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.

The role of nutritional interventions in the prevention and treatment of chronic lung disease of prematurity.

Chronic lung disease of prematurity or bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Nutrition may affect incidence and severity of BPD. In this context, the Section on Nutrition, Gastroenterology and Metabolism, the Pulmonary Section of the European Society for Paediatric Research (ESPR) and SPR have joined forces to review the current knowledge on nutritional issues related to BPD. The aim of this narrative review is to discuss the clinical implications for nutritional practice. Nutrient deficiencies may influence pathogenesis of BPD. Adequate nutrition and growth can play a crucial role in the prevention of and recovery from BPD. Optimal nutrition strategy is an important principle, especially in the early postnatal period. As optimal energy intake in infants at risk of BPD or with evolving BPD is not yet defined, further research with well-designed studies on nutritional strategies for preterm infants with BPD is urgently needed. IMPACT: Based on current evidence it seems reasonable to recommend that BPD diagnosed infants should receive an energy supply ranging from 120 to 150 Kcal/kg/d. Exclusive MOM feed with adequate fortification should be encouraged as this is associated with a significant reduction in the risk of BPD. Suboptimal nutritional delivery is often seen in preterm infants with BPD compared to controls.

Evidence on docosahexaenoic acid and arachidonic acid supplementation for preterm infants.

PURPOSE OF REVIEW: For many decades, docosahexaenoic acid (DHA) supplementation was tested in premature infants to achieve an intake equivalent to the average level in breast milk, but this approach has led to conflicting results in terms of development and health outcomes. Higher doses of DHA closer to fetal accumulation may be needed. RECENT FINDINGS: The efficacy of DHA supplementation for preterm infants at a dose equivalent to the estimated fetal accumulation rate is still under investigation, but this may be a promising approach, especially in conjunction with arachidonic acid supplementation. Current data suggest benefit for some outcomes, such as brain maturation, long-term cognitive function, and the prevention of retinopathy of prematurity. The possibility that supplementation with highly unsaturated oils increases the risk of neonatal morbidities should not be ruled out, but current meta-analyzes do not support a significant risk. SUMMARY: The published literature supports a DHA intake in preterm infants that is closer to the fetal accumulation rate than the average breast milk content. Supplementation with DHA at this level in combination with arachidonic acid is currently being investigated and appears promising.

Lung function in preterm infants at 3 months corrected age after neonatal LC-PUFA supplementation.

OBJECTIVE: To test the hypothesis that long-chain polyunsaturated fatty acid (LC-PUFA) supplementation improves lung function at 3 months corrected age (CA) compared with standard treatment in very preterm infants. We also aimed to investigate the association between bronchopulmonary dysplasia (BPD), longitudinal growth, and lung function at 3 months CA. METHODS: A secondary analysis from the ImNuT trial, in which 121 infants with gestational age <29 weeks were randomized to a daily supplement with arachidonic acid (ARA) and docosahexaenoic acid (DHA) (ARA:DHA group) or MCT-oil (control group) from birth up to 36 weeks postmenstrual age (PMA). Lung function was assessed at 3 months CA by tidal flow volume loops and the outcomes were the ratio of time to peak tidal expiratory flow to expiratory time (tPTEF /tE ) and tidal volume (VT ) per body weight (mL/kg). RESULTS: Thirty-nine infants in the ARA:DHA group versus 51 in the control group had a successful lung function test. There was no mean difference (MD) in tPTEF /tE ratio (MD: 0.01, 95% confidence interval [CI]: -0.04 to 0.05; p = .77) or VT (MD: 0.09 mL/kg, 95% CI: -0.79 to 0.62; p = .81) between the study groups. The multivariable regression model showed that BPD was associated with tPTEF /tE ratio ≤ 0.25 (p = .03) and that an increase in z score for length after 36 weeks PMA correlated positively with VT (mL/kg) (p = .03). CONCLUSION: Neonatal LC-PUFA supplementation did not improve lung function at 3 months CA in very preterm infants. BPD was independently associated with reduced lung function, while improved linear growth correlated with higher tidal volumes.

Arachidonic and docosahexaenoic acid supplementation and brain maturation in preterm infants; a double blind RCT.

