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Background: The global climate crisis requires a paradigm shift in dietary concepts, respecting the needs of children. A global reference diet has been suggested by the EAT-Lancet Commission. On this basis, the detailed "Planetary Health Diet Index" (PHDI) has been proposed. The objective of this assessment is (1) to apply the PHDI to the Food-Based Dietary Guidelines, the so-called Optimized Mixed Diet (OMD) for children and adolescents in Germany in its original composition and (2) to check how the planetary value of the OMD could be improved by modifying food selection within meals while keeping the high nutrient densities of the guideline diet., Methods: The PHDI specifies 16 food groups and their proportion of total daily energy intake. The PHDI of the original OMD was calculated by assigning the foods of the 7-day menu to the PHDI food groups in order to score them. In this way, it became apparent which food groups had the potential to improve the sustainability. The diet was then updated by either reducing or increasing individual foods from these food groups in the meals and deriving the resulting PHDI. The nutrient densities of the original and updated daily OMD were calculated., Results: The original diet obtained a PHDI score of 68.24 points, representing 45.5% of the theoretical maximum of 150 points. The following food groups achieved 9.9 to 10 out of 10 points: fruits, total vegetables, fish & seafood, vegetable oils, chicken (and substitutes). Conversely, food groups receiving a zero score included tubers & potatoes, dairy, red meat, animal fat, and added sugars. The updated diet resulted in increased consumption of 'nuts & peanuts', 'legumes', 'green vegetables', 'whole grains', and decreased consumption of 'tubers & potatoes' and 'red meat'. Overall, the PHDI increased from 68.24 to 81.51 points with the updated OMD, reflecting a 13.27% increase compared to the original diet. The nutrient densities were not significantly affected, but even slightly increased for most nutrients., Conclusions: The PHDI was applied to demonstrate how the sustainability of the guideline diet for children and adolescents in Germany could be improved through changes in individual food groups that can be easily implemented in practice while maintaining high nutrient densities and acceptability for children., Trial Registration: NA., Competing Interests: Declarations Conflict of interest The authors declare that they have no competing interests. Ethics approval and consent to participate Not applicable. Consent for publication Not applicable., (© 2024. The Author(s).)

Pathogenic variants in the ryanodine receptor 1 ( RYR1 ) gene are causative for a wide spectrum of muscular phenotypes, ranging from malignant hyperthermia over mild, non-progressive to severe congenital myopathy. Both autosomal dominant and recessive inheritance can occur, with the more severe forms usually showing recessive inheritance. However, genotype-phenotype correlations are complicated due to the large size of the gene and heterogeneous phenotypes. We present a 6-year-old patient with severe congenital myopathy, carrying a heterozygous pathogenic RYR1 variant inherited from the healthy mother. Through whole genome sequencing we identified a second, deep intronic RYR1 variant that has recently been described in another patient with severe congenital myopathy and shown to affect splicing. Segregation analyses confirmed the variants to be compound heterozygous. We compared our patient's phenotype to that of the patient from the literature as well as five additional patients with compound heterozygous RYR1 variants from our center. The main overlapping features comprised congenital onset, predominant muscular hypotonia, and normal creatine kinase (CK) levels, while overall clinical expression varied substantially. Interestingly, both patients carrying the new intronic splice variant showed a very severe disease course. More widespread use of genome sequencing will open the way for better genotype-phenotype correlations., Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Background: The COVID-19 pandemic contact restrictions considerably changed maternal visiting contacts during the time in which breastfeeding is initiated. We wanted to know how maternity ward staff and mothers rated the conditions of starting breastfeeding under contact restrictions., Methods: In the Breastfeeding in North Rhine-Westphalia (SINA) study, Germany, 2021/22, chief physicians as well as ward staff from 41 (out of 131) maternity hospitals (82 members of the healthcare sector in total) were surveyed by telephone concerning structural and practical conditions for breastfeeding support before and during the pandemic; 192 (out of 426 eligible) mothers answered an online-questionnaire about their breastfeeding experiences at 2 weeks and 2 months after birth., Results: In almost all of the hospitals, visits were restricted due to the pandemic, with the exception of the primary support person. After more than one year of pandemic experience, the ward staff were convinced that the restrictions were mostly positive for the mothers (97.6%) and for the ward staff themselves (78.0%). A total of 80.5% of the ward staff would maintain the restrictions beyond the pandemic. The mothers themselves mostly rated the restrictions in the hospital as being just right; moreover, many mothers voluntarily maintained the restrictions at home, at least in part., Conclusions: The unprecedented visiting restrictions in hospitals during the pandemic were like an "experiment" born out of necessity. Restricting visiting arrangements may be an underestimated beneficial component for the development of the mother-infant dyad in perinatal breastfeeding care, particularly in healthcare systems where almost all births occur in the maternity hospital., Trial Registration: German Clinical Trials Register (DRKS) (DRKS00027975)., (© 2024. The Author(s).)

