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Background: Formula-fed preterm infants require nutrient-enriched formulas with optimized protein levels to support growth and neurodevelopment. The purpose of this study was to evaluate the safety, tolerability, and effectiveness of a new liquid two-staged formula system designed to provide tailored nutrition during hospital stay and after discharge., Methods: Male and female very-low-birth-weight preterm infants (birth weight ≤1,500 g; gestational age ≤32 weeks) were recruited from three neonatal units in Poland and Slovakia in a prospective, open-label, interventional study. Stage 1 formula providing 3.6 g intact protein/100 kcal was consumed from enrollment until reaching 1,800 g, followed by a post-discharge (PD) Stage 2 formula with 2.8 g/100 kcal protein, which was consumed for 30 days. Weight gain velocity (WGV in g/kg/day) between the first day of achieving full enteral feeding (FEF D1 rate of 150 ml/kg/day and cessation of parenteral feeding) and day reaching 1,800 g was compared to the minimally required WGV (15 g/kg/day) for non-inferiority (primary endpoint), and to the Fenton median growth rate for superiority (17.3 g/kg/day), adjusting for sex, gestational age, site, visit, and WGV. Changes in z -scores, feeding tolerance, nutritional biomarker status, and safety were also assessed from FEF D1 to 30 days PD. In an observational follow-up at 2 years of age, neurodevelopment was evaluated using the Bayley Scales of Infant and Toddler Development (BSID-III)., Results: Adjusted weight gain velocity (95% CI) between the first day of full enteral feeding and day reaching 1,800 g in per protocol (PP, N  = 18) was 23.0 (20.1-25.9) g/kg/day; lower limit of the 95% CIs exceeded the non-inferiority margin (15 g/kg/day, p  < 0.001) and the superiority margin (17.3 g/kg/day, p  < 0.001). Mean stool frequency ranged from 2.5 to 3.3 stools per day. The two-stage formula supported adequate growth patterns throughout the study and nutritional biomarkers of protein and mineral status were within normal ranges. At 24 months corrected age, the mean ± SD of the BSID cognitive scale was 97.3 ± 13.9 in PP, with all infants achieving a score >70. None of the adverse events reported were related to the study formulas., Conclusion: The two-stage preterm formulas supported postnatal weight gain, adequate growth, cognitive development within normal ranges, and a safe profile of protein and bone biomarkers., Clinical Trial Registration: Clinicaltrials.gov registration, NCT03728764, NCT04962035., Competing Interests: SL, YC, MH, LF-K, CF, and TS are Nestlé employees. PK, KD, AB, WD, ZU, MK, and MZ have received a research grant from Nestlé to conduct this study., (© 2024 Kwinta, Lazarova, Demová, Chen, Hartweg, Krattinger, Fumero, Buczyńska, Durlak, Uhrikova, Kozar, Samuel and Zibolen.)

Background: This paper demonstrates how available data can be explored and utilized to conclude generic patterns in the temporal changes in Human Milk (HM) composition., Methods: The temporal trajectories of selected human milk components (HMC-s) were described, in the first four months postpartum, by a primary model consisting of two phases: a short linear phase in the colostrum, triggered by the parturition; and a longer second phase, where the concentration of the component converges to a steady state. The model was fitted to data available in a recently published database of temporal HMC trajectories both at the levels of individual molecules (such as specific fatty acid, oligosaccharide, and mineral molecules) and molecule-groups (such as total protein, total fat)., Results: The properties of the trajectories suggest that experimental designs should follow non-equidistant sampling times, with increasingly longer time intervals after the first week postpartum. A selected parameter, the final stationary level, of the primary model was then studied as a function of geographical location (secondary modelling)., Conclusions: We found that the total variation of the concentration of specific HMC-s is dominantly due to the inherent biological differences between individual mothers and to less extent to the geographical location., Competing Interests: Declarations Ethics approval and consent to participate Not applicable. Consent for publication Not applicable. Competing interests T.M.S and S.K.T are employees of Société des Produits Nestlé SA. The other authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Bifidobacterium longum subspecies infantis ( B. infantis ) may play a key role in infant gut development. This trial evaluated safety, tolerability, and efficacy of B. infantis LMG11588 supplementation., Methods: This randomized, placebo-controlled, double-blind study conducted in the Philippines included healthy breastfed and/or formula-fed infants (14-21 days old) randomized for 8 weeks to a control group (CG; n  = 77), or any of two B. infantis experimental groups (EGs): low (Lo-EG; 1*10 8 CFU/day; n  = 75) or high dose (Hi-EG; 1.8*10 10 CFU/day; n  = 76). Primary endpoint was weight gain; secondary endpoints included stooling patterns, gastrointestinal symptoms, adverse events, fecal microbiome, biomarkers, pH, and organic acids., Results: Non-inferiority in weight gain was demonstrated for Hi-EG and Lo-EG vs. CG. Overall, probiotic supplementation promoted mushy-soft stools, fewer regurgitation episodes, and increased fecal acetate production, which was more pronounced in the exclusively breastfed infants (EBF) and positively correlated with B. infantis abundance. In EBF, fecal pro-inflammatory cytokines (IL-1 beta, IL-8) were reduced. Strain-level metagenomic analysis allowed attributing the increased abundance of B. infantis in EGs versus CG, to LMG11588 probiotic colonization. Colonization by autochthonous B. infantis strains was similar between groups., Discussion: B. infantis LMG11588 supplementation was associated with normal infant growth, was safe and well-tolerated and promoted a Bifidobacterium -rich microbiota driven by B. infantis LMG11588 colonization without disturbing the natural dispersal of autochthonous B. infantis strains. In EBF, supplementation stimulated microbial metabolic activity and beneficially modulated enteric inflammation., Competing Interests: Authors employed by Nestlé Nutrition and Nestlé Research, Société des Produits Nestlé SA, Switzerland were involved in the study design (CIC), data analysis (CM, MN, KV, GLC, AF, BB, CB, CIC), as well as preparation and decision to submit the manuscript (TS, MN, KV, GLC, AF, BB, CIC). In addition, JMM, JKV, PM, and HBN, employees of Clinical Microbiomics, were involved in data analysis and preparation of the manuscript. 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 Capeding, Phee, Ming, Noti, Vidal, Le Carrou, Frézal, Moll, Vogt, Myers, Nielsen, Boulangé, Samuel, Berger and Cercamondi.)

