Reevaluating the FDA's warning against the use of probiotics in preterm neonates: A societal statement by ESPGHAN and EFCNI.

The recent advisory issued by the United States Food and Drug Administration, cautioning against the routine administration of probiotics in preterm neonates, has sparked a lively debate within the scientific community. This commentary presents a perspective from members of the Special Interest Group on Gut Microbiota and Modifications within the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and other authors who contributed to the ESPGHAN position paper on probiotics for preterm infants, as well as representatives from the European Foundation for the Care of Newborn Infants. We advocate for a more nuanced and supportive approach to the use of certain probiotics in this vulnerable population, balancing the demonstrated benefits and risks.

The Umbilical Cord Creatine Flux and Time Course of Human Milk Creatine across Lactation.

(1) Background: The aim of the present paper was to study fetal and infant creatine (Cr) supply to improve nutrition and neuroprotection in term and especially in preterm infants. The primary outcomes were the placental Cr flux at the end of pregnancy and the time course of human milk (HM) Cr. (2) Methods: The estimation of placental Cr flux was based on umbilical arterial and venous cord blood Cr in 10 term infants after elective caesarian section. HM Cr, creatinine (Crn), and macronutrients were measured longitudinally in 10 mothers across the first 6 months of breastfeeding. (3) Results: At the end of pregnancy, the mean fetal Cr flux was negative (-2.07 mmol/min). HM Cr was highest in colostrum, decreased significantly within the first 2 weeks of breastfeeding (p < 0.05), and did not change significantly thereafter. HM Cr was not correlated with HM Crn or macronutrient composition. (4) Conclusions: The present data suggest that fetal endogenous Cr synthesis covers the needs at the end of pregnancy. However, high colostrum Cr and HM Cr levels, independent of macronutrient composition, suggest that there may be a critical Cr demand immediately after birth that needs to be covered by enteral supply.

Effects of liberalising visiting policy and staff education on parental visiting duration in the neonatal unit.

AIM: The effect of different neonatal unit access hour policies on parental visiting duration is unknown. Therefore, we analysed the effects of access hours policies and parental education on parental visiting duration. METHOD: This prospective longitudinal cohort study was carried out in a level III neonatal unit from October 2020 to May 2022. Three cohorts were compared. The baseline cohort included 51 preterm infants with restricted visiting hours (October 2020 to May 2021). Cohort 1 comprised 35 preterm infants after liberalisation of visiting hours (June 2021 to November 2021). Cohort 2 consisted of 26 preterm infants after an educational program was implemented (December 2021 to May 2022). The primary outcome was the mean daily parental visiting duration. RESULTS: Mean maternal visiting duration was 172 (standard deviation, SD ± 49.2), 195 (SD ± 64.4.), and 258 (SD ± 71.1) minutes/day at baseline and in cohorts 1 and 2 (significant increase from baseline and cohort 1 to cohort 2, p < 0.001). Mean paternal visiting duration did not change significantly across the cohorts: 133 (SD ± 47.2), 135 (SD ± 83.5), and 165 (SD ± 71.3) minutes/day. CONCLUSION: Liberalisation of access hours did not increase parental visiting duration. Parental and staff education significantly increased maternal but not paternal visiting duration.

Multidimensional assessment of infant, parent and staff outcomes during a family centered care enhancement project in a tertiary neonatal intensive care unit: study protocol of a longitudinal cohort study.