Background: Primary ciliary dyskinesia (PCD) is a rare genetical disease with malfunction of the motile cilia leading to impaired muco-ciliary clearance in the respiratory tract. There is no cure for PCD, only supportive therapy aimed at minimizing the progression of the disease and improving the patient's quality of life (QoL). Physical activity (PA) is one of these recommended supportive therapies for people with PCD (pwPCD). However, there is no scientific evidence to support this recommendation. In addition, regular medical advice to increase PA remains largely ineffective in pwPCD., Methods: To test the main hypothesis, that an individualized and supported PA program leads to a better QoL 6 months after randomization (QoL-PCD questionnaire) compared to usual recommendation in pwPCD, 158 pwPCD aged 7 to 55 years are to be included in this multi-center randomized controlled trial (RCT). After the screening visit, a 1:1 randomization stratified by age group and FEV1 will be performed. A QoL-PCD questionnaire, motor test, and lung function will be carried out at regular intervals in both groups. PA is recorded in both groups using activity trackers during the study period. The main aim of the trial is to estimate the difference in the change of QoL between the groups after 6 months. Therefore, our full analysis set consists of all randomized patients and analysis is performed using the intention-to-treat principle. Statistical software R ( http://www.r-project.org ) is used. Ethical approvement without any reservations: RUB Bochum Ethics Committee (No. 23-7938; December 4, 2023). Recruitment start: March 2024., Discussion: Limitations result from the rarity of PCD with its broad disease spectrum and the large age range. These are reduced by stratified randomization and the measurement of the individual change in QoL as primary endpoint. In our view, only a PA program tailored to individual needs with close contact to trainers offers the chance to meet personal needs of pwPCD and to establish PA as a pillar of therapy in the long term. The study protocol explains all procedures and methods of recruitment, implementation of the study visits and intervention, measures for patient and data safety, and for minimizing risks and bias., Trial Registration: German Clinical Trials Register (DRKS) 00033030. Registered on December 7, 2023. Update 10 July 2024. STUDY PROTOCOL VERSION 10: Version 1.2; 12 June 2024., (© 2024. The Author(s).)

Purpose: In contrast to adults, immune protection against SARS-CoV-2 in children and adolescents with natural or hybrid immunity is still poorly understood. The aim of this study was to analyze different immune compartments in different age groups and whether humoral immune reactions correlate with a cellular immune response., Methods: 72 children and adolescents with a preceding SARS-CoV-2 infection were recruited. 37 were vaccinated with an RNA vaccine (BNT162b2). Humoral immunity was analyzed 3-26 months (median 10 months) after infection by measuring Spike protein (S), nucleocapsid (NCP), and neutralizing antibodies (nAB). Cellular immunity was analyzed using a SARS-CoV-2-specific interferon-γ release assay (IGRA)., Results: All children and adolescents had S antibodies; titers were higher in those with hybrid immunity (14,900 BAU/ml vs. 2118 BAU/ml). NCP antibodies were detectable in > 90%. Neutralizing antibodies (nAB) were more frequently detected (90%) with higher titers (1914 RLU) in adolescents with hybrid immunity than in children with natural immunity (62.5%, 476 RLU). Children with natural immunity were less likely to have reactive IGRAs (43.8%) than adolescents with hybrid immunity (85%). The amount of interferon-γ released by T cells was comparable in natural and hybrid immunity., Conclusion: Spike antibodies are the most reliable markers to monitor an immune reaction against SARS-CoV-2. High antibody titers of spike antibodies and nAB correlated with cellular immunity, a phenomenon found only in adolescents with hybrid immunity. Hybrid immunity is associated with markedly higher antibody titers and a higher probability of a cellular immune response than a natural immunity., (© 2024. The Author(s).)