While ample research on independent associations between infant cognition and gut microbiota composition and human milk (HM) oligosaccharides (HMOs) has been reported, studies on how the interactions between gut microbiota and HMOs may yield associations with cognitive development in infancy are lacking. We aimed to determine how HMOs and species of Bacteroides and Bifidobacterium genera interact with each other and their associations with cognitive development in typically developing infants. A total of 105 mother-infant dyads were included in this study. The enrolled infants [2.9-12 months old (8.09 ± 2.48)] were at least predominantly breastfed at 4 months old. A total of 170 HM samples from the mothers and fecal samples of the children were collected longitudinally. Using the Mullen Scales of Early Learning to assess cognition and the scores as the outcomes, linear mixed effects models including both the levels of eight HMOs and relative abundance of Bacteroides and Bifidobacterium species as main associations and their interactions were employed with adjusting covariates; infant sex, delivery mode, maternal education, site, and batch effects of HMOs. Additionally, regression models stratifying infants based on the A-tetrasaccharide (A-tetra) status of the HM they received were also employed to determine if the associations depend on the A-tetra status. With Bacteroides species, we observed significant associations with motor functions, while Bif. catenulatum showed a negative association with visual reception in the detectable A-tetra group both as main effect (value of p  = 0.012) and in interaction with LNFP-I (value of p  = 0.007). Additionally, 3-FL showed a positive association with gross motor ( p  = 0.027) and visual reception ( p  = 0.041). Furthermore, significant associations were observed with the interaction terms mainly in the undetectable A-tetra group. Specifically, we observed negative associations for Bifidobacterium species and LNT [ breve ( p  = 0.011) and longum ( p  = 0.022)], and positive associations for expressive language with 3'-SL and Bif. bifidum ( p  = 0.01), 6'-SL and B. fragilis ( p  = 0.019), and LNFP-I and Bif. kashiwanohense ( p  = 0.048), respectively. Our findings suggest that gut microbiota and HMOs are both independently and interactively associated with early cognitive development. In particular, the diverse interactions between HMOs and Bacteroides and Bifidobacterium species reveal different candidate pathways through which HMOs, Bifidobacterium and Bacteroides species potentially interact to impact cognitive development in infancy., Competing Interests: TS, JH, and NS are employees of Société des Produits Nestlé, SA, Switzerland. This study was supported in part by a grant from Nestlé Product Technology Center-Nutrition, Société des Produits Nestlé S.A., Switzerland. WL was a consultant of and received travel support from Nestlé SA, Switzerland. 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 Cho, Samuel, Li, Howell, Baluyot, Hazlett, Elison, Zhu, Hauser, Sprenger and Lin.)

Background: Perinatal mood disorders such as depression and anxiety are common, with subclinical symptomology manifesting as perinatal mood disturbances being even more prevalent. These could potentially affect breastfeeding practices and infant development. Pregnant and lactating women usually limit their exposure to medications, including those for psychological symptoms. Interestingly, the naturally occurring probiotic Bifidobacterium longum (BL) NCC3001 has been shown to reduce anxious behavior in preclinical models and feelings of low mood in nonpregnant human adults. During the COVID-19 pandemic, mental health issues increased, and conventionally conducted clinical trials were restricted by social distancing regulations., Objective: This study, Probiotics on Mothers' Mood and Stress (PROMOTE), aimed to use a decentralized clinical trial design to test whether BL NCC3001 can reduce symptoms of depression, anxiety, and stress over the perinatal period., Methods: This double-blind, placebo-controlled, randomized, and 3-parallel-arm study aimed to recruit 180 women to evaluate the efficacy of the probiotic taken either during pregnancy and post partum (from 28-32 weeks' gestation until 12 weeks after delivery; n=60, 33.3%) or post partum only (from birth until 12 weeks after delivery; n=60, 33.3%) in comparison with a placebo control group (n=60, 33.3%). Participants consumed the probiotic or matched placebo in a drink once daily. Mood outcomes were measured using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale questionnaires, captured electronically at baseline (28-32 weeks' gestation) and during e-study sessions over 5 further time points (36 weeks' gestation; 9 days post partum; and 4, 8, and 12 weeks post partum). Saliva and stool samples were collected longitudinally at home to provide mechanistic insights., Results: In total, 520 women registered their interest on our website, of whom 184 (35.4%) were eligible and randomized. Of these 184 participants, 5 (2.7%) withdrew after randomization, leaving 179 (97.3%) who completed the study. Recruitment occurred between November 7, 2020, and August 20, 2021. Advertising on social media brought in 46.9% (244/520) of the prospective participants, followed by parenting-specific websites (116/520, 22.3%). Nationwide recruitment was achieved. Data processing is ongoing, and there are no outcomes to report yet., Conclusions: Multiple converging factors contributed to speedy recruitment and retention of participants despite COVID-19-related restrictions. This decentralized trial design sets a precedent for similar studies, in addition to potentially providing novel evidence on the impact of BL NCC3001 on symptoms of perinatal mood disturbances. This study was ideal for remote conduct: because of the high digital literacy and public trust in digital security in Singapore, the intervention could be self-administered without regular clinical monitoring, and the eligibility criteria and outcomes were measured using electronic questionnaires and self-collected biological samples. This design was particularly suited for a group considered vulnerable-pregnant women-during the challenging times of COVID-19-related social restrictions., Trial Registration: ClinicalTrials.gov NCT04685252; https://clinicaltrials.gov/ct2/show/NCT04685252., International Registered Report Identifier (irrid): DERR1-10.2196/41751., (©Melissa P S Toh, Chui Yuen Yang, Phei Cze Lim, Hui Li J Loh, Gabriela Bergonzelli, Luca Lavalle, Elias Mardhy, Tinu Mary Samuel, Elvira Suniega-Tolentino, Irma Silva Zolezzi, Lisa R Fries, Shiao Yng Chan. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.04.2023.)

Fatty acids (FA) play a key role in infant growth and development. The aim of this study was to study the temporal evolution of FA from 3 or 4 weeks to 4 months postpartum in human milk (HM) from Filipino mothers. Mid-morning HM samples (n = 41) were collected after full expression from a single breast and FA were assessed using gas-liquid chromatography coupled to flame ionization detector. The total FA content remained relatively constant over the study period. The most abundant FA in HM were oleic acid (OA), palmitic acid (PA) and linoleic acid (LA), a trend similarly reported in HM from European and Chinese mothers. The former two were unchanged over the course of lactation while there was a slight increase in LA content over time. Similarly, the saturated fatty acid (SFA) and monounsaturated FA (MUFA) contents did not vary over the first four months of lactation. The SFA content was much higher than that reported in HM from Europe and China, mainly driven by PA, lauric and myristic acids. The MUFA content on the other hand, while comparable to that reported in HM from Chinese populations was lower than that reported in Europe. There was a small increase in the polyunsaturated FA (PUFA) content over the study duration. The levels of essential FA, linoleic acid (LA) and α-linolenic acid (ALA) were found to be much lower than that reported in other populations. The concentrations of arachidonic acid (AA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) remained stable over the study duration. AA and DHA in HM from Filipino mothers were comparable to global averages, however in case of the latter the concentration was found to be lower than in previous reports. DHA is of great clinical significance as it plays a key role in infant growth and development. In our study, we observed a wide inter- and intra-individual variability in the levels of DHA in HM, presumably reflecting diverse intakes of DHA rich foods and bioconversion in vivo. Personalized recommendations may help achieve recommended levels of DHA amongst population with levels below global averages. This may help achieve HM sufficiency and therefore be linked to clinical benefits for the mother and the baby. SUMMARY: This study details the temporal evolution of human milk (HM) fatty acids (FA) in Filipino mothers up to four months postpartum. The total FA content remained relatively constant over the study period. The most abundant FA were oleic, palmitic and linoleic acids. HM from Filipino mothers had relatively higher saturated FA content driven by palmitic, lauric and myristic acids, while the levels of essential FA, linoleic and α-linoleic acids were lower compared to other populations. Similarly, the concentration of monounsaturated FA were also lower than that reported in HM from European mothers. Arachidonic acid and docosahexaenoic acid (DHA) concentrations were comparable to global averages however the HM DHA levels were seen to have decreased when compared to previous reports from the Philippines. Additionally, a wide variability was seen in HM DHA levels suggesting a need for strategies such as personalized recommendations in order to ensure HM DHA sufficiency., Competing Interests: Declaration of Competing Interest Francesca Giuffrida, Tinu Mary Samuel, Sagar K. Thakkar, Surabhi Devaraj and Mickaël Hartweg are employees of Société des Produits Nestlé SA., (Copyright © 2023. Published by Elsevier Ltd.)

Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: (1) test the association between the dietary inflammatory index (DII®) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.

Human milk oligosaccharides play a key role in the maturation of the infant gut microbiome and immune system and are hypothesized to affect growth. This study examined the temporal changes of 24 HMOs and their associations to infant growth and appetitive traits in an exploratory, prospective, observational, study of 41 Filipino mother-infant dyads. Exclusively breastfed, healthy, term infants were enrolled at 21-26 days of age (≈ 0.75 mo) and followed for 6 months. Infant growth measures and appetitive traits were collected at visit 1 (V1) (≈ 0.75 mo), V2 (≈ 1.5 mo), V3 (2.5 mo), V4 (2.75 mo), V5 (4 mo), and V6 (6 mo), while HMOs were measured at V1, V2, V3 and V5. Overall exposure to each HMO was summarized as area under the curve from baseline to 4 months of age and examined in association with each measure of growth at 6 months using linear regression adjusted for maternal age at birth, infant sex, birth weight, and mode of delivery. We saw modest associations between several HMOs and infant growth parameters. Our results suggest that specific HMOs, partly as proxy for milk groups (defined by Secretor and Lewis status), may be associated with head circumference and length, increasing their relevance especially in populations at the lower end of the WHO growth curve. We did not identify the same HMOs associated with infant appetitive traits, indicating that at least in our cohort, changes in appetite were not driving the observed associations between HMOs and growth.Clinical trial registration: NCT03387124., (© 2022. The Author(s).)

Early dietary exposure via human milk nutrients offers a window of opportunity to support cognitive and temperament development. While several studies have focused on associations of few pre-selected human milk nutrients with cognition and temperament, it is highly plausible that human milk nutrients synergistically and jointly support cognitive and behavioral development in early life. We aimed to discern the combined associations of three major classes of human milk nutrients with cognition and temperament during the first 6 months of life when human milk is the primary source of an infant's nutrition and explore whether there were persistent effects up to 18 months old. The Mullen Scales of Early Learning and Infant Behavior Questionnaires-Revised were used to assess cognition and temperament, respectively, of 54 exclusively/predominantly breastfed infants in the first 6 months of life, whose follow-ups were conducted at 6-9, 9-12, and 12-18 months old. Human milk samples were obtained from the mothers of the participants at less than 6 months of age and analyzed for fatty acids [total monounsaturated fatty acids, polyunsaturated fatty acid, total saturated fatty acid (TSFA), arachidonic acid (ARA), docosahexaenoic acid (DHA), ARA/DHA, omega-6/omega-3 polyunsaturated fatty acids ratio (n-6/n-3)], phospholipids [phosphatidylcholine, phosphatidylethanolamine (PE), phosphatidylinositol (PI), sphingomyelin], and choline [free choline, phosphocholine (PCho), glycerophosphocholine]. Feature selection was performed to select nutrients associated with cognition and temperament. The combined effects of selected nutrients were analyzed using multiple regression. A positive association between the arachidonic acid (ARA) and surgency was observed ( p = 0.024). A significant effect of DHA, n-6/n-3, PE, and TSFA concentrations on receptive language ( R 2 = 0.39, p = 0.025) and the elevated ARA, PCho, and PI with increased surgency ( R 2 = 0.43, p = 0.003) was identified, suggesting that DHA and ARA may have distinct roles for temperament and language functions. Furthermore, the exploratory association analyses suggest that the effects of human milk nutrients on R.L. and surgency may persist beyond the first 6 months of life, particularly surgency at 12-18 months ( p = 0.002). Our study highlighted that various human milk nutrients work together to support the development of cognition and temperament traits during early infancy., Competing Interests: TS, JH, and NS were the employees of Société des Produits Nestlé SA, Switzerland. WL was a consultant of and received travel support from Nestlé SA, Switzerland. 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 © 2022 Li, Samuel, Zhu, Howell, Cho, Baluyot, Hazlett, Elison, Wu, Hauser, Sprenger, Zhu and Lin.)

