Infant formulas for the treatment of functional gastrointestinal disorders: A position paper of the ESPGHAN Nutrition Committee.

Functional gastrointestinal disorders (FGID), such as infant regurgitation, infant colic, and functional constipation, are common and typically physiological phenomena during the early months of an infant's life and account for frequent consultations with pediatricians. Various infant formulas are marketed for their management and are frequently given by parents to infants before a medical consultation. However, the evidence supporting their effectiveness is limited and some have altered nutritional compositions when compared to standard formulas. Thus, these products should only be used under medical supervision and upon medical advice. Marketing and over-the-counter sales do not ensure proper medical guidance and supervision. The aim of this position paper is to review the current evidence regarding the safety and efficacy of formulas specifically formulated for addressing regurgitation, colic, and constipation, recognized as FGID. The objective is to provide guidance for clinical management based on the highest quality of available evidence. A wide search using Pubmed, MEDLINE, EMBASE and Cochrane Database of Systematic Reviews was performed including the MESH terms infant formula, colic, constipation, regurgitation, reflux, palmitate, lactase, lactose, magnesium, hydrolyzed protein, prebiotics or probiotics. 752 papers were identified and screened. Finally, 72 papers were included in the paper. In the absence of evidence, recommendations reflect the authors' combined expert opinion. Final consensus was obtained by multiple e-mail exchange and meetings of the Nutrition Committee. (1) For breastfed infants experiencing FGID such as regurgitation, colic, or constipation, transitioning from breastfeeding to commercial formulas is not recommended. (2) In general, whether an infant is breastfed or formula-fed, it's crucial to reassure parents that FGIDs are normal and typically do not necessitate treatment or change to a special formula. (3) Thickened formulas, often termed anti-reflux formulas, may be considered in specific cases of regurgitation. (4) The usage of specialized formulas for infants with colic is not advised due to a lack of clinical evidence. (5) In the case of constipation in infants, the use of formulas enriched with high ß-palmitate and increased magnesium content may be considered to soften the stool. Generally, there is limited evidence supporting the use of specialized formulas for FGID. Breastfeeding should never be discontinued in favor of formula feeding.

Two-year neurodevelopmental outcome in extremely preterm-born children: The Austrian Preterm Outcome Study Group.

AIM: The current study determined the neurodevelopmental outcome of extremely preterm infants at 2 years of age. METHODS: All live-born infants 23-27 weeks of gestation born between 2011 and 2020 in Austria were included in a prospective registry. Neurodevelopmental outcome at 2 years of corrected age was assessed using Bayley Scales of Infant Development for both motor and cognitive scores, along with a neurological examination and an assessment of neurosensory function. RESULTS: 2378 out of 2905 (81.9%) live-born infants survived to 2 years of corrected age. Follow-up data were available for 1488 children (62.6%). Overall, 43.0% had no, 35.0% mild and 22.0% moderate-to-severe impairment. The percentage of children with moderate-to-severe neurodevelopmental impairment decreased with increasing gestational age and was 31.4%, 30.5%, 23.3%, 19.0% and 16.5% at 23, 24, 25, 26 and 27 weeks gestational age (p < 0.001). Results did not change over the 10-year period. In multivariate analysis, neonatal complications as well as male sex were significantly associated with an increased risk of neurodevelopmental impairment. CONCLUSION: In this cohort study, a 22.0% rate of moderate-to-severe neurodevelopmental impairment was observed among children born extremely preterm. This national data is important for both counselling parents and guiding the allocation of health resources.

Multiparametric Prediction Models for Coronavirus Disease 2019 Vaccine Selection: Results of a Comparative Population-Based Cohort Study.

