI sub-domain, but they were not consistent at 1 and 3·5 years as well as across sensitivity analyses. The use of hydrolysed formula appears safe in terms of overall neurodevelopment, and research should further investigate specific neurodevelopmental domains.

Human milk oligosaccharides (HMOs) are a class of structurally diverse and complex unconjugated glycans present in breast milk, which act as selective substrates for several genera of select microbes and inhibit the colonisation of pathogenic bacteria. Yet, not all infants are breastfed, instead being fed with formula milks which may or may not contain HMOs. Currently, formula milks only possess two HMOs: 2′-fucosyllactose (2’FL) and lacto-N-neotetraose (LNnT), which have been suggested to be similarly effective as human breast milk in supporting age-related growth. However, the in vivo evidence regarding their ability to beneficially reduce respiratory infections along with altering the composition of an infant’s microbiota is limited at best. Thus, this review will explore the concept of HMOs and their metabolic fate, and summarise previous in vitro and in vivo clinical data regarding HMOs, with specific regard to 2’FL and LNnT.

Mounting evidence suggests that the first few months of life are critical for the development of obesity. The relationships between the timing of solid food introduction and the risk of childhood obesity have been examined previously; however, evidence for the association of timing of infant formula introduction remains scarce. This study aimed to examine whether the timing of infant formula introduction is associated with growth z-scores and overweight at ages 1 and 3 years. This study included 5733 full-term (≥ 37 gestational weeks) and normal birth weight (≥ 2500 and < 4000 g) children in the Born in Guangzhou Cohort Study, a prospective cohort study with data collected at 6 weeks, 6, 12 and 36 months. Compared with infant formula introduction at 0–3 months, introduction at 4–6 months was associated with the lower BMI, weight-for-age and weight-for-length z-scores at 1 and 3 years old. Also, introduction at 4–6 months was associated with the lower odds of at-risk of overweight at age 1 (adjusted OR 0·72, 95 % CI 0·55, 0·94) and 3 years (adjusted OR 0·50, 95 % CI 0·30, 0·85). Introduction at 4–6 months also decreased the odds of overweight at age 1 year (adjusted OR 0·42, 95 % CI 0·21, 0·84) but not at age 3 years. Based on our findings, compared with introduction within the first 3 months, introduction at 4–6 months has a reduction on later high BMI risk and at-risk of overweight. However, these results need to be replicated in other well-designed studies before more firm recommendations can be made.

The consumer survey reported in this research paper aims to understand how Chinese mothers learn about and confirm the origin of powdered infant formulas (henceforward formulas), their knowledge level and preferences between formulas from different origins. With globalization, dairy companies can source ingredients for domestic production and manufacture finished products across the world. Chinese consumers are now facing a variety of formulas with different brand origin, main ingredient origin (‘nai yuan’), manufacturing origin, and country-of-purchase. Drawing on a large representative sample of Chinese mothers who have purchased formulas, we found that most of them had intensively engaged in learning about and confirming formulas' origin through different strategies. However, they may not interpret related cues correctly: a majority of Chinese mothers incorrectly considered the ‘main ingredient origin’ as the ‘manufacturing place’ and could not necessarily recognize between ‘foreign’ and ‘domestic’ brands. Among formulas from different origins, authentic foreign branded, produced and packaged formulas showed a high popularity in Tier 1 & 2 cities and among more knowledgeable consumers. In low-tier cities, these products were equally popular as domestically branded and produced formulas using imported milk powders and other ingredients. Formulas directly acquired from overseas markets through unofficial channels were least favoured by consumers. The study shows that Chinese consumers' previous one-sided endorsement towards foreign formulas appears to have weakened. Decisions made by formula companies on the origin of the main ingredient and the place of manufacture would influence product attractiveness, and the segments of Chinese consumers to target.

Type of feeding during early life influences growth trajectory and metabolic risk at later ages. Modifications in infant formula composition have led to evaluate their effects on growth and energetic efficiency (EE) compared with breast-feeding. Main goal was to analyse type of feeding potential effects during first months of life, plus its EE, on growth patterns in healthy formula fed (standard infant formula (SF) vs. experimental infant formula enriched with bioactive nutrients (EF)) and breastfed (BF) infants participating in the COGNIS RCT (http://www.ClinicalTrials.gov, Identifier: NCT02094547) up to 18 months of age. Infants follow-up to 18 months of age (n 141) fed with a SF (n 48), EF(n 56), or BF (n 37), were assessed for growth parameters using WHO standards. Growth velocity (GV) and catch-up were calculated to identify growth patterns. EE of breast milk/infant formula was also estimated. Infants’ growth at 6 months showed higher length and lower head circumference gains in SF and EF infants than BF infants. Both weight-for-length and weight-for-age catch-up growth showed significant differences in formula fed groups compared with the BF. No significant differences in GV or catch-up were found at 6–12 and 12–18 months. Regarding EE, infant formula groups showed significantly lower weight and length gains/g of milk protein, and higher weight and length gains/g of milk lipids, than the BF infants. GV during first 6 months, which may be influenced by feeding, seems to be the main predictor of subsequent growth trajectory. Breast-feeding may have positive effects on growth programming due to its nutrients’ EE.

Industrial heat treatment of milk results in protein glycation. A high protein glycation level has been suggested to compromise the post-prandial rise in plasma amino acid availability following protein ingestion. In the present study, we assessed the impact of glycation level of milk protein on post-prandial plasma amino acid responses in humans. Fifteen healthy, young men (age 26 (SEM 1) years, BMI 24 (SEM 1) kg/m2) participated in this randomised cross-over study and ingested milk protein powder with protein glycation levels of 3, 20 and 50 % blocked lysine. On each trial day, arterialised blood samples were collected at regular intervals during a 6-h post-prandial period to assess plasma amino acid concentrations using ultra-performance liquid chromatography. Plasma essential amino acid (EAA) concentrations increased following milk protein ingestion, with the 20 and 50 % glycated milk proteins showing lower overall EAA responses compared with the 3 % glycated milk protein (161 (SEM 7) and 142 (SEM 7) v. 178 (SEM 9) mmol/l × 6 h, respectively; P ≤ 0·011). The lower post-prandial plasma amino acid responses were fully attributed to an attenuated post-prandial rise in circulating plasma lysine concentrations. Plasma lysine responses (incremental AUC) following ingestion of the 20 and 50 % glycated milk proteins were 35 (SEM 4) and 92 (SEM 2) % lower compared with the 3 % glycated milk protein (21·3 (SEM 1·4) and 2·8 (SEM 0·7) v. 33·3 (SEM 1·7) mmol/l × 6 h, respectively; P < 0·001). Milk protein glycation lowers post-prandial plasma lysine availability in humans. The lower post-prandial availability of lysine following ingestion of proteins with a high glycation level may compromise the anabolic properties of a protein source.