Purpose: Human milk (HM) composition is influenced by factors, like maternal diet and body stores, among other factors. For evaluating the influence of maternal fatty acid (FA) status on milk FA composition, the correlation between FA content in HM and in maternal plasma, erythrocytes, and adipose tissue was investigated., Methods: 223 European women who delivered at term, provided HM samples over first four months of lactation. Venous blood and adipose tissue (only from mothers who consented and underwent a C-section delivery) were sampled at delivery. FAs were assessed in plasma, erythrocytes, adipose tissue, and HM. Evolution of HM FAs over lactation and correlations between FA content in milk and tissues and between mother's blood and cord blood were established., Results: During lactation, arachidonic acid (ARA) and docosahexaenoic acid (DHA) significantly decreased, while linoleic acid (LA), alpha-linolenic acid (ALA), and eicosapentaenoic acid (EPA) remained stable. Positive correlations were observed between HM and adipose tissue for palmitic, stearic, oleic, and polyunsaturated fatty acids (PUFAs). Correlations were found between milk and plasma for oleic, LA, ARA, ALA, DHA, monounsaturated fatty acids (MUFAs), and PUFAs. No correlation was observed between erythrocytes and HM FAs. LA and ALA were more concentrated in maternal blood than in infant blood, contrary to ARA and DHA, supporting that biomagnification of LCPUFAs may have occurred during pregnancy., Conclusions: These data show that maternal adipose tissue rather than erythrocytes may serve as reservoir of PUFAs and LCPUFAs for human milk. Plasma also supplies PUFAs and LCPUFAs to maternal milk. If both, adipose tissue and plasma PUFAs, are reflection of dietary intake, it is necessary to provide PUFAs and LCPUFAs during pregnancy or even before conception and lactation to ensure availability for mothers and enough supply for the infant via HM., (© 2022. The Author(s).)

Background: The effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months., Objective: This study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life., Design: Milk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother's country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode., Results: Over the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally ( n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses ( p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation., Conclusion: Our data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life., Competing Interests: ’This study received funding from Société des Produits Nestlé S.A. The funder had the following involvement with the study: study design, data analysis, interpretation of the results, and reporting in scientific journal. TS, LL, CC, FG, SD, and ST are currently employees of Société des Produits Nestlé S.A. PF and FT are consultants to Société des Produits Nestlé S.A. CM-C, KH, GM, MA, TR, MC, J-CP, and CB received funding from Société des Produits Nestlé S.A. to conduct the study. FT received funding for the research and drafting the manuscript., (Copyright © 2022 Samuel, Thielecke, Lavalle, Chen, Fogel, Giuffrida, Dubascoux, Martínez-Costa, Haaland, Marchini, Agosti, Rakza, Costeira, Picaud, Billeaud and Thakkar.)

Eating habits of lactating women can influence the nutrient composition of human milk, which in turn influences nutrient intake of breastfed infants. The aim of the present study was to identify food patterns and nutritional adequacy among lactating women in Europe. Data from a multicentre European longitudinal cohort (ATLAS study) were analysed to identify dietary patterns using cluster analysis. Dietary information from 180 lactating women was obtained using 3-d food diaries over the first 4 months of lactation. Four dietary patterns were identified: 'vege-oils', 'fish-poultry', 'confectionery-salads' and 'mixed dishes'. Nutrition adequacy was not significantly different between clusters, but the 'vege-oils' cluster tended to yield the highest nutrition adequacy measured by Mean Adequacy Ratio. Compared with European dietary reference values (DRVs) for lactating women, women in all clusters had inadequate intakes of energy, pantothenic acid, folate, vitamin C, vitamin A, vitamin D, zinc, iodine, potassium and linoleic acid. Adequate intake for fibre and α-linolenic acid was only achieved in the 'vege-oils' cluster. Overall, fat intake was above DRVs. The present study showed that various dietary patterns do not adequately supply all nutrients, indicating a need to promote overall healthy dietary habits for European lactating women., (© The Author(s) 2021.)

Human milk (HM) is dynamic and shows a high inter- and intra-individual variability. To characterize HM with precision, it is necessary to understand the factors that modulate its composition. The objective of this narrative review is to summarize the maternal, infant and methodological factors that affect HM composition. We searched SCOPUS and PubMed databases for articles related to factors that are known to or could potentially influence HM composition and volume across lactation periods. Our comprehensive review encompasses various maternal-, infant-related, and methodological factors that modulate aspects of HM composition including macro- and micronutrients, vitamins and minerals, as well as volume. The most profound changes were observed in HM lipids and lipophiles. Evidence exists for many of the infant-related factors known to affect the nutritive and non-nutritive components of HM (e.g., birth weight, gestational age, infant age/stage of lactation). In contrast, less is known with respect to maternal factors; where there is either limited research or conflicting evidence (e.g., maternal lifestyle, obstetric history, medical conditions), except for the mother's diet, for which there is a relatively well-established understanding. Equally, although many of the methodological factors (e.g., HM sampling, handling and analytics) are known to impact HM composition, few studies have investigated this as a primary outcome, making it an important area of future research in HM. Here we propose a systematic capture of numerous maternal- and infant-related characteristics to facilitate associative comparisons of HM data within and across studies. Additionally, it would be prudent to standardize the methodological aspects known to affect HM composition in analytics, not only for HM lipids and lipophiles, but also for those nutrients whose variability is yet less well-understood. Defining the factors determining HM composition with accuracy will open perspectives for maternal intervention to optimize milk composition for specific needs of infants., (Copyright © 2020 Samuel, Zhou, Giuffrida, Munblit, Verhasselt and Thakkar.)

Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother-infant cohort from seven European countries. Methods: HM samples were obtained from 305 mothers at 2, 17, 30, 60, 90, and 120 days postpartum. SCM status was assessed using HM Sodium (Na): Potassium (K) ratio >0.6. Levels of different macro- and micronutrients were analyzed in HM. Results: SCM prevalence in the first month of lactation was 35.4%. Mean gestational age at delivery was lower and birth by C-section higher in SCM mothers ( p ≤ 0.001). HM concentrations of lactose, DHA, linolenic acid, calcium, and phosphorous ( p < 0.05 for all) was lower, while total protein, alpha-lactalbumin, lactoferrin, albumin, arachidonic acid to DHA ratio, n -6 to n -3 ratio and minerals (iron, selenium, manganese, zinc, and copper) were higher ( p < 0.001 for all) in mothers with SCM. There were no differences in infant growth and HM intake between non-SCM and SCM groups. Conclusion: We document, for the first time, in a large European standardized and longitudinal study, a high prevalence of SCM in early lactation and demonstrate that SCM is associated with significant changes in the macro- and micronutrient composition of HM. Future studies exploring the relation of SCM with breastfeeding behaviors and developmental outcomes are warranted.

Human milk oligosaccharide (HMO) composition varies among lactating mothers and changes during the course of lactation period. Interindividual variation is largely driven by fucosyltransferase (FUT2 and FUT3) polymorphisms resulting in 4 distinct milk groups. Little is known regarding whether maternal physiological status contributes to HMO variability. We characterized the trajectories of 20 major HMOs and explored whether maternal pre-pregnancy body mass index (ppBMI), mode of delivery, or parity may affect milk HMO composition. Using longitudinal breastmilk samples from healthy mothers (n = 290) across 7 European countries, we characterized HMO composion and employed mixed linear models to explore associations of maternal characteristics with individual HMOs. We observed HMO-specific temporal trajectories and milk group dependencies. We observed relatively small but significant differences in HMO concentrations based on maternal ppBMI, mode of delivery and parity. Our findings suggest that HMO composition to be regulated time-dependently by an enzyme as well as substrate availability and that ppBMI, mode of delivery, and parity may influence maternal physiology to affect glycosylation marginally within the initital period of lactation. Our observational study is the largest European standardized and longitudinal (up to 4 months) milk collection study assessing HMO concentrations and basic maternal characteristics. Time of lactation and milk groups had the biggest impact on HMO variation. Future studies need to elucidate these observations and assess the physiological significance for the breastfed infant.

Preterm birth (PTB) (<37 weeks of gestation) is the leading cause of newborn death and a risk factor for short and long-term adverse health outcomes. Most cases are of unknown cause. Although the mechanisms triggering PTB remain unclear, an inappropriate increase in net inflammatory load seems to be key. To date, interventions that reduce the risk of PTB are effective only in specific groups of women, probably due to the heterogeneity of its etiopathogenesis. Use of progesterone is the most effective, but only in singleton pregnancies with history of PTB. Thus, primary prevention is greatly needed and nutritional and bioactive solutions are a promising alternative. Among these, docosahexaenoic acid (DHA) is the most promising to reduce the risk for early PTB. Other potential nutrient interventions include the administration of zinc (possibly limited to populations with low nutritional status or poor zinc status) and vitamin D; additional preliminary evidence exists for vitamin A, calcium, iron, folic acid, combined iron-folate, magnesium, multiple micronutrients, and probiotics. Considering the public health relevance of PTB, promising interventions should be studied in large and well-designed clinical trials. The objective of this review is to describe, summarize, and discuss the existing evidence on nutritional and bioactive solutions for reducing the risk of PTB.

A main characteristic of children perceived as picky eaters is their tendency to avoid certain foods or food groups. The goal of this narrative review is to provide an overview of published studies that have examined whether picky eating in childhood is in fact associated with measurable differences in food and/or nutrient intakes and growth. While picky eaters appear to consume less vegetables compared to non-picky eaters, no consistent differences were observed for the intakes of other food groups or the intakes of energy, macronutrients and dietary fiber. Although, in some studies, picky eaters had lower intakes of certain vitamins and minerals, the levels consumed generally exceeded the recommended values, suggesting nutritional requirements are being met. No consistent relationship between childhood picky eating and growth status was observed, although significant differences in body weight/growth between picky and non-picky eaters were most discernible in studies where multiple defining criteria were used to identify picky eating. The research area would benefit from the adoption of a uniform definition of picky eating. More longitudinal assessments are also required to understand the long-term impact of picky eating on nutritional status and growth.

Gestational diabetes mellitus (GDM) is currently defined as glucose intolerance that is of variable severity with onset or first recognition during pregnancy. The Hyperglycemia and Adverse Pregnancy Outcome Study, including 25 000 nondiabetic pregnant women in 15 centers across the world, reported that an average of 17.8% of pregnancies are affected by GDM and its frequency can be as high as 25.5% in some countries, based on the International Association of Diabetes and Pregnancy Study Groups criteria. Nevertheless, true global prevalence estimates of GDM are currently lacking due to the high level of heterogeneity in screening approaches, diagnostic criteria, and differences in the characteristics of the populations that were studied. The presence of systemic high blood glucose levels in pregnancy results in an adverse intrauterine environment, which has been shown to have a negative impact on short- and long-term health outcomes for both the mother and her offspring, including increased risks for the infant to develop obesity and for both mother and child to develop type 2 diabetes mellitus later in life. Epigenetic mechanisms that are directly influenced by environmental factors, including nutrition, may play a key role in shaping these future health risks and may be part of this vicious cycle. This article reviews the burden of GDM and the current evidence that supports maternal nutritional interventions as a promising strategy to break the cycle by addressing risk factors associated with GDM., (© The Author(s) 2016. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved.)

Purpose: Little is known regarding nutritional adequacy of the gluten free diet (GFD) in children and adolescents with celiac disease (CD). The study aim was to examine macro- and micronutrient intake in children with CD., Methods: A cross-sectional study was conducted in children and adolescents (4-18 years of age) with CD (n = 32) and healthy controls (n = 32). Macro- and micronutrient intake, and glycemic index (GI) and glycemic load (GL) intake was assessed using validated measures. Diet quality was assessed using the Canadian Healthy Eating Index (HEI-C) and the Alberta Nutrition Guidelines. Values are shown as mean ± SE., Results: Age (10.4 ± 0.7 years vs 8.7 ± 0.7 years; P = 0.06), weight-for-age z score (P = 0.27), and height-for-age z score (P = 0.23) were not different between groups. CD children consumed more fibre (15.9 ± 1.2 g per day(CD) vs 10.8 ± 0.8 g per day (controls); P < 0.001), had higher GI (CD: 54 ± 2 vs 48 ± 1; P < 0.01) and GL (CD: 118 ± 8 vs 93 ± 7; P = 0.02), and lower folate (146.7 ± 15.3 (CD) vs 245.4 ± 21.8 µg per day (controls); P < 0.001) than controls. No differences in HEI-C scores (≤ and > 80) were observed between groups (P > 0.05)., Conclusion: Children with CD had high intakes of fibre, GI, and GL and lower intakes of folate. This has implications for dietary counselling in this population.

Zinc (Zn) deficiency in infancy and early childhood is of public health concern in developing countries. This study aimed to longitudinally assess Zn intake of urban South Indian term infants in the first 6 months of life using measures of breast milk (BM) volume and BM Zn concentrations and, additionally, to study the effect of BM Zn intake on infant length and weight gain. BM intake by the deuterium dilution technique, BM Zn concentration at months 1, 3 and 6, as well as serum Zn level at months 3 and 6 were assessed in 50 mother-infant pairs. BM intake significantly declined from 627 mL day(-1) at month 1 to 608 mL day(-1) at month 6 (P < 0.01). BM Zn concentration and intake significantly declined from month 1 to month 6 (P < 0.001 for both). Mean infant serum Zn level at months 3 and 6 were 93.0 ± 27.1 and 99.6 ± 30.1 µg dL(-1), respectively. Infant BM Zn intake at months 1 and 3 was not associated with the weight and length gain between 1-3 and 3-6 months, respectively. Zn intake from BM, maternal BM Zn content and serum Zn levels were not significantly different between small-for-gestational age and appropriate-for-gestational age infants. Therefore, among urban south Indian term infants less than 6 months of age, BM Zn intakes were low, owing to low volumes of BM intake, despite BM Zn concentrations being in the normal range. Promotion of breastfeeding and thereby increasing the volumes of milk produced is a first important step towards improving Zn intake among infants., (© 2012 John Wiley & Sons Ltd.)