BACKGROUND: An understanding vaccine-dependent effects on protective and sustained humoral immune response is crucial to planning future vaccination strategies against coronavirus disease 2019 (COVID-19). METHODS: In this multicenter, population-based, cohort study including 4601 individuals after primary vaccination against COVID-19 ≥ 4 months earlier we compared factors associated with residual antibody levels against severe acute respiratory syndrome coronavirus-2 receptor-binding domain (RBD) across different vaccination strategies (BNT162b2, mRNA-1273, or ChAdOx1). RESULTS: Our main model including 3787 individuals (2 × BNT162b2, n = 2271; 2 × mRNA-1273, n = 251; 2 × ChAdOx1, n = 1265), predicted significantly lower levels of anti-RBD antibodies after 6 months in individuals vaccinated with ChAdOx1 (392.7 binding antibody units per milliliter [BAU/mL]) compared with those vaccinated with BNT162b2 (1179.5 BAU/mL) or mRNA-1273 (2098.2 BAU/mL). Vaccine-dependent association of antibody levels was found for age with a significant predicted difference in BAU/ml per year for BNT162b2 (-21.5; 95% confidence interval [CI], -24.7 to -18.3) and no significant association for mRNA-1273 (-4.0; 95% CI, -20.0 to 12.1) or ChAdOx1 (1.7; 95% CI, .2 to 3.1). The predicted decrease over time since full immunization was highest in mRNA-1273 (-23.4; 95% CI, -31.4 to -15.4) compared with BNT162b2 (-5.9; 95% CI, -7 to -4.8). CONCLUSIONS: Our study revealed population-based evidence of vaccine-dependent effects of age and time since full immunization on humoral immune response. Findings underline the importance of individualized vaccine selection, especially in elderly individuals.

A secondary Outcome Analysis of a Randomized Trial Using a Mixed Lipid Emulsion Containing Fish Oil in Infants with Extremely Low Birth Weight: Cognitive and Behavioral Outcome at Preschool Age.

OBJECTIVE: To evaluate the impact of a parenteral lipid emulsion containing fish oil compared with a soybean oil based-lipid emulsion on the cognitive outcome and behavior of preschool children with extremely low birth weight. STUDY DESIGN: This was a retrospective secondary outcome analysis of a randomized controlled trial performed between June 2012 and June 2015. Infants with extremely low birth weight received either a mixed (soybean oil, medium chain triglycerides, olive oil, fish oil) or a soybean oil-based lipid emulsion for parenteral nutrition. Data from the Kaufman Assessment Battery for Children II, the Child Behavior Checklist 1.5-5, and anthropometry were collected from medical charts at 5.6 years of age. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 5 years 6 months of age, data of 153 of 206 infants (74%) were available for analysis. There were no significant differences in Kaufman Assessment Battery for Children II scores for Sequential/Gsm, Simultaneous/Gv, Learning/Glr, and Mental Processing Index (mixed lipid: median, 97.5 [IQR, 23.5]; soybean oil: median, 96 [IQR, 19.5]; P = .43) or Child Behavior Checklist 1.5-5 scores for internalizing problems, externalizing problems, or total problems (mixed lipid: median, 37 [IQR, 12.3]; soybean oil: median, 37 [IQR, 13.5]; P = .54). CONCLUSIONS: A RandomForest machine learning regression analysis did not show an effect of type of lipid emulsion on cognitive and behavioral outcome. Parenteral nutrition using a mixed lipid emulsion containing fish oil did not affect neurodevelopment and had no impact on child behavior of infants with extremely low birth weights at preschool age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

Make Bayley III Scores Comparable between United States and German Norms-Development of Conversion Equations.

AIM: Bayley Scales of Infant and Toddler Development (Bayley-III) determines scaled scores and converts these into composite scores. It was shown that applying the German and the U.S. manual leads to different results. This study aims to systematically analyze the differences between the U.S. and German Bayley-III version and to develop conversion equations. METHODS: This simulation study generated a dataset of pairs of U.S. and German Bayley-III composite scores (cognitive: n = 4,416, language: n = 240,000, motor: n = 314,000) by converting the same number of achievable tasks for 48 age groups. Bland-Altman plot and regression analyses were performed to develop conversion equations for all age groups. RESULTS: German and US Bayley-III scores demonstrate distinct slope and interception for cognitive, language, and motor composite scores. Lower developmental performance leads to higher composite scores with U.S. norms compared with German norms (up to 15 points). These differences varied between age groups. With newly developed conversion equations, the results can be converted (R 2 > 0.98). INTERPRETATION: This study confirms systematic differences between U.S. and German Bayley test results due to different reference cohorts. Our data consider the full age range and add conversion equations. These findings need to be acknowledged when comparing Bayley Scores internationally.

