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Background: To develop and maintain suturing skills, clinical exposure is important. When clinical exposure cannot be guaranteed, an adequate training schedule for suturing skills is required. This study evaluates the effect of continuous training, 'reflection before practice' and self-assessment on basic open suturing skills., Methods: Medical students performed four basic suturing tasks on a simulation set up before ('pre-test') and after their surgical rotation ('after-test'). Participants were divided in three groups; the 'clinical exposure group' ( n  = 44) had clinical exposure during their rotation only, the 'continuous training group' ( n  = 16) completed a suturing interval training during their rotation and the 'self-assessment group' ( n  = 16) also completed a suturing interval training, but with the use of reflection before practice and self-assessment. Parameters measured by a tracking system during the suturing tasks and a calculated 'composite score' were compared between groups and test-moments., Results: A significantly better composite score was found at the after-test compared to the pre-test for all groups for all basic suturing tasks (0.001 ≤ p  ≤ 0.049). The self-assessment group scored better at the pre-test than the other two groups for all tasks, except for 'knot tying by hand' (0.004 ≤ p  ≤ 0.063). However, this group did not score better at the after-test for all tasks, compared to the other two groups. This resulted in a smaller delta of time ('transcutaneous suture', p  = 0.013), distance ('Donati suture' and 'intracutaneous suture', 0.005 ≤ p  ≤ 0.009) or composite score (all tasks, except for knot tying by hand, 0.007 ≤ p ≤ 0.061) in the self-assessment group., Conclusion: Reflection before practice and self-assessment during continuous training of basic open suturing tasks, may improve surgical skills at the start of the learning curve.

This study aims to investigate and categorize health problems in children with profound intellectual and multiple disabilities (PIMD). We conducted a scoping review in five electronic databases (PubMed, Embase, Medline, PsychInfo, and Web of Science), including peer-reviewed studies that describe health problems in children with PIMD. Articles on PIMD were included when mentioning children with severe or profound intellectual disability (IQ/DQ < 35 or developmental age < 24 months) AND severe/profound motor impairment (GMFCS IV/V, non-ambulatory/not walking without support or gross motor function measure (GMFM-66) score < 40). Health problems were divided into 11 different categories based on literature and the experiences of the authors. Both health problems reported by caregivers and diagnosed by health professionals were included. A data extraction tool was developed using the JBI checklist recommendations. The review included 22 studies, with a total of 894 patients across all the articles. The most reported health problems in children with PIMD were epilepsy, respiratory infections, feeding difficulties, GERD, scoliosis, and visual impairment. There was no uniformity in the definition and terminology of PIMD., Conclusion: The studies in this review covered a wide range of health problems, with only a few focusing on the entire range. Given the lack of knowledge about children with PIMD, further research is required on the presence of health problems, the age of onset, and appropriate treatments. Awareness, early detection, and treatment of the health problems could optimize the medical care and quality of life of children with PIMD., What Is Known: • Children with profound intellectual and multiple disabilities (PIMD) have severe intellectual and motor disabilities and various comorbidities. • Children often visit the hospital and provided care is complex and fragmented., What Is New: • Children with PIMD develop a wide range of health problems; most reported are epilepsy, respiratory infections, and feeding difficulties. • Little is known about treatment of health problems in children with PIMD., Competing Interests: Declarations. Ethics approval: This was a review and no ethical approval was required. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Anorectal malformations (ARM) encompass a spectrum of rare congenital defects of the rectum and anus, requiring specialized reconstructive surgery. To improve epidemiological and clinical research in rare diseases such as ARM, collaborative efforts and patient registries are key. This retrospective study pools clinical data over a 30-year period from two ARM patient registries (The Royal Children's Hospital (RCH) in Melbourne, Australia, and the ARM-Network Consortium in Europe). It aims to draw comparisons on demographics, management, and outcomes between ARM patients in Australia and Europe. A total of 2947 ARM patients were included in the analyses. The RCH cohort had more complex ARM types (including rectal atresia and recto-vaginal fistula) and more associated anomalies, specifically skeletal, cardiac, and/or trachea-esophageal, than ARM-Net patients. Other patient characteristics were similar. Treatments clearly differed between the groups. European surgeons favoured the PSARP approach for both less complex and more complex ARM types, where Australian surgeons opted more often for cutback surgery in less complex, and laparoscopic assistance in more complex types. Complications were differently distributed, with less complications after LAARP and more after PSARP at RCH, compared to ARM-Net. While RCH patients more often required a redo, ARM-Net patients more commonly underwent anal dilatations. Anorectal malformation patients in Australia and Europe had minor differences in disease characteristics, and both operative and medical approaches differed. Joint efforts such as the present study emphasize the importance of collaboration to elucidate areas of improvement where surgeons may learn from each other across the world, ultimately improving patient outcomes. TYPE OF STUDY: Original Research. LEVEL OF EVIDENCE: III., Competing Interests: Conflict of interest None to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To identify indications for exchange transfusions, assess the use and waste of exchange transfusion products (ie, reconstituted whole blood exchange transfusions), and determine nationwide distribution and prevalence of these transfusions in the Netherlands., Study Design: All 9 neonatal intensive care units and 15 non-neonatal intensive care unit hospitals participated in this retrospective, observational, cohort study. We retrieved data on the indications for and use of all exchange transfusion products ordered by participating centers over an 11-year period., Results: A total of 574 patients for whom 1265 products were ordered were included for analyses. Severe ABO (32.6%) and non-ABO (25.2%) immune hemolysis and subsequent hyperbilirubinemia were the most frequent indications. Rare indications were severe leukocytosis in Bordetella pertussis (2.1%) and severe anemia (1.5%). Approximately one-half of all ordered products remained unused. In 278 of 574 neonates (48.4%), ≥1 products were not used, of which 229 (82.7%) were due to the resolving of severe hyperbilirubinemia with further intensification of phototherapy. The overall prevalence of neonates who received an exchange transfusion was 14.6:100 000 liveborn neonates., Conclusions: A considerable proportion of products remained unused, and annually a limited number of patients are treated with an exchange transfusion in the Netherlands, highlighting the rarity of the procedure in the Netherlands., Competing Interests: Declaration of Competing Interest This study is researcher initiated and not externally funded. No funds, grants, or other support were received. D.P.d.W. received funding from Momenta Pharmaceuticals, Inc., which was acquired by Johnson & Johnson, and is an investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of HDFN. E.J.T.V. is the principal investigator for a phase 2 trial (NCT03842189) and a phase 3 trial (NCT05912517) of a new drug for the treatment of HDFN, which is sponsored by Janssen Pharmaceuticals. E.L. is a sub-investigator for a phase 2 trial (NCT03842189) of a new drug for the treatment of HDFN, which is sponsored by Janssen Pharmaceuticals. All other authors reported to have no conflict of interest or financial disclosures., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Complexity science is a discipline which explores how complex systems behave and how we interact with them. Though it is widely implemented outside medicine, particularly in the sciences involving human behavior, but also in the natural sciences such as physics and biology, there are only a few applications within medical research. We propose that complexity science can provide new and helpful perspectives on complex pediatric medical problems. It can help us better understand complex systems and develop ways to cope with their inherent unpredictabilities. In this article, we provide a brief introduction of complexity science, explore why many medical problems can be considered 'complex', and discuss how we can apply this perspective to pediatric research. IMPACT: Current methods in pediatric research often focus on single mechanisms or interventions instead of systems, and tend to simplify complexity. This may not be appropriate. Complexity science provides a framework and a toolbox to better address complex problems. This review provides a starting point for the application of complexity science in pediatric research., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