Our clinical experience led us to reassess the effect of sole omega-3 lipid therapy on hemostasis. We compared thromboelastography platelet mapping in neonatal piglets given sole omega-3 lipid. We identified abnormalities in reaction time (P = .025) and the arachidonic acid pathway (P = .025). The potential for bleeding complications from parenteral omega-3 lipid emulsion therapy in high-risk infants with liver disease has been dismissed but, on the basis of this data, should be reconsidered., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Objective: To identify correlates of anaemia during the first trimester of pregnancy among 366 urban South Indian pregnant women., Design: Cross-sectional study evaluating demographic, socio-economic, anthropometric and dietary intake data on haematological outcomes., Setting: A government maternity health-care centre catering predominantly to the needs of pregnant women from the lower socio-economic strata of urban Bangalore., Subjects: Pregnant women (n 366) aged ≥18 and ≤40 years, who registered for antenatal screening at ≤14 weeks of gestation., Results: Mean age was 22·6 (sd 3·4) years, mean BMI was 20·4 (sd 3·3) kg/m2 and 236 (64·5 %) of the pregnant women were primiparous. The prevalence of anaemia (Hb <11·0 g/dl) was 30·3 % and of microcytic anaemia (anaemia with mean corpuscular volume <80 fl) 20·2 %. Mean dietary intakes of energy, Ca, Fe and folate were well below the Indian RDA. In multivariable log-binomial regression analysis, anaemia was independently associated with high dietary intakes of Ca (relative risk; 95 % CI: 1·79; 1·16, 2·76) and P (1·96; 1·31, 2·96) and high intake of meat, fish and poultry (1·94; 1·29, 2·91)., Conclusions: Low dietary intake of multiple micronutrients, but higher intakes of nutrients that inhibit Fe absorption such as Ca and P, may help explain high rates of maternal anaemia in India.

Aim: To evaluate the vitamin B(12) status of South Indian women in early pregnancy and its relationship with sociodemographic, anthropometry and dietary intake., Methods: Cross-sectional study among 366 pregnant urban South Indian women ≤14 weeks of gestation with outcome variables defined as low vitamin B(12) blood concentration (<150 pmol/l) and impaired vitamin B(12) status [low vitamin B(12) plus elevated methylmalonic acid (MMA) >0.26 µmol/l)]., Results: Low plasma vitamin B(12) concentration was observed in 51.1% of the women, while 42.4% had impaired B(12) status. Elevated MMA, elevated homocysteine (>10 µmol/l) and low erythrocyte folate (<283 nmol/l) were observed among 75.8, 43.3 and 22.2% of the women, respectively. The median (25th, 75th percentile) dietary intake of vitamin B(12) was 1.25 (0.86, 1.96) µg/day. Lower maternal body weight was associated with higher vitamin B(12) concentration [prevalence ratios (PR) (95% CI) 0.57 (0.39, 0.84)]. The predictors of impaired vitamin B(12) status were no consumption of yoghurt [PR (95% CI) 1.63 (1.03, 2.58)] or fish [PR (95% CI) 1.32 (1.01, 1.71)] and primiparity [PR (95% CI) 1.41 (1.05, 1.90)]., Conclusion: A high prevalence of vitamin B(12) deficiency in early pregnancy among urban South Indian women was related to primiparity and to a low consumption of yoghurt and fish., (Copyright © 2013 S. Karger AG, Basel.)

Background/objectives: To objectively measure rates of breast-feeding to infants born in a baby-friendly hospital in Bangalore, India, and to capture home-based compliance to exclusive breastfeeding (EBF)., Subjects/methods: Breast-milk (BM) and non-breast-milk (NBM) water intake were assessed in 50 mother-infant pairs using a deuterium dilution technique at months 1, 3 and 6., Results: Complementary feeding (CF) was introduced as early as 1 month among 44% of the infants, and only 14.2% remained as exclusively breastfed by month 6. Intake of BM significantly declined from 166 to 87 ml/kg/day and NBM significantly increased from 23 to 51 ml/kg/day from month 1-6 (P<0.01). There was a significant negative correlation between BM and NBM at months 3 (r = -0.59, P<0.001) and 6 (r = -0.61, P<0.001). The most common barrier to EBF was 'a persistently crying infant'. BM intake significantly correlated with weight for age (WAZ; month 1: r = 0.56, P<0.001; month 3: r = 0.60, P<0.001) and weight for height (WHZ; month 1: r = 0.59, P<0.001; month 3: r = 0.57, P<0.001). NBM intake showed a significant negative correlation with WHZ (r = -0.33, P = 0.02) at month 3 and correlated positively with WAZ (r = 0.37, P = 0.01) and height for age (r = 0.30, P = 0.03) at month 6., Conclusions: Despite intensive counseling at birth and during the immediate postnatal period in a baby-friendly hospital, early CF was observed at home. Reason for the early introduction of CF was primarily a crying infant. Home- and community-oriented approaches should be designed to address barriers and improve EBF rates.