BACKGROUND: Arachidonic acid (ARA) and docosahexaenoic acid (DHA) are important structural components of neural cellular membranes and possess anti-inflammatory properties. Very preterm infants are deprived of the enhanced placental supply of these fatty acids, but the benefit of postnatal supplementation on brain development is uncertain. The aim of this study was to test the hypothesis that early enteral supplementation with ARA and DHA in preterm infants improves white matter (WM) microstructure assessed by diffusion-weighted MRI at term equivalent age. METHODS: In this double-blind, randomized controlled trial, infants born before 29 weeks gestational age were allocated to either 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) or medium chain triglycerides (control). Supplements were started on the second day of life and provided until 36 weeks postmenstrual age. The primary outcome was brain maturation assessed by diffusion tensor imaging (DTI) using Tract-Based Spatial Statistics (TBSS) analysis. RESULTS: We included 120 infants (60 per group) in the trial; mean (range) gestational age was 26+3 (22+6 - 28+6) weeks and postmenstrual age at scan was 41+3 (39+1 - 47+0) weeks. Ninety-two infants underwent MRI imaging, and of these, 90 had successful T1/T2 weighted MR images and 74 had DTI data of acceptable quality. TBSS did not show significant differences in mean or axial diffusivity between the groups, but demonstrated significantly higher fractional anisotropy in several large WM tracts in the ARA:DHA group, including corpus callosum, the anterior and posterior limb of the internal capsula, inferior occipitofrontal fasciculus, uncinate fasciculus, and the inferior longitudinal fasciculus. Radial diffusivity was also significantly lower in several of the same WM tracts in the ARA:DHA group. CONCLUSION: This study suggests that supplementation with ARA and DHA at doses matching estimated fetal accretion rates improves WM maturation compared to control treatment, but further studies are needed to ascertain any functional benefit. CLINICAL TRIAL REGISTRATION: www. CLINICALTRIALS: gov; ID:NCT03555019.

Effect of arachidonic and docosahexaenoic acid supplementation on quality of growth in preterm infants: A secondary analysis of a randomized controlled trial.

BACKGROUND & AIMS: A balanced supply of arachidonic acid (ARA) and docosahexaenoic acid (DHA) may be crucial for quality of growth in preterm infants. This secondary analysis of a randomized controlled trial aimed to determine the effect of enhanced ARA and DHA supplementation on growth and body composition in infants born before 29 weeks of gestation. Furthermore, we aimed to study associations between human milk feeding, growth patterns and body composition. METHODS: The ImNuT-trial randomized 121 infants to receive a daily supplement with medium chain triglycerides (control) or 100 mg/kg ARA and 50 mg/kg DHA (ARA:DHA group) from the second day of life until 36 weeks postmenstrual age. Growth and body composition were evaluated up to 3 months corrected age. RESULTS: The ARA:DHA group showed better linear growth from birth to term equivalent age compared to the control group; mean difference in z score change from birth for length was 0.74 ([95% CI, 0.17-1.3]; p = 0.010). There were no differences in growth and body composition outcomes at 3 months corrected age between the groups. An increase in z score for weight after 36 weeks postmenstrual age and breastfeeding at 3 months corrected age were the strongest positive predictors of fat mass% at 3 months corrected age (both, p < 0.001). CONCLUSION: Early enhanced supplementation of ARA and DHA may be beneficial with respect to somatic growth in very preterm infants. CLINICAL TRIAL REGISTRATION: The trial has been registered on www. CLINICALTRIALS: gov, ID: NCT03555019.

Inter-site generalizability of EEG based age prediction algorithms in the preterm infant.

Objective. To overcome the effects of site differences in EEG-based brain age prediction in preterm infants.Approach. We used a 'bag of features' with a combination function estimated using support vector regression (SVR) and feature selection (filter then wrapper) to predict post-menstrual age (PMA). The SVR was trained on a dataset containing 138 EEG recordings from 37 preterm infants (site 1). A separate set of 36 EEG recordings from 36 preterm infants was used to validate the age predictor (site 2). The feature distributions were compared between sites and a restricted feature set was constructed using only features that were not significantly different between sites. The mean absolute error between predicted age and PMA was used to define the accuracy of prediction and successful validation was defined as no significant differences in error between site 1 (cross-validation) and site 2.Main results. The age predictor based on all features and trained on site 1 was not validated on site 2 (p< 0.001; MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 2.1 weeks,n= 36). The MAE was improved by training on a restricted features set (MAE site 1 = 1.0 weeks,n= 59 versus MAE site 2 = 1.1 weeks,n= 36), resulting in a validated age predictor when applied to site 2 (p= 0.68). The features selected from the restricted feature set when training on site 1 closely aligned with features selected when trained on a combination of data from site 1 and site 2.Significance. The ability of EEG classifiers, such as brain age prediction, to maintain accuracy on data collected at other sites may be challenged by unexpected, site-dependent differences in EEG signals. Permitting a small amount of data leakage between sites improves generalization, leading towards universal methods of EEG interpretation in preterm infants.

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.

Essential Fatty Acid Supplementation and Early Inflammation in Preterm Infants: Secondary Analysis of a Randomized Clinical Trial.

INTRODUCTION: Postnatal inflammation is associated with increased mortality and adverse outcomes in preterm infants. The essential fatty acids arachidonic acid (ARA) and docosahexaenoic acid (DHA) are precursors of lipid mediators with a key role in resolving inflammation. Our aim was to investigate the effect of ARA and DHA supplementation on systemic inflammation in very preterm infants and to identify clinical factors associated with early inflammation. METHODS: Secondary analysis of data from a randomized clinical trial (ImNuT study). Infants with gestational age (GA) less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (ARA:DHA group) or MCT oil (control group) from the second day of life to 36 weeks postmenstrual age. ARA, DHA, and four proinflammatory cytokines (IL-1ß, IL-6, IL-8, and TNF-α) were analyzed in repeated dried blood samples from birth to day 28 and the area under the curve (AUC) for each variable was calculated. RESULTS: The intention to treat population included 120 infants with mean (SD) GA 26.4 (1.7). The ARA:DHA group had significantly lower IL-6 levels from day 3 to day 28 compared to the control group, mean difference AUC log10 (95% CI): 0.16 (0.03-0.30) pg/mL, p = 0.018. There was no correlation between ARA or DHA blood concentrations and cytokine levels. Having a low gestational age was independently associated with increased levels of all cytokines during the first 4 weeks of life. CONCLUSIONS: Enhanced supplementation with ARA and DHA may modulate inflammation in very preterm infants.

Vitamin A Status in Preterm Infants Is Associated with Inflammation and Dexamethasone Exposure.

Vitamin A has a key role in lung development and its deficiency is associated with an increased risk of bronchopulmonary dysplasia. This secondary cohort analysis of the ImNuT trial (Immature, Nutrition Therapy NCT03555019) aimed to (1) explore vitamin A status in preterm infants <29 weeks gestation and (2) assess the influence of inflammation and postnatal dexamethasone exposure on vitamin A concentrations in blood. We report detailed information on vitamin A biochemistry, vitamin A intake, markers of inflammation and dexamethasone exposure. After four weeks of age, infants exposed to dexamethasone (n = 39) showed higher vitamin A concentrations compared to unexposed infants (n = 41); median (IQR) retinol was 1.0 (0.74, 1.5) vs. 0.56 (0.41, 0.74) µmol/L, p < 0.001. Pretreatment retinol concentrations were lower in the dexamethasone group compared to non-exposed infants (p < 0.001); 88% vs. 60% of the infants were considered deficient in vitamin A (retinol < 0.7 µmol/L) at one week of age. Small size for gestational age, mechanical ventilation and elevated levels of interleukin-6 were factors negatively associated with first-week retinol concentrations. In conclusion, preterm infants <29 weeks gestation are at risk of vitamin A deficiency despite intakes that accommodate current recommendations. The presence of inflammation and dexamethasone exposure should be considered when interpreting vitamin A status.

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.

A standardized feeding protocol ensured recommended nutrient intakes and prevented growth faltering in preterm infants < 29 weeks gestation.

BACKGROUND & AIMS: Nutrition is a cornerstone of postnatal care to prevent compromised growth and support short- and long-term health outcomes in preterm infants. We aimed to evaluate nutritional intakes and growth among infants <29 weeks gestation after implementation of a standardized feeding protocol. METHODS: This is an observational cohort secondary analysis of data from the ImNuT study (Immature, Nutrition Therapy, NCT03555019). To reduce variations in nutritional practice and ensure accommodation to current guidelines, we developed a standardized feeding protocol. Detailed information on actual nutritional intakes, growth and biochemistry was prospectively collected and assessed from birth to 36 weeks postmenstrual age (PMA). RESULTS: Median (range) gestational age and birth weight were 26+6 (22+6-28+6) weeks and 798 (444-1485) g. Energy and macronutrient intakes progressively increased from birth through transition to exclusive enteral feeds. Parenteral nutrition was weaned at median (IQR) day 11 (9, 14) when nutritional requirements were met by exclusively enteral feeds. Infants exhibited a median (IQR) weight loss of 7.8% (5.7, 11.6) and regained birth weight by day 8 (7, 11). Average velocity in weight, length and head circumference from birth to 36 weeks PMA were in accordance with target growth rates; median (IQR) 15.8 (14.7, 17.7) g/kg/d, 1.1 (0.98, 1.3) cm/week and 0.82 (0.83, 0.89) cm/week. At 36 weeks PMA, only 3% of infants exhibited moderate growth faltering (decline in weigh-for-age z score >1.2 from birth), and none severe. CONCLUSIONS: In infants <29 weeks gestation, the standardized feeding protocol was well tolerated. Nutrient intakes and growth were close to recommendations.

Effect of arachidonic and docosahexaenoic acid supplementation on respiratory outcomes and neonatal morbidities in preterm infants.