This systematic review aims at presenting the ethical debate on the artificial placenta (AP) by identifying, distinguishing, and organizing the different ethical arguments described in the literature. Articles were selected based on predefined inclusion criteria: discussing ethical arguments, on AP, written in English. QUAGOL methodology was used for analysis. Forty-five articles were included. We identified three themes. First, foundational-ethical issues. There is disagreement on whether the AP subject should be considered an infant or a new moral entity. While physiologically it stays in the fetus, it sits outside the womb. Second, reproductive ethics issues. Few authors believed that the AP would increase reproductive choices. The majority warned that the AP could limit reproductive choices by creating pressure to use it in healthy pregnancies or as an alternative to abortion. Third, research ethics issues. Publications mostly focused on the selection of the in-human trial participants. We concluded that AP ethical literature focuses mostly on the potential use of AP as an alternative to abortion or healthy pregnancies rather than on its intended use as a treatment after extremely premature birth. Therefore, we conclude that the current ethical literature on AP is imbalanced: it leans more toward science fiction than actual clinical and technological reality., (© 2024 John Wiley & Sons Ltd.)

Anorectal malformations (ARM) are rare congenital anomalies with an overall prevalence of 3.32 per 10,000 pregnancies. ARM describe a spectrum of anomalies of the anus and rectum ranging from a minimally displaced anal canal to a complete fusion of the anorectum, vagina and urethra with hypoplastic sphincter and pelvic floor muscle. Aberrant septation of the hindgut with anomalous cloacal membrane during weeks 6 to 9 of gestation form the developmental basis for a spectrum of anomalies defined as ARM. Although underlying specific syndromes and occasional familiar occurrence suggest genetic aetiology, most ARM are non-syndromic and their causal genetic mechanisms and non-genetic insults remain unclear. ARM is a clinical diagnosis, generally made early after birth via careful inspection of the perineum. Prenatal detection remains rare, and modern technical developments have added little to prenatal diagnostics. ARM is corrected surgically. Since its introduction in 1982, posterior sagittal anorectoplasty is the most common surgery for ARM reconstruction. Subsequent surgical adaptations focus on minimizing iatrogenic operative injury by limiting surgical invasiveness. They include laparoscopic procedures and shortening of incisions with confined dissection in open surgery. Although outcomes in patients with ARM have evolved throughout the past decades, there is urgent need for further improvements both in functional outcomes and quality of life. The importance of psychosocial experiences of affected patients is increasingly recognized. Continued research is necessary to improve prenatal detection, to elucidate genetic and epigenetic alterations and to refine optimal surgical procedures., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. Springer Nature Limited.)

Infants requiring admission to the neonatal intensive care unit (NICU) are particularly vulnerable to developing brain injury. The severity of the underlying clinical conditions and the complexity of care call for continuous, cot-side, non-invasive monitoring tools. Near-infrared spectroscopy (NIRS) measures the regional tissue oxygen saturation of hemoglobin (rStO 2 ) and provides continuous information on the net-result of several factors. Cerebral rStO 2 correlates with echocardiography-derived measures of blood flow. Cerebral fractional tissue oxygen extraction provides information on the balance between oxygen supply and demand and can be continuously derived from the combined use of cerebral rStO 2 and arterial oