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Importance: Nutritional status before and during pregnancy is important for maternal health and fetal growth and development., Objective: To describe secular trends in nutrient intake from foods, beverages, and supplements among pregnant and nonpregnant women of reproductive age in the US., Design, Setting, and Participants: This was a secondary series of cross-sectional analyses of the 1999-2018 National Health and Nutrition Examination Survey (NHANES). Pregnant (n = 1392) and nonpregnant (n = 9737) women aged 20 to 44 years who provided at least 1 reliable dietary recall were included for analysis. These analyses were performed between February 2022 and July 2024., Main Outcomes and Measures: The primary outcomes included the mean usual intake of macronutrients and micronutrients, as well as the prevalence of inadequate intake of micronutrients., Results: This representative sample included 1392 pregnant women (mean [SE] age, 28.5 [0.3] years) and 9737 nonpregnant women (mean [SE] age, 32.2 [0.1] years). Among pregnant women, a weighted mean (SE) of 27.0% (1.8%) of women were in their first trimester, and 33.8% (2.2%) were in their second trimester. Mean (SE) carbohydrate intake decreased between 1999-2000 and 2013-2018 among pregnant women (306.9 [7.6] to 274.9 [5.7] g/d; β = -2.1 [0.4]; P < .001) and between 1999-2000 and 2017-2018 among nonpregnant women (251.9 [4.9] to 216.9 [3.3] g/d; β = -1.9 [0.4]; P = .002). Between 1999-2000 and 2013-2018, the proportion of pregnant women who consumed below the Estimated Average Requirement of vitamin A increased by 10.9 percentage points (pp) (95% CI, 5.2-16.7 pp), and the proportion of pregnant women who consumed below the Estimated Average Requirement of vitamin C increased by 8.9 pp (95% CI, 3.9-14.0 pp). Similarly, the proportion of nonpregnant women with inadequate intake of vitamin A, vitamin C, and iron increased by 19.9 pp (95% CI, 12.3-27.5 pp), 11.1 pp (95% CI, 4.5-17.7 pp), and 4.9 pp (95% CI, 1.7-8.2 pp), respectively, between 1999-2000 and 2017-2018. The mean (SE) calcium intake increased from 1120.6 (41.4) to 1308.7 (49.0) mg/d for pregnant women (β = 11.7 [4.3]; P = .03) and from 849.5 (19.8) to 981.2 (27.9) mg/d for nonpregnant women (β = 6.7 [2.6]; P = .03; β2 = -1.3 [0.2]; P < .001). Among pregnant women, the prevalence of inadequate intake decreased by 16.1 pp (95% CI, 8.3-23.9 pp) for magnesium (P < .001) and 33.2 pp (95% CI, 24.0-42.4 pp) for vitamin K (P < .001); among nonpregnant women, the proportion with inadequate intake decreased by 16.1 pp (95% CI, 10.4-21.7 pp) for calcium (P < .001), 15.5 pp (95% CI, 7.3-23.6 pp) for magnesium (P < .001), and 33.3 pp (23.5-43.0 pp) for vitamin K (P < .001)., Conclusions and Relevance: This cross-sectional study of pregnant and nonpregnant women of reproductive age found that vitamin A, vitamin C, and iron intake decreased over the past 2 decades, which may have substantial maternal and fetal health implications. By identifying these nutrient gaps and trends in inadequate intake in this at-risk population, scientific, health care, and regulatory communities may be better poised to adopt recommendations to improve nutrient intake.

Background: Infant formulas, and pediatric and adult nutritional products, are being fortified with bovine lactoferrin (bLF) due to its beneficial impacts on immune development and gut health. Lactoferrin supplementation into these products requires an analytical method to accurately quantify the concentrations of bLF to meet global regulatory and quality standards., Objective: To develop and validate a lactoferrin method capable of meeting the AOAC INTERNATIONAL Standard Method Performance Requirements (SMPR®) 2020.005., Methods: Powder formula samples are extracted using warm dibasic phosphate buffer, pH 8, then centrifuged at 4°C to remove insoluble proteins, fat, and other solids. The soluble fraction is further purified on a HiTrap heparin solid-phase extraction (SPE) column to isolate bLF from interferences. Samples are filtered, then analyzed by LC-UV using a protein BEH C4 analytical column and quantitated using an external calibrant., Results: The LOQ (2 mg/100 g), repeatability (RSD: 2.0-4.8%), recovery (92.1-97.7%), and analytical range (4-193 mg/100 g) all meet the method requirements as stated in SMPR 2020.005 for lactoferrin., Conclusion: The reported single-laboratory validation (SLV) results demonstrate the ability of this lactoferrin method to meet or exceed the method performance requirements to measure soluble, intact, non-denatured bLF in infant and adult nutritional powder formulas., Highlights: The use of a heparin affinity column to isolate lactoferrin from bovine milk products combined with a selective analytical chromatographic column provides suitable analyte specificity without requiring proprietary equipment or reagents., (© The Author(s) 2024. Published by Oxford University Press on behalf of AOAC INTERNATIONAL.)

Glycerol monolaurate (GML), a monoglyceride found in human milk (HM), has antimicrobial properties against a broad spectrum of bacteria, viruses, and fungi. In this study, an LC-MS/MS method was developed and validated for quantifying GML in HM based on quantification of two distinct isomers, 1-monolaurin and 2-monolaurin. The method validation included assessments of selectivity (no interferences), linearity (r 2 range of 0.9954- 0.9985 and 96 of 98 individual points having residual <15%), accuracy (average recovery of 96.4% across both isomers and a range of spiked levels), and precision (total GML repeatability 6.6% RSD and intermediate precision 9.7% RSD). This validated method was used to measure the concentration of GML in unpasteurized HM from 60 mothers and compared geographical locations (Cincinnati and Shanghai), lactation time (weeks 2 and 26), and self-reported maternal allergy status (yes or no). Our findings suggest GML concentration in unpasteurized HM is considerably lower than previously reported in a study characterizing pasteurized HM. The data reported here highlights a novel, validated method used to quantify GML in HM and identified no differences in total GML concentrations when comparing HM from different geographical locations, lactation times, and mother's allergy status., Competing Interests: Declaration of Competing Interest TV, NAM, SDM, LB, RS, MAG, and SCP are all employees of Reckitt/Mead Johnson Nutrition, NS was previously employed by Reckitt/Mead John Nutrition and ALM received funding from Reckitt/Mead Johnson Nutrition for the GEHM study., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Here, we explored the vast potential of microbiome-based interventions in preventing and managing non-communicable diseases including obesity, diabetes, allergies, celiac disease, inflammatory bowel diseases, malnutrition, and cardiovascular diseases across different life stages. We discuss the intricate relationship between microbiome and non-communicable diseases, emphasizing on the "window of opportunity" for microbe-host interactions during the first years after birth. Specific biotics and also live biotherapeutics including fecal microbiota transplantation emerge as pivotal tools for precision medicine, acknowledging the "one size doesn't' fit all" aspect. Challenges in implementation underscore the need for advanced technologies, scientific transparency, and public engagement. Future perspectives advocate for understanding maternal-neonatal microbiome, exploring the maternal exposome and delving into human milk's role in the establishment and restoration of the infant microbiome and its influence over health and disease. An integrated scientific approach, employing multi-omics and accounting for inter-individual variance in microbiome composition and function appears central to unleash the full potential of early-life microbiome interventions in revolutionizing healthcare.

An effective analysis method with multiple accelerant factors is needed for shelf-life determination and prediction for food products with reduced analysis time. Raising the storage temperature is the most common approach utilized in the conventional accelerated shelf-life test (ASLT) to reduce the shelf-life testing time of food. Oxygen pressure as an accelerant for the shelf-life determination of food products has not been given much attention even though it has shown a negative impact on food shelf-life. Combining oxygen pressure and temperature as accelerants has the potential to further reduce the overall analysis time compared to the ASLT. This study focuses on the effects of applying oxygen pressure and temperature as multi-accelerants on the shelf-life of a shelf-stable product by investigating the extent of vitamins degradation and modeling the reaction using a mechanistic approach. A shelf-stable model food fortified with vitamins A, B1, C and D3 was developed to investigate the effect of multiple accelerants on the quality indicators of shelf-stable foods in a polyethylene terephthalate (PET) container. PET bottles filled with model food were placed in a high-pressure (138 kPa) 100% oxygen environment at 40 °C. This novel process is named as the ultra-accelerated shelf-life test (UASLT). Samples were also subjected to ASLT conditions at 40 °C and control condition at 22.5 °C, both at ambient pressure for comparison. UASLT treatment induced a rapid degradation of 27.1 ± 1.9%, 35.8 ± 1.0%, and 35.4 ± 0.7% in vitamins A, C and D3, respectively, in just 50 days. Slower degradation was observed with samples kept under the ASLT conditions for 105 days with a degradation of 24.0 ± 2.0%, 32.0 ± 3.1% and 25.1 ± 1.5% for vitamin A, C and D3, respectively. The control samples that were studied for 210 days showed 14.9 ± 5.0%, 13.8 ± 2.2% and 10.6 ± 0.8% degradation in vitamins A, C and D3, respectively. The increase in the ΔE values due to browning in samples kept at the UASLT, ASLT and control conditions were 11.67 ± 0.09, 7.49 ± 0.19 and 2.51 ± 0.11, respectively. The degradation of vitamin B1 was similar across the treatments. The addition of oxygen pressure significantly increased the degradation reaction rates of the vitamins and color due to the rapid influx of oxygen. A mechanistic model that coupled oxygen diffusion and simultaneous vitamin degradation provided a good fit to the experimental data for the UASLT treatment with a rate constant of 0.686, 0.631 and 0.422 M -1 day -1 for vitamins C, D3 and A, respectively. Elevated external oxygen pressure can be used as an accelerant along with moderate temperatures for rapid shelf-life testing of products in polymeric packaging with two-fold reduction in the overall analysis time as compared to ASLT., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Increased insulin levels may support the development of neural circuits involved in cognition, while chronic mild inflammation may also result in cognitive impairment. This study aimed to gain more insight into whether cognition is already impacted during adolescence in a genetic rat model for obesity and type 2 diabetes. Visual discrimination learning throughout adolescence and the level of motivation during early adulthood were investigated in Zucker Diabetic Fatty (ZDF) obese and ZDF lean rats using operant touchscreens. Blood glucose, insulin, and lipids were longitudinally analyzed. Histological analyses were performed in the liver, white adipose tissues, and the prefrontal cortex. Prior to the experiments with the genetic ZDF research model, all experimental assays were performed in two groups of outbred Long Evans rats to investigate the effect of different feeding circumstances. Adolescent ZDF obese rats outperformed ZDF lean rats on visual discrimination performance. During the longitudinal cognitive testing period, insulin levels sharply increased over weeks in ZDF obese rats and were significantly enhanced from 6 weeks of age onwards. Early signs of liver steatosis and enlarged adipocytes in white adipose tissue were observed in early adult ZDF obese rats. Histological analyses in early adulthood showed no group differences in the number of prefrontal cortex neurons and microglia, nor PSD95 and SIRT1 mRNA expression levels. Together, our data show that adolescent ZDF obese rats even display enhanced cognition despite their early diabetic profile.

