Feeding intolerance scoring system in very preterm and very low birth weight infants using clinical and ultrasound findings.

Very preterm infants are at a high risk of developing feeding intolerance; however, there are no widely accepted definitions of feeding intolerance. This study aimed to develop a scoring system for feeding intolerance in very preterm infants by combining clinical symptoms and ultrasonography (US) findings. This prospective cohort study included very preterm and/or very low birth weight infants. We defined feeding intolerance as the inability to achieve full feeding (150 ml/kg/day) by 14 days of life. The clinical findings included vomiting, abdominal distention, and gastric fluid color. US findings included intestinal peristaltic frequency, gastric residual volume, peak systolic velocity, and the resistive index of the superior mesenteric artery. We conducted multivariate analyses to evaluate the potential predictors and developed a scoring system to predict feeding intolerance. A total of 156 infants fulfilled the eligibility criteria; however, 16 dropped out due to death. The proportion of patients with feeding intolerance was 60 (42.8%). Based on the predictive ability, predictors of feeding intolerance were determined using data from the US at 5-7 days of age. According to multivariate analysis, the final model consisted of 5 predictors: abdominal distention (score 1), hemorrhagic gastric fluid (score 2), intestinal peristaltic movement ≤18x/2 min (score 2), gastric fluid residue >25% (score 2), and resistive index >0.785 (score 2). A score equal to or above 5 indicated an increased risk of feeding intolerance with a positive predictive value of 84.4% (95% confidence interval:73.9-95.0) and a negative predictive value of 76.8% (95% confidence interval:68.4-85.3). The scoring system had good discrimination (area under the receiver operating characteristic curve:0.90) and calibration (p = 0.530) abilities. This study developed an objective, accurate, easy, and safe scoring system for predicting feeding intolerance based on clinical findings, 2D US, and color Doppler US.

Near adult height and BMI changes in growth hormone treated short children with Noonan syndrome: the Belgian experience.

Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no mutation group). Results After a median (P10; P90) duration of 5.4 (2.2-10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.4; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta=0.90, p<0.001), mid-parental height SDS (beta =0.27; p=0.005), birth weight SDS (beta=0.15; p=0.051), age at start (beta=0.07; p=0032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p<0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.

Nutritional management of high-output ileostomies in paediatric patients is vital and more evidence-based guidelines are needed.

AIM: Paediatric patients with high-output ileostomies (HOI) face an elevated risk of complications. This study aimed to comprehensively review the existing literature and offer nutritional management recommendations for paediatric patients with an HOI. METHODS: PubMed and Embase were searched for relevant English or French language papers up to 31 June 2022. The emphasis was placed on studies involving paediatric ileostomy patients, but insights were obtained from adult literature and other intestinal failure pathologies when these were lacking. RESULTS: We identified 16 papers that addressed nutritional issues in paediatric ileostomy patients. Currently, no evidence supports a safe paediatric HOI threshold exceeding 20 mL/kg/day on two consecutive days. Paediatric HOI patients were at risk of dehydration, electrolyte disturbances, micronutrient deficiencies and growth failure. The primary dietary choice for neonates is bolus feeding with breastmilk. In older children, an enteral fluid restriction should be installed favouring isotonic or slightly hypotonic glucose-electrolyte solutions. A diet that is high in calories, complex carbohydrates and proteins, low in insoluble fibre and simple carbohydrates, and moderate in fat is recommended. CONCLUSION: Adequate nutritional management is crucial to prevent complications in children with an HOI. Further research is needed to establish more evidence-based guidelines.

Clinical performance of the infant nutrition early warning score in routine practice across four international clinical settings in Europe: A study by the ESPGHAN special interest group in clinical malnutrition.

There is a scarcity of nutritional screening tools for use in infants (<1 year). The infant Nutrition Early Warning Score (iNEWS) has been developed to identify infants who need further dietetic review. We introduced the iNEWS into clinical practice and evaluated its performance in Scotland, Belgium, Athens and Bulgaria. Of the 352 infants screened, 72 (20%) were placed in the high iNEWS category, and of these, 70 (97%) were reviewed by a hospital dietitian. iNEWS produced a true positive rate of 80% which increased to 96% after accounting for anticipated misclassified cases due to prematurity. In Belgium, false positive screens had a shorter length of stay (p = 0.014). Otherwise, misclassification was not related to a specific iNEWS component. This study corroborates previous research, underscoring the validity of iNEWS as a dietetic referral tool and demonstrating that it can be integrated into "real-world" clinical practice across international settings with diverse healthcare resources.

