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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).)