Background: In 2020, a multidose human-milk fortifier (MDHMF) was designed to improve the process of human-milk (HM) fortification. The bottle of MDHMF (5.5 oz, 163 ml) allows aseptic removal of HMF in a precise measure. This survey aimed to examine the experience of nutrition care team (NCT) members who used the MDHMF in a hospital setting., Methods: A survey link (Qualtrics XM) was sent to NCT leaders (N = 108) at hospitals who participated in an evaluation of the MDHMF from June 1, 2020, through April 30, 2021. The NCT leaders sent the survey to members at their prospective hospitals (n = 344). The investigators did not know the identities of the recipients of the survey and collected no identifying information on respondents. Respondents were asked to evaluate their experience with the MDHMF compared with their previous practice., Results: The majority of respondents (n = 63, 72%) reported that the MDHMF improved their HM preparation practices and was better than their previous practice for reducing the time to prepare (n = 33, 71.7%), ensuring the accuracy of fortified HM (n = 32, 69.6%), ensuring aseptic preparation (n = 24, 52.2%), reducing HM waste (n = 27, 58.7%), and being easy to use (n = 30, 65.2%). Those responsible for evaluating nutrition status answered that the MDHMF was the same for feeding tolerance (n = 41, 58.6%), weight gain (n = 47, 67.1%), head growth (n = 56, 81.2%), and length growth (n = 53, 76.8%)., Conclusion: US neonatal intensive care unit NCT members perceived that the MDHMF resulted in improved HM preparation practices while maintaining growth and tolerance., (© 2022 Reckitt Mead Johnson Nutrition. Nutrition in Clinical Practice published by Wiley Periodicals LLC on behalf of American Society for Parenteral and Enteral Nutrition.)

Effects of micronutrients on brain connectivity are incompletely understood. Analyzing human milk samples across global populations, we identified the carbocyclic sugar myo -inositol as a component that promotes brain development. We determined that it is most abundant in human milk during early lactation when neuronal connections rapidly form in the infant brain. Myo -inositol promoted synapse abundance in human excitatory neurons as well as cultured rat neurons and acted in a dose-dependent manner. Mechanistically, myo -inositol enhanced the ability of neurons to respond to transsynaptic interactions that induce synapses. Effects of myo -inositol in the developing brain were tested in mice, and its dietary supplementation enlarged excitatory postsynaptic sites in the maturing cortex. Utilizing an organotypic slice culture system, we additionally determined that myo -inositol is bioactive in mature brain tissue, and treatment of organotypic slices with this carbocyclic sugar increased the number and size of postsynaptic specializations and excitatory synapse density. This study advances our understanding of the impact of human milk on the infant brain and identifies myo -inositol as a breast milk component that promotes the formation of neuronal connections.

Growth patterns of breastfed infants show substantial inter-individual differences, partly influenced by breast milk (BM) nutritional composition. However, BM nutritional composition does not accurately indicate BM nutrient intakes. This study aimed to examine the associations between both BM intake volumes and macronutrient intakes with infant growth. Mother-infant dyads ( n 94) were recruited into the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) from a single maternity hospital at birth; all infants received exclusive breast-feeding (EBF) for at least 6 weeks. Infant weight, length and skinfolds thicknesses (adiposity) were repeatedly measured from birth to 12 months. Post-feed BM samples were collected at 6 weeks to measure TAG (fat), lactose (carbohydrate) (both by 1 H-NMR) and protein concentrations (Dumas method). BM intake volume was estimated from seventy infants between 4 and 6 weeks using dose-to-the-mother deuterium oxide ( 2 H 2 O) turnover. In the full cohort and among sixty infants who received EBF for 3+ months, higher BM intake at 6 weeks was associated with initial faster growth between 0 and 6 weeks ( β + se 3·58 + 0·47 for weight and 4·53 + 0·6 for adiposity gains, both P < 0·0001) but subsequent slower growth between 3 and 12 months ( β + se - 2·27 + 0·7 for weight and -2·65 + 0·69 for adiposity gains, both P < 0·005). BM carbohydrate and protein intakes at 4-6 weeks were positively associated with early (0-6 weeks) but tended to be negatively related with later (3-12 months) adiposity gains, while BM fat intake showed no association, suggesting that carbohydrate and protein intakes may have more functional relevance to later infant growth and adiposity.

Cow's milk protein allergy (CMPA) is children's most common food allergy. Therapeutic infant formulas for CMPA lead to symptom-free and potentially benefit early tolerance induction and reducing the allergic march in non-breastfed babies. This study assessed the cost-effectiveness of CMPA management with different therapeutic infant formulas in Thailand, which may reflect situations in developing countries throughout Asia. An analytic decision model was developed to simulate the occurrence of eczema, urticaria, asthma, rhinoconjunctivitis, or being symptom-free in infants with CMPA over 36 months. Extensively hydrolyzed casein formula with added probiotic Lacticaseibacillus rhamnosus (previously Lactobacillus rhamnosus ) strain GG (EHCF+LGG), extensively hydrolyzed whey formula (EHWF), soy protein-based formula (SPF), and amino acid formula (AAF) were compared from the healthcare payer perspective. The results from a prospective cohort study were used for comparative effectiveness measures, while local experts were interviewed to estimate the healthcare resource used in the management of CMPA. The costs of healthcare resources were obtained from standard, publicly available sources. The direct medical cost of CMPA management was lowest for EHCF+LGG (USD 1,720), followed by SPF (USD 2,090), EHWF (USD 2,791), and AAF (USD 7,881). Compared with other formulas, EHCF+LGG was expected to save USD 370 (SPF), USD 1,071 (EHWF), and USD 6,161 (AAF) in the total cost of CMPA management over 36 months. In conclusion, EHCF+LGG was the most cost-effective strategy for managing non-breastfed infants with CMPA. This strategy was associated with more children developing immune tolerance to cow's milk and being symptom-free, contributing to overall cost-saving potential., Competing Interests: PP and AS are employees of Mead Johnson Nutrition, Thailand. NS, PT, PC, and KP are clinicians and received minimal financial support for contributing inputs as key opinion leaders for clinical (NS, PT, and PC) and methodological (KP) aspects of this study., (Copyright © 2023 Suratannon, Prapansilp, Srinarongsook, Tanpowpong, Chatchatee and Pongpirul.)

Objectives: We aimed to compare the effects of nutrient-enriched formula with standard term formula on rate of body weight gain of late preterm infants appropriately grown for gestational age., Study Design: A multi-center, randomized, controlled trial. Late preterm infants (34-37 weeks' gestation), with weight appropriate for gestational age (AGA), were randomized to nutrient enriched formula (NEF) with increased calories (22 kcal/30 ml) from protein, added bovine milk fat globule membrane, vitamin D and butyrate or standard term formula 20 kcal/30 ml (STF). Breastfed term infants were enrolled as an observational reference group (BFR). Primary outcome was rate of body weight gain from enrollment to 120 days corrected age (d/CA). Planned sample size was 100 infants per group. Secondary outcomes included body composition, weight, head circumference and length gain, and medically confirmed adverse events to 365 d/CA., Results: The trial was terminated early due to recruitment challenges and sample size was substantially reduced. 40 infants were randomized to NEF ( n  = 22) and STF ( n  = 18). 39 infants were enrolled in the BFR group. At 120 d/CA there was no evidence of a difference in weight gain between randomized groups (mean difference 1.77 g/day, 95% CI, -1.63 to 5.18, P  = 0.31). Secondary outcomes showed a significant reduction in risk of infectious illness in the NEF group at 120 d/CA [relative risk 0.37 (95% CI, 0.16-0.85), P  = 0.02]., Conclusion: We saw no difference in rate of body weight gain between AGA late preterm infants fed NEF compared to STF. Results should be interpreted with caution due to small sample size., Clinical Trial Registration: The Australia New Zealand Clinical Trials Registry (ACTRN 12618000092291). "mailto:maria.makrides@sahmri.com" maria.makrides@sahmri.com., Competing Interests: TM-P is employed by Reckitt|Mead-Johnson and TRC is a former employee of Reckitt|Mead-Johnson. All other authors declare no conflict of interest. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Best, Yelland, Collins, McPhee, Rogers, Choo, Gibson, Murguia-Peniche, Varghese, Cooper and Makrides.)