BACKGROUND: The therapeutic advances and progress in the care for preterm infants have enabled the regular survival of very immature infants. However, the high burden of lifelong sequelae following premature delivery constitutes an ongoing challenge. Regardless of premature delivery, parental mental health and a healthy parent-child relationship were identified as essential prerogatives for normal infant development. Family centered care (FCC) supports preterm infants and their families by respecting the particular developmental, social and emotional needs in the Neonatal Intensive Care Unit. Due to the large variations in concepts and goals of different FCC initiatives, scientific data on the benefits of FCC for the infant and family outcome are sparse and its effects on the clinical team need to be elaborated. METHODS: This prospective single centre longitudinal cohort study enrols preterm infants ≤ 32 + 0 weeks of gestation and/or birthweight ≤ 1500 g and their parents at the neonatal department of the Giessen University Hospital, Giessen, Germany. Following a baseline period, the rollout of additional FCC elements is executed following a stepwise 6-months approach that covers the NICU environment, staff training, parental education and psychosocial support for parents. Recruitment is scheduled over a 5.5. year period from October 2020 to March 2026. The primary outcome is corrected gestational age at discharge. Secondary infant outcomes include neonatal morbidities, growth, and psychomotor development up to 24 months. Parental outcome measures are directed towards parental skills and satisfaction, parent-infant-interaction and mental health. Staff issues are elaborated with particular focus on the item workplace satisfaction. Quality improvement steps are monitored using the Plan- Do- Study- Act cycle method and outcome measures cover the infant, the parents and the medical team. The parallel data collection enables to study the interrelation between these three important areas of research. Sample size calculation was based on the primary outcome. DISCUSSION: It is scientifically impossible to allocate improvements in outcome measures to individual enhancement steps of FCC that constitutes a continuous change in NICU culture and attitudes covering diverse areas of change. Therefore, our trial is designed to allocate childhood, parental and staff outcome measures during the stepwise changes introduced by a FCC intervention program. TRIAL REGISTRATION: Clinicaltrials.gov, trial registration number NCT05286983, date of registration 03/18/2022, retrospectively registered, http://clinicaltrials.gov .

Systematic Review on Individualized Versus Standardized Parenteral Nutrition in Preterm Infants.

The need for high quality evidence is recognized for optimizing practices of parenteral nutrition (PN). The purpose of the present systematic review is to update the available evidence and investigate the effect of standardized PN (SPN) vs. individualized PN (IPN) on protein intake, immediate morbidities, growth, and long-term outcome in preterm infants. A literature search was performed on articles published in the period from 1/2015 to 11/2022 in PubMed and Cochrane database for trials on parenteral nutrition in preterm infants. Three new studies were identified. All new identified trials were nonrandomized observational trials using historical controls. SPN may increase weight and occipital frontal circumference gain and lower the value of maximum weight loss. More recent trials suggest that SPN may easily increase early protein intake. SPN may reduce the sepsis incidence, but overall, no significant effect was found. There was no significant effect of standardization of PN on mortality or stage ≥2 necrotizing enterocolite (NEC) incidence. In conclusion SPN may improve growth through higher nutrient (especially protein) intake and has no effect on sepsis, NEC, mortality, or days of 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.

Probiotics for the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Probiotics, defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host, are widely used despite uncertainty regarding their efficacy and discordant recommendations about their use. The European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) Special Interest Group on Gut Microbiota and Modifications provides updated recommendations for the use of probiotics for the management of selected pediatric gastrointestinal disorders. METHODS: All systematic reviews and/or meta-analyses, as well as subsequently published randomized controlled trials (RCTs) (until December 2021), that compared the use of probiotics in all delivery vehicles and formulations, at any dose, with no probiotic (ie, placebo or no treatment), were eligible for inclusion. The recommendations were formulated only if at least 2 RCTs on a similar well-defined probiotic strain were available. The modified Delphi process was used to establish consensus on the recommendations. RESULTS: Recommendations for the use of specific probiotic strains were made for the management of acute gastroenteritis, prevention of antibiotic-associated diarrhea, nosocomial diarrhea and necrotizing enterocolitis, management of Helicobacter pylori infection, and management of functional abdominal pain disorders and infant colic. CONCLUSIONS: Despite evidence to support the use of specific probiotics in some clinical situations, further studies confirming the effect(s) and defining the type, dose, and timing of probiotics are still often required. The use of probiotics with no documented health benefits should be discouraged.

