Novel Bacteroides Vulgatus strain protects against gluten-induced break of human celiac gut epithelial homeostasis: a pre-clinical proof-of-concept study.

BACKGROUND AND AIMS: We have identified a decreased abundance of microbial species known to have a potential anti-inflammatory, protective effect in subjects that developed Celiac Disease (CeD) compared to those who did not. We aim to confirm the potential protective role of one of these species, namely Bacteroides vulgatus, and to mechanistically establish the effect of bacterial bioproducts on gluten-dependent changes on human gut epithelial functions. METHODS: We identified, isolated, cultivated, and sequenced a unique novel strain (20220303-A2) of B. vulgatus found only in control subjects. Using a human gut organoid system developed from pre-celiac patients, we monitored epithelial phenotype and innate immune cytokines at baseline, after exposure to gliadin, or gliadin plus B. vulgatus cell free supernatant (CFS). RESULTS: Following gliadin exposure, we observed increases in epithelial cell death, epithelial monolayer permeability, and secretion of pro-inflammatory cytokines. These effects were mitigated upon exposure to B. vulgatus 20220303-A2 CFS, which had matched phenotype gene product mutations. These protective effects were mediated by epigenetic reprogramming of the organoids treated with B. vulgatus CFS. CONCLUSIONS: We identified a unique strain of B. vulgatus that may exert a beneficial role by protecting CeD epithelium against a gluten-induced break of epithelial tolerance through miRNA reprogramming. IMPACT: Gut dysbiosis precedes the onset of celiac disease in genetically at-risk infants. This dysbiosis is characterized by the loss of protective bacterial strains in those children who will go on to develop celiac disease. The paper reports the mechanism by which one of these protective strains, B. vulgatus, ameliorates the gluten-induced break of gut epithelial homeostasis by epigenetically re-programming the target intestinal epithelium involving pathways controlling permeability, immune response, and cell turnover.

Zonulin as a Biomarker for the Development of Celiac Disease.

OBJECTIVES: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability. METHODS: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin. RESULTS: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = ß = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04). CONCLUSIONS: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.

Pooling Strategies to Modify Macronutrient Content of Pasteurized Donor Human Milk.

Background: Donor human milk (DHM) is the recommended feeding for preterm infants when mother's own milk is unavailable or insufficient. DHM macronutrient's variability may have significant implications on preterm growth. Different pooling strategies could be used to improve the macronutrient content, facilitating the achievement of nutritional requirements of preterm. Objective: The aim was to compare the impact of random pooling (RP) and target pooling (TP) strategies on the macronutrient content of DHM and to identify which RP practice allows the achievement of a macronutrient composition as similar as possible to that achievable with TP. Methods: The macronutrient content of 1,169 single-donor pools was analyzed, and a TP strategy combining 2,3,4, or 5 single-donor pools was adopted. On the bases of single-donor pools' analyses, a simulation of 10,000 randomly selected pools for each configuration of donor considered and for different milk volume proportions was performed. Results: Regardless of the type of strategy and milk volume, as the number of donor per pool increases, the percentage of pools with a macronutrient content equal or higher than the reference values for human milk increases. Conclusion: When a TP strategy is not feasible, a RP strategy combining at least five donors should be performed to obtain a better macronutrient content of DHM.

Cohort profile: Celiac disease genomic, environmental, microbiome and metabolome study; a prospective longitudinal birth cohort study of children at-risk for celiac disease.

