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.

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.

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.

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.

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.

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.

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.

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

s, Sharing Progress in Neonatal (SPIN) Brain, Gut, Heart, and Lung, 2017 Neonatology 2017;111:437–445 DOI: 10.1159/000464310 438 gene expression in the IGF1 signaling pathway, including CCN1, a matricellular protein. Objective: To combine a clinically relevant preterm lamb model with a conditional gene-targeted analysis in mice to investigate the role of IGF1 signaling in lung development and disease. Methods: Lamb lungs were from Dr. Kurt Albertine (University of Utah). Mouse experiments and tissue procurement were strictly compliant to USC, IACUC regulations. Ccn1 (floxed) mice were from Dr. L. Lau (University of Illinois, Chicago). mRNA extraction was by the Trizol method. Quantitative RT-PCR was according to our published protocols [Li et al., 2015]. Results: Igf1 mRNA was measured in preterm lambs treated with two modes of ventilation. Lung Igf1 was strongly repressed by mechanical ventilation (MV) compared to non-invasive high-frequency ventilation (HFNV). A downstream target of IGF1 signaling, Ccn1, increased during alveogenesis in both mice and sheep. We generated mesodermal-specific Ccn1 mouse mutants, designated Ccn1dermo1. Ccn1dermo1 mice were born alive with birth weight similar to control siblings. By 1 month, Ccn1dermo1 mice weighed only 46% of controls with overt respiratory distress. Lung histology at PN14 showed alveolar simplification akin to human BPD. The endothelial progenitor marker Flk1 was decreased in Ccn1dermo1 lungs as was Pdgfr-alpha, a critical regulator of alveogenesis. Ccn1 mRNA was repressed in preterm lambs treated acutely with MV compared to HFNV. However, chronic ventilation with either strategy repressed Ccn1 significantly. Conclusions: The studies described here reveal the key role of IGF1 network and its downstream target CCN1 in alveolar formation and in a clinically relevant premature lamb model of BPD.

BACKGROUND:Late preterm infants show a major fat mass accretion from birth to term. The contribution of preterm birth to the development of the metabolic syndrome is still under investigation.OBJECTIVES:To evaluate body composition changes in late preterm infants during the first 3 months and to investigate their insulin sensitivity and resistance.METHODS:We conducted an observational, longitudinal study. A total of 216 late preterm infants underwent body composition assessment using an air displacement plethysmograph at term and at 3 months of corrected age. In a subgroup of infants (n = 48) the blood glucose and insulin concentration were determined at term and insulin resistance (homeostasis model assessment for insulin resistance; HOMA-IR) and sensitivity (quantitative insulin sensitivity check index; QUICKI) were then calculated. The reference group comprised 71 healthy term infants.RESULTS:The mean birth weight and gestational age were 2,390 ± 391 g and 35.2 ± 0.8 weeks, respectively. At term the fat mass index (kg/m2) of late preterm infants, born adequate for their gestational age and small for their gestational age, was higher than that of term infants (2.08 ± 0.82 vs. 1.62 ± 0.64 vs. 1.03 ± 0.36, p < 0.005, respectively), whereas at 3 months of corrected age no difference was found among the groups. The mean values of glucose, insulin, HOMA-IR, and QUICKI were within the 5th and 95th percentiles.CONCLUSIONS:On the basis of these preliminary findings, fat mass accretion of late preterm infants appears not to be associated with perturbation of the glucose homeostasis.

Late preterm birth accounts for 70 % of all preterm births. While the impact of feeding problems in very preterm infants has been widely investigated, data on late preterm infants’ feeding issues are scarce. The aim of the present study was to investigate the need of nutritional support during hospital stay in a cohort of late preterm infants and to identify the factors that most contribute to its occurrence.

BACKGROUND:Early feeding choices may affect long-term health outcomes. Therefore, understanding body composition changes in healthy breastfed infants has become an important research focus.OBJECTIVES:The aims of this review were to investigate the body composition changes that occur during weight loss in breastfed term newborns and to examine body composition differences between exclusively/predominantly breastfed and exclusively formula-fed infants in the first 6 months of life.METHODS:We performed a review of the existing literature using PubMed. We searched for studies published in English since January 1, 2000, that involved human infants ranging in age from birth to 6 months. We used the following MEDLINE Medical Subject Headings: ((breastfeeding) OR (infant formula)) AND ((body composition) OR (bioelectrical impedance) OR (absorptiometry, photon) OR (total body potassium) OR (isotope dilution) OR (air-displacement plethysmography)). Our search yielded 6 studies.RESULTS:Two studies reported that newborn weight loss was due to a reduction in the quantity of both fat mass and fat-free mass. Three out of 4 articles that evaluated body composition changes according to method of feeding reported no differences in body composition between exclusively/predominantly breastfed and exclusively formula-fed infants in the first 4.5 months of life. One study reported that exclusively breastfed infants at 3 months of age and exclusively breastfed boys at 6 months of age had higher fat mass contents compared to exclusively formula-fed infants.CONCLUSION:Because of the limited number of studies available, larger studies are needed to clarify the differences in body composition between exclusively/predominantly breastfed and exclusively formula-fed infants.

Pre-term infants who develop bronchopulmonary dysplasia (BPD) are at risk of postnatal growth failure. It has been reported that energy expenditure is higher in infants with BPD than in those without BPD. The aim of the study was to evaluate whether increasing the enteral energy intake of pre-term infants with BPD can improve post-natal growth.