The Use of Blended Diets in Children With Enteral Feeding Tubes: A Joint Position Paper of the ESPGHAN Committees of Allied Health Professionals and Nutrition.

OBJECTIVES: This joint position paper of the Committees of Allied Health Professionals (CAHP) and Nutrition (CON) of the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) provides a comprehensive guide for health professionals to manage blended diets in children via gastrostomy tubes. METHODS: A systematic literature search was performed from 1992 to 2021 using Pubmed, MEDLINE, and Cochrane Database of Systematic Reviews and recent guidelines reviewed. In the absence of evidence, recommendations reflect the authors' expert opinion. Final consensus was obtained by multiple e-mail exchange and virtual meetings of the CAHP and CON. RESULTS: Reported benefits of blended diets include reduced GERD and infections, improved defecation, level of alertness and attention span, skin conditions, and appearance of hair and nails. Families report a sense of greater normality. Small case series, cross-sectional surveys, questionnaire-based small case studies, reports of personal experience, and single-center pilot studies are available in the medical literature. A total of 20 recommendations for practice were made based on the results and consensus process. CONCLUSIONS: There is little evidence published to formally inform about the potential health benefits or risks of this practice and how to use it in the best way. This leaves health professionals caring for such patients in a relative vacuum regarding what to consider when providing a duty of care to patients and carers who wish to pursue this method of feeding. This article provides guidelines for safe and appropriate use of a BD, but more research is needed.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 2: Long-Term Follow-Up on Home Parenteral Nutrition.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The preferred treatment for IF is parenteral nutrition which may be required until adulthood. The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their expertise. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. This second part of the position paper is dedicated to the long-term management of children with SBS-IF. The paper mainly focuses on how to achieve intestinal rehabilitation, treatment of complications, and on possible surgical and medical management to increase intestinal absorption.

Nutrition and Intestinal Rehabilitation of Children With Short Bowel Syndrome: A Position Paper of the ESPGHAN Committee on Nutrition. Part 1: From Intestinal Resection to Home Discharge.

Short bowel syndrome (SBS) is the leading cause of intestinal failure (IF) in children. The mainstay of treatment for IF is parenteral nutrition (PN). The aim of this position paper is to review the available evidence on managing SBS and to provide practical guidance to clinicians dealing with this condition. All members of the Nutrition Committee of the European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) contributed to this position paper. Some renowned experts in the field joined the team to guide with their experience. A systematic literature search was performed from 2005 to May 2021 using PubMed, MEDLINE, and Cochrane Database of Systematic Reviews. In the absence of evidence, recommendations reflect the expert opinion of the authors. Literature on SBS mainly consists of retrospective single-center experience, thus most of the current papers and recommendations are based on expert opinion. All recommendations were voted on by the expert panel and reached >90% agreement. The first part of this position paper focuses on the physiological mechanism of intestinal adaptation after surgical resection. It subsequently provides some clinical practice recommendations for the primary management of children with SBS from surgical resection until discharged home on PN.

Enteral Nutrition in Preterm Infants (2022): A Position Paper From the ESPGHAN Committee on Nutrition and Invited Experts.