BACKGROUND & AIMS: Studies have suggested that supplementation with docosahexaenoic acid (DHA) to preterm infants might be associated with an increased risk of bronchopulmonary dysplasia (BPD). Our aim was to investigate the effect of enteral supplementation with arachidonic acid (ARA) and DHA on short-term respiratory outcomes and neonatal morbidities in very preterm infants. METHODS: This is a secondary analysis of data from the ImNuT (Immature, Nutrition Therapy) study, a randomized double blind clinical trial. Infants with gestational age less than 29 weeks were randomized to receive a daily enteral supplement with ARA 100 mg/kg and DHA 50 mg/kg (intervention) or medium chain triglycerides (MCT) oil (control), from second day of life to 36 weeks postmenstrual age. Study outcomes included duration of respiratory support, incidence of BPD and other major morbidities associated with preterm birth. RESULTS: 120 infants with mean (SD) gestational age 26.4 (1.7) weeks were randomized and allocated to either the intervention or control group. Supplementation with ARA and DHA led to a significant reduction in number of days with respiratory support (mean (95% CI) 63.4 (56.6-71.3) vs 80.6 (72.4-88.8); p = 0.03) and a lower oxygen demand (FiO2) (mean (95% CI) 0.26 (0.25-0.28) vs 0.29 (0.27-0.30); p = 0.03) compared to control treatment. There were no clinically important differences in incidence of BPD and other major morbidities between the treatment groups. CONCLUSIONS: Supplementation with ARA and DHA to preterm infants was safe and might have a beneficial effect on respiratory outcomes. CLINICAL TRIAL REGISTRATION: The trial has been registered in www. CLINICALTRIALS: gov, ID: NCT03555019.

Estimated daily intake of phthalates, parabens, and bisphenol A in hospitalised very low birth weight infants.

Very low birth weight infants (VLBW, birth weight (BW) < 1500 g) are exposed to phthalates, parabens and bisphenol A (BPA) early in life. We estimated daily intake (EDI) of these excipients in 40 VLBW infants the first and fifth week of life while hospitalised. Based on urinary samples collected in 2010, EDI was calculated and compared to the tolerable daily intake (TDI) with hazard quotients (HQs) evaluated. A HQ > 1 indicates that EDI exceeded TDI with increased risk of adverse health effects. EDI was higher in VLBW infants compared to term-born infants and older children. VLBW infants born at earlier gestational age (GA), or with lower BW, had higher EDI than infants born at later GA or with higher BW. First week median EDI for BPA was higher than TDI in 100% of infants, in 75% for di(2-ethylhexyl) phthalate (DEHP), 90% for the sum of butyl benzyl phthalate (BBzP), di-n-butyl phthalate (DnBP), DEHP and di-iso-nonyl phthalate (DiNP) = ∑BBzP+DnBP+DEHP+DiNP, and in 50% of infants for propylparaben (PrPa), indicating increased risk of adverse effects. Fifth week EDI remained higher than TDI in all infants for BPA, in 75% for DEHP and ∑BBzP+DnBP+DEHP+DiNP, and 25% of infants for PrPa, indicating prolonged risk. Maximum EDI for di-iso-butyl phthalate was higher than TDI suggesting risk of adverse effects at maximum exposure. VLBW infants born earlier than 28 weeks GA had higher EDI, above TDI, for PrPa compared to infants born later than 28 weeks GA. Infants with late-onset septicaemia (LOS) had higher EDI for DEHP, ∑BBzP+DnBP+DEHP+DiNP and BPA, above TDI, compared to infants without LOS. More 75% of the infants' EDI for DEHP and ∑BBzP+DnBP+DEHP+DiNP, 25% for PrPa, and 100% of infants' EDI for BPA, were above TDI resulting in HQs > 1, indicating increased risk of adverse health effects.

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.

Role of Dietary Factors, Food Habits, and Lifestyle in Childhood Obesity Development: A Position Paper From the European Society for Paediatric Gastroenterology, Hepatology and Nutrition Committee on Nutrition.

ABSTRACT: Childhood obesity has high societal and economic impact but current treatment approaches are sub-optimal. In the last decade, important studies have been conducted aiming to identify strategies to prevent obesity during critical periods of life. Updated recommendations for childhood obesity prevention are needed. We present data from systematic reviews and meta- analysis, randomised controlled trials (RCTs) and large observational studies, published from 2011 onwards that consider the possible role of the following factors in obesity development: breast-feeding; macronutrient composition and method of complementary feeding; parenting style; dietary patterns; sugar-sweetened beverage consumption; eating behaviour (eg, skipping breakfast, family dinners. etc); meal frequency and composition (fast foods, snacking), portion size; dietary modulators of gut microbiota (including pre-, pro-, and synbiotics); physical activity and sedentary behaviour. We used the Medline database and the Cochrane Library to search for relevant publications. Important research gaps were also identified. This position paper provides recommendations on dietary factors, food habits, and lifestyle to prevent childhood obesity development, based on the available literature and expert opinion. Clinical research and high-quality trials are urgently needed to resolve numerous areas of uncertainty.