OBJECTIVE:The health benefits provided by breast milk are significant in preterm infants. Despite recommendations, rates of breastfeeding in preterm infants are lower than in term infants. The aim of this study was to evaluate the efficacy of a multidisciplinary intervention in promoting any breastfeeding in preterm infants at discharge.METHODS:A prospective non-randomized interventional cohort study was conducted. One hundred and twenty-two preterm infants constituted the historical group. A multidisciplinary intervention was performed including staff training and setting up and implementation of a written breastfeeding procedure.RESULTS:One hundred and ten preterm infants were enrolled in the intervention group. The percentage of infants fed human milk at discharge was 69 and 62 in the intervention group and in the historical group, respectively. The percentage change from any breastfeeding at full enteral feeding attainment to formula feeding at discharge was lower in the intervention group than in the historical group (-9 versus -23). Belonging to the intervention group and having at least one stress factor during pregnancy were independently associated with any breast milk feeding at discharge.CONCLUSIONS:The multidisciplinary intervention performed appears to be effective in promoting any breastfeeding in preterm infants at discharge.

BACKGROUND: Prevention of postnatal growth restriction of very preterm infants still represents a challenge for neonatologists. As standard feeding regimens have proven to be inadequate. Improved feeding strategies are needed to promote growth. Aim of the present study was to evaluate whether a set of nutritional strategies could limit the postnatal growth restriction of a cohort of preterm infants. METHODOLOGY/PRINCIPAL FINDINGS: We performed a prospective non randomized interventional cohort study. Growth and body composition were assessed in 102 very low birth weight infants after the introduction of a set of nutritional practice changes. 69 very low birth weight infants who had received nutrition according to the standard nutritional feeding strategy served as a historical control group. Weight was assessed daily, length and head circumference weekly. Body composition at term corrected age was assessed using an air displacement plethysmography system. The cumulative parenteral energy and protein intakes during the first 7 days of life were higher in the intervention group than in the historical group (530 ± 81 vs 300 ± 93 kcal/kg, p<0.001 and 21 ± 2.9 vs 15 ± 3.2 g/kg, p<0.01). During weaning from parenteral nutrition, the intervention group received higher parental/enteral energy and protein intakes than the historical control group (1380 ± 58 vs 1090 ± 70 kcal/kg; 52.6 ± 7 vs 42.3 ± 10 g/kg, p<0.01). Enteral energy (kcal/kg/d) and protein (g/kg/d) intakes in the intervention group were higher than in the historical group (130 ± 11 vs 100 ± 13; 3.5 ± 0.5 vs 2.2 ± 0.6, p<0.01). The negative changes in z score from birth to discharge for weight and head circumference were significantly lower in the intervention group as compared to the historical group. No difference in fat mass percentage between the intervention and the historical groups was found. CONCLUSIONS: The optimization and the individualization of nutritional intervention promote postnatal growth of preterm infants without any effect on percentage of fat mass.

OBJECTIVE: To investigate whether the consumption of a nutrient-enriched formula after hospital discharge determines different growth and weight gain composition in preterm infants according to intra- and extrauterine growth pattern. METHODS: Two hundred seven preterm infants were randomized at term-corrected age to receive treatment A (term formula) or B (nutrient-enriched formula) up to 6 months of corrected age, using 2 computer-generated randomization lists, 1 for adequate for gestational age (AGA) and 1 for small for gestational age (SGA) infants. Infants were weaned according to our clinical practice after 6 months’ corrected age. Anthropometric parameters and body composition by an air displacement plethysmography system were assessed at term and 1, 3, and 6 months’ corrected age. Anthropometric parameters were also assessed at 12 months. RESULTS: Protein intakes were higher in infants receiving treatment B than in infants receiving treatment A at each study point. There were no differences between the feeding groups in weight and length SD scores in either the AGA and SGA group through the study. The mean head circumference values were higher in AGA infants receiving treatment B than in AGA infants receiving treatment A at 6 and 12 months, whereas at 6 months, the percentage of fat mass was lower. No difference in body composition was detected among SGA infants through the study. CONCLUSIONS: This randomized controlled trial demonstrates the beneficial effect of the consumption of a nutrient-enriched formula after hospital discharge by AGA infants both in terms of head circumference growth and fat-free mass gain.

The aim of nutrition in neonatology is to achieve a healthy growth that mimics, both in terms of growth rates and quality of growth, that of a normal fetus of the same gestational age. In addition, providing an optimal amount and quality of nutrients significantly contributes to the attainment of a neurodevelopment similar to that of an infant born at term. Yet, a high risk of developing metabolic syndrome in relation to aggressive nutrition and accelerated postnatal growth velocity has been reported in former preterm infants. Considering the strict interrelationship that exists between early nutrition, growth, and subsequent health, the development of body composition in early infancy, in terms of fat mass, may contribute to the long-term "programming" process. Hence, accurate and non-invasive measurement of infant body composition, which evaluates the quality in addition to the amount of weight gain, represents a useful tool for gaining further insight into the relationship between birth weight or time in utero and future development. Preterm infants, including those born small for gestational age, have been reported to develop an increased and/or aberrant adiposity, in addition to postnatal growth retardation, when assessed at term-corrected age. However, within the first 5 months, preterm infants, either born adequate or small for gestational age, show a recovery of fat mass, and attain fat mass values comparable to those of full-term infants assessed at birth. The metabolic consequences of these findings on the long-term health need to be further clarified.