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Arginine is an essential amino acid in neonates synthesized by gut epithelial cells and a precursor for NO that regulates vasodilatation and blood flow. Arginine supplementation has been shown to improve intestinal integrity in ischemia-reperfusion models and low plasma levels are associated with necrotizing enterocolitis. We hypothesized that enteral arginine is a specific stimulus for neonatal intestinal blood flow and mucosal growth under conditions of total parenteral nutrition (TPN) or partial enteral nutrition (PEN). We first tested the dose dependence and specificity of acute (3 h) enteral arginine infusion on superior mesenteric artery (SMA) blood flow in pigs fed TPN or PEN. We then determined whether chronic (4 d) arginine supplementation of PEN increases mucosal growth and if this was affected by treatment with the NO synthase inhibitor, N(G)-nitro-l-arginine methyl ester (L-NAME). Acute enteral arginine infusion increased plasma arginine dose dependently in both TPN and PEN groups, but the plasma response was markedly higher (100-250%) in the PEN group than in the TPN group at the 2 highest arginine doses. Baseline SMA blood flow was 90% higher in the PEN (2.37 ± 0.32 L⋅kg(-1)⋅h(-1)) pigs than in the TPN pigs (1.23 ± 0.17 L⋅kg(-1)⋅h(-1)), but was not affected by acute infusion individually of arginine, citrulline, or other major gut fuels. Chronic dietary arginine supplementation in PEN pigs induced mucosal growth in the intestine, but this effect was not prevented by treatment with L-NAME. Intestinal crypt cell proliferation, protein synthesis, and phosphorylation of mammalian target of rapamycin and p70S6 kinase were not affected by dietary arginine. We conclude that partial enteral feeding, but not acute enteral arginine, increases SMA blood flow in the neonatal pig. Furthermore, supplementing arginine in partial enteral feeding modestly increases intestinal mucosal growth and was NO independent. [ABSTRACT FROM AUTHOR]

PURPOSE OF REVIEW: The prevalence of malnutrition among children admitted to a pediatric intensive care unit is still high. Assessment of nutrient supply is essential in the care of critically ill children because inadequate nutrition can increase morbidity and mortality. This review covers the causes and consequences of inadequate nutrient supply to critically ill children. RECENT FINDINGS: A major factor contributing to the cause of inadequate nutrient supply is the difficulty in estimating nutritional needs of the individual child. Reasonable values for energy expenditure can be derived from prediction formulae but measuring energy expenditure by indirect calorimetry is useful in selected cases. Furthermore, under-prescription and inadequate delivery of nutrients caused by fluid volume restriction, procedural interruptions or cessation because of gastrointestinal intolerance or mechanical problems cause additional nutritional deficits. As routine nutritional assessment is lacking in many pediatric intensive care units, the ability to monitor the adequacy of nutritional support is poor. SUMMARY: In the majority of children admitted to a pediatric intensive care unit, nutritional problems - both underfeeding and overfeeding - occur during admission due to poor estimation of nutritional needs, under-prescribing and problems in the delivery of the nutrients. Recommendations are made in order to prevent inadequate nutritional supply and its potentially harmful consequences in critically ill children. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glucose is a major oxidative substrate for intestinal energy generation in neonatal animals; however, few data in preterm infants are available. Early administration of enteral nutrition, including glucose, may be an effective strategy to support intestinal adaptation to extrauterine life in preterm neonates. OBJECTIVE: The purpose of the present study was to quantify the first-pass uptake and oxidation of glucose by the splanchnic tissues (intestine and liver) in human neonates. DESIGN: Eight preterm infants [birth weight ( +/- SD): 1.19 +/- 0.22 kg, gestational age: 29 +/- 1 wk] were studied while they received 2 different enteral intakes (A: 40% enteral, 60% parenteral, total glucose intake = 7.5 +/- 0.5 mg. kg(-1). min(-1), and B: 100% enteral, total glucose intake = 7.8 +/- 0.4 mg. kg(-1). min(-1)). Splanchnic and whole-body glucose kinetics were measured by use of dual-tracer techniques. RESULTS: During both feeding periods, approximately one-third of dietary glucose intake was utilized during the first pass by the splanchnic tissues. More than three-quarters of this utilized glucose was oxidized in both periods (79 +/- 36% with A and 84 +/- 45% with B). Whole-body glucose oxidation was substantial under both circumstances: 72 +/- 5% and 77% +/- 6% of the glucose flux was oxidized during partial (A) and full (B) enteral feeding, respectively. CONCLUSIONS: Approximately one-third of dietary glucose is utilized during the first pass by the splanchnic tissues, irrespective of the dietary intake. Most of the utilized glucose is used for energy generation. Copyright © 2004 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