The relative immaturity of the infant digestive system has the potential to affect the bioavailability of dietary lipids, proteins, and their digested products. We performed a lipidomic analysis of a commercial bovine milk fat globule membrane ingredient (MFGMi) and determined the profile of lipids and proteins in the bioaccessible fraction after in vitro digestion of both the ingredient and whey-casein-based infant formula without and with MFGMi. Test materials were digested using a static 2-phase in vitro model, with conditions simulating those in the infant gut. The extent of digestion and the bioaccessibility of various classes of neutral and polar lipids were monitored by measuring a wide targeted lipid profile using direct infusion-mass spectrometry. Digestion of abundant proteins in the ingredient and whey-casein infant formula containing the ingredient was determined by denaturing PAGE with imaging of Coomassie Brilliant Blue stained bands. Cholesterol esters, diacylglycerides, triacylglycerides, phosphatidylcholines, and phosphatidylethanolamines in MFGMi were hydrolyzed readily during in vitro digestion, which resulted in marked increases in the amounts of free fatty acids and lyso-phospholipids in the bioaccessible fraction. In contrast, sphingomyelins, ceramides, and gangliosides were largely resistant to simulated digestion. Proteins in MFGMi and the infant formulas also were hydrolyzed efficiently. The results suggest that neutral lipids, cholesterol esters, phospholipids, and proteins in MFGMi are digested efficiently during conditions that simulate the prandial lumen of the stomach and small intestine of infants. Also, supplementation of whey-casein-based infant formula with MFGMi did not appear to alter the profiles of lipids and proteins in the bioaccessible fraction after digestion., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Infant gut microbiota composition is influenced by various factors early in life. Here, we investigate associations between infant gut microbiome development, infant age, breastfeeding duration, and human milk oligosaccharides (HMO) composition in breastmilk., Methods: A total of 94 mother-infant pairs were recruited as part of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) (Cambridge, UK). Infant stool samples ( n = 337) were collected at 2 week, 6 week, 3 month, and 6 month of age. The 16S rRNA V3-V4 rRNA region was sequenced using MiSeq Illumina to determine microbiota composition and diversity. Mother's hindmilk samples were collected at birth, 2 week, 6 week, 3 month, and 6 month postpartum. Concentrations of five neutral [2'FL, 3'FL, lacto-N-fucopentaose 1 (LNFP1), LNnT, LNT] and two acidic (3'SL, and 6'SL) HMOs were measured in all milk samples using High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (HPAEC-PAD). We explored the associations between infant gut microbiome parameters and age, duration of exclusive breastfeeding (EBF), and levels of individual HMOs., Results: Bifidobacterium was the most abundant genus in infant stool at all-time points, irrespective of breastfeeding duration, with an overall mean relative abundance of 70%. The relative abundance of B. bifidum in stool from infants who were breastfed for longer than 6 months was significantly higher compared to the infant breastfed up to 3 months ( p = 0.0285). Alpha-diversity (both Shannon and ASV-level Richness) of infant gut microbiota showed a biphasic change with infant age, decreasing from 2 weeks until 3 months and then increasing until 6 months of age. Bifidobacterium relative abundance was associated with higher concentrations of 2'FL and LNFP1 in breastmilk across all time-points ( p = 0.049 and 0.017, respectively), with trends toward a higher abundance of B. longum species. No significant association with Bifidobacterium was found for breastmilk LNnT, 3'SL, and 6'SL levels., Conclusion: Our study is in line with previous data demonstrating that EBF duration in the first months of life impacts infant gut microbiota composition. The observed links between specific HMOs in breastmilk and bacteria in infant stool provide evidence of how mother's milk affects infant microbiome development., Competing Interests: The authors declare that this study received funding from Reckitt/Mead Johnson Nutrition. The CBGS BF was funded by a research project award by Reckitt/Mead Johnson Nutrition. The funder advised in the study design, data collection, data discussions and preparation of the manuscript. At the time of study execution MC, JD, and GG were employed by Reckitt/Mead Johnson Nutrition. AP and GK were employed by the NIZO Food Research BV. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chichlowski, van Diepen, Prodan, Olga, Ong, Kortman, Dunger and Gross.)

Butyrate in human milk (HM) has been suggested to reduce excessive weight and adipo-sity gains during infancy. However, HM butyrate's origins, determinants, and its influencing mechanism on weight gain are not completely understood. These were studied in the prospective longitudinal Cambridge Baby Growth and Breastfeeding Study (CBGS-BF), in which infants ( n = 59) were exclusively breastfed for at least 6 weeks. Infant growth (birth, 2 weeks, 6 weeks, 3 months, 6 months, and 12 months) and HM butyrate concentrations (2 weeks, 6 weeks, 3 months, and 6 months) were measured. At age 6 weeks, HM intake volume was measured by deuterium-labelled water technique and HM microbiota by 16S sequencing. Cross-sectionally at 6 weeks, HM butyrate was associated with HM microbiota composition ( p = 0.036) although no association with the abundance of typical butyrate producers was detected. In longitudinal analyses across all time points, HM butyrate concentrations were overall negatively associated with infant weight and adiposity, and associations were stronger at younger infant ages. HM butyrate concentration was also inversely correlated with HM intake volume, supporting a possible mechanism whereby butyrate might reduce infant growth via appetite regulation and modulation of HM intake.

Background: Bovine milk fat globule membrane (MFGM) added in infant formula supports typical growth and safety through 24 mo of age in term infants., Objectives: To assess micronutrient (zinc, iron, ferritin, transferrin receptor), metabolic [glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), insulin-like growth factor-1 (IGF-1), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)], and inflammatory (leptin, adiponectin, high sensitivity C-reactive protein) secondary outcomes through 24 mo of age in infants who received standard cow's milk-based infant formula (SF), similar formula with added bovine MFGM (EF), or human milk (HM) through 1 y., Methods: Infants whose parents agreed to a blood draw at baseline (<120 d of age) (SF = 80; EF = 80; HM = 83) were included. Subsequent collections (2-4 h fasting) occurred at D180, D365, and D730. Biomarker concentrations were analyzed and group changes tested using generalized estimating equations models., Results: Only serum iron (+22.1 μg/dL) and HDL-C (+2.5 mg/dL) were significantly higher for EF compared with SF at D730. Prevalence of zinc deficiency for EF (-17.4%) and SF (-16.6%) at D180 and depleted iron stores for SF (+21.4%) at D180 and EF (-34.6%) and SF (-28.0%) at D365 were significantly different compared with HM. IGF-1 (ng/mL) for EF and SF was significantly higher at D180 (+8.9) and for EF (+8.8) at D365, and (+14.5) at D730 compared with HM. Insulin (μUI/mL) for EF (+2.5) and SF (+5.8) and HOMA-IR for EF (+0.5) and SF (+0.6) were significantly higher compared with HM at D180. TGs (mg/dL) for SF (+23.9) at D180, for EF (+19.0) and SF (+17.8) at D365, and EF (+17.3) and SF (+14.5) at D730 were significantly higher compared with HM. Zinc, ferritin, glucose, LDL-C and total cholesterol changes were higher in formula groups compared with HM between various time points., Conclusions: Micronutrient, metabolic, and inflammatory biomarkers were generally similar through 2 y in infants who received infant formula with or without added bovine MFGM. Over the 2 y, differences were observed between infant formulas and HM reference group. This trial was registered at clinicaltrials.gov as NTC02626143., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

The process of gradually reintroducing food allergens into an individual's diet is referred to as a food allergen "ladder", and the most recent edition of the original Milk Allergy in Primary (MAP) Care Guidelines, as well as the International Milk Allergy in Primary Care (IMAP), includes a shortened, improved, and international version with specific recipes, indicating the exact milk protein content, as well as the duration of heating and the temperature for each step of the ladder. Food allergen ladders are being used increasingly in clinical practice. The aim of this study was to develop a Mediterranean milk ladder based on the principles of the Mediterranean eating pattern. The protein content delivered in a portion of the final food product in each step of the ladder in the Mediterranean version corresponds to that provided in the IMAP ladder. Different recipes for the various steps were provided to increase acceptability and variety. Quantification of the total milk protein, casein content, and beta-lactoglobulin by Enzyme-linked immunosorbent assay (ELISA) could detect the gradual increase in concentrations, but the accuracy of the method was affected by the presence of the other ingredients in the mixtures. When developing the Mediterranean milk ladder, a key consideration was to reduce the amount of sugar by using limited amounts of brown sugar and substituting sugar with fresh fruit juice or honey for children aged older than one year. The proposed Mediterranean milk ladder includes principles of (a) healthy eating based on the Mediterranean diet and (b) the acceptability of foods across different age groups.

The intestinal microbiota plays a major role in infant health and development. However, the role of the breastmilk microbiota in infant gut colonisation remains unclear. A systematic review was performed to evaluate the composition of the breastmilk microbiota and evidence for transfer to/colonisation of the infant gut. Searches were performed using PUBMED, OVID, LILACS and PROQUEST from inception until 18th March 2020 with a PUBMED update to December 2021. 88 full texts were evaluated before final critique based on study power, sample contamination avoidance, storage, purification process, DNA extraction/analysis, and consideration of maternal health and other potential confounders. Risk of skin contamination was reduced mainly by breast cleaning and rejecting the first milk drops. Sample storage, DNA extraction and bioinformatics varied. Several studies stored samples under conditions that may selectively impact bacterial DNA preservation, others used preculture reducing reliability. Only 15 studies, with acceptable sample size, handling, extraction, and bacterial analysis, considered transfer of bacteria to the infant. Three reported bacterial transfer from infant to breastmilk. Despite consistent evidence for the breastmilk microbiota, and recent studies using improved methods to investigate factors affecting its composition, few studies adequately considered transfer to the infant gut providing very little evidence for effective impact on gut colonisation.

Objective: While several studies have shown that milk formula feeding is associated with faster infant weight gain compared with exclusively breast feeding (EBF), we explored the possible reverse association that infant weight gain influences the duration of EBF., Design: Prospective birth cohort study (Cambridge Baby Growth Breastfeeding Study) born 2015-2018., Setting: Cambridge, UK., Participants: Full-term, singleton, normal birthweight infants who received EBF for 2-5 completed weeks (n=54), 6-11 weeks (n=14) or 12 or more weeks (n=80)., Intervention: Weight gain from birth to 2 and 6 weeks., Main Outcome and Measure: Duration of EBF., Results: Faster infant weight gain during EBF predicted longer duration of EBF. Among all 148 infants, each +1 unit gain in weight SD score (SDS) between birth and 2 weeks (while all infants received EBF) reduced the likelihood of stopping EBF between 2 and 5 weeks by ~70% (OR 0.32; 95% CI 0.12 to 0.77; adjusted for sex, gestational age at birth, birth weight and mother's age, prepregnancy BMI and education). Similarly, among infants EBF for 6 or more weeks (n=94), each +1 unit gain in weight SDS between birth and 6 weeks reduced the likelihood of stopping EBF between 6 and 11 weeks by ~80% (OR 0.18; 95% CI 0.05 to 0.63)., Conclusions: Slower early infant weight gain was consistently associated with subsequent earlier discontinuation of EBF. We conjecture that broader recognition of the wide range of normal infant growth might encourage parents to not stop EBF earlier than they intended., Competing Interests: Competing interests: JAvD and GG are employees of Reckitt/Mead Johnson Nutrition., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Scope: Milk fat globule membrane (MFGM) is an essential component of milk. Bovine MFGM (bMFGM) has been shown to support cognitive development and increase relative concentrations of serum phospholipids. This study investigates bioavailability of bMFGM components after oral administration in two preclinical models to explore whether dietary bMFGM induces parallel changes to plasma and brain lipidomes., Methods and Results: Transgenic APOE*3.Leiden mice (n = 18 per group) and Sprague-Dawley rats (n = 12 per group) are fed bMFGM-enriched (MFGM+) or Control diet, followed by phospholipid profile-determination in plasma, hippocampus, and prefrontal cortex tissue by targeted mass spectrometry. Multivariate analysis of lipidomic profiles demonstrates a separation between MFGM+ and Control plasma across rodents. In plasma, sphingomyelins contributed the most to the separation of lipid patterns among both models, where three sphingomyelins (d18:1/14:0, d18:1/23:0, d18:1/23:1[9Z]) are consistently higher in the circulation of MFGM+ groups. A similar trend is observed in rat prefrontal cortex, although no significant separation of the brain lipidome is demonstrated., Conclusion: bMFGM-enriched diet alters plasma phospholipid composition in rodents, predominantly increasing sphingomyelin levels in the systemic circulation with similar, but non-significant, trends in central brain regions. These changes may contribute to the beneficial effects of bMFGM on neurodevelopment during early life., (© 2022 Wiley-VCH GmbH.)

Background: Our aim was to evaluate infant behavioral state, stool microbiome profile and calprotectin in infants with infantile colic receiving a partially hydrolyzed protein formula with or without added Lacticaseibacillus (formerly Lactobacillus) rhamnosus GG (LGG)., Methods: In this single-center, double-blind, controlled, parallel, prospective study, term infants (14-28 days of age) identified with colic (using modified Wessel's criteria: cried and/or fussed ≥ 3 h/day for ≥ 3 days/week, in a one-week period) were randomized to receive one of two formulas over a three-week feeding period: marketed partially hydrolyzed cow's milk-based infant formula (PHF, n = 35) or a similar formula with added LGG (PHF-LGG, n = 36). Parent-reported infant behavior was recorded at three time points (Study Days 2-4, 10-12, and 18-20). Duration (hours/day) of crying/fussing (averaged over each three-day period) was the primary outcome. Stool samples were collected at Baseline and Study End (Days 19-21) to determine stool LGG colonization (by qPCR) and microbial abundance (using 16S rRNA gene sequencing) and calprotectin (μg/g)., Results: Duration of crying/fussing (mean ± SE) decreased and awake/content behavior increased over time with no significant group differences over the course of the study. There were no group differences in the percentage of infants who experienced colic by study end. Colic decreased by Study End vs Baseline in both groups. Change in fecal calprotectin also was similar between groups. Comparing Study End vs Baseline, LGG abundance was greater in the PHF-LGG group (P < 0.001) whereas alpha diversity was greater in the PHF group (P = 0.022). Beta diversity was significantly different between PHF and PHF-LGG at Study End (P = 0.05). By study end, relative abundance of L. rhamnosus was higher in the PHF-LGG vs PHF group and vs Baseline., Conclusions: In this pilot study of infants with colic, both study formulas were well tolerated. Crying/fussing decreased and awake/content behavior increased in both study groups over the course of the study. Study results demonstrate a successful introduction of the probiotic to the microbiome. The partially hydrolyzed protein formula with added LGG was associated with significant changes in the gut microbiome., Trial Registration: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT02340143 . Registered 16/01/2015., (© 2022. The Author(s).)

Humans often show variable responses to dietary, prebiotic, and probiotic interventions. Emerging evidence indicates that the gut microbiota is a key determinant for this population heterogeneity. Here, we provide an overview of some of the major computational and experimental tools being applied to critical questions of microbiota-mediated personalized nutrition and health. First, we discuss the latest advances in in silico modeling of the microbiota-nutrition-health axis, including the application of statistical, mechanistic, and hybrid artificial intelligence models. Second, we address high-throughput in vitro techniques for assessing interindividual heterogeneity, from ex vivo batch culturing of stool and continuous culturing in anaerobic bioreactors, to more sophisticated organ-on-a-chip models that integrate both host and microbial compartments. Third, we explore in vivo approaches for better understanding of personalized, microbiota-mediated responses to diet, prebiotics, and probiotics, from nonhuman animal models and human observational studies, to human feeding trials and crossover interventions. We highlight examples of existing, consumer-facing precision nutrition platforms that are currently leveraging the gut microbiota. Furthermore, we discuss how the integration of a broader set of the tools and techniques described in this piece can generate the data necessary to support a greater diversity of precision nutrition strategies. Finally, we present a vision of a precision nutrition and healthcare future, which leverages the gut microbiota to design effective, individual-specific interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Various lifestyle factors, including diet, physical activity, and sleep, have been studied in the context of children's health. However, how these lifestyle factors contribute to the development of cognitive abilities, including spatial cognition, remains vastly understudied. One landmark in spatial cognitive development occurs between 2.5 and 3 years of age. For spatial orientation at that age, children learn to use allocentric reference frames (using spatial relations between objects as the primary reference frame) in addition to, the already acquired, egocentric reference frames (using one's own body as the primary reference frame). In the current virtual reality study in a sample of 30-36-month-old toddlers ( N = 57), we first demonstrated a marginally significant developmental shift in spatial orientation. Specifically, task performance with allocentric performance increased relative to egocentric performance ( η p 2 = 0.06). Next, we explored a variety of lifestyle factors, including diet, in relation to task performance, to explain individual differences. Screen time and gestational weight gain of the mother were negatively associated with spatial task performance. The findings presented here can be used to guide future confirmatory studies about the role of lifestyle factors in the development of spatial cognition.

Improving nutritional status during pregnancy is a global interest. Frequently, women either fail to meet or exceed nutrient recommendations. Current strategies to improve maternal nutrition focus on a "one-size-fits-all" approach and fail to consider individual factors that affect the mother's overall nutritional status. The objectives of this review were to determine the importance of key nutrients for optimal maternal and fetal health, to explore to what extent current recommendations consider individual factors, and to explore novel strategies to close the gap between current guidelines and real-world challenges through more personalized approaches. This review intercalated different nutritional guidelines and recent scientific publications and research initiatives related to maternal nutrition. Based on that, an overview of current recommendations, challenges related to present approaches, and perspectives for future directions are described. Current guidelines are not optimally supporting adequate nutrient intake and health of expectant mothers and their offspring. Existing recommendations are not consistent and do not sufficiently take into account how interindividual variation leads to differences in nutrient status. Personalized nutrition offers women the opportunity to improve their health by using strategies that are tailored to their unique nutritional needs. Such strategies can include personalized supplementation, holistic lifestyle interventions, digital and application-based technologies, and dietary assessment through blood biomarker and genetic analysis. However, these approaches warrant further investigation and optimization. More personalized approaches have the potential to optimize mothers' and their offspring's health outcomes more appropriately to their nutritional needs before, during, and after pregnancy. Moving away from a generalized "one-size-fits-all" approach can be achieved through a variety of means. Future aims should be to provide supporting evidence to create customized subpopulation-based or individualized recommendations, improve nutrition education, and develop novel approaches to improve adherence to dietary and lifestyle interventions., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Nutritional approaches have emerged over the past number of years as suitable interventions to ameliorate the enduring effects of early life stress. Maternal separation (MS) is a rodent model of early life stress which induces widespread changes across the microbiota-gut-brain axis. Milk fat globule membrane (MFGM) is a neuroactive membrane structure that surrounds milk fat globules in breast milk and has been shown to have positive health effects in infants, yet mechanisms behind this are not fully known. Here, we investigated the effects of MFGM supplementation from birth on a variety of gut-brain signalling pathways in MS and non-separated control animals across the lifespan. Specifically, visceral sensitivity as well as spatial and recognition memory were assessed in adulthood, while gut barrier permeability, enteric nervous system (ENS) and glial network structure were evaluated in both early life and adulthood. MS resulted in visceral hypersensitivity, which was ameliorated to a greater extent by supplementation with MFGM from birth. Modest effects of both MS and dietary supplementation were noted on spatial memory. No effects of MS were observed on enteric neuronal or glial networks in early life or adulthood, however an increase in the immunoreactivity of βIII-tubulin in adult colonic myenteric ganglia was noted in the MFGM intervention non-separated group. In conclusion, dietary supplementation with MFGM from birth is sufficient to block MS-induced visceral hypersensitivity, highlighting its potential value in visceral pain-associated disorders, but future studies are required to fully elucidate the mechanistic role of this supplementation on MS-induced visceral pain., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To evaluate stool consistency in infants with reported hard or infrequent stools fed hydrolyzed protein formula with added prebiotics designed to promote stool softening., Methods: In this multi-center, double-blind, controlled study, eligible infants (28-300 days of age at enrollment) were randomized to: partially hydrolyzed cow's milk protein formula (PHF, 75% carbohydrate as lactose; 12 mg Mg/100 kcal; n = 49) or routine intact protein cow's milk-based infant formula (Control, 92% carbohydrate as lactose; 8 mg Mg/100 kcal; n = 51) over a 14-day period. Both formulas had a prebiotic blend (polydextrose and galactooligosaccharides, 4 g/L; 1:1 ratio). Parent-reported stool consistency (hard = 1 through watery = 5) and other daily outcomes were collected by diary. Endpoint stool consistency (mean score over last 3 days of study feeding) was the primary outcome. Adverse events were recorded., Results: Baseline stool consistency (Control: 1.4 ± 0.1, PHF: 1.4 ± 0.1) and frequency were similar between groups; the majority had hard ( n = 61, 64%) or formed ( n = 30, 32%) stools. Stool consistency became softer over Day 1-3 (Control: 2.5 ± 0.1, PHF: 2.6 ± 0.1) and remained similar from Day 4 to 6 through study end ( post hoc analysis). For PHF vs Control, endpoint stool consistency was significantly softer (3.4 ± 0.1 vs 3.0 ± 0.1; P = 0.019) and frequency significantly higher (1.5 ± 0.1 vs 1.0 ± 0.1; P = 0.002). Crying, fussing, and appearance of pain during stooling decreased from baseline to study end in both groups. Formula intake, infant fussiness and incidence of adverse events were similar between groups., Conclusion: An infant formula designed to promote stool softening was well-tolerated and associated with softer, more frequent stools in infants with reported hard or infrequent stools., Competing Interests: VF, CLH, JLW, WZ, and SSW are currently employed by Reckitt|Mead Johnson Nutrition, Evansville, IN, United States. KRW was previously employed by Reckitt|Mead Johnson Nutrition, Evansville, IN, United States., (Copyright © 2022 Fabrizio, Harris, Walsh, Wampler, Zhuang and Wu.)