Development of the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC) using a modified Delphi technique.

One in three hospitalized children have disease-related malnutrition (DRM) upon admission to hospital, and all children are at risk for further nutritional deterioration during hospital stay; however, systematic approaches to detect DRM in Canada are lacking. To standardise and improve hospital care, the multidisciplinary pediatric working group of the Canadian Malnutrition Taskforce aimed to develop a pediatric, inpatient nutritional care pathway based on available evidence, feasibility of resources, and expert consensus. The working group (n = 13) undertook a total of four meetings: an in-person meeting to draft the pathway based on existing literature and modelled after the Integrated Nutrition Pathway for Acute Care (INPAC) in adults, followed by three online surveys and three rounds of online Delphi consensus meetings to achieve agreement on the draft pathway. In the first Delphi survey, 32 questions were asked, whereas in the second and third rounds 27 and 8 questions were asked, respectively. Consensus was defined as any question/issue in which at least 80% agreed. The modified Delphi process allowed the development of an evidence-informed, consensus-based pathway for inpatients, the Pediatric Integrated Nutrition Pathway for Acute Care (P-INPAC). It includes screening <24 h of admission, assessment with use of Subjective Global Nutritional Assessment (SGNA) <48 h of admission, as well as prevention, and treatment of DRM divided into standard, advanced, and specialized nutrition care plans. Research is necessary to explore feasibility of implementation and evaluate the effectiveness by integrating P-INPAC into clinical practice.

Cow's Milk-related Symptom Score (CoMiSS) values in presumed healthy European infants aged 6-12 months: a cross-sectional study.

The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating cow's milk-related symptoms. Previous studies have focused on providing CoMiSS values for healthy and symptomatic infants aged 0-6 months. However, there is a notable gap in the literature concerning CoMiSS values for infants older than 6 months. This cross-sectional study aimed to determine CoMiSS values in presumed healthy infants who have completed 6 months and are up to 12 months old, hereafter referred to as 6 to 12 months old. Physicians from six European countries prospectively determined CoMiSS values in infants attending well-child clinics. Exclusion criteria included preterm delivery, acute or chronic disease, and the consumption of a therapeutic formula, dietary supplements (except vitamins), or medication. The following information was collected: gestational age, gender, age, type of feed (breast milk or infant formula), and complementary feeding. Descriptive statistics were summarized with mean and standard deviation for normally distributed continuous variables, median and IQR for non-normally distributed variables, and differences in CoMiSS values were analyzed with appropriate tests. Data from 609 infants were obtained. The overall median (Q1-Q3) CoMiSS values were 3 (1-5). Significant differences were found across age groups (p < 0.001), but not across groups based on gender (p = 0.551) or feeding type (p = 0.880).   Conclusions: This study provided CoMiSS values in presumed healthy infants aged 6-12 months. Additional studies should be conducted to establish the use of CoMiSS to assess cow's milk-related symptoms in infants 6 months and older. What is Known: • The Cow's Milk-related Symptom Score (CoMiSS) is an awareness tool for evaluating symptoms related to cow's milk. • CoMiSS values for presumed healthy infants aged 0-6 months infants are already available. What is New: • CoMiSS values in European infants aged 6-12 months are provided. • These CoMiSS values differed across various age groups but not across groups based on gender or feeding type.

Malnutrition in Institutionalized and Non-Institutionalized Neurologically Impaired Children in Bulgaria.

INTRODUCTION: The nutritional status of children with neurological impairment affects their health and quality of life. Bulgaria has many abandoned disabled children in residential homes. Lack of parental care puts them at risk for poor growth, suboptimal nutrition, and physical and mental development. Our study aims to identify factors associated with poor nutrition in Bulgarian children with neurological impairment living in different environments. METHODS: From January to December 2017, a cross-sectional study was conducted in northeastern Bulgaria. We recruited 109 residential and nonresidential children. The study included demographics, medical history, anthropometric measurements, biochemical tests, nutritional assessment, and gastrointestinal signs and symptoms. Data were analyzed with Jamovi 2.2.5 at a 0.05 significance level. Logistic regression was used to predict wasting in both environmental settings. RESULTS: About 70% of the neurologically impaired children living in residential settings have malnutrition based on weight-for-age Z-score, compared to 25% of the non-residential children. Prematurity, low gross motor function (as measured by the gross motor function classification system), pureed food consumption, birth before 37 weeks, and living in residential care homes are linked to poor nutrition. CONCLUSION: Neurologically impaired children have a poor nutritional state, especially those living in residential homes. The study underscores the pressing need for the allocation of additional nutrition resources to effectively address the nutritional and developmental needs of children with neurological disabilities in Bulgaria.

How Best to Estimate Insertion Length of Multichannel Intraluminal Impedance pH Probes in Children.

OBJECTIVE: To assess the reliability of the KidZ Health Castle formula (KHC-F) to determine the correct probe position of a multichannel intraluminal impedance pH. STUDY DESIGN: A retrospective cohort study was performed on 222 children between 1 month and 18 years of age undergoing multichannel intraluminal impedance pH. The primary outcome was the comparison of the pH sensor location determined by the KHC-F with the radiological target position. The margin of error was defined as 1 cm from the target position. Performance of the KHC-F and existing formulas was determined via the percentage with a correct position, mean error, 95% limits of agreement (Bland-Altman plots), and Spearman correlation. A post hoc analysis was performed with an updated KHC-F v2, subtracting -0.5 cm from the KHC-F. RESULTS: Positioning with KHC-F was correct in two-thirds of the participants, with a very strong correlation (ρ = 0.91) with the target position. Bland-Altman plots showed good agreement between KHC-F and target position (mean error of -0.44 cm, lower limit -3.2 cm, upper limit 2.3 cm). A post hoc analysis with the KHC-F v2 showed a correct positioning in 74% of patients. Comparison with other formulas showed a stronger performance of KHC-F and KHC-F v2 on correct positioning, mean error, and 95% limits of agreement. CONCLUSIONS: The KHC-F leads to reliable results. KHC-F v2 outperforms all other existing formulas in children, thereby reducing the need for repositioning and the amount of x-ray exposure. The age distribution of the sample may be a limitation, as well as the retrospective nature of the study.

Catch-Up Growth in Infants and Young Children With Faltering Growth: Expert Opinion to Guide General Clinicians.

Faltering growth (FG) is a problem regularly seen by clinicians in infants and young children (<2 years of age). It can occur due to non-disease-related and disease-related causes and is associated with a wide range of adverse outcomes, including shorter-term effects such as impaired immune responses and increased length of hospital stay, and longer-term consequences, including an impact on schooling and cognitive achievements, short stature, and socioeconomic outcomes. It is essential to detect FG, address underlying causes and support catch-up growth where this is indicated. However, anecdotal reports suggest misplaced fear of promoting accelerated (too rapid) growth may deter some clinicians from adequately addressing FG. An invited international group of experts in pediatric nutrition and growth reviewed the available evidence and guidelines on FG resulting from disease-related and non-disease-related effects on nutritional status in healthy term and small for gestational age infants and children up to the age of 2 years in low-, middle-, and high-income countries. Using a modified Delphi process, we developed practical consensus recommendations to provide clarity and practical recommendations for general clinicians on how FG should be defined in different young child populations at risk, how FG should be assessed and managed, and the role of catch-up growth after a period of FG. We also suggested areas where further research is needed to answer remaining questions on this important issue.

Generation and application of a convolutional neural networks algorithm in evaluating stool consistency in diapers.

AIM: The aim of the study was to develop a deep convolutional neural networks (CNNs) algorithm for automated assessment of stool consistency from diaper photographs and test its performance under real-world conditions. METHODS: Diaper photographs were enrolled via a mobile phone application. The stool consistency was assessed independently according to the Brussels Infant and Toddler Stool Scale (BITSS) by paediatricians. These images were randomised into a training data set and a test data set. After training and testing, the new algorithm was used under real-world conditions by parents. RESULTS: There was an overall agreement of 92.9% between paediatricians and the CNN-generated algorithm. Post hoc classification into the validated 4 categories of the BITSS yielded an agreement of 95.4%. Spearman correlation analysis across the ranking of 7 BITSS photographs and validated 4 categories showed a significant correlation of rho = 0.93 (95% CI, 0.92, 0.94; p < 0.001) and rho = 0.92 (95% CI, 0.90, 0.93; p < 0.001), respectively. The real-world application yielded further insights into changes in stool consistency between age categories and mode of feeding. CONCLUSION: The new CNN-based algorithm is able to reliably identify stool consistency from diaper photographs and may support the communication between parents and paediatricians.