BACKGROUND: Currently available preterm formulas with energy contents of 3350 kJ (800 kcal)/L promote weight and length gain at rates at or above intrauterine growth rates but disproportionately increase total body fat. OBJECTIVE: The objective of this study was to determine whether fat accretion in formula-fed, very-low-birth-weight (VLBW) infants could be decreased and net protein gain maintained by reducing energy intakes from 502 kJ (80 kcal) x kg(-)(1) x d(-)(1) [normal-energy (NE) formula] to 419 kJ (100 kcal) x kg(-)(1) x d(-)(1) [low-energy (LE) formula] while providing similar protein intakes (3.3 g x kg(-)(1) x d(-)(1)). DESIGN: The study was a randomized, controlled trial enrolling 20 appropriate-for-gestational-age (AGA) and 16 small-for-gestational-age (SGA) VLBW infants (mean birth weight: 1.1 kg; mean gestational age: 31 wk); energy expenditure and nutrient balance were measured at 4 wk of age and anthropometric measurements were made when infants weighed 2 kg. RESULTS: The percentage of fat in newly formed tissue was significantly lower in AGA infants fed the LE formula (n = 9) than in those fed the NE formula (n = 10) (9% compared with 23%; analysis of variance, P = 0.001). Energy expenditure was higher in AGA infants fed the NE formula than in those fed the LE formula. Skinfold thickness was markedly lower in AGA infants fed the LE formula than in those fed the NE formula, resulting in a lower estimated percentage body fat (8.0 +/- 1.9% and 10.8 +/- 3.5%, respectively; P < 0.05). Three of 6 SGA infants fed the LE formula were excluded during the study because of poor weight gain. CONCLUSIONS: Body composition can easily be altered by changing the energy intakes of formula-fed VLBW infants. Energy intakes in these infants should be >419 kJ (100 kcal) x kg(-)(1) x d(-)(1). Copyright © 2000 American Society for Clinical Nutrition [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the effect of intrauterine and neonatal growth, prematurity and personal and environmental risk factors on intelligence in adulthood in survivors of the early neonatal intensive care era. METHODS: A large geographically based cohort comprised 94% of all babies born alive in the Netherlands in 1983 with a gestational age below 32 weeks and/or a birth weight >1500 g (POPS study). Intelligence was assessed in 596 participants at 19 years of age. Intrauterine and neonatal growth were assessed at birth and 3 months of corrected age. Environmental and personal risk factors were maternal age, education of the parent, sex and origin. RESULTS: The mean (SD) IQ of the cohort was 97.8 (15.6). In multiple regression analysis, participants with highly educated parents had a 14.2-point higher IQ than those with less well-educated parents. A 1 SD increase in birth weight was associated with a 2.6-point higher IQ, and a 1-week increase in gestational age was associated with a 1.3-point higher IQ. Participants born to young mothers (<25 years) had a 2.7-point lower IQ, and men had a 2.1-point higher IQ than women. The effect on intelligence after early (symmetric) intrauterine growth retardation was more pronounced than after later (asymmetric) intrauterine or neonatal growth retardation. These differences in mean IQ remained when participants with overt handicaps were excluded. CONCLUSIONS: Prematurity as well as the timing of growth retardation are important for later intelligence. Parental education, however, best predicted later intelligence in very preterm or very low birthweight infants. [ABSTRACT FROM AUTHOR]

Objective: To compare growth and body composition in preterm infants with bronchopulmonary dysplasia (BPD) with normal healthy term infants during the first year of life.Design: Twenty nine preterm infants with BPD (mean (SD) gestational age 27.1 (1.6) weeks; birth weight 852 (173) g) were followed prospectively. Anthropometry and body composition determined by total body electrical conductivity were measured and compared with those of healthy term infants at the same post-term age.Results: In infants with BPD, the mean weight standard deviation scores (SD scores) 6 weeks after term were significantly lower (-1.44 and -2.68, boys and girls respectively) than in healthy term infants of the same age and did not improve during the first year. The mean length SD score was significantly lower in infants with BPD 6 weeks after term than in healthy term infants of the same age, and, although it improved significantly during the first year, the mean length SD score in girls with BPD was significantly below 0 12 months