Objective: The aim of this study was to assess the effects of an experimental formula (EF) with added whey protein-lipid concentrate (5 g/L; source of bovine milk fat globule membrane [bMFGM]) on growth, body composition, and safety through 24 mo of age in term infants., Methods: This was a double-blinded, randomized controlled trial conducted in Santiago, Chile. Infants were enrolled before 120 d and randomized to receive standard cow's milk-based formula (SF) or EF through the first year of life. Breastfed infants were the reference (HM). Growth (weight-for-age [WAZ], length-for-age [LAZ], BMI-for-age [BAZ], headcircumference-for-age [HCZ] z-scores); body composition (fat mass [FM] and fat-free mass, percentage body fat [%BF]); and adverse events through day 730 were recorded. Outcome trajectories were analyzed using a single generalized estimating equation testing the interaction between group and visit., Results: We recruited 582 infants (HM = 235; SF = 174; EF = 173); 478 (>80%) completed the study. At baseline, only WAZ was different between the formula groups (0.14 lower in EF versus SF group, P = 0.035). WAZ, LAZ, and BAZ trajectories were higher from baseline to days 365 and 730 in EF or SF compared with HM (all P < 0.05). No differences in changes in body composition were observed between the formula groups. For EF versus HM, %BF was lower at day 180; however, this difference reversed from day 365. Fat-free mass was higher in formula groups compared with HM at all time points. No group difference in adverse event incidence rate was detected., Conclusion: During the first 2 y of life, infant formula with added bMFGM supports typical growth and safety compared with a standard formula., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Maternal gestational obesity is a risk factor for offspring's neurodevelopment and later neuro-cognitive disorders. Altered gut microbiota composition has been found in patients with neurocognitive disorders, and in relation to maternal metabolic health. We explored the associations between gut microbiota and cognitive development during infancy, and their link with maternal obesity. In groups of children from the Pisa birth Cohort (PISAC), we analysed faecal microbiota composition by 16S rRNA marker gene sequencing of first-pass meconium samples and of faecal samples collected at age 3, 6, 12, 24, 36 months, and its relationship with maternal gestational obesity or diabetes, and with cognitive development, as measured from 6 to 60 months of age by the Griffith's Mental Development Scales. Gut microbiota composition in the first phases of life is dominated by Bifidobacteria (Actinobacteria phylum), with contribution of Escherichia/Shigella and Klebsiella genera (Proteobacteria phylum), whereas Firmicutes become more dominant at 36 months of age. Maternal overweight leads to lower abundance of Bifidobacterium, Blautia and Ruminococcus, and lower practical reasoning scores in the offspring at the age of 36 months. In the whole population, microbiota in the first-pass meconium samples shows much higher alpha diversity compared to later samples, and its composition, particularly Bifidobacterium and Veillonella abundances, correlates with practical reasoning scores at 60 months of age. Maternal overweight correlates with bacterial colonization and with the development of reasoning skills at pre-school age. Associations between neonatal gut colonization and later cognitive function provide new perspectives of primary (antenatal) prevention of neurodevelopmental disorders., (Copyright © 2021. Published by Elsevier Inc.)

Background: Milk-fat globule membrane (MFGM) is a complex structure secreted by the mammary gland and present in mammalian milk. MFGM contains lipids and glycoproteins as well as gangliosides, which may be involved in myelination processes. Notably, myelination and thereby white matter integrity are often altered in obesity. Furthermore, MFGM interventions showed beneficial effects in obesity by affecting inflammatory processes and the microbiome. In this study, we investigated the impact of a dietary MFGM intervention on fat storage, neuroinflammatory processes and myelination in a rodent model of high fat diet (HFD)-induced obesity., Methods: 12-week-old male low density lipoprotein receptor-deficient Leiden mice were exposed to a HFD, a HFD enriched with 3% whey protein lipid concentrate (WPC) high in MFGM components, or a low fat diet. The impact of MFGM supplementation during 24-weeks of HFD-feeding was examined over time by analyzing body weight and fat storage, assessing cognitive tasks and MRI scanning, analyzing myelinization with polarized light imaging and examining neuroinflammation using immunohistochemistry., Results: We found in this study that 24 weeks of HFD-feeding induced excessive fat storage, increased systolic blood pressure, altered white matter integrity, decreased functional connectivity, induced neuroinflammation and impaired spatial memory. Notably, supplementation with 3% WPC high in MFGM components restored HFD-induced neuroinflammation and attenuated the reduction in hippocampal-dependent spatial memory and hippocampal functional connectivity., Conclusions: We showed that supplementation with WPC high in MFGM components beneficially contributed to hippocampal-dependent spatial memory, functional connectivity in the hippocampus and anti-inflammatory processes in HFD-induced obesity in rodents. Current knowledge regarding exact biological mechanisms underlying these effects should be addressed in future studies., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Inclusion of bovine-derived milk fat globule membrane (bMFGM) or bMFGM components in infant formulas (IFs) may support healthy brain development. This double-blind, prospective trial evaluated growth, tolerance, and iron status in infants receiving added bMFGM and modified protein, iron, and arachidonic acid (ARA) concentrations in IF. Healthy term infants were randomized to: control (marketed, routine cow's milk-based IF/100 kcal: 2.1 g protein, 1.8 mg iron, 34 mg ARA) or INV-MFGM (investigational cow's milk-based IF/100 kcal: 1.9 g protein, 1.2 mg iron, 25 mg ARA and whey protein-lipid concentrate, 5 g/L (source of bMFGM)). Anthropometrics, stool characteristics, fussiness, and gassiness through day 365 and blood markers of iron status at day 365 were evaluated. The primary outcome was rate of weight gain from 14-120 days of age. Of 373 infants enrolled (control: 191, INV-MFGM: 182), 275 completed the study (control: 141; INV-MFGM: 134). No group differences in growth rate (g/day) from day 14-120 or study discontinuation were detected. Few group differences in growth or parent-reported fussiness, gassiness, or stool characteristics were detected. No group differences were detected in hemoglobin, hematocrit, or incidence of anemia. In healthy term infants, bMFGM and modified protein, iron, and ARA concentrations in a cow's milk-based IF were well-tolerated, associated with adequate growth throughout the first year of life, and supported normal iron status at one year of age.

Objectives: The pig is a common model utilized to support substantiation of novel bioactive components in infant formula. However, reference ranges for outcomes to determine safety are unclear. Our objective was to use historical data to objectively define typical body and organ growth metrics of the domesticated pig in research. Methods: Twenty-two studies were compiled to assess typical growth of body and organ weights in young pigs. Metadata were organized to include milk replacer sources, bioactive components, sex, breed, source of herd, feeding regimen, and rearing environment. A combination of statistical models including simple linear regression and linear mixed effect models were used to assess typical growth patterns. Results: Over 18,000 data points from 786 animals were available. In general, minimal differences in the growth of pigs who were male and female, artificially- or sow-reared, or fed ad libitum - or by scheduled-feeding, were observed in the first 30 days of life ( P > 0.05). A weight-for-age chart from reference pigs was developed to compare body weights of pigs demonstrating growth characterized as accelerated, typical, reduced, and failure to thrive to illustrate effects of dietary interventions. Distributions of relative brain, liver, and intestine weights (as % of total body weight) were similar between rearing environments and sexes. An alternative bivariate level approach was utilized for the analysis of organ weights. This approach revealed significant biologically-relevant insights into how deficient diets can affect organ weight that a univariate level assessment of weight distribution was unable to detect. Conclusions: Ultimately, these data can be used to better interpret whether bioactive ingredients tested in the pig model affect growth and development within typical reference values for pigs in the first 30 days of life., Competing Interests: QL, GG, and LB are employees of Reckitt. VV, and SF are employees of Traverse Science. RD and SF have ownership in Traverse Science. SM is an advisor for Traverse Science. SM and RD have received grant funding from Reckitt for previous projects, but received no funding from Reckitt for this study. Reckitt provided funding to Traverse Science for conceptualization, execution, and administration of the project. Aside from project funding and employment of some of the authors, Reckitt had no other involvement in this publication., (Copyright © 2021 Vu, Donovan, Brink, Li, Gross, Dilger and Fleming.)