The Celiac Disease Genomic, Environmental, Microbiome and Metabolomic (CDGEMM) study is an international prospective birth cohort in children at-risk of developing celiac disease (CD). The CDGEMM study has been designed to take a multi-omic approach to predicting CD onset in at-risk individuals. Participants are required to have a first-degree family member with biopsy diagnosed CD and must be enrolled prior to the introduction of solid food. Participation involves providing blood and stool samples longitudinally over a period of five years as well as answering questionnaires related to the participant, their family, and environment. Recruitment and data collection have been ongoing since 2014. As of 2022 we have a total of 554 participants and the average age of the cohort is 56.4 months. A total of 54 participants have developed positive antibodies for CD and 31 have confirmed CD. Approximately 80% of the 54 participants with CD have developed it by 3 years of age. To date we have identified several microbial strains, pathways, and metabolites occurring in increased abundance and detected before CD onset, which have previously been linked to autoimmune and inflammatory conditions while others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects. Our ongoing analysis includes expanding our metagenomic and metabolomic analyses, evaluating environmental risk factors linked to CD onset, and mechanistic studies investigating how alterations in the microbiome and metabolites may protect against or contribute to CD development.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Neonatal intestinal failure: Growth pattern and nutrition intakes in accordance with weaning from parenteral nutrition.

BACKGROUND: Short bowel syndrome is the most common cause of intestinal failure (IF) in infants. We aimed to evaluate growth, nutrition intakes, and predictors of weaning from parenteral nutrition (PN) of infants with IF. METHODS: Clinical parameters, nutrition intakes, body weight and length z-scores were compared monthly from the 1st to 12th and at 18 and 24 months among infants receiving PN and those weaned. Logistic regression analysis was conducted to explore the predictors of weaning. RESULTS: We included 23 infants (10/23 weaned). Median [range: minimum; maximum] birth weight and gestational age were 1620 [590; 3490] g and 31 [24; 39] weeks, respectively. All infants showed growth retardation with similar median delta weight z-score from birth to discharge: -1.48 [-1.92; -0.94] in not-weaned and -1.18 [-2.70; 0.31] in weaned infants (P = 0.833) and a subsequent regain after the discharge: 0.20 [-3.47; 3.25] and 0.84 [-0.03; 2.58], respectively (P = 0.518). No differences in length z-score were found. After the sixth month, infants weaned from PN received lower PN energy and protein intakes compared with those not-weaned. Infants weaned from PN showed lower PN dependency index (PNDI%) from 5 months onward (45% for weaned and 113% for not-weaned infants at 5 months: P < 0.001). The Belza score, a predictor of enteral autonomy computed at 6 months, is associated with being weaned from PN within 24 months (odds ratio: 1.906; P = 0.039). CONCLUSION: Infants weaned and not-weaned showed similar growth patterns. Our findings support the clinical relevance of Belza score and PNDI% as predictors of weaning from PN.

Don't Forget the Bones: Incidence and Risk Factors of Metabolic Bone Disease in a Cohort of Preterm Infants.

Metabolic bone disease of prematurity (MBD) is a condition of reduced bone mineral content (BMC) compared to that expected for gestational age (GA). Preterm birth interrupts the physiological process of calcium (Ca) and phosphorus (P) deposition that occurs mostly in the third trimester of pregnancy, leading to an inadequate bone mineralization during intrauterine life (IUL). After birth, an insufficient intake of Ca and P carries on this alteration, resulting in overt disease. If MBD is often a self-limited condition, in some cases it could hesitate the permanent alteration of bone structures with growth faltering and failure to wean off mechanical ventilation due to excessive chest wall compliance. Despite advances in neonatal intensive care, MBD is still frequent in preterm infants, with an incidence of 16−23% in very-low-birth-weight (VLBW, birth weight <1500 g) and 40−60% in extremely low-birth-weight (ELBW, birth weight <1000 g) infants. Several risk factors are associated with MBD (e.g., malabsorption syndrome, parenteral nutrition (PN), pulmonary bronchodysplasia (BPD), necrotizing enterocolitis (NEC), and some chronic medications). The aim of this study was to evaluate the rate of MBD in a cohort of VLBWI and the role of some risk factors. We enrolled 238 VLBWIs (107 male). 52 subjects were classified as increased risk (G1) and 186 as standard risk (G2) according to serum alkaline phosphatase (ALP) and phosphorus (P) levels. G1 subjects have lower GA (p < 0.01) and BW (p < 0.001). Moreover, they need longer PN support (p < 0.05) and invasive ventilation (p < 0.01). G1 presented a higher rate of BPD (p = 0.026). At linear regression analysis, BW and PN resulted as independent predictor of increased risk (p = 0.001, p = 0.040, respectively). Preventive strategies are fundamental to prevent chronic alteration in bone structures and to reduce the risk of short stature. Screening for MBD based on serum ALP could be helpful in clinical practice to identify subjects at increased risk.