Early-Life Gut Health Indicators and Reported Prevalence of Infant Functional Constipation by Healthcare Professionals.

A healthy gut during early childhood is important. However, it seems that there are no standard indicators used to assess it. Healthcare professionals (HCPs) were asked via an electronic survey question about gut health indicators (GHIs) for infants and toddlers, in addition to an estimated prevalence of infant's functional constipation (FC) and its management. HCPs from eight countries participated in the survey (Russia (66.0%, 1449), Indonesia (11.0%, 242), Malaysia (6.0%, 132), Mexico (5.7%, 125), KSA (5.1%, 113), Turkey (3.0%, 66), Hong Kong (2.2%, 49), and Singapore (1.0%, 23)). The 2199 participating respondents were further classified into three continents (Asia (20.2%), Europe (68.8%), and others (11.0%)). Most of them were pediatricians (80.3%), followed by pediatric gastroenterologists (7.0%), general practitioners (6.4%), and others (6.3%). The top three preferred GHIs were similar for infants and toddlers: an absence of gastrointestinal (GI) symptoms, effective digestion/absorption as assessed by normal growth, and a general feeling of well-being. The absence of GI-related infection was the least preferred indicator. Most of the respondents reported the prevalence of FC among infants was less than 5%, with the peak incidence between the ages of 3 and 6 months. The reported choices of intervention to manage FC in infants were a change to a specific nutritional solution from a standard formula (40.2%), parental reassurance (31.7%), and lactulose (17.0%). Conclusion: The HCPs in the eight countries preferred the absence of GI symptoms, normal growth for effective digestion and absorption, and general well-being as the gut health indicators in infants and toddlers. The reported prevalence of FC in infants was less than 5%.

Use of a combined transient elastography and biochemical strategy to determine liver fibrosis in pediatric intestinal failure.

BACKGROUND & AIMS: Non-invasive monitoring of intestinal failure (IF) associated liver disease is an ongoing challenge in children with IF. Our objective was to develop a combined algorithm of clinical, transient elastography (TE) and biochemical parameters to identify liver fibrosis in this population. METHODS: A retrospective cohort study of IF patients followed by our intestinal rehabilitation program between November 2015 to October 2019. Patients with a liver biopsy and TE were included. Demographic and liver function tests were collected. Fibrosis on liver biopsies was graded using the modified Scheuer score. Decision tree based algorithms classified low (F0-F1) versus high (F2-F4) fibrosis scores based on a combination of TE, biochemical and demographic parameters, using 6-fold classification error, sensitivity and specificity cross-validation (CV) scores. RESULTS: 42 patients (74% male, median age 7.6 (4.6; 42.7) months) were evaluated. Median length of PN therapy was 182 (121; 556) days. High fibrosis was present in 40.5% with a median TE of 12.1 (6.7; 12.9) kPa in high fibrosis children. An algorithm, based on cut-off values for TE of 11.3 kPa and AST of 40 U/L, and grouping of the underlying etiology resulted in a correct classification of 88.1% of the pathology scores; with sensitivity 0.82 (95% CI 0.57; 0.96), specificity 0.92 (95% CI 0.74; 0.99), positive predictive value 0.88 (95% CI 0.64; 0.96) and negative predictive value 0.88 (95% CI 0.73; 0.96). The CV classification error was 28.6%, CV sensitivity 72.2% and CV specificity 75.5%. CONCLUSIONS: This algorithm shows promising results that could simplify non-invasive monitoring of liver fibrosis in children with IF. Validation in additional IF cohorts is needed.

Reported Prevalence and Nutritional Management of Functional Constipation among Young Children from Healthcare Professionals in Eight Countries across Asia, Europe and Latin America.