With the emergence of SARS-CoV-2, various non-pharmaceutical interventions were adopted to control virus transmission, including school closures. Subsequently, the introduction of vaccines mitigated not only disease severity but also the spread of SARS-CoV-2. This study leveraged an adapted SIR model and non-linear mixed-effects modeling to quantify the impact of remote learning, school holidays, the emergence of Variants of Concern (VOCs), and the role of vaccinations in controlling SARS-CoV-2 spread across 16 German federal states with an age-stratified approach. Findings highlight a significant inverse correlation (Spearman's ρ = -0.92, p < 0.001) between vaccination rates and peak incidence rates across all age groups. Model-parameter estimation using the observed number of cases stratified by federal state and age allowed to assess the effects of school closure and holidays, considering adjustments for vaccinations and spread of VOCs over time. Here, modeling revealed significant (p < 0.001) differences in the virus's spread among pre-school children (0-4), children (5-11), adolescents (12-17), adults (18-59), and the elderly (60+). The transition to remote learning emerged as a critical measure in significantly reducing infection rates among children and adolescents (p < 0.001), whereas an increased infection risk was noted among the elderly during these periods, suggesting a shift in infection networks due to altered caregiving roles. Conversely, during school holiday periods, infection rates among adolescents mirrored those observed when schools were open. Simulation exercises based on the model provided evidence that COVID-19 vaccinations might serve a dual purpose: they protect the vaccinated individuals and contribute to the broader community's safety., 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., (© 2024 The Authors.)

Background: Emergence delirium is a complication of pediatric anesthesia during the early recovery period. Children undergoing ear, nose, and throat surgery are at high risk. The Pediatric Assessment of Emergence Delirium (PAED) scale is used for diagnosis and founded to specify the degree of emergence delirium. However, there is no consensus regarding a threshold value for emergence delirium diagnosis. Homeostasis-guided pediatric general anesthesia aims to maintain physiological parameters within normal ranges. In this prospective, observational study we evaluated the incidence of emergence delirium in children undergoing elective ear, nose, and throat surgery under standardized homeostasis-guided general anesthesia. Secondarily, we identified risk factors associated with an increased PAED score., Methods: In children aged 0-6 years, we collected data from standard monitoring, depth of anesthesia, and preoperative glucose and ketone body levels. These variables were studied as risk or protective factors for increased PAED >0 scores using multivariate logistic regression., Results: Of the 105 children analyzed, only five children (4.7%) had emergence delirium according to a threshold PAED score ≥10, while 37 children (35%) had PAED scores >0. Statistical analysis of the PAED outcome identified two significant positive associations with pain (P<0.001) and preoperative blood glucose levels (P=0.006) and one negative association with preoperative ketone body levels (P<0.001)., Conclusions: Our cohort observed a lower incidence of emergence delirium than in the literature. Higher pain intensity and lower blood glucose levels were risk factors for PAED > 0, whereas preoperative ketone body levels were protective.

Patients with phenylketonuria (PKU) present signs of impaired executive functioning and bone health in adolescence and adulthood, depending in part on the success of therapy in childhood. Therefore, nine children with well-treated PKU (4-7 years old, 22.2% ♀, seven with a full set of data, two included into partial analysis) and 18 age-, gender- and season-matched controls were analyzed for differences in executive functioning and bone parameters in plasma. Plasma was analyzed with commercially available kits. Cognitive performance in tonic alertness, visuo-spatial working memory, inhibitory control and task switching was assessed by a task battery presented on a touch screen. Regarding cognition, only the performance in incongruent conditions in inhibitory control was significantly better in children with PKU than in controls. No further differences in cognitive tests were detected. Furthermore, no significant difference in the bone turnover markers osteocalcin, undercarboxylated osteocalcin and CTX were detected between children with PKU and controls, while children with PKU had a significantly higher vitamin D concentration (69.44 ± 12.83 nmol/L vs. 41.87 ± 15.99 nmol/L, p < 0.001) and trended towards lower parathyroid hormone concentrations than controls (48.27 ± 15.16 pg/mL vs. 70.61 ± 30.53 pg/mL, p = 0.066). In this small group of well-treated preschoolers with PKU, no impairments in cognitive performance and bone turnover were observed, while vitamin D supplementation of amino acid supplements seems to be sufficient to achieve good vitamin D status.