Energy Expenditure, Protein Oxidation and Body Composition in a Cohort of Very Low Birth Weight Infants.

The nutritional management of preterm infants is a critical point of care, especially because of the increased risk of developing extrauterine growth restriction (EUGR), which is associated with worsened health outcomes. Energy requirements in preterm infants are simply estimated, so the measurement of resting energy expenditure (REE) should be a key point in the nutritional evaluation of preterm infants. Although predictive formulae are available, it is well known that they are imprecise. The aim of our study was the evaluation of REE and protein oxidation (Ox) in very low birth weight infants (VLBWI) and the association with the mode of feeding and with body composition at term corrected age. METHODS: Indirect calorimetry and body composition were performed at term corrected age in stable very low birth weight infants. Urinary nitrogen was measured in spot urine samples to calculate Ox. Infants were categorized as prevalent human milk (HMF) or prevalent formula diet (PFF). RESULTS: Fifty VLBWI (HMF: 23, PFF: 27) were evaluated at 36.48 ± 0.85 post-conceptional weeks. No significant differences were found in basic characteristics or nutritional intake in the groups at birth and at the assessment. No differences were found in the REE of HMF vs. PFF (59.69 ± 9.8 kcal/kg/day vs. 59.27 ± 13.15 kcal/kg/day, respectively). We found statistical differences in the protein-Ox of HMF vs. PFF (1.7 ± 0.92 g/kg/day vs. 2.8 ± 1.65 g/kg/day, respectively, p < 0.01), and HMF infants had a higher fat-free mass (kg) than PFF infants (2.05 ± 0.26 kg vs. 1.82 ± 0.35 kg, respectively, p < 0.01), measured with air displacement plethysmography. CONCLUSION: REE is similar in infants with a prevalent human milk diet and in infants fed with formula. The HMF infants showed a lower oxidation rate of proteins for energy purposes and a better quality of growth. A greater amount of protein in HMF is probably used for anabolism and fat-free mass deposition. Further studies are needed to confirm our hypothesis.

Adherence to the Mediterranean diet and body composition of breast-feeding mothers: the potential role of unsaturated fatty acids.

A paucity of evidence is available regarding the impact of diet's quality during pregnancy and lactation on the body composition of breast-feeding mothers. The purpose of the present study was to evaluate the association between maternal degree of adherence to the Mediterranean diet (MD) and body composition measures specifically those relating to body fat, in the lactation period. A cross-sectional study on healthy mothers of full-term babies has been conducted. At 30 ± 10 d after delivery, anthropometric measurements and body composition were assessed. A food frequency questionnaire was performed to compute the Italian Mediterranean Index (IMI) score as an index of adherence to the MD. Data related to pregnancy such as pre-pregnancy weight, gestational weight gain and morbidities were also collected. The 147 mothers included were categorised in IMI-1 (IMI score < 5; n 92) and IMI-2 (IMI score ≥ 5; n 55) groups. IMI-2 mothers showed higher daily energy, total carbohydrates, starch and fibre intakes than IMI-1. The dietary habits of IMI-2 mothers reflect the typical characteristics of MD: they consumed higher quantities of proteins and lipids of vegetal origin, higher amounts of monounsaturated and polyunsaturated fatty acids (PUFAs) and lower saturated to PUFAs ratio. The IMI-2 group showed lower absolute fat mass and fat mass index compared to IMI-1 [(20⋅2 ± 5⋅9) v. (22⋅9 ± 8⋅4) kg; P 0⋅036 and (7⋅5 ± 2⋅2) v. (8⋅5 ± 3⋅1) kg/m2; P 0⋅036, respectively], whereas body weight [(61⋅1 ± 8⋅0) v. (63⋅3 ± 9⋅2) kg] and body mass index [(22⋅4 ± 2⋅6) v. (23⋅3 ± 3⋅5) kg/m2] were similar. The degree of adherence to the MD during pregnancy and lactation is positively associated with lower maternal fat deposition in the breast-feeding period. The higher quality of dietary lipids, probably in synergy with the assumption of starchy carbohydrates and fibre, could influence maternal body fat.

The indirect calorimetry in very low birth weight preterm infants: An easier and reliable procedure.

OBJECTIVES: Preterm infants are at increased risk of developing extrauterine growth restriction, which is associated with worse health outcomes. The energy needs are not well known, as the measurement of resting energy expenditure (REE) using indirect calorimetry has critical issues when applied to infants. One of the main issues is the time required to obtain reliable data owing to the difficulty in keeping infants quiet during the entire examination. Thus, the aim of this study was to define the minimum duration of calorimetry to obtain reliable data. METHODS: The volume of oxygen consumption (VO2) and the volume of carbon dioxide production (VCO2) were recorded for a mean duration of 90 consecutive minutes. REE was calculated using a neonatal prototype calculator. We extracted data regarding VO2, VCO2, and REE at 10(T1), 20(T2), 30(T3), 40(T4), and 50(T5) minutes of steady state and compared these data to those of entire steady state period. RESULTS: Twenty-six very low birth weight preterm infants were evaluated at 36.58 ± 0.99 wk corrected age. Infants were appropriate for gestational age and clinically stable without comorbidities. There were no significant differences between mean VO2 and REE at T1 (8.26 ± 1.45 mL/kg to 57.80 ± 10.51 kcal/kg), T2 (8.15 ± 1.41 mL/kg to 56.87 ± 10.05 kcal/kg), T3 (8.04 ± 1.41 mL/kg to 56.32 ± 9.73 kcal/kg), T4 (8.05 ± 1.41 mL/kg to 56.07 ± 10.28 kcal/kg), and T5 (8.06 ± 1.55 mL/kg to 57.17 ± 11.62 kcal/kg), respectively, compared to steady state (8.13 ± 1.33 mL/kg to 56.77 ± 9.34 kcal/kg). The median values of VCO2 were significantly different only when T1 data were compared with other time slots (7.02 ± 1.02 mL/kg at steady state; 7.26 ± 1.23 mL/kg at T1; 7.13 ± 1.20 mL/kg at T2; 7.02 ± 1.19 mL/kg at T3; 6.85 ± 1.16 mL/kg at T4; 6.91 ± 1.24 mL/kg at T5). CONCLUSION: Twenty consecutive minutes in steady state condition are sufficient to obtain reliable data on REE in stable, very low birth weight infants.

Protein Intakes during Weaning from Parenteral Nutrition Drive Growth Gain and Body Composition in Very Low Birth Weight Preterm Infants.

Weaning from parenteral to enteral nutrition is a critical period to maintain an adequate growth in very low birth weight preterm infants (VLBWI). We evaluated the actual daily nutritional intakes during the transition phase (TP) in VLBWI with adequate and inadequate weight growth velocity (GV ≥ 15 vs. GV < 15 g/kg/day). Fat-free mass (FFM) at term-corrected age (TCA) was compared between groups. Based on actual nutritional intakes of infants with adequate growth, we defined a standardized parenteral nutrition bag (SPB) for the TP. One hundred and six VLBWI were categorized as group 1 (G1): [GV < 15 (n = 56)] and group 2 (G2): [GV ≥ 15 (n = 50)]. The TP was divided into two periods: main parenteral nutritional intakes period (parenteral nutritional intakes >50%) (M-PNI) and main enteral nutritional intakes period (enteral nutritional intakes >50%) (M-ENI). Anthropometric measurements were assessed at discharge and TCA, FFM deposition at TCA. During M-PNI, G2 showed higher enteral protein intake compared to G1 (p = 0.05). During M-ENI, G2 showed higher parenteral protein (p = 0.01) and energy intakes (p < 0.001). A gradual reduction in SPB volume, together with progressive increase in enteral volume, allowed nutritional intakes similar to those of G2. At TCA, G2 had higher FFM compared to G1 (p = 0.04). The reasoned use of SPB could guarantee an adequate protein administration, allowing an adequate growth and higher FFM deposition.