OBJECTIVES: To review the current literature and develop consensus conclusions and recommendations on nutrient intakes and nutritional practice in preterm infants with birthweight <1800 g. METHODS: The European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Committee of Nutrition (CoN) led a process that included CoN members and invited experts. Invited experts with specific expertise were chosen to represent as broad a geographical spread as possible. A list of topics was developed, and individual leads were assigned to topics along with other members, who reviewed the current literature. A single face-to-face meeting was held in February 2020. Provisional conclusions and recommendations were developed between 2020 and 2021, and these were voted on electronically by all members of the working group between 2021 and 2022. Where >90% consensus was not achieved, online discussion meetings were held, along with further voting until agreement was reached. RESULTS: In general, there is a lack of strong evidence for most nutrients and topics. The summary paper is supported by additional supplementary digital content that provide a fuller explanation of the literature and relevant physiology: introduction and overview; human milk reference data; intakes of water, protein, energy, lipid, carbohydrate, electrolytes, minerals, trace elements, water soluble vitamins, and fat soluble vitamins; feeding mode including mineral enteral feeding, feed advancement, management of gastric residuals, gastric tube placement and bolus or continuous feeding; growth; breastmilk buccal colostrum, donor human milk, and risks of cytomegalovirus infection; hydrolyzed protein and osmolality; supplemental bionutrients; and use of breastmilk fortifier. CONCLUSIONS: We provide updated ESPGHAN CoN consensus-based conclusions and recommendations on nutrient intakes and nutritional management for preterm infants.

[Process for the Implementation of Evidence-Based Parenteral Nutrition in German Perinatal Centres - Outcomes of a Multidisciplinary Network]. / Prozess zur Implementierung Evidenzbasierter Parenteraler Ernährung in Deutschen Perinatalzentren ­ Ergebnisse eines Multidisziplinären Netzwerks.

INTRODUCTION: Parenteral nutrition, usually indicated for preterm infants with a birthweight<1500 g and sick newborns, enables the supply with critical nutrients. As a high degree of therapy safety is required, a European guideline provides recommendations for safe therapy procedures. The present project aimed to evaluate the implementation of the European guideline in German perinatal centers and to identify possible barriers that impede its implementation. A further goal was to develop solution approaches to overcome possible barriers. METHODS AND RESULTS: A multidisciplinary cooperation conducted an online survey questioning the current implementation procedures of the European guideline among pediatricians and hospital pharmacists. Results show barriers in the provisioning process of parenteral nutrition that hinder a guideline-compliant implementation in practice. Based on results of this survey, an expert network developed an interactive toolkit with simplified guideline recommendations, guideline-compliant advice for practice, best-practice examples, forms, and handouts. It seeks to encourage critical reflection of routine processes and provides concrete solutions to overcome barriers in practice. CONCLUSION: The current procedures related to parenteral nutrition deviate from guideline recommendations. The developed toolkit provides practice-oriented support aiming to enhance the guideline-compliant implementation of parenteral nutrition in perinatal centers.

A Randomized Trial of Parenteral Nutrition Using a Mixed Lipid Emulsion Containing Fish Oil in Infants of Extremely Low Birth Weight: Neurodevelopmental Outcome at 12 and 24 Months Corrected Age, A Secondary Outcome Analysis.

OBJECTIVE: To examine whether parenteral nutrition using a mixed lipid emulsion containing fish oil improves the neurodevelopmental outcomes of extremely low birth weight infants. STUDY DESIGN: The study is a secondary outcome analysis of a double-blind randomized trial of 230 extremely low birth weight infants performed at a single level IV neonatal care unit (Medical University Vienna; June 2012 to June 2015). Participants received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil, or a soybean oil-based lipid emulsion for parenteral nutrition. Neurodevelopment of study participants was assessed at 12 and 24 months corrected age (August 2013 to October 2017) using the Bayley Scales of Infant-Toddler Development, third edition. RESULTS: At discharge, 206 of the 230 study participants were eligible. At 12 and 24 months corrected age, 174 of 206 (85%) and 164 of 206 (80%) infants were evaluated. At 12 months, there was no significant difference in cognitive (mixed lipid: median, 95 [IQR, 85-101]; soybean oil: median, 95 [IQR, 85-100]; P = .71), language (mixed lipid: median, 86 [IQR, 77-94], soybean oil: median, 89 [IQR, 79-94]; P = .48), or motor scores (mixed lipid: median, 88 [IQR, 76-94], soybean oil: median, 88 [IQR, 79-94]; P = .69). At 24 months, there was again no significant difference in cognitive (mixed lipid: median, 95 [IQR, 80-105], soybean oil: median, 95 [IQR, 90-105]; P = .17), language (mixed lipid: median, 89 [IQR, 75-97], soybean oil 89 [IQR, 77-100]; P = .54), and motor scores (mixed lipid: median, 94 [IQR, 82-103], soybean oil: median, 94 [IQR, 85-103]; P = .53). CONCLUSIONS: Parenteral nutrition using a mixed lipid emulsion containing fish oil did not improve neurodevelopment of extremely low birth weight infants at 12 and 24 months corrected age. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

ELBW infants receive inadvertent sodium load above the recommended intake.