Synbiotics in the Management of Pediatric Gastrointestinal Disorders: Position Paper of the ESPGHAN Special Interest Group on Gut Microbiota and Modifications.

BACKGROUND: Synbiotics are a mixture comprising of live microorganisms and substrate(s) selectively utilized by host microorganisms that confers a health benefit on the host. There is an increasing number of studies investigating their role in different diseases and disorders. AIM: The purpose of this article is to provide recommendations for the use of synbiotics in the management of pediatric gastrointestinal disorders. The recommendations are developed by the ESPGHAN Special Interest Group on Gut Microbiota and Modifications. METHODS: From existing literature databases, we searched and appraised all systematic reviews and/or meta-analyses, and subsequently published randomized controlled trials (RCTs) that compared the use of synbiotics, in all delivery vehicles and formulations, at any dose, compared to no synbiotics. Synbiotics which are part of infant formula were not assessed. The recommendations were formulated only if at least 2 RCTs that used a well-defined synbiotic were available. RESULTS: Based on the currently available evidence, no recommendation can be formulated in favor or against the use of evaluated synbiotic combination in the treatment of acute gastroenteritis, prevention of necrotizing enterocolitis, Helicobacter pylori infection, inflammatory bowel disease, functional gastrointestinal disorders, and allergy in infants and children. CONCLUSIONS: There is a need for more, well-designed RCTs on the role of synbiotics in gastrointestinal disorders with the same outcome measures to enable the inter-studies comparisons.

A cross-sectional survey of German PA employment and workforce entry.

OBJECTIVE: The contribution of physician assistants (PAs) to the German healthcare workforce has increased significantly since their introduction in 2005. From five training programs, the number has increased to the current 18, with 560 PAs awarded the PA bachelor of science degree as of 2020. Despite the growth, researchers lack systemic and reliable empirical data that provide insight into the German PA educational and professional profile. The German University Association Physician Assistant (DHPA) undertook the first nationwide cross-sectional survey on PAs in Germany to understand the German PA movement. This survey aimed to describe German PAs' entry into the profession and PA educational and job satisfaction. METHODS: PA alumni of all universities affiliated with the DHPA and all subscribers of the Facebook online social media platform PA Blog were invited to complete an online questionnaire. RESULTS: Of the 282 PAs who completed the survey, 77% were female and under age 25 years. Almost all (94%) were employed, predominantly as PAs (91%, 241 of 265), although some held other positions. Most worked full time (87%), with some citing child-care needs as reasons for part-time employment (n = 21). Few reported unemployment (1.4%, 4 of 282). Eighty-two percent said they would probably or very likely choose the same course of study again. Most employed participants found the inclusion of frequent rotations between didactic and clinical training in PA programs beneficial. However, a small number of participants (26.8%) agreed that German PA programs' didactic and clinical teaching objectives were well aligned. CONCLUSIONS: German PAs have a high level of satisfaction with their profession and report low unemployment. Improvement in the alignment of didactic and clinical educational objectives to improve academic qualifications and satisfaction emerged as an area of research.

Infant formulas with synthetic oligosaccharides and respective marketing practices.

Human milk contains more than 150 different oligosaccharides, which together are among to the quantitatively predominant solid components of breast milk. The oligosaccharide content and composition of human milk show large inter-individual differences. Oligosaccharide content is mostly influenced by genetic variants of the mother's secretor status. Oligosaccharides in human milk are utilized by infants' intestinal bacteria, affecting bacterial composition and metabolic activity. Maternal secretor status, and respective differing fucosylated oligosaccharide content, has been associated both with reduced and increased risk of infection in different populations of breastfed infants, possibly due to environmental conditions and the infant's genotype. There are no safety concerns regarding the addition of previously approved oligosaccharides to infant formula; however, no firm conclusions can be drawn about clinically relevant benefits either. Therefore, infant formulas with synthetic oligosaccharide additives are currently not preferentially recommended over infant formulas without such additives. We consider the use of terms such as "human milk oligosaccharides" and corresponding abbreviations such as "HMO" in any advertising of infant formula to be an inappropriate idealization of infant formula. Manufacturers should stop this practice, and such marketing practices should be prevented by responsible supervisory authorities. Pediatricians should inform families that infant formulas supplemented with synthetic oligosaccharides do not resemble the complex oligosaccharide composition of human milk.