How does gestational age affect growth and body composition of preterm twins?

BACKGROUND: Twins experience altered growth compared to singletons. The primary aim of this study was to compare growth and body composition (BC) of twin and singleton preterm infants from birth to 3 months according to gestational age (GA). Secondary aims were to evaluate the effect of chorionicity and mode of feeding on twins' BC. METHODS: Anthropometric measurements and BC were performed at term and 3 months in preterm infants (GA < 37 weeks). Infants were categorized as: extremely, very, moderate and late preterm infants. Chorionicity was assigned as monochorionic, dichorionic or multichorionic. Mode of feeding was recorded as any human milk feeding vs formula feeding. RESULTS: Five hundred and seventy-six preterm infants were included (223 twins). Late-preterm twins were lighter and shorter at each study point; fat-free mass (FFM) was lower in these infants at each study point, compared to singletons. No differences were found between twins and singleton on the other category. Multichorionic infants had an FFM deficit compared to monochorionic and dichorionic at term, whereas no differences were found at 3 months. FFM at term was negatively associated with being twin and formula-fed. CONCLUSIONS: Twins and singletons born before 34 weeks' GA showed similar anthropometry and BC. Conversely, twin late-preterm infants showed different growth and BC compared to singletons.

Effect of Target Fortification on Osmolality and Microbiological Safety of Human Milk Over Time.

OBJECTIVES: The fortification of human milk can result in increased osmolality, which may be associated with adverse effects for preterm infants. To evaluate the effect of target fortification on the osmolality and microbiological safety of donor human milk and raw mature milk during the first 72 hours of storage. METHODS: We performed target fortification of 63 pasteurized donor human milk (PDHM) and 54 raw mature milk (RMM) samples in a laminar flow hood. Osmolality (mOsm/kg) was evaluated before fortification (T0), immediately after fortification (T1), at 6 (T2), 24 (T3), 48 (T4), and 72 hours (T5) after fortification. Microbiological analysis was performed at T0, T4, and T5. During the study, all samples were stored at 4°C. RESULTS: Mean osmolality at each study point for PDHM and RMM were, respectively: T0: 291.4 ±â€Š11.0 versus 288.4 ±â€Š5.6 (P = 0.06); T1: 384.8 ±â€Š16.7 versus 398.3 ±â€Š23.7; T2: 393.9 ±â€Š17.7 versus 410.1 ±â€Š27.0; T3: 397.8 ±â€Š17.6 versus 417.9 ±â€Š26.1; T4: 400.0 ±â€Š16.5 versus 420.2 ±â€Š24.9; T5: 399.6 ±â€Š16.5 versus 425.2 ±â€Š25.8 (P < 0.001 from T1 to T5). Microbiological analyses were negative at each study points for PDHM. At T0 16.1% of RMM samples had positive cultures, whereas the bacterial count remained stable thought the study. CONCLUSIONS: PDHM's osmolality increases during the first 6 hours after fortification and remains stable and safe until 72 hours. RMM's osmolality increases during the first 24 hours and remains stable and safe until 72 hours. The storage at 4°C and the manipulation of PDHM and RMM samples in a laminar flow hood seem to be safe and preserve the microbiological safety of fortified pasteurized human milk until 72 hours.

Macronutrient content of pooled donor human milk before and after Holder pasteurization.