Human milk oligosaccharides (HMOs) are indigestible carbohydrates with prebiotic, pathogen decoy and immunomodulatory activities that are theorized to substantially impact infant health. The objective of this study was to monitor HMO concentrations over 1 year to develop a long-term longitudinal dataset. HMO concentrations in the breast milk of healthy lactating mothers of the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) were measured at birth, 2 weeks, 6 weeks, 3 months, 6 months and 12 months postpartum. HMO quantification was conducted by high-performance anion-exchange chromatography with pulsed amperometric detection using a newly validated "dilute-and-shoot" method. This technique minimizes sample losses and expedites throughput, making it particularly suitable for the analysis of large sample sets. Varying patterns of individual HMO concentrations were observed with changes in lactation timepoint and maternal secretor status, with the most prominent temporal changes occurring during the first 3 months. These data provide valuable information for the development of human milk banks in view of targeted distribution of donor milk based on infant age. Maternal FUT2 genotype was determined based on identification at single-nucleotide polymorphism rs516246 and compared with the genotype expected based on phenotypic markers in the HMO profile. Surprisingly, two mothers genotyped as secretors produced milk that displayed very low levels of 2'-fucosylated moieties. This unexpected discrepancy between genotype and phenotype suggests that differential enzyme expression may cause substantial variation in HMO profiles between genotypically similar mothers, and current genotypic methods of secretor status determination may require validation with HMO markers from milk analysis., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The milk fat globule membrane (MFMG) is a complex milk component that has been shown to inhibit rotavirus (RV) binding to cell membranes in vitro . Herein, a whey protein lipid concentrate high in MFGM components (WPLC) and whey protein concentrate (WPC; control) were screened for anti-infective activity against porcine OSU and human Wa strains of RV in both the African Green Monkey kidney (MA104) and the human colorectal adenocarcinoma (Caco-2) cell lines. Materials and Methods: Confluent cells were exposed to OSU or Wa RV in the presence of WPLC or WPC (control) at 0, 0.1, 0.5, 1.0, 2.5, or 5 mg/ml. Infectivity was detected by immunohistochemistry and expressed as % inhibition relative to 0 mg/ml. WPLC efficacy over WPC was expressed as fold-change. One-way ANOVA analyzed data for the independent and interactive effects of concentration, test material, and RV strain. Results: Both WPLC and WPC exhibited concentration-dependent inhibition of human Wa and porcine OSU RV infectivity in MA104 and Caco-2 cells ( p < 0.0001). WPLC was 1.5-4.8-fold more effective in reducing infectivity than WPC. WPLC efficacy was independent of RV strains, but varied between cell lines. WPLC and WPC at concentrations ≥0.5 mg/mL were most effective in reducing human Wa RV infectivity in MA104 cells ( p < 0.0001). Conclusions: WPLC decreased infectivity of two strains for RV which differ in their dependency on sialic acid for binding to cells. Inhibition was observed in the most commonly used cell type for RV infectivity assays (MA104) and an intestinal cell line (Caco-2). An effect on virus infectivity might be a potential mechanisms of action contributing to beneficial effects of supplementation of infant formula with MGFM reducing the risk of infections and consequently diarrhea incidence in infants., Competing Interests: GG is an employee of Reckitt Benckiser/Mead Johnson Nutrition. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The authors declare that this study received funding from Mead Johnson Nutrition/Reckitt Benckiser. The funder had the following involvement in the study: review of study design and review of the final manuscript prior to publication., (Copyright © 2021 Monaco, Gross and Donovan.)

Thermal conductivity determination of food at temperatures > 100 °C still remains a challenge. The objective of this study was to determine the temperature-dependent thermal conductivity of food using rapid heating (TPCell). The experiments were designed based on scaled sensitivity coefficient (SSC), and the estimated thermal conductivity of potato puree was compared between the constant temperature heating at 121.10 °C (R12B10T1) and the rapid heating (R22B10T1). Temperature-dependent thermal conductivity models along with a constant conductivity were used for estimation. R22B10T1 experiment using the k model provided reliable measurements as compared to R12B10T1 with thermal conductivity values from 0.463 ± 0.011 W m -1 K -1 to 0.450 ± 0.016 W m -1 K -1 for 25-140 °C and root mean squares error ( RMSE ) of 1.441. In the R12B10T1 experiment, the analysis showed the correlation of residuals, which made the estimation less reliable. The thermal conductivity values were in the range of 0.444 ± 0.012 W m -1 K -1 to 0.510 ± 0.034 W m -1 K -1 for 20-120 °C estimated using the k model. Temperature-dependent models (linear and k models) provided a better estimate than the single parameter thermal conductivity determination with low RMSE for both types of experiments. SSC can provide insight in designing dynamic experiments for the determination of thermal conductivity coefficient.

Growth and nutrition during early life have been strongly linked to future health and metabolic risks. The Cambridge Baby Growth Study (CBGS), a longitudinal birth cohort of 2229 mother-infant pairs, was set up in 2001 to investigate early life determinant factors of infant growth and body composition in the UK setting. To carry out extensive profiling of breastmilk intakes and composition in relation to infancy growth, the Cambridge Baby Growth and Breastfeeding Study (CBGS-BF) was established upon the original CBGS. The strict inclusion criteria were applied, focusing on a normal birth weight vaginally delivered infant cohort born of healthy and non-obese mothers. Crucially, only infants who were exclusively breastfed for the first 6 weeks of life were retained in the analysed study sample. At each visit from birth, 2 weeks, 6 weeks, and then at 3, 6, 12, 24, and 36 months, longitudinal anthropometric measurements and blood spot collections were conducted. Infant body composition was assessed using air displacement plethysmography (ADP) at 6 weeks and 3 months of age. Breast milk was collected for macronutrients and human milk oligosaccharides (HMO) measurements. Breast milk intake volume was also estimated, as well as sterile breastmilk and infant stool collection for microbiome study.

Background: Optimal 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., Methods: In 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 × 10 7  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., Results: No 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., Conclusions: This 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 Registration: ClinicalTrials.gov, ClinicalTrials.gov Identifier: NCT01354366 . Registered 13 May 2011., (© 2021. The Author(s).)

Objective: To determine feasibility of providing a concentrated emulsified long-chain polyunsaturated fatty acids (LCPUFA) supplement to very low birth weight infants, and to evaluate blood LCPUFA concentrations at 2 and 8 weeks of study supplementation., Study Design: This prospective, randomized, double-blind, placebo-controlled trial randomized infants to receive (1) LCPUFA-120 (a supplement of 40 mg/kg/day docosahexaenoic acid [DHA] and 80 mg/kg/day arachidonic acid [ARA]; DHA:ARA at 1:2 ratio), (2) LCPUFA-360 (a supplement of 120 mg/kg/day DHA and 240 mg/kg/day ARA), or (3) sunflower oil (placebo control). Infants received supplement daily for 8 weeks or until discharge, whichever came first. Whole blood LCPUFA levels (wt%; g/100 g) were measured at baseline, 2 weeks, and 8 weeks., Results: Infants were 28 weeks of gestation (IQR, 27-30 weeks of gestation) and weighed 1040 g (IQR, 910-1245 g). At 2 weeks, the change in blood DHA (wt%) from baseline differed significantly among groups (sunflower oil, n = 6; -0.63 [IQR, -0.96 to -0.55]; LCPUFA-120: n = 12; -0.14 [IQR, -0.72 to -0.26]; LCPUFA-360, n = 12; 0.46 [IQR, 0.17-0.81]; P = .002 across groups). Change in blood ARA (wt%) also differed by group (sunflower oil: -2.2 [IQR, -3.9 to -1.7]; LCPUFA-120: 0.1 [IQR, -2.1 to 1.1] vs LCPUFA-360: 2.9 IQR, 1.5 to 4.5]; P = .0002). Change from baseline to 8 weeks significantly differed between groups for DHA (P = .02) and ARA (P = .003)., Conclusions: Enteral LCPUFA supplementation supported higher blood DHA by 2 weeks. LCPUFA supplementation at 360 mg of combined DHA and ARA is likely necessary to reduce declines as well as allow increases in whole blood concentrations in the first 8 weeks of life., Trial Registration: Clinicaltrials.gov: NCT03192839., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Milk fat globule membrane (MFGM) and lactoferrin (LF) are human-milk bioactive components demonstrated to support gastrointestinal and immune development. Significantly fewer diarrhea and respiratory-associated adverse events through 18 mo of age were previously reported in healthy term infants fed a cow-milk-based infant formula with an added source of bovine MFGM and bovine LF through 12 mo of age., Objectives: The aim was to compare microbiota and metabolite profiles in a subset of study participants., Methods: Stool samples were collected at baseline (10-14 d of age) and day 120. Bacterial community profiling was performed via 16S rRNA gene sequencing and alpha and beta diversity were analyzed (QIIME 2). Differentially abundant taxa were determined using linear discriminant analysis effect size (LefSE) and visualized (Metacoder). Untargeted stool metabolites were analyzed (HPLC/MS) and expressed as the fold-change between group means (control to MFGM+LF ratio)., Results: Alpha diversity increased significantly in both groups from baseline to 4 mo. Subtle group differences in beta diversity were demonstrated at 4 mo (Jaccard distance; R 2  = 0.01, P  = 0.042). Specifically, Bacteroides uniformis and Bacteroides plebeius were more abundant in the MFGM+LF group at 4 mo. Metabolite profile differences for MFGM+LF versus control included lower fecal medium-chain fatty acids, deoxycarnitine, and glycochenodeoxycholate, and some higher fecal carbohydrates and steroids ( P  < 0.05). After applying multiple test correction, the differences in stool metabolomics were not significant., Conclusions: Addition of bovine MFGM and LF in infant formula was associated with subtle differences in stool microbiome and metabolome by 4 mo of age, including increased prevalence of Bacteroides species. Stool metabolite profiles may be consistent with altered microbial metabolism. This trial was registered at https://clinicaltrials.gov as NCT02274883., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, physiology, or metabolic status., Methods: In this double-blind randomized study, infants (n = 161) received cow's milk-based infant formula (Control) or similar formula with an added prebiotic blend (polydextrose and galactooligosaccharides [PDX/GOS]) from 14-35 to 112 days of age. Infant wake behavior (crying/fussing, awake/content) and 24-h sleep-wake actograms were analyzed (Baseline, Days 70 and 112). Salivary cortisol was immunoassayed (Days 70 and 112). In a subset, exploratory stool 16S ribosomal RNA-sequencing was analyzed (Baseline, Day 112)., Results: One hundred and thirty-one infants completed the study. Average duration of crying/fussing episodes was similar at Baseline, significantly shorter for PDX/GOS vs. Control at Day 70, and the trajectory continued at Day 112. Latency to first and second nap was significantly longer for PDX/GOS vs. Control at Day 112. Cortisol awakening response was demonstrated at Days 70 and 112. Significant stool microbiome beta-diversity and individual taxa abundance differences were observed in the PDX/GOS group., Conclusions: Results indicate faster consolidation of daytime waking state in infants receiving prebiotics and support home-based actigraphy to assess early sleep-wake patterns. A prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation., Impact: Few studies have evaluated nutritive effects of prebiotics on infant behavior state, cortisol awakening response, sleep-wake entrainment, and gut microbiome. Faster consolidation of daytime waking state was demonstrated in infants receiving a prebiotic blend in infant formula through ~4 months of age. Shorter episodes of crying were demonstrated at ~2 months of age (time point corresponding to age/developmental range associated with peak crying) in infants receiving formula with added prebiotics. Results support home-based actigraphy as a suitable method to assess early sleep-wake patterns. Prebiotic effect on wake organization is consistent with influence on the gut-brain axis and warrants further investigation.