Research priorities in pediatric parenteral nutrition: a consensus and perspective from ESPGHAN/ESPEN/ESPR/CSPEN.

Parenteral nutrition is used to treat children that cannot be fully fed by the enteral route. While the revised ESPGHAN/ESPEN/ESPR/CSPEN pediatric parenteral nutrition guidelines provide clear guidance on the use of parenteral nutrition in neonates, infants, and children based on current available evidence, they have helped to crystallize areas where research is lacking or more studies are needed in order to refine recommendations. This paper collates and discusses the research gaps identified by the authors of each section of the guidelines and considers each nutrient or group of nutrients in turn, together with aspects around delivery and organization. The 99 research priorities identified were then ranked in order of importance by clinicians and researchers working in the field using a survey methodology. The highest ranked priority was the need to understand the relationship between total energy intake, rapid catch-up growth, later metabolic function, and neurocognitive outcomes. Research into the optimal intakes of macronutrients needed in order to achieve optimal outcomes also featured prominently. Identifying research priorities in PN should enable research to be focussed on addressing key issues. Multicentre trials, better definition of exposure and outcome variables, and long-term metabolic and developmental follow-up will be key to achieving this. IMPACT: The recent ESPGHAN/ESPEN/ESPR/CSPEN guidelines for pediatric parenteral nutrition provided updated guidance for providing parenteral nutrition to infants and children, including recommendations for practice. However, in several areas there was a lack of evidence to guide practice, or research questions that remained unanswered. This paper summarizes the key priorities for research in pediatric parenteral nutrition, and ranks them in order of importance according to expert opinion.

Update on Calcium and Phosphorus Requirements of Preterm Infants and Recommendations for Enteral Mineral Intake.

BACKGROUND: With current Ca and P recommendations for enteral nutrition, preterm infants, especially VLBW, fail to achieve a bone mineral content (BMC) equivalent to term infants. During the first 3 years, most notably in light at term equivalent age (<-2 Z score) VLBW infants' BMC does not catch up. In adults born preterm with VLBW or SGA, lower adult bone mass, lower peak bone mass, and higher frequency of osteopenia/osteoporosis have been found, implying an increased risk for future bone fractures. The aim of the present narrative review was to provide recommendation for enteral mineral intake for improving bone mineral accretion. METHODS: Current preterm infant mineral recommendations together with fetal and preterm infant physiology of mineral accretion were reviewed to provide recommendations for improving bone mineral accretion. RESULTS: Current Ca and P recommendations systematically underestimate the needs, especially for Ca. CONCLUSION: Higher enteral fortifier/formula mineral content or individual supplementation is required. Higher general mineral intake (especially Ca) will most likely improve bone mineralization in preterm infants and possibly the long-term bone health. However, the nephrocalcinosis risk may increase in infants with high Ca absorption. Therefore, individual additional enteral Ca and/or P supplementations are recommended to improve current fortifier/formula mineral intake.

Bone Mineral Density, Body Composition, and Metabolic Health of Very Low Birth Weight Infants Fed in Hospital Following Current Macronutrient Recommendations during the First 3 Years of Life.