BACKGROUND: To determine total sodium load, including inadvertent load, during the first 2 postnatal weeks, and its influence on serum sodium, morbidity, and mortality in extremely low birth weight (ELBW, birth weight <1000 g) infants and to calculate sodium replacement models. METHODS: Retrospective data analysis on ELBW infants with a gestational age <28 + 0/7 weeks. RESULTS: Ninety patients with a median birth weight of 718 g and a median gestational age of 24 + 6/7 weeks were included. Median sodium intake during the first 2 postnatal weeks was 10.2 mmol/kg/day, which was significantly higher than recommended (2-5 mmol/kg/day). Sodium intake did not affect the risk for hypernatremia. Each mmol of sodium intake during the first postnatal week was associated with an increased risk of bronchopulmonary dysplasia (45%) and higher-grade intraventricular hemorrhage (31%), during the second postnatal week for necrotizing enterocolitis (19%), and during both postnatal weeks of mortality (13%). Calculations of two sodium replacement models resulted in a decrease in sodium intake during the first postnatal week of 3.2 and 4.0 mmol/kg/day, respectively. CONCLUSIONS: Sodium load during the first 2 postnatal weeks of ELBW infants was significantly higher than recommended owing to inadvertent sodium intake and was associated with a higher risk of subsequent morbidity and mortality, although the study design does not allow conclusions on causality. Replacement of 0.9% saline with alternative carrier solutions might reduce sodium intake. IMPACT: Sodium intake in ELBW infants during the first 2 postnatal weeks was twofold to threefold higher than recommended; this was mainly caused by inadvertent sodium components. High sodium intake is not related to severe hypernatremia but might be associated with a higher morbidity in terms of BPD, IVH, and NEC. Inadvertent sodium load can be reduced by replacing high sodium-containing carrier solutions with high levels of sodium with alternative hypotonic and/or balanced fluids, model based.

Donor human milk programs in German, Austrian and Swiss neonatal units - findings from an international survey.

BACKGROUND: Donor human milk (DHM) has been recommended for premature infants if mothers' own milk is not available. The aim of this study was to increase the knowledge about the utilization rate and handling of DHM among neonatal units in Germany, Austria und Switzerland. METHODS: Online survey of utilization rates and handling practices of DHM of all neonatal units within Germany, Austria and Switzerland providing care for premature infants less than 32 weeks of gestation. RESULTS: DHM utilization rate of 35% is low (50/142) within those 54% of units that responded to our survey (142/261). Only 26/50 units have DHM routinely integrated into their nutritional management protocols. Lacking access and difficult procurement were cited as the main obstacles for not using DHM. However, eight out of ten respondents currently not using DHM would like to introduce DHM in their unit if available. There were differences in most aspects of DHM handling including donor recruitment and screening, testing and treatment of milk microbiota and commencement of DHM utilization. Breastmilk feeding rates were increased in units utilizing DHM compared to those not utilizing DHM. CONCLUSIONS: DHM is underutilized in most neonatal units caring for premature infants within participating countries. Lacking access to DHM represents the main barrier for utilizing DHM for premature infants.

A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial.

