A pilot study to disentangle the infant gut microbiota composition and identification of bacteria correlates with high fat mass.

Background: At birth, the human intestine is colonized by a complex community of microorganisms known as gut microbiota. These complex microbial communities that inhabit the gut microbiota are thought to play a key role in maintaining host physiological homeostasis. For this reason, correct colonization of the gastrointestinal tract in the early stages of life could be fundamental for human health. Furthermore, alterations of the infant microbiota are correlated with the development of human inflammatory diseases and disorders. In this context, the possible relationships between intestinal microbiota and body composition during infancy are of great interest. Methods: In this study, we have performed a pilot study based on 16S rRNA gene profiling and metagenomic approaches on repeatedly measured data on time involving a cohort of 41 Italian newborns, which is aimed to investigate the possible correlation between body fat mass percentage (FM%) and the infant gut microbiota composition. Results and conclusion: The taxonomical analysis of the stool microbiota of each infant included in the cohort allowed the identification of a specific correlation between intestinal bacteria, such as Bifidobacterium and Veillonella, and the increase in FM%. Moreover, the analysis of the infant microbiome's metabolic capabilities suggested that the intestinal microbiome functionally impacts the human host and its possible influence on host physiology.

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.

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.

Complementary feeding in preterm infants: a position paper by Italian neonatal, paediatric and paediatric gastroenterology joint societies.

Nutrition in the first 1000 days of life is essential to ensure appropriate growth rates, prevent adverse short- and long-term outcomes, and allow physiologic neurocognitive development. Appropriate management of early nutritional needs is particularly crucial for preterm infants. Although the impact of early nutrition on health outcomes in preterm infants is well established, evidence-based recommendations on complementary feeding for preterm neonates and especially extremely low birth weight and extremely low gestational age neonates are still lacking. In the present position paper we performed a narrative review to summarize current evidence regarding complementary feeding in preterm neonates and draw recommendation shared by joint societies (SIP, SIN and SIGENP) for paediatricians, healthcare providers and families with the final aim to reduce the variability of attitude and timing among professionals.

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.

Complementary Feeding: Recommendations for the Introduction of Allergenic Foods and Gluten in the Preterm Infant.

BACKGROUND: The aim of this systematic review is to analyze the available literature on the introduction of allergenic foods and gluten among preterm infants. METHODS: A systematic review of published studies concerning the introduction of gluten and allergenic foods in preterm infants was performed on PubMed and on the Cochrane Library. RESULTS: Of the 174 PubMed results, 15 papers were considered suitable for the review. A total of 83 records were identified through the Cochrane Library search; eight papers were included in the review. Additional papers were identified from the reference lists of included studies. A secondary search was conducted on the same databases to find recommendations and advice regarding healthy full-term infants that could be translated to preterm infants. Therefore, 59 additional papers were included in the review. CONCLUSIONS: Current guidelines for the introduction of solid food cannot be directly transposed to preterm infants. Further research is needed to provide evidence-based guidelines regarding weaning in preterm infants. To date, we can suggest that in preterm infants allergenic foods and gluten may be introduced when complementary feeding is started, any time after 4 months of corrected age, avoiding delayed introduction and irrespective of infants' relative risk of developing allergy. Avoiding large amounts of gluten during the first few weeks after gluten introduction and during infancy is advised, despite limited evidence to support this recommendation.

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.

The Potential Effects of Human Milk on Morbidity in Very-Low-Birth-Weight Preterm Infants.

Improvements in quality of care have led to a significant reduction in mortality and morbidity in preterm infants, especially very-low-birth-weight (VLBW) infants [...].

Complementary Feeding in Preterm Infants: A Systematic Review.

BACKGROUND: This systematic review summarizes available literature regarding complementary feeding (CF) in preterm infants, with or without comorbidities that may interfere with oral functions. METHODS: A literature search was conducted in PubMed and the Cochrane Library. Studies relating to preterm infants (gestational age <37 weeks) were included in the analysis. Retrieved papers were categorized according to their main topic: CF timing and quality; clinical outcome; recommendations; strategies in infants with oral dysfunction. RESULTS: The literature search in PubMed retrieved 6295 papers. Forty met inclusion criteria. The Cochrane search identified four additional study protocols, two related to studies included among PubMed search results, and two ongoing trials. Moreover, among 112 papers dealing with oral feeding, four aiming at managing CF in preterm infants with oral dysfunctions were identified. CONCLUSIONS: The available literature does not provide specific guidelines on the management of CF in preterm infants, who are generally weaned earlier than term infants. There is a paucity of data regarding the relationship between CF and growth/quality of growth and health outcomes in preterm infants. It could be suggested to start CF between five and eight months of chronological age if infants have reached three months corrected age and if they have acquired the necessary developmental skills. An individualized multidisciplinary intervention is advisable for preterm infants with oral dysfunctions.

New Insights in Preterm Nutrition.

Nutrition of preterm infants has a crucial role in the promotion of organ's optimal growth and development [...].

Analysis of immune, microbiota and metabolome maturation in infants in a clinical trial of Lactobacillus paracasei CBA L74-fermented formula.

Mother's milk is the best choice for infants nutrition, however when it is not available or insufficient to satisfy the needs of the infant, formula is proposed as an effective substitute. Here, we report the results of a randomized controlled clinical trial (NCT03637894) designed to evaluate the effects of two different dietary regimens (standard formula and Lactobacillus paracasei CBA L74-fermented formula) versus breastfeeding (reference group) on immune defense mechanisms (primary endpoint: secretory IgA, antimicrobial peptides), the microbiota and its metabolome (secondary outcomes), in healthy full term infants according to the type of delivery (n = 13/group). We show that the fermented formula, safe and well tolerated, induces an increase in secretory IgA (but not in antimicrobial peptides) and reduces the diversity of the microbiota, similarly, but not as much as, breastmilk. Metabolome analysis allowed us to distinguish subjects based on their dietary regimen and mode of delivery. Together, these results suggest that a fermented formula favors the maturation of the immune system, microbiota and metabolome.

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.

Protein content of infant formula for the healthy full-term infant.

Healthy full-term breastfed infants show a different growth pattern compared to formula fed infants and this can reduce the risk of obesity and metabolic syndrome later in life. The increasing knowledge of breast milk composition led to the hypothesis that high dietary protein intake derived from formula milk feeding could have a role in determining the different growth rates and body composition of formula-fed infants compared to breastfed infants. In efforts to simulate human milk, many studies have investigated the safety of infant formulas with reduced protein levels. Nevertheless, feeding a "very-low" protein infant formula may cause limited protein synthesis during a phase of rapid growth. For this reason, using a low-protein formula with an amino acid composition modified according on the estimated infant requirements was suggested. In this edition of the American Journal of Clinical Nutrition, Kouwenhoven et al. concluded that the use of a modified low protein formula (1.7 g protein/100 kcal) is safe. Therefore, if this data is confirmed by longer follow up, the current European legal standards for protein amount in infant formula could be reduced with a potential reduction of the later risk of childhood obesity.

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.