The present study longitudinally evaluated growth, bone mineral density, body composition, and metabolic health outcome in very low birth weight (VLBW) infants whose in-hospital target nutrient intake was within recent recommendations. From six months to three years, bone mineral density (dual-energy X-ray absorptiometry, DXA), body composition, and metabolic health outcome were compared with a reference group of term infants. The aim was to test whether in-hospital achieved weight gain until 36 weeks of gestation (light or appropriate for term equivalent age; LTEA or ATEA) predicts later growth, bone mineral density (BMD), abdominal obesity, or metabolic health outcomes such as insulin resistance, relative to term infants, during the first three years of life. Target in-hospital energy and protein intake was not achieved. Growth in weight, length and head circumference, mid arm circumference, adiposity, fat free mass (FFM), and bone mineralization in VLBW infants was less than those in term infants and influenced by nutritional status at discharge. Preterm infants had poorer motor and cognitive outcomes. Post-discharge body composition patterns indicate FFM proportional to height but lower fat mass index in LTEA preterm infants than term infants, with no evidence of increased truncal fat in preterm infants. The hypothesis of early BMD catch-up in VLBW infants after discharge was not supported by the present data. The clinical significance of these findings is unclear. The data may suggest a reduced obesity risk but an increased osteoporosis risk. Since postnatal growth restriction may have permanent negative health effects, LTEA VLBW infants would especially appear to benefit from targeted preventive interventions. Further follow-up of the infants is required.

Editorial: Light shielding of bags and tubing used for parenteral nutrition of infants.

PURPOSE OF REVIEW: In July 2019, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended light protection of all parenteral nutrition (PN) solutions containing amino acids (AA) and/or lipids, with or without admixture of vitamins or trace elements, during administration for preterm infants, term infants and children less than 2 years of age. The aim of the present paper was to review the available evidence and to provide recommendations for in hospital and home PN light protection in children. RECENT FINDINGS: Lipid emulsions and multivitamins are susceptible to photooxidation and generation of oxidation products. There is no conclusive evidence to justify recommending light protection for PN solutions without lipid emulsions and/or vitamins during administration (solutions containing e.g. AA, glucose, electrolytes, or trace elements). SUMMARY: Lipid emulsions and/or vitamins containing PN solutions should be protected from light during administration (bags and tubing) to reduce the generation of oxidation products.

Safety and Parental Satisfaction With Early Discharge of Preterm Infants on Nasogastric Tube Feeding and Outpatient Clinic Follow-Up.

Aim: To evaluate our early discharge program of preterm infants with nasogastric tube feeding (NTF) and close outpatient clinic follow-up with regard to safety, parent satisfaction and parental stress level. Methods: 119 preterm infants were discharged on NTF from our tertiary care neonatal unit (median gestational age 31.0 weeks, median birthweight 1,650 g). Parental satisfaction was evaluated by a standardized questionnaire. For safety assessment growth until term equivalent age and re-hospitalizations within 2 months after discharge were evaluated. Results: Infants were discharged home at a median gestational age of 35.4 weeks after a median hospital stay of 22 days. Follow up was attained in 95 of 104 parent-infant dyads. The majority of parents (94%) reported that they had made the right decision in taking their infant home on NTF. At the time of discharge 86% of parents felt very well-prepared to perform NTF. 70% Of parents rated their stress level at home as low (≤2 out of 5). There were no NTF associated readmissions and no growth faltering until term equivalent age. Conclusion: Early discharge of preterm infants with NTF together with outpatient clinic follow-up is very well-accepted by parents and appears to be safe.

Probiotics and Preterm Infants: A Position Paper by the European Society for Paediatric Gastroenterology Hepatology and Nutrition Committee on Nutrition and the European Society for Paediatric Gastroenterology Hepatology and Nutrition Working Group for Probiotics and Prebiotics.