OBJECTIVE: To assess whether parenteral nutrition for infants of extremely low birth weight using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation. STUDY DESIGN: The study is a prespecified secondary outcome analysis of a randomized controlled trial of 230 infants of extremely low birth weight receiving a mixed (soybean oil, medium-chain triglycerides, olive oil, and fish oil; intervention) or a soybean oil-based lipid emulsion (control). The study was conducted at a single-level IV neonatal care unit (Medical University Vienna; June 2012 to October 2015). Electrophysiological brain maturation (background activity, sleep-wake cycling, and brain maturational scores) was assessed biweekly by amplitude-integrated electroencephalography (birth to discharge). RESULTS: A total of 317 amplitude-integrated electroencephalography measurements (intervention: n = 165; control: n = 152) from 121 (intervention: n = 63; control: n = 58) of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. By 28 weeks of postmenstrual age, infants receiving the intervention displayed significantly greater percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling, and bandwidth were significantly greater. Maximum maturational scores were reached 2 weeks earlier in the intervention group (36.4 weeks, 35.4-37.5) compared with the control group (38.4 weeks, 37.1-42.4) (median, IQR; P < .001). CONCLUSIONS: Using a mixed parenteral lipid emulsion that contains fish oil, we found that electrophysiological brain maturation was accelerated in infants who were preterm. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01585935.

The anti-inflammatory effect of milk and dairy products on periodontal cells: an in vitro approach.

OBJECTIVE: Milk can reduce intestinal tissue damage in colitis models, and protects infants against necrotizing enterocolitis. However, whether milk can decrease inflammation related to peri-implantitis and oral mucosal dehiscence remains unclear. We therefore investigated whether or not milk and fermented by-products have any anti-inflammatory effects on the cells of the oral cavity. MATERIAL AND METHODS: Human gingival fibroblasts and the human oral epithelial cell line HSC2 were exposed to pasteurized human milk, pasteurized cow's milk, dairy products, and powdered milk. An inflammatory response was then provoked with IL1 and TNFα. The expression changes of IL1, IL6, and IL8 were detected by reverse transcriptase PCR and immunoassay. RESULTS: We can report that pasteurized human milk and pasteurized cow's milk as well as yoghurt, buttermilk, sour milk, whey, and powdered milk can lower the expression of inflammatory cytokines in gingival fibroblasts being stimulated by IL1 and TNFα. A similar anti-inflammatory response to pasteurized milk and dairy products was observed with the human oral epithelial cell line HSC2. CONCLUSION: These data suggest that pasteurized and powdered milk, as well as fermented dairy products, display an anti-inflammatory effect on oral fibroblasts and oral epithelial cells. CLINICAL RELEVANCE: Our in vitro findings provide the scientific basis to extend this research towards testing the anti-inflammatory effects of milk in a pre-clinical periodontitis and peri-implantitis model.

A Mixed Lipid Emulsion for Prevention of Parenteral Nutrition Associated Cholestasis in Extremely Low Birth Weight Infants: A Randomized Clinical Trial.

OBJECTIVES: To examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants. STUDY DESIGN: This double-blind randomized trial of 230 ELBW infants (June 2012-October 2015) was performed at a single level IV neonatal intensive care unit. Patients received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil-(intervention) or a soybean oil-based lipid emulsion (control) for parenteral nutrition. The primary outcome measure was PNAC (conjugated bilirubin >1.5 mg/dL [25 µmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%. RESULTS: Reasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity. CONCLUSIONS: The incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants. TRIAL REGISTRATION: ClinicalTrials.govNCT01585935.

Hydrolyzed Formula With Reduced Protein Content Supports Adequate Growth: A Randomized Controlled Noninferiority Trial.