BACKGROUND: Donor human milk (DHM) is the best alternative for preterm infants when their own mother's milk is unavailable. DHM should be pasteurized to guarantee microbiological safety; however, this process can influence the macronutrient content. The aim of this study was to investigate the effect of Holder pasteurization (HoP) on DHM macronutrient content. METHODS: Protein, lactose, lipids (g/100 ml) and energy (kcal/100 ml) of DHM pools were analysed before and after HoP (62.5 °C for 30 min) using mid-infrared spectroscopy (HM analyser Miris AB®). The mean macronutrient content before and after HoP was compared by paired t-test. The percentage decreases (Delta%) were calculated. RESULTS: The change in macronutrient content of 460 pools was determined. Protein, lipids and lactose decreased significantly after HoP (0.88 ± 0.20 vs 0.86 ± 0.20 and 2.91 ± 0.89 vs 2.75 ± 0.84 and 7.19 ± 0.41 vs 7.11 ± 0.48 respectively). The Delta% values were - 2.51 ± 13.12, - 4.79 ± 9.47 and - 0.92 ± 5.92 for protein, lipids and lactose, respectively (p ≤ 0.001). CONCLUSION: This study confirms that the macronutrient content of DHM, especially in terms of lipids and protein, is reduced after HoP. Therefore, in order to perform a tailored fortification of DHM, the clinicians need to be aware of the somewhat diminished nutrient content of DHM.

The Effect of Human Milk on Modulating the Quality of Growth in Preterm Infants.

Introduction: Human milk is the optimal nutrition for preterm infants. When the mother's own milk is unavailable, donor human milk is recommended as an alternative for preterm infants. The association among early nutrition, body composition and the future risk of disease has recently attracted much interest. The aim of this study was to investigate the effect of human milk on the body composition of preterm infants. Materials and Methods: Very low birth weight infants (VLBW: birth weight <1,500 g) with a gestational age (GA) between 26 and 34 weeks were included. Clinical data, anthropometric measurements and nutritional intake in terms of the volume of human milk were extracted from computerized medical charts. The human milk intake was expressed as a percentage of target fortified donor human milk and/or target fortified fresh mother's milk, compared with the total volume of milk intake during the hospital stay. All included infants underwent anthropometric measurements and body composition analysis (expressed as fat-free mass percentage) at term corrected age (CA) by air-displacement plethysmography. A comparison between infants fed human milk at <50% (group 1) and infants fed human milk at ≥50% of the total volume of milk intake (group 2) was conducted. Multiple linear regression analyses were conducted to explore the modulating effect of fortified human milk on fat-free mass at term CA. Results: Seventy-three VLBW infants were included in the study. The mean weight and GA at birth were 1,248 ± 198 g and 30.2 ± 2.0 weeks, respectively. No differences were found regarding anthropometric measurements at birth, at discharge and at term CA between the two groups. The mean fortified human milk intake was 34.9 ± 12.5 and 80.9 ± 15.5% in groups 1 and 2, respectively (p < 0.001). A multiple regression analysis corrected for sex and birth weight demonstrated that intake of ≥50% fortified human milk was associated with a higher fat-free mass percentage at term CA than intake of <50% fortified human milk. Conclusion: The use of target fortified human milk modulated growth and improved growth quality in vulnerable preterm infants. Thus, the use of donor human milk should be encouraged when fresh mother's milk is insufficient or not available.

Correction to: Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial.

Following the publication of the original article [1], it was brought to our attention that the authors' names and surnames were erroneously interchanged.

Clinical evaluation of two different protein content formulas fed to full-term healthy infants: a randomized controlled trial.

BACKGROUND: A high early protein intake is associated with rapid postnatal weight gain and altered body composition. We aimed to evaluate the safety of a low-protein formula in healthy full-term infants. METHODS: A randomized controlled trial was conducted. A total of 118 infants were randomized to receive two different protein content formulas (formula A or formula B (protein content: 1.2 vs. 1.7 g/100 mL, respectively)) for the first 4 months of life. Anthropometry and body composition by air displacement plethysmography were assessed at enrolment and at two and 4 months. The reference group comprised 50 healthy, exclusively breastfed, full-term infants. RESULTS: Weight gain (g/day) throughout the study was similar between the formula groups (32.5 ± 6.1 vs. 32.8 ± 6.8) and in the reference group (30.4 ± 5.4). The formula groups showed similar body composition but a different fat-free mass content from breastfed infants at two and 4 months. However, the formula A group showed a fat-free mass increase more similar to that of the breastfed infants. The occurrence of gastrointestinal symptoms or adverse events was similar between the formula groups. CONCLUSIONS: Feeding a low-protein content formula appears to be safe and to promote adequate growth, although determination of the long-term effect on body composition requires further study. TRIAL REGISTRATION: The present study was retrospectively registered in ClinicalTrials.gov (trial number: NCT03035721 on January 18, 2017).