after term. In infants with BPD, the mean free fat mass (FFM) SD score and the mean total body fat (TBF) SD score at 6 weeks post-term age were significantly below 0. The mean FFM SD scores (-1.01 and -2.56, boys and girls respectively) and the mean TBF SD scores (-1.14 and -2.40, boys and girls respectively) 12 months after term were significantly lower than in healthy term infants of the same age.Conclusions: Preterm infants with BPD have impaired growth, with a deficit in TBF and FFM already 6 weeks after term; FFM and TBF remain low compared with healthy term infants during the first year of life. Nutritional intervention studies in infants with BPD are needed to evaluate if nutrition is the major determinant of growth and body composition or if this pattern of growth in preterm infants with BPD is the result of disturbed endocrine control. [ABSTRACT FROM AUTHOR]

Background: Maternal stress is associated with negative early-life development and (mental)health outcomes. There is recent evidence that maternal stress in the postpartum period impacts the nutrient composition of human milk (HM). However, it is currently not known whether maternal stress is associated with changes in the HM microbiome during the critical early postpartum period., Methods: In this prospective observational cohort study, lactating women were recruited into a high-stress (HS, n = 23) and control (CTL, n = 69) group. The HS group included mothers with infants hospitalized for at least two days. Maternal stress was assessed using validated questionnaires and cortisol concentrations in hair, saliva and HM. HM was collected at days 10 and 24 and its microbiome was analyzed using 16 s rRNA sequencing. HM bacterial composition was compared between study groups and their correlation with maternal stress levels, maternal characteristics and infant outcomes was determined., Results: HM microbiome β-diversity differed significantly between study groups, with HS mothers displaying decreased abundance of Streptococcus, Gemella, and Veillonella, and increased levels of Staphylococcus, Corynebacterium and Acinetobacter compared to the control group. While the strongest correlation of β-diversity was with stress, HM microbiome β-diversity also correlated significantly with maternal education level and infant sex. No correlation between HM microbiome composition and HM cortisol concentrations was found., Conclusions: This study demonstrates stress-associated alterations in the early HM microbiome that could potentially contribute to early gut colonization and subsequent (mental)health outcomes. Future research is needed to elucidate the physiological significance of these changes for infant development and health., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: Human milk composition is dynamic. While extensive research has focused on its macronutrient concentrations during the first 6 months of lactation, limited research exists for extended lactation periods. This study aims to examine the nutritional composition of human milk during these longer lactation phases., Design: A retrospective longitudinal cohort study performed within the National Dutch Human Milk Bank., Participants: We selected donors who had provided milk donations at least once after the 6-month postpartum mark., Main Outcome Measures: The Miris Human Milk Analyser was used to analyse macronutrient concentrations in the milk samples. Linear mixed models were used for longitudinal analysis of these concentrations, factoring in time variables established for six sequential lactation periods., Results: We analysed 820 milk samples from 86 women, collected between 5 weeks and 28 months postpartum. Initially, milk protein concentrations dropped over the first 8 months of lactation (diff = -0.19 g/dL, p<0.001) and stabilised between 8 and 18 months before increasing again by 0.21 (95% CI 0.06-0.21) g/dL. Carbohydrate concentrations remained steady throughout the study period. Fat concentrations were stable for the first 8 months but saw an increase afterwards. Post 18 months, the fat content saw a rise of 1.90 (95% CI 1.59-2.21) g/dL. The caloric density mirrored the pattern of the fat concentrations., Conclusion: The nutritional content of human milk does not decrease after 6 months of lactation. Therefore, human milk banks may accept donations from mothers up to 2 years post-birth., Competing Interests: Competing interests: JM, JIAL, JWRT, BJvK, AS: All report no conflict of interest. JBvG: Member of the Dutch National Health Institute and founder and director of the Dutch National Human Milk Bank. CHPVDA: Reports receipt of speakers and consultancy honoraria from Nestlé Nutrition Institute, Nutricia Early Life Nutrition and Baxter., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Moderate and late preterm infants (MLPTI) (gestational age 32 0/7-36 6/7 weeks), are at risk for suboptimal