OBJECTIVE: A high protein content of nonhydrolyzed infant formula exceeding metabolic requirements can induce rapid weight gain and obesity. Hydrolyzed formula with too low protein (LP) content may result in inadequate growth. The aim of this study was to investigate noninferiority of partial and extensively hydrolyzed formulas (pHF, eHF) with lower hydrolyzed protein content than conventionally, regularly used formulas, with or without synbiotics for normal growth of healthy term infants. METHODS: In an European multi-center, parallel, prospective, controlled, double-blind trial, 402 formula-fed infants were randomly assigned to four groups: LP-formulas (1.9 g protein/100 kcal) as pHF with or without synbiotics, LP-eHF formula with synbiotics, or regular protein eHF (2.3 g protein/100 kcal). One hundred and one breast-fed infants served as observational reference group. As primary endpoint, noninferiority of daily weight gain during the first 4 months of life was investigated comparing the LP-group to a regular protein eHF group. RESULTS: A comparison of daily weight gain in infants receiving LPpHF (2.15 g/day CI -0.18 to inf.) with infants receiving regular protein eHF showed noninferior weight gain (-3.5 g/day margin; per protocol [PP] population). Noninferiority was also confirmed for the other tested LP formulas. Likewise, analysis of metabolic parameters and plasma amino acid concentrations demonstrated a safe and balanced nutritional composition. Energetic efficiency for growth (weight) was slightly higher in LPeHF and synbiotics compared with LPpHF and synbiotics. CONCLUSIONS: All tested hydrolyzed LP formulas allowed normal weight gain without being inferior to regular protein eHF in the first 4 months of life. This trial was registered at clinicaltrials.gov, NCT01143233.

Starting enteral nutrition with preterm single donor milk instead of formula affects time to full enteral feeding in very low birthweight infants.

AIM: This study compared the impact of using either single donor breastmilk or formula to start enteral feeding in preterm infants, on the time to full enteral feeding, growth and morbidity. The milk was provided by other preterm mothers. METHODS: This was an observational prospective study, carried out from June 2012 to March 2013 at the Medical University of Vienna, Austria, on the effects of preterm single donor milk on 133 very low birthweight infants with a birthweight <1500 g and a gestational age <32 weeks until they were on full enteral feeding. They were compared to a retrospective group of 150 infants from March 2011 to May 2012 who received preterm formula. RESULTS: The time to full enteral feeding, defined as 140 mL/kg, was significantly shorter in the donor milk group than in the formula group (18 vs. 22 days, p = 0.01). Feeding donor milk was also associated with a lower incidence for retinopathy of prematurity (4% vs. 13%, p < 0.01) and culture-proven sepsis (11% vs. 23%, p < 0.01). CONCLUSION: Feeding preterm infants breastmilk from a single donor rather using formula was associated with a shorter time to full enteral feeding and lower incidences of retinopathy of prematurity and sepsis.

Human Milk Banking.

Human milk banks play an essential role by providing human milk to infants who would otherwise not be able to receive human milk. The largest group of recipients are premature infants who derive very substantial benefits from it. Human milk protects premature infants from necrotizing enterocolitis and from sepsis, two devastating medical conditions. Milk banks collect, screen, store, process, and distribute human milk. Donating women usually nurse their own infants and have a milk supply that exceeds their own infants' needs. Donor women are carefully selected and are screened for HIV-1, HIV-2, human T-cell leukemia virus 1 and 2, hepatitis B, hepatitis C, and syphilis. In the milk bank, handling, storing, processing, pooling, and bacterial screening follow standardized algorithms. Heat treatment of human milk diminishes anti-infective properties, cellular components, growth factors, and nutrients. However, the beneficial effects of donor milk remain significant and donor milk is still highly preferable in comparison to formula.

Nutritive and Bioactive Proteins in Breastmilk.

Protein ingested with breast milk provides indispensable amino acids which are necessary for new protein synthesis for growth and replacement of losses via urine, feces, and the skin. Protein gain in the body of an infant is highest during the first months when protein concentrations in breast milk are higher than during later stages of lactation. Low-birth-weight infants have higher protein needs than term infants and need protein supplements during feeding with breastmilk. Based on our better understanding of protein evolution in breastmilk during the stages of lactation, new infant formulas with lower protein concentration but better protein quality have been created, successfully tested, and are now available in many countries. Besides providing indispensable amino acids, bioactive protein in breast milk can be broadly classified into 4 major functions, that is, providing protection from microbial insults and immune protection, aiding in digestive functions, gut development, and being carriers for other nutrients. Individual proteins and their proposed bioactivities are summarized in this paper in brief. Indeed, some proteins like lactoferrin and sIgA have been extensively studied for their biological functions, whereas others may require more data in support to further validate their proposed functions.