Background: The prevalence of functional constipation (FC) among children varies widely. A survey among healthcare professionals (HCPs) was conducted to better understand the HCP-reported prevalence and (nutritional) management of FC in children 12−36 months old. Methods: An anonymous e-survey using SurveyMonkey was disseminated via emails or WhatsApp among HCPs in eight countries/regions. Results: Data from 2199 respondents were analyzed. The majority of the respondents (65.9%) were from Russia, followed by other countries (Indonesia (11.0%), Malaysia (6.0%)), Mexico, KSA (5.1% (5.7%), Turkey (3.0%), Hong Kong (2.2%), Singapore (1.1%)). In total, 80% of the respondents (n = 1759) were pediatricians. The prevalence of FC in toddlers was reported at less than 5% by 43% of the respondents. Overall, 40% of the respondents reported using ROME IV criteria in > 70% of the cases to diagnose FC, while 11% never uses Rome IV. History of painful defecation and defecations < 2 x/week are the two most important criteria for diagnosing FC. In total, 33% of the respondents reported changing the standard formula to a specific nutritional solution, accompanied by parental reassurance. Conclusion: The most reported prevalence of FC in toddlers in this survey was less than five percent. ROME IV criteria are frequently used for establishing the diagnosis. Nutritional management is preferred over pharmacological treatment in managing FC.

Intra-rater Variability of the Brussels Infants and Toddlers Stool Scale (BITSS) Using Photographed Stools.

OBJECTIVES: The Brussels Infants and Toddlers Stool Scale (BITSS) was developed for the assessment of stool consistency in non-toilet-trained children. This study aimed to (1) investigate the intra-rater reliability of the BITSS among health care professionals (HCPs) and caregivers (CGs); (2) study a potential learning curve; (3) explore the impact of photo quality on intra-rater reliability. METHODS: Photos of diapers containing stool were assessed twice by 4 HCP (2432 photos) and 8 CGs (492 photos) using the BITTS. Intra-rater reliability was calculated by the percentage of exact agreement and a κ-value. A learning effect and the impact of photo quality was explored using mixed linear model and generalized estimating equations. RESULTS: HCPs generated 24,320 stool consistency ratings: 12.1% were scored as watery, 31.0% loose, 29.4% formed, and 27.6% hard. CGs performed 7872 ratings: 9.2% classified as watery, 34.6% loose, 28.9% formed, and 27.3% hard. Intra-rater reliability (κ) for HCPs ranged from 0.64 [95% confidence interval (CI) = 0.61-0.66] to 0.78 (95% CI = 0.76-0.80) and from 0.68 (95% CI = 0.63-0.73) to 0.94 (95% CI = 0.91-0.97) in the CG group. Both groups had <1% improvement in the odds of identical classification per 50 photos. The percentage of absolute agreement was higher in photos rated as good quality than those that were not (HCPs: 80.3% vs 69.5%, P < 0.001; CGs: 90.4% vs 86.3%, P < 0.001). CONCLUSIONS: The BITSS has an excellent intra-rater reliability for the stool consistency scoring of photographs of stools in diapers, but can be influenced by photo quality. A clinically meaningless learning effect was found.

Characterization of Eosinophilic Esophagitis From the European Pediatric Eosinophilic Esophagitis Registry (pEEr) of ESPGHAN.

OBJECTIVES: Few pediatric data on phenotypic aspects of eosinophilic esophagitis (EoE) are available. The pEEr registry was developed to prospectively characterize children with EoE from Europe and Israel. METHODS: pEEr is an ongoing prospective registry enrolling children with esophageal eosinophilia (≥15 eos/HPF). Anonymized data were collected from 19 pediatric centers. Data regarding demographics, clinical manifestations, endoscopy, histology, and therapies were collected. RESULTS: A total of 582 subjects (61% male) were analyzed. The median age at diagnosis was 10.5 years [interquartile range (IQR): 5.7-17.7], whereas the age at symptom onset was 9.2 years (IQR: 4.3-16.4), resulting in a median diagnostic delay of 1.2 years (IQR: 0.7-2.3). The diagnostic delay was longer below age <6 years. Shorter diagnostic delays were associated with the presence of food allergy or a family history for EoE. Symptoms varied by age with dysphagia and food impaction more common in adolescents, while vomiting and failure to thrive more common in younger children ( P < 0.001). Among endoscopic findings, esophageal rings were more common in adolescents, whereas exudates were more frequent in younger children( P < 0.001). Patients who responded to proton pump inhibitors (PPIs) were more likely to be older, males, and less often presented severe endoscopic findings. Patients unresponsive to PPIs received topical steroids (40%), elimination diet (41%), or a combined therapy (19%). CONCLUSIONS: EoE findings vary according to age in pediatric EoE. Young children are commonly characterized by non-specific symptoms, atopic dermatitis, food allergy, and inflammatory endoscopic lesions. Adolescents usually have dysphagia or food impaction, fibrostenotic lesions, and a better PPI response.