More than 10,000 preterm infants have participated in randomised controlled trials on probiotics worldwide, suggesting that probiotics in general could reduce rates of necrotising enterocolitis (NEC), sepsis, and mortality. Answers to relevant clinical questions as to which strain to use, at what dosage, and how long to supplement are, however, not available. On the other hand, an increasing number of commercial products containing probiotics are available from sometimes suboptimal quality. Also, a large number of units around the world are routinely offering probiotic supplementation as the standard of care despite lacking solid evidence. Our recent network meta-analysis identified probiotic strains with greatest efficacy regarding relevant clinical outcomes for preterm neonates. Efficacy in reducing mortality and morbidity was found for only a minority of the studied strains or combinations. In the present position paper, we aim to provide advice, which specific strains might potentially be used and which strains should not be used. In addition, we aim to address safety issues of probiotic supplementation to preterm infants, who have reduced immunological capacities and occasional indwelling catheters. For example, quality reassurance of the probiotic product is essential, probiotic strains should be devoid of transferable antibiotic resistance genes, and local microbiologists should be able to routinely detect probiotic sepsis. Provided all safety issues are met, there is currently a conditional recommendation (with low certainty of evidence) to provide either Lactobacillus rhamnosus GG ATCC53103 or the combination of Bifidobacterium infantis Bb-02, Bifidobacterium lactis Bb-12, and Streptococcus thermophilus TH-4 in order to reduce NEC rates.

Vegetarian diets in childhood and adolescence : Position paper of the nutrition committee, German Society for Paediatric and Adolescent Medicine (DGKJ).

In Western countries, vegetarian diets are associated with lower intakes of energy, saturated fatty acids and animal protein and higher intakes of fibre and phytochemicals, compared to omnivorous diets. Whether the corresponding health benefits in vegetarians outweigh the risks of nutrient deficiencies has not been fully clarified. It should be noted that vegetarians often have a higher socioeconomic status, follow a more health-conscious lifestyle with higher physical activity, and refrain from smoking more often than non-vegetarians. The nutritional needs of growing children and adolescents can generally be met through a balanced, vegetable-based diet; however, due to their higher nutrient requirements per kilogramme of body weight, vegetarian children have a higher risk for developing nutrient deficiencies than adults. With a vegetarian diet, the mean intakes of some nutrients, such as the omega-3 fatty acid docosahexaenoic acid (DHA), are lower than in omnivores or those eating fish. For other nutrients, such as iron and zinc, the bioavailability from vegetable foodstuffs is reduced when the intake of phytates and fibre is high; thus, the prevalence of iron deficiency can be increased despite high vitamin C intake. In addition, vitamin B12 is only found in animal-source foods. Vitamin B12 should be supplemented in people of all age groups who follow a strict vegan diet without consuming animal products. A vegetarian diet in childhood and adolescence requires good information and supervision by a paediatrician, if necessary, in cooperation with an appropriately trained dietary specialist.

Vitamin D supplementation after the second year of life: joint position of the Committee on Nutrition, German Society for Pediatric and Adolescent Medicine (DGKJ e.V.), and the German Society for Pediatric Endocrinology and Diabetology (DGKED e.V.).

BACKGROUND: Low vitamin D serum concentrations have been associated with rickets and other disorders in observational studies. Since vitamin D serum concentrations in children and adolescents are frequently below reference values, it is debated whether vitamin D should be supplemented after infancy. METHODS: The effects of vitamin D supplementation in children > 2 years of age are analyzed based on a literature review of randomized controlled trials (RCTs). RESULTS: Vitamin D supplementation can potentially reduce the risk for influenza infections and improve asthma bronchiale exacerbation; however, it has no impact on asthma bronchiale severity. Vitamin D supplementation has no relevant effect on attention-deficit/hyperactivity disorders, cardiac failure, hypertension, or incidence of type II diabetes mellitus. Vitamin D supplementation has no effect on the rate of multiple sclerosis relapses, but on the number of new lesions detected by MRI. For other endpoints, RCTs are lacking. CONCLUSION: Based on currently available studies, routine vitamin D supplementation is not be recommended for children aged > 2 years, even when they have serum concentrations below reference values. Routine vitamin D supplementation is not recommended in children who do not have risk factors and chronic diseases which are associated with calcium or vitamin D resorption disorders.