The early years, between the ages of one and six, are a period of rapid physical, social and cognitive growth and a nutritionally adequate diet is an important factor for optimum development. We investigated the micronutrient adequacy and status of young US children aged 1-6 years ( n = 9848) using 24-h dietary recall interviews completed by parents and caregivers participating in the National Health and Nutrition Examination Survey (NHANES) 2001-2016. data. The proportion of the sample not meeting the Dietary Reference Intakes (DRI) increased with increasing age and was most pronounced for calcium. Despite adequate iron intake, 7.4% and 2.5% had signs of iron deficiency and anemia based on serum ferritin and hemoglobin levels, with younger children and WIC participants at most risk and Non-Hispanic Black children the least. Vitamin B6 intake was adequate, but 6.4% had serum pyridoxal-5-phosphate deficiency. For vitamin E, 69% had intakes below the estimated average requirement (EAR), yet serum deficiency was only detected in 0.9%. Vitamin D intake was inadequate for 87%, but true deficiency may be overestimated. Mean DHA intake was 24 mg/d, well below expert recommendations of 70-100 mg/day. Iron and vitamin B6 deficiency and inadequate calcium, fiber, choline, potassium and DHA intakes are a concern for a significant percentage of young children. The discrepancy between nutrient intakes and serum deficiency levels needs to be further investigated.

The fouling of indirect shell and coil heat exchanger by heavy whipping cream (HWC) and non-fat dry milk (NFDM) was studied at aseptic Ultra-High Temperature (UHT) processing conditions (140 °C) using a novel non-intrusive sensor. The sensor emitted a heat pulse intermittently throughout the duration of the process causing an incremental increase in temperature at the tube external surface. The temperature response of the sensor varied due to the radial growth of the fouling layer formed by certain components of the products. Each heating pulse and the temperature response was studied to estimate the thermal conductivity of the fouling layer using inverse problems and parameter estimation. The changes in thermal conductivity were used as an indication of the fouling layer development during food processing at UHT temperatures. The estimated parameters from experimental results showed a decreasing trend in the thermal conductivity of HWC and NFDM from 0.35 to 0.10 and 0.63 to 0.37, respectively. An image analysis tool was developed and used to measure the fouling layer thickness at the end of each trial. The measured thickness was found to be 0.58 ± 0.15 for HWC and 0.56 ± 0.07 mm for NFDM. The fouling layer resistance for HWC and NFDM was 5.95 × 10 -3 ± 1.53 × 10 -3 and 1.53 × 10 -3 ± 2.0 × 10 -4 (m 2 K)/W, respectively.

The trend toward using phytonutrients and/or nutraceuticals (P/Ns) with the aim of impacting immune health has increased in recent years. The main reason is that properties of P/Ns are associated with possible immunomodulating effects in the prevention and complementary treatment of viral diseases, including COVID-19 and other respiratory infections. In the present review, we assess the scientific plausibility of specific P/Ns for this purpose of preventative and therapeutic interventions against COVID-19, with an emphasis on safety, validity, and evidence of efficacy against other viruses. Five potential candidates have been identified after reviewing available studies (in silico, in vitro, and in vivo) in which certain flavonoids have demonstrated a potential for use as adjuvant therapeutic agents against viral infections, including COVID-19. As these are often better tolerated than pharmacological treatments, their use could be more widely considered if additional detailed studies can validate the existing evidence.

Background: Early infant feeding with intact or extensively hydrolyzed (EH) proteins or free amino acids (AA) may differentially affect intestinal microbiota composition and immune reactivity. This multicenter, double-blind, controlled, parallel-group, pilot study compared stool microbiota from Baseline (1-7 days of age) up to 60 days of age in healthy term infants who received mother's own milk (assigned to human milk [HM] reference group) (n = 25) or were randomized to receive one of two infant formulas: AA-based (AAF; n = 25) or EH cow's milk protein (EHF; n = 28). Stool samples were collected (Baseline, Day 30, Day 60) and 16S rRNA genes were sequenced. Alpha (Shannon, Simpson, Chao1) and beta diversity (Bray Curtis) were analyzed. Relative taxonomic enrichment and fold changes were analyzed (Wilcoxon, DESEq2). Short/branched chain fatty acids (S/BCFA) were quantified by gas chromatography. Mean S/BCFA and pH were analyzed (repeated measures ANOVA)., Results: At baseline, alpha diversity measures were similar among all groups; however, both study formula groups were significantly higher versus the HM group by Day 60. Significant group differences in beta diversity at Day 60 were also detected, and study formula groups were compositionally more similar compared to HM. The relative abundance of Bifidobacterium increased over time and was significantly enriched at Day 60 in the HM group. In contrast, a significant increase in members of Firmicutes for study formula groups were detected at Day 60 along with butyrate-producing species in the EHF group. Stool pH was significantly higher in the AAF group at Days 30 and 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group and was significantly higher in study formula groups vs HM at Day 60. Propionate was also significantly higher for EHF and AAF at Day 30 and AAF at Day 60 vs HM. Total and individual BCFA were higher for AAF and EHF groups vs HM through Day 60., Conclusions: Distinct patterns of early neonatal microbiome, pH, and microbial metabolites were demonstrated for infants receiving mother's own milk compared to AA-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites., Trial Registration: ClinicalTrials.gov Identifier: NCT02500563 . Registered July 28, 2015.

Evidence is accumulating that short chain fatty acids (SCFA) play an important role in the maintenance of gut and metabolic health. The SCFA acetate, propionate and butyrate are produced from the microbial fermentation of indigestible carbohydrates and appear to be key mediators of the beneficial effects elicited by the gut microbiome. Microbial SCFA production is essential for gut integrity by regulating the luminal pH, mucus production, providing fuel for epithelial cells and effects on mucosal immune function. SCFA also directly modulate host metabolic health through a range of tissue-specific mechanisms related to appetite regulation, energy expenditure, glucose homeostasis and immunomodulation. Therefore, an increased microbial SCFA production can be considered as a health benefit, but data are mainly based on animal studies, whereas well-controlled human studies are limited. In this review an expert group by ILSI Europe's Prebiotics Task Force discussed the current scientific knowledge on SCFA to consider the relationship between SCFA and gut and metabolic health with a particular focus on human evidence. Overall, the available mechanistic data and limited human data on the metabolic consequences of elevated gut-derived SCFA production strongly suggest that increasing SCFA production could be a valuable strategy in the preventing gastro-intestinal dysfunction, obesity and type 2 diabetes mellitus. Nevertheless, there is an urgent need for well controlled longer term human SCFA intervention studies, including measurement of SCFA fluxes and kinetics, the heterogeneity in response based on metabolic phenotype, the type of dietary fibre and fermentation site in fibre intervention studies and the control for factors that could shape the microbiome like diet, physical activity and use of medication.