Does Human Milk Modulate Body Composition in Late Preterm Infants at Term-Corrected Age?

(1) Background: Late preterm infants account for the majority of preterm births and are at risk of altered body composition. Because body composition modulates later health outcomes and human milk is recommended as the normal method for infant feeding, we sought to investigate whether human milk feeding in early life can modulate body composition development in late preterm infants; (2) Methods: Neonatal, anthropometric and feeding data of 284 late preterm infants were collected. Body composition was evaluated at term-corrected age by air displacement plethysmography. The effect of human milk feeding on fat-free mass and fat mass content was evaluated using multiple linear regression analysis; (3) Results: Human milk was fed to 68% of the infants. According to multiple regression analysis, being fed any human milk at discharge and at  term-corrected and being fed exclusively human milk at term-corrected age were positively associated with fat-free mass content(ß = -47.9, 95% confidence interval (CI) = -95.7; -0.18; p = 0.049; ß = -89.6, 95% CI = -131.5; -47.7; p < 0.0001; ß = -104.1, 95% CI = -151.4; -56.7, p < 0.0001); (4) Conclusion: Human milk feeding appears to be associated with fat-free mass deposition in late preterm infants. Healthcare professionals should direct efforts toward promoting and supporting breastfeeding in these vulnerable infants.

Is targeted fortification of human breast milk an optimal nutrition strategy for preterm infants? An interventional study.

BACKGROUND: Fortifying human milk contributes to the prevention of postnatal growth failure in preterm infants. Because of the natural variability of human milk, targeted fortification of human milk has been advocated. However, data regarding the efficacy and safety of prolonged targeted fortification are scarce. We aimed to assess the safety of targeted fortification of human milk in preterm infants compared with standard fortification, as well as the effects on infant growth. METHODS: We conducted an interventional study during hospital stay in healthy very low birth weight preterm infants who were exclusively fed human milk. Pools of human milk collected for 24 h were analysed using mid-infrared transmission spectroscopy. Targeted fortification of human milk was performed by adding macronutrients to native human milk to obtain optimal ratios of fat (4.4 g), carbohydrates (8.8 g), and protein (3 g) per 100 ml. The intervention period lasted 4-7 weeks. Weekly weight and daily growth rates were compared with those of a standardized fortification group of very low birth weight preterm infants who received standard fortified human milk (n = 10). The osmolality as well as the metabolic and gastrointestinal tolerance were monitored. Intergroup differences were evaluated using the Mann-Whitney U-test. RESULTS: A total of 10 preterm infants (birth weight 1223 ± 195 g; gestational age 29.1 ± 1.03 weeks) were enrolled and 118 samples of pooled milk were analysed. On average, 1.4 ± 0.1 g of protein, 2.3 ± 0.5 g of carbohydrate, and 0.3 ± 0.1 g of fat per 100 ml were added to the milk. Osmolality values after target fortification were within recommended limits (376 ± 66 mOsml/kg). Weekly weight gain (205.5 g; 95 % CI 177-233 vs 155 g; 95 % CI 132-178; p = 0.025) and daily growth rates (15.7 g/kg/day; 95 % CI 14.5-16.9 vs 12.3 g/kg/day; 95 % CI 10.7-13.9; p = 0.005) were higher in infants receiving target fortification than in infants receiving standardized fortification. The infants receiving targeted fortified milk consumed similar volumes as infants in the standardized fortification group (148 ± 4.5 vs 146 ± 4 ml/kg/day). No signs of either gastrointestinal or metabolic intolerance were observed. CONCLUSIONS: Target fortification appears to promote growth in very low birth weight preterm infants without any detrimental effects. Trial registration NCT02716337.