A Practical Approach to Identifying Pediatric Disease-Associated Undernutrition: A Position Statement from the ESPGHAN Special Interest Group on Clinical Malnutrition.

ABSTRACT: Disease-associated undernutrition (DAU) is still common in hospitalized children and is generally accepted to be associated with adverse effects on disease outcomes; hence making proper identification and assessment essential in the management of the sick child. There are however several barriers to routine screening, assessment, and treatment of sick children with poor nutritional status or DAU, including limited resources, lack of nutritional awareness, and lack of agreed nutrition policies. We recommend all pediatric facilities to 1) implement procedures for identification of children with (risk of) DAU, including nutritional screening, criteria for further assessment to establish diagnosis of DAU, and follow-up, 2) assess weight and height in all children asa minimum, and 3) have the opportunity for children at risk to be assessed by a hospital dietitian. An updated descriptive definition of pediatric DAU is proposed as "Undernutrition is a condition resulting from imbalanced nutrition or abnormal utilization of nutrients which causes clinically meaningful adverse effects on tissue function and/or body size/composition with subsequent impact on health outcomes." To facilitate comparison of undernutrition data, it is advised that in addition to commonly used criteria for undernutrition such as z score < -2 for weight-for-age, weight-for-length, or body mass index <-2, an unintentional decline of >1inthese z scores over time should be considered as an indicator requiring further assessment to establish DAU diagnosis. Since the etiology of DAU is multifactorial, clinical evaluation and anthropometry should ideally be complemented by measurements of body composition, assessment of nutritional intake, requirements, and losses, and considering disease specific factors.

The Diverse Phenotype of Intestinal Dysmotility Secondary to ACTG2-related Disorders.

BACKGROUND AND AIMS: The initial description of a heterozygous dominant ACTG2 variant in familial visceral myopathy was followed by the identification of additional variants in other forms of intestinal dysmotility disorders. we aimed to describe the diverse phenotype of this newly reported and rare disease. METHODS: Report of 4 new patients, and a systematic review of ACTG2-related disorders. we analyzed the population frequency and used in silico gene damaging predictions. Genotype-phenotype correlations were explored. RESULTS: One hundred three patients (52% girls), from 14 publications, were included. Twenty-eight unique variants were analyzed, all exceedingly rare, and 27 predicted to be highly damaging. The median Combined Annotation Dependent Depletion (CADD) score was 29.2 (Interquartile range 26.3-29.4). Most patients underwent abdominal surgery (66%), about half required intermittent bladder catheterization (48.5%), and more than half were parenteral nutrition (PN)-dependent (53%). One-quarter of the patients died (25.7%), and 6 required transplant (5.8%). Girls had a higher rate of microcolon (P  = 0.009), PN dependency (P = 0.003), and death/transplant (P = 0.029) compared with boys, and early disease onset (<2 years of age) was associated with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) features. There was no statistical association between disease characteristics and CADD scores. CONCLUSIONS: Damaging ACTG2 variants are rare, often associated with MMIHS phenotype, and overall have a wide phenotypic variation. Symptoms usually present in the perinatal period but can also appear at a later age. The course of the disease is marked by frequent need for surgical interventions, PN support, and mortality. Poor outcomes are more common among girls with ACTG2 variants.

Plant-Based Formulas and Liquid Feedings for Infants and Toddlers.

Exclusive breastfeeding is the recommended feeding for all infants. Recent research has focused on the importance of balanced feeding during the first 1000 days, starting at conception with a balanced diet of the pregnant woman, up to the age of two years. The following step, a balanced diet after the age of two years is a challenge, as the dietary intake becomes more diversified. The role of young-child formula in this process is debated. This paper discusses the use of planted-based drinks, since they are a valuable and progressively more popular alternative for cow's milk, if nutritionally adapted to the requirements of toddlers. Plant-based drinks are per definition lactose free.