growth. This study evaluated adherence to nutritional recommendations until 6 months corrected age (CA), growth until 2 years CA, and associations between nutritional intake and growth until 2 years CA., Methods: We prospectively collected nutritional intakes from 100 MLPTI during the first week of life and at 6 weeks, 3 months, and 6 months CA. Anthropometry was assessed at birth, discharge, term age, and at 6 weeks, 3 months, 6 months, 1 year, and 2 years CA., Results: On day 7, <40% reached nutritional recommendations. Thereafter, >80% reached protein recommendations until 6 months of life, but <60% reached energy recommendations. Weight z-scores increased from -0.44 at term-age to 0.59 at 3 months CA, but declined to -0.53 at 2 years CA on the TNO curves. No significant associations were found between nutritional intake and growth until 2 years CA., Conclusion: No associations were demonstrated between nutritional intakes and growth until 2 years CA, despite not reaching recommended intakes. Despite high efforts to optimize growth, MLPTI find their own growth curve in the first 2 years of life., Impact: This research is pioneering in identifying how nutrition influences growth in moderate and late preterm infants (MLPTI) up to 2 years corrected age (CA). MLPTI often do not meet the recommended protein and energy intake in their first week of life, suggesting that current guidelines might be too high. No association was demonstrated between nutritional intake and growth of MLPTI in the first 2 years of life. Initially, MLPTI show an increase in weight z-scores from term age up to 3 months CA but experience a decline in weight z-scores at 2 years CA, according to TNO growth charts., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: To determine the prevalence of pediatric Post-COVID-19 condition (PPCC), identify risk factors, and assess the quality of life in children with differing severities of acute COVID-19., Methods: During a prospective longitudinal study with a 1-year follow-up, we compared non-hospitalized (mild) and hospitalized (severe) COVID-19 cases to a negatively tested control group., Results: 579 children were included in this study. Of these, 260 had mild acute disease (median age:8, IQR:6-10), 60 had severe acute disease (median age:1, IQR:0.1-4.0), and 259 tested negative for SARS-CoV-2 (NT) (median age:8, IQR:5-10). At three months, 14.6% of the SARS-CoV-2 positive mild group (RR:6.31 (CI 95%: 2.71-14.67)) and 29.2% of the severe group (RR:12.95 (CI 95%: 5.37-31.23)) reported sequelae, versus 2.3% of the NT group. PPCC prevalence in the mild group decreased from 16.1% at one month to 4.4% at one year. Children with PPCC exhibited lower physical health-related quality of life scores and higher fatigue scores than the NT children., Conclusions: Severe acute COVID-19 in children leads to a higher PPCC prevalence than in mild cases. PPCC prevalence decreases over time. Risk factors at three months include prior medical history, hospital admission, and persistent fatigue one month after a positive test., Impact: We demonstrate children with severe COVID-19 are more likely to develop Post-COVID-19 condition than those with mild or no infections, and highlights the risk factors. Here we have stratified by acute disease severity, prospectively included a negative control group, and have demonstrated the heterogeneity in prevalence when utilizing various recent definitions of post-COVID. Identifying risk factors for pediatric post-COVID and highlighting the heterogeneity in prevalence based on various current definitions for post-COVID should aid in correctly identifying potential pediatric post-COVID cases, aiding in early intervention., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Serum alpha-fetoprotein (AFP) is often used as tumour marker for recurrent sacrococcygeal teratoma (SCT). We aimed to assess the normal dynamics of serum AFP levels after initial resection and diagnostic accuracy of serum AFP levels the follow-up for recurrence in SCT., Methods: This retrospective study included 57 patients treated for SCT in the six pediatric surgical centers in the Netherlands from 1980 to 2018., Main Results: 57 patients were included in the study of whom 19 children developed 20 recurrences at a median of 14.0 months after initial resection. No significant difference was found in serum AFP level dynamics between the recurrence and non-recurrence group after initial resection (p = 0.950). Serum AFP levels did not significantly increase before recurrence (p = 0.106) compared to serum AFP levels of children without recurrence at the same time. However, serum AFP levels did significantly increase in malignant recurrences (n = 7) (p = 0.03) compared to patients without recurrence. A cut-off value of 55 μg/L was found to be predictive for recurrent SCT with an Area Under the Curve (AUC) of 0.636 with sensitivity of 50% and specificity of 100%., Conclusion: Dynamics of serum AFP levels are not different between patients with and without recurrence after initial resection of SCT. Serum AFP levels are not predictive for mature or immature recurrent SCT and normal AFP levels do not rule out recurrent SCT. However, serum AFP levels exceeding 55 μg/L can indicate recurrent SCT, especially malignant recurrences., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Infants born moderate-to-late preterm (i.e., 32 wk-35 wk 6 d gestation) are, analogous to those born very preterm, at risk of later obesity, hypertension, and diabetes. Appropriate early life nutrition is key for ensuring optimal growth and body composition, thereby mitigating potential cardiometabolic risks., Objectives: We aimed to compare growth and body composition between infants born moderate-to-late preterm fed isocaloric but protein- and mineral-enriched postdischarge formula (PDF) or standard term formula (STF) until 6 mo corrected age (CA; i.e., after term equivalent age [TEA])., Methods: After enrollment (≤7 d postpartum), infants received PDF if (fortified) mother's own milk (MOM) was insufficient. At TEA, those receiving >25% of intake as formula were randomized to either continue the same PDF (n = 47) or switch to STF (n = 50); those receiving ≥75% of intake as MOM (n = 60) served as references. At TEA and 6 mo CA, we assessed anthropometry and body composition using both dual-energy x-ray absorptiometry (DXA) and air displacement plethysmography (ADP)., Results: Feeding groups had similar gestational age (median [25th percentile;75th percentile]: 34.3 [33.5; 35.1] wk), birthweight (mean ± standard deviation [SD]: 2175 ± 412 g), anthropometry, and body composition at TEA. At 6 mo CA, infants fed PDF had slightly, but significantly, greater length (67.6 ± 2.5 and 66.9 ± 2.6 cm, P < 0.05) and larger head circumference (43.9 ± 1.3 and 43.4 ± 1.5 cm, P < 0.05) compared to infants fed STF. Also, infants fed PDF had higher lean mass (LM) and bone mineral content estimated by DXA (4772 ± 675 and 4502 ± 741 g; 140 ± 20 and 131 ± 23 g, respectively; P < 0.05). ADP estimates, however, were not statistically different between feeding groups., Conclusions: Infants born moderate-to-late preterm demonstrated modest increases in length, head circumference, LM, and bone mineral content when fed PDF compared to STF for 6 mo after TEA. This trial was registered at the International Clinical Trial Registry Platform as NTR5117 and NTR NL4979., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

To explore the needs, expectations, and experiences of asylum-seeking parents and unaccompanied minors under the age of 18 years on the initial health assessment for children and adolescents and access to care upon entry in the Netherlands, We conducted five semi-structured focus group discussions with asylum-seeking parents and unaccompanied minors, from Syria, Eritrea, Afghanistan, and other Middle-East and African countries, supported by professional interpreters. To triangulate findings, semi-structured interviews with health care professionals involved in care for refugee children were conducted. Transcripts of focus group discussions were inductively and deductively coded and content analyzed; transcripts of interviews were deductively coded and content analyzed. In total, 31 asylum-seeking participants: 23 parents of 101 children (between 0 and 18 years old), 8 unaccompanied minors (between 15 and 17 years), and 6 healthcare professionals participated. Parents and minors expressed that upon entry, their needs were met for vaccinations, but not for screening or care for physical and mental health problems. Parents, minors, and health professionals emphasized the necessity of appropriate information and education about health, diseases, and the health system. Cultural change was mentioned as stressful for the parent-child interaction and parental well-being.     Conclusion: The perspectives of refugee parents and unaccompanied minors revealed opportunities to improve the experience of and access to health care of refugees entering the Netherlands, especially risk-specific screening and more adequate education about health, diseases, and the Dutch health care system. What is Known: •  Refugees have specific health needs due to pre-flight, flight, and resettlement conditions. Health assessment upon entry was non-obligatory in the Netherlands, except for the tuberculosis screening. Health needs were not always met, and refugees experienced barriers in access to care. What is New: • The initial health assessment met the needs concerning vaccinations but mismatched the needs regarding physical and mental health assessment. Screening for specific risk-related diseases and mental health could enable refugee parents and minors to engage better with the health system., (© 2024. The Author(s).)

Background: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care., Methods: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care., Results: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support., Conclusions: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration., Impact: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Pediatric post coronavirus disease 2019 (COVID-19) condition (PPCC) is a heterogeneous syndrome, which can significantly affect the daily lives of children. This study aimed to identify clinically meaningful phenotypes in children with PPCC, to better characterize and treat this condition., Methods: Participants were children with physician-diagnosed PPCC, referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March 2023. Demographic factors and information on post-COVID symptoms, comorbidities, and impact on daily life were collected. Clinical clusters were identified using an unsupervised and unbiased approach for mixed data types., Results: Analysis of 111 patients (aged 3-18 years) revealed three distinct clusters within PPCC. Cluster 1 (n = 62, median age = 15 years) predominantly consisted of girls (74.2%). These patients suffered relatively more from exercise intolerance, dyspnea, and smell disorders. Cluster 2 (n = 33, median age = 13 years) contained patients with an even gender distribution (51.5% girls). They suffered from relatively more sleep problems, memory loss, gastrointestinal symptoms, and arthralgia. Cluster 3 (n = 16, median age = 11 years) had a higher proportion of boys (75.0%), suffered relatively more from fever, had significantly fewer symptoms (median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively), and experienced a lower impact on daily life., Conclusions: This study identified three distinct clinical PPCC phenotypes, with variations in sex, age, symptom patterns, and impact on daily life. These findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children., (© 2024. The Author(s).)

Aim: To explore parents' perspectives regarding participation in neonatal care, with focus on the family integrated care (FICare) model utilised as a tool to enhance parent-infant closeness. Additionally, we describe experiences in different architectural settings., Methods: An online survey, categorised by four FICare pillars, was distributed through social media to parents of newborns hospitalised to Dutch neonatal wards between 2015 and 2020. Quantitative findings were summarised using descriptive statistics, while open-ended responses were thematically analysed., Results: Among the 344 respondents (98% mothers), most reported feeling involved in care (315/340). However, 79% also felt separated from their infant (265/337). Irrespective of architectural settings, parents reported incomplete implementation of FICare pillars: 14% was invited to educational sessions (parent education), 51% discussed family-specific care plans (staff education), 21% was facilitated in connecting with veteran parents (psychosocial support) and 22% received couplet-care (environment). Although 65% of parents were invited to attend clinical rounds, 32% actively participated in decision making. Thematic analysis revealed fundamentals for feeling welcome on the ward, peer-to-peer support, psychosocial support and participation in clinical rounds., Conclusion: Overall, parents expressed satisfaction with participation in neonatal care. However, structural implementation of FICare lacks. Regardless of architecture, expanding parent participation beyond presence requires attention., (© 2024 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: The fecal microbiota and metabolome are hypothesized to be altered before late-onset neonatal meningitis (LOM), in analogy to late-onset sepsis (LOS). The present study aimed to identify fecal microbiota composition and volatile metabolomics preceding LOM., Methods: Cases and gestational age-matched controls were selected from a prospective, longitudinal preterm cohort study (born <30 weeks' gestation) at nine neonatal intensive care units. The microbial composition (16S rRNA sequencing) and volatile metabolome (gas chromatography-ion mobility spectrometry (GC-IMS) and GC-time-of-flight-mass spectrometry (GC-TOF-MS)), were analyzed in fecal samples 1-10 days pre-LOM., Results: Of 1397 included infants, 21 were diagnosed with LOM (1.5%), and 19 with concomitant LOS (90%). Random Forest classification and MaAsLin2 analysis found similar microbiota features contribute to the discrimination of fecal pre-LOM samples versus controls. A Random Forest model based on six microbiota features accurately predicts LOM 1-3 days before diagnosis with an area under the curve (AUC) of 0.88 (n=147). Pattern recognition analysis by GC-IMS revealed an AUC of 0.70-0.76 (P<0.05) in the three days pre-LOM (n=92). No single discriminative metabolites were identified by GC-TOF-MS (n=66)., Conclusion: Infants with LOM could be accurately discriminated from controls based on preclinical microbiota composition, while alterations in the volatile metabolome were moderately associated with preclinical LOM., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Several metabolites of the essential amino acid tryptophan have emerged as key players in gut homeostasis through different cellular pathways, particularly through metabolites which can activate the aryl hydrocarbon receptor (AHR). This study aimed to map the metabolism of tryptophan in early life and investigate the effects of specific metabolites on epithelial cells and barrier integrity. Twenty-one tryptophan metabolites were measured in the feces of full-term and preterm neonates as well as in human milk and formula. The ability of specific AHR metabolites to regulate cytokine-induced IL8 expression and maintain barrier integrity was assessed in Caco2 cells and human fetal organoids (HFOs). Overall, higher concentrations of tryptophan metabolites were measured in the feces of full-term neonates compared to those of preterm ones. Within AHR metabolites, indole-3-lactic acid (ILA) was significantly higher in the feces of full-term neonates. Human milk contained different levels of several tryptophan metabolites compared to formula. Particularly, within the AHR metabolites, indole-3-sulfate (I3S) and indole-3-acetic acid (IAA) were significantly higher compared to formula. Fecal-derived ILA and milk-derived IAA were capable of reducing TNFα-induced IL8 expression in Caco2 cells and HFOs in an AHR-dependent manner. Furthermore, fecal-derived ILA and milk-derived IAA significantly reduced TNFα-induced barrier disruption in HFOs.

Introduction: Upon vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) humans will start to produce antibodies targeting virus specific antigens that will end up in circulation. In lactating women such antibodies will also end up in breastmilk, primarily in the form of secretory immunoglobulin A1 (SIgA1), the most abundant immunoglobulin (Ig) in human milk. Here we set out to investigate the SIgA1 clonal repertoire response to repeated SARS-CoV-2 vaccination, using a LC-MS fragment antigen-binding (Fab) clonal profiling approach., Methods: We analyzed the breastmilk of six donors from a larger cohort of 109 lactating mothers who received one of three commonly used SARS-CoV-2 vaccines. We quantitatively monitored the SIgA1 Fab clonal profile over 16 timepoints, from just prior to the first vaccination until 15  days after the second vaccination., Results: In all donors, we detected a population of 89-191 vaccine induced clones. These populations were unique to each donor and heterogeneous with respect to individual clonal concentrations, total clonal titer, and population size. The vaccine induced clones were dominated by persistent clones (68%) which came up after the first vaccination and were retained or reoccurred after the second vaccination. However, we also observe transient SIgA1 clones (16%) which dissipated before the second vaccination, and vaccine induced clones which uniquely emerged only after the second vaccination (16%). These distinct populations were observed in all analyzed donors, regardless of the administered vaccine., Discussion: Our findings suggest that while individual donors have highly unique human milk SIgA1 clonal profiles and a highly personalized SIgA1 response to SARS-CoV-2 vaccination, there are also commonalities in vaccine induced responses., Competing Interests: JBvG is the founder and director of the Dutch National Human Milk Bank and a member of the National Health Council. JBvG has been a member of the National Breastfeeding Council from March 2010 to March 2020. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 de Graaf, Bondt, van Rijswijck, Juncker, Mulleners, Damen, Hoek, van Keulen, van Goudoever, Heck and Dingess.)