Pectin is a fermentable soluble fiber that can be used as a thickener in formulas for infants and young children. The Joint FAO/WHO Expert Committee on Food Additives concluded that pectin is not of concern for inclusion in infant formula at up to 0.2%. As part of the safety assessment of the suitability of pectin for young infants (≤12 weeks of age), we conducted a 3-week dietary study in a neonatal pig model to 1) investigate the impact of pectin at different doses on neonatal pigs' growth and 2) explore the potential explanation for the dose response. Male and female neonatal pigs were fed milk replacer containing 0, 0.2%, or 1% pectin beginning on postnatal day 2 for 21 days. Body weight, feed intake, and apparent ileal digestibility of dry matter, crude protein, and energy were reduced in pigs fed diets containing 1% pectin (P < 0.01) but not in pigs fed with 0.2% pectin. These data indicate that inclusion of pectin in the diet at 0.2%, equivalent to 704 mg/kg BW/day is safe, well tolerated, and did not result in any adverse health effects in this neonatal pig study., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: This study was funded by RB Mead Johnson Nutrition. Authors Jim Richards, Cristine Bradley, Xiao Pan, and Qian Li were employees of RB Mead Johnson Nutrition at the time the work was conducted. Jim Richards, Xiao Pan, and Ryan Dilger contributed to project conceptualization. Ryan Dilger provided project administration and completed all statistical analyses. Stephen Fleming and Ryan Dilger contributed to the original manuscript draft. All authors contributed to the review and editing of the final manuscript. Stephen Fleming and Ryan Dilger have consulted for and received grant funding from RB Mead Johnson Nutrition. In addition, both Stephen Fleming and Ryan Dilger both share ownership in Traverse Science, a consulting firm., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The milk fat globule membrane (MFGM) is a complex, highly conserved structure surrounding fat droplets secreted into mammalian milk. This study evaluated the impact of MFGM on Lactobacillus rhamnosus GG (LGG). MFGM-10 (2.5 g/L, 5 g/L, and 10 g/L) did not affect LGG growth in MRS medium but enhanced the ability of LGG to survive in the presence of 0.5% porcine bile. In the presence of MFGM-10 (5 g/L) and bile (0.5%), there were less complex polysaccharides in the media and less capsular polysaccharides associated with the LGG cells compared to the bile exposure alone ( p < 0.05). The expression of four EPS genes was modulated by bile stress and MFGM. Biofilm thickness was increased ( p < 0.05) during bile stress with MFGM compared to other treatments. Furthermore, MFGM increased LGG survival during transit in the murine GI tract. Future experiments will determine the impact of MFGM on LGG probiotic functionality.

Research on milk fat globule membrane (MFGM) is gaining traction. The interest is two-fold; on the one hand, it is a unique trilayer structure with specific secretory function. On the other hand, it is the basis for ingredients with the presence of phospho- and sphingolipids and glycoproteins, which are being used as food ingredients with valuable functionality, in particular, for use as a supplement in infant nutrition. This last application is at the center of this Review, which aims to contribute to understanding MFGM's function in the proper development of immunity, cognition, and intestinal trophism, in addition to other potential effects such as prevention of diseases including cardiovascular disease, impaired bone turnover and inflammation, skin conditions, and infections as well as age-associated cognitive decline and muscle loss. The phospholipid composition of MFGM from bovine milk is quite like human milk and, although there are some differences due to dairy processing, these do not result in a chemical change. The MFGM ingredients, as used to improve the formulation in different clinical studies, have indeed increased the presence of phospholipids, sphingolipids, glycolipids, and glycoproteins with the resulting benefits of different outcomes (especially immune and cognitive outcomes) with no reported adverse effects. Nevertheless, the precise mechanism(s) of action of MFGM remain to be elucidated and further basic investigation is warranted., Competing Interests: The authors J.F., Y.P., F.V. and R.J.-F. declare no conflict of interest. L.B. and S.W. are employees of Mead Johnson Nutrition-RB, Medical and Scientific Affairs.

A bstract: Since originally isolated in 1899, the genus Bifidobacterium has been demonstrated to predominate in the gut microbiota of breastfed infants and to benefit the host by accelerating maturation of the immune response, balancing the immune system to suppress inflammation, improving intestinal barrier function, and increasing acetate production. In particular, Bifidobacterium longum subspecies infantis ( B. infantis ) is well adapted to the infant gut and has co-evolved with the mother-infant dyad and gut microbiome, in part due to its ability to consume complex carbohydrates found in human milk. B. infantis and its human host have a symbiotic relationship that protects the preterm or term neonate and nourishes a healthy gut microbiota prior to weaning. To provide benefits associated with B. infantis to all infants, a number of commercialized strains have been developed over the past decades. As new ingredients become available, safety and suitability must be assessed in preclinical and clinical studies. Consideration of the full clinical evidence for B. infantis use in pediatric nutrition is critical to better understand its potential impacts on infant health and development. Herein we summarize the recent clinical studies utilizing select strains of commercialized B. infantis ., Competing Interests: M.C., N.S., J.L.W. and S.S.W. are employed by the study sponsor, Mead Johnson Nutrition. Mead Johnson Nutrition’s parent company, Reckitt Benckiser, entered into a partnership with Evolve Biosystems in December 2019; however, this had no influence on the outcome of the review. J.A.V. has been a consultant for Mead Johnson Nutrition.

Background: A central aim for pediatric nutrition is to develop infant formula compositionally closer to human milk. Milk fat globule membranes (MFGM) have shown to have functional components that are found in human milk, suggesting that addition of bovine sources of MFGM (bMFGM) to infant formula may promote beneficial outcomes potentially helping to narrow the gap between infants who receive human breast milk or infant formula. The objective of the current study is to determine how the addition of bMFGM in infant formula and consumption in early infancy affects physical growth and brain development when compared to infants fed with a standard formula and a reference group of infants fed with mother's own milk., Methods: Single center, double-blind, and parallel randomized controlled trial. Planned participant enrollment includes: infants exclusively receiving breast milk (n = 200; human milk reference group; HM) and infants whose mothers chose to initiate exclusive infant formula feeding before 4 months of age (n = 340). The latter were randomized to receive one of two study formulas until 12 months of age: 1) cow's milk based infant formula that had docosahexaenoic (DHA) (17 mg/100 kcal) and arachidonic acid (ARA) (25 mg/100 kcal); 1.9 g protein/100 kcal; 1.2 mg Fe/100 kcal (Standard formula; SF) or 2) a similar infant formula with an added source of bovine MFGM (whey protein-lipid concentrate (Experimental formula; EF). Primary outcomes will be: 1) Physical growth (Body weight, length, and head circumference) at 730 days of age; and 2) Cognitive development (Auditory Event-Related Potential) at 730 days of age. Data will be analyzed for all participants allocated to each study feeding group., Discussion: The results of this study will complement the knowledge regarding addition of bMFGM in infant formula including support of healthy growth and improvement of neurodevelopmental outcomes., Trial Registration: NCT02626143, registered on December 10th 2015.

Background: Compared to breast-fed (BF), formula-fed (FF) infants exhibit more rapid weight gain, a different fecal microbial profile, as well as elevated serum insulin, insulin growth factor 1 (IGF-1), and branched chain amino acids (BCAAs). Since infant formula contains more protein and lower free amino acids than breast milk, it is thought that protein and/or free amino acids may be key factors that explain phenotypic differences between BF and FF infants. Methods: Newborn rhesus monkeys ( Macaca mulatta ) were either exclusively BF or fed regular formula or reduced protein formula either supplemented or not with a mixture of amino acids. Longitudinal sampling and clinical evaluation were performed from birth to 16 weeks including anthropometric measurements, intake records, collection of blood for hematology, serum biochemistry, hormones, and metabolic profiling, collection of urine for metabolic profiling, and collection of feces for 16s rRNA fecal microbial community profiling. Results: Reducing protein in infant formula profoundly suppressed intake, lowered weight gain and improved the FF-specific metabolic phenotype in the first month of age. This time-dependent change paralleled an improvement in serum insulin. All lower protein FF groups showed reduced protein catabolism with lower levels of blood urea nitrogen (BUN), urea, ammonia, albumin, creatinine, as well as lower excretion of creatinine in urine compared to infants fed regular formula. Levels of fecal microbes ( Bifidobacterium and Ruminococcus from the Ruminococcaceae family), that are known to have varying ability to utilize complex carbohydrates, also increased with protein reduction. Adding free amino acids to infant formula did not alter milk intake or fecal microbial composition, but did significantly increase urinary excretion of amino acids and nitrogen-containing metabolites. However, despite the lower protein intake, these infants still exhibited a distinct FF-specific metabolic phenotype characterized by accelerated weight gain, higher levels of insulin and C-peptide as well as elevated amino acids including BCAA, lysine, methionine, threonine and asparagine. Conclusions: Reducing protein and adding free amino acids to infant formula resulted in growth and metabolic performance of infants that were more similar to BF infants, but was insufficient to reverse the FF-specific accelerated growth and insulin-inducing high BCAA phenotype., (Copyright © 2020 He, Sotelo-Orozco, Rudolph, Lönnerdal and Slupsky.)

Objective: To evaluate neurodevelopment, growth, and health outcomes in infants receiving bovine milk fat globule membrane (MFGM) and lactoferrin in infant formula., Study Design: Healthy term infants were randomized to a cow's milk-based infant formula or MFGM + LF (a similar infant formula, with an added source of bovine milk fat globule membrane [bMFGM; whey protein-lipid concentrate, 5 g/L] and bovine lactoferrin [0.6 g/L]) through 365 days of age. The Bayley Scales of Infant Development, 3rd edition cognitive composite score at day 365 was the primary outcome. Secondary outcomes included tolerance measures through day 365, additional neurodevelopmental and language outcomes, growth, and medically confirmed adverse events through day 545., Results: Of 451 infants enrolled (control, 228; MFGM + LF, 223), 291 completed study feeding and Bayley-III testing at day 365 (control, 148; MFGM + LF, 143). The mean cognitive (+8.7), language (+12.3), and motor (+12.6) scores were higher (P < .001) for the MFGM + LF group; no differences were observed at day 545. Global development scores from day 120 to day 275 and attention at day 365 were significantly improved. Few group differences in day 545 neurodevelopmental outcomes were detected, however scores of some subcategories of the MacArthur-Bates Communicative Development Inventories were higher (P < .05) in the MFGM + LF group. The overall incidence of respiratory-associated adverse events and diarrhea were significantly lower for the MFGM + LF group through day 545., Conclusions: Infants receiving formula with added bovine MFGM and bovine lactoferrin had an accelerated neurodevelopmental profile at day 365 and improved language subcategories at day 545. Formulas were associated with age-appropriate growth and significantly fewer diarrhea and respiratory-associated adverse events through 545 days of age. TRIAL REGISTRATION CLINICALTRIALS.GOV:: NCT02274883., (Copyright © 2019 Elsevier Inc. All rights reserved.)