Early infant feeding and swallowing are complex motor processes involving numerous muscles in coordination, e.g. the orofacial muscles as well as the muscles of the pharynx, larynx and esophagus. The newborn's reflexive drinking develops into the ability to ingest pureed complementary food as infancy progresses. Finally, in the last part of the first year of life, a differentiated eating, chewing and swallowing process develops allowing the voluntary intake of different foods of the family diet. The dietary schedule for the first year of life, which describes the recommended nutrition of infants in Germany, corresponds to these milestones in eating development. Disturbances in gross motor development, sensory processing issues, and organic and behavioral problems are known to interfere with the development of eating skills. Swallowing disorders (dysphagia) in children can have a detrimental effect on food intake and pose a serious risk to growth and development. Their prevention treatment requires a multidisciplinary approach with the aim of enabling the child to eat independently in the long term., (© 2024. The Author(s).)

The objective of the study is to evaluate the evolving phenotype and genetic spectrum of patients with succinic semialdehyde dehydrogenase deficiency (SSADHD) in long-term follow-up. Longitudinal clinical and biochemical data of 22 pediatric and 9 adult individuals with SSADHD from the patient registry of the International Working Group on Neurotransmitter related Disorders (iNTD) were studied with in silico analyses, pathogenicity scores and molecular modeling of ALDH5A1 variants. Leading initial symptoms, with onset in infancy, were developmental delay and hypotonia. Year of birth and specific initial symptoms influenced the diagnostic delay. Clinical phenotype of 26 individuals (median 12 years, range 1.8-33.4 years) showed a diversifying course in follow-up: 77% behavioral problems, 76% coordination problems, 73% speech disorders, 58% epileptic seizures and 40% movement disorders. After ataxia, dystonia (19%), chorea (11%) and hypokinesia (15%) were the most frequent movement disorders. Involvement of the dentate nucleus in brain imaging was observed together with movement disorders or coordination problems. Short attention span (78.6%) and distractibility (71.4%) were the most frequently behavior traits mentioned by parents while impulsiveness, problems communicating wishes or needs and compulsive behavior were addressed as strongly interfering with family life. Treatment was mainly aimed to control epileptic seizures and psychiatric symptoms. Four new pathogenic variants were identified. In silico scoring system, protein activity and pathogenicity score revealed a high correlation. A genotype/phenotype correlation was not observed, even in siblings. This study presents the diversifying characteristics of disease phenotype during the disease course, highlighting movement disorders, widens the knowledge on the genotypic spectrum of SSADHD and emphasizes a reliable application of in silico approaches., (© 2024 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.)

Mitchell syndrome is a very rare genetic disorder due to a specific de novo gain-of-function variant in acyl-CoA oxidase 1 ( ACOX1 ). So far, only five patients with this disease have been described worldwide. We present here two additional unrelated German patients found to carry the same heterozygous ACOX1  N237S variant through exome sequencing (ES). Both patients showed neurodegenerative clinical features starting from ∼4 to 5 years of age including progressive hearing loss, ataxia, ichthyosis, as well as progressive visual impairment leading to amaurosis, and died at the ages of 16 and 8 years, respectively. The first patient was clinically suspected to have anti-myelin oligodendrocyte glycoprotein-antibody-associated myelitis, but the disease course overall deteriorated despite extensive immunomodulatory therapy. The second patient was originally suspected to have a mitochondrial disorder due to intermittent elevated blood lactate. Since Mitchell syndrome has only been identified in 2020, the diagnosis in this second patient was only established through re-evaluation of ES data years after the original analysis. Comparison of all seven reported patients suggests that Mitchell syndrome often (but not always) clinically mimics autoimmune-inflammatory disease. Therefore, in patients with autoimmune central nervous system disease who do not respond adequately to standard therapies, re-evaluation of this diagnosis is needed and genetic analyses such as trio ES should be considered., Competing Interests: None declared., (Thieme. All rights reserved.)

Purpose: Our aim was to assess intelligence, visual perception and working memory in children with new-onset Rolandic epilepsy (RE) and children with Rolandic discharges without seizures (RD)., Methods: The participants in the study were 12 children with RE and 26 children with RD aged 4 to 10 years (all without medication and shortly after diagnosis) and 31 healthy controls. Their cognitive performance was assessed using the German versions of the Wechsler Preschool and Primary Scale of Intelligence (WPPSI-III), the Wechsler Intelligence Scale for Children (WISC-IV), the Developmental Test of Visual Perception-2 (DTVP-2), the Developmental Test of Visual Perception-Adolescent and Adult (DTVP-A) (each according to age) and the Word Order, Hand Movements and Spatial Memory subtests of the German version of the Kaufman Assessment Battery for Children (K-ABC)., Results: The comparison of the entire group of children with RE/RD and the control group conducted in the first step of our analysis revealed a weaker performance of the children with RE/RD in all cognitive domains. Significant deficits, however, were found exclusively in the RD group. Compared to the controls, they performed significantly weaker regarding IQ (full scale IQ: p < 0.001; verbal IQ: p < 0.001; performance IQ: p = 0.002; processing speed: p = 0.005), visual perception (general visual perception: p = 0.005; visual-motor integration: p = 0.002) and working memory (WISC working memory: p = 0.002 and K-ABC Word Order (p = 0.010) and Hand Movements (p = 0.001) subtests. Also, the children without seizures scored significantly lower than those with seizures on the WISC Working Memory Index (p = 0.010) and on the K-ABC Word Order (p = 0.021) and Hand Movements (p = 0.027) subtests. Further analysis of our data demonstrated the particular importance of the family context for child development. Significant cognitive deficits were found only in children with RD from parents with lower educational levels. This group consistently scored lower compared to the control group regarding IQ (full scale IQ: p < 0.001; verbal IQ: p < 0.001; performance IQ: p = 0.012; processing speed: p = 0.034), visual perception (general visual perception: p = 0.018; visual-motor integration: p = 0.010) and auditory working memory (WISC working memory: p = 0.014). Furthermore, compared to the children with RE, they performed significantly weaker on verbal IQ (p = 0.020), auditory working memory consistently (WISC working memory: p = 0.027; K-ABC: Word Order: p = 0.046) as well as in one of the K-ABC spatial working memory subtests (Hand Movements: p = 0.029). Although we did not find significant deficits in children with new-onset RE compared to healthy controls, the performance of this group tended to be weaker more often. No statistically significant associations were observed between selected clinical markers (focus types: centrotemporal/other foci/laterality of foci and spread of Rolandic discharges) and cognitive test results. Except for spatial working memory, we also found no evidence that the age of our patients at the time of study participation was of significant importance to their cognitive performance., Conclusions: Our study provides some evidence that children with Rolandic discharges, with and without seizures, may be at higher risk of cognitive impairment. In addition to medical care, we emphasise early differentiated psychosocial diagnostics to provide these children and their families with targeted support if developmental problems are present., Competing Interests: Declaration of competing interest 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 Elsevier Inc. All rights reserved.)

Pompe disease is a lysosomal storage disorder, with onset between the first weeks after birth and adulthood, depending on its phenotype. It can affect multiple organ systems and presents itself with a wide variety of symptoms. Thus, recognizing Pompe disease is difficult. Especially since enzyme replacement therapy for Pompe disease was introduced (in Germany in 2006), early diagnosis by means of enzyme activity determination from dried blood spot analysis and genetic verification has become important for outcome and quality of life. When facing an obscure muscular disorder, it is crucial to consider Pompe disease. This article provides an overview about Pompe disease and focuses on the diagnosis of the late onset type. The most important aspects of interdiciplinary care for patients with Pompe disease are presented. Additionally, it contains a section focusing on psychosocial challenges for children with Pompe disease and their families, which may include mental disorders and social retreat, and gives advice on how to support parents of affected children., Competing Interests: TL erhielt 2019 ein Honorar der Firma Sanofi Genzyme für einen Workshop zum Thema „Klinische Symptome von MPS mit Schwerpunkt MPS I“, die übrigen Autoren erklären, dass kein Interessenskonflikt besteht., (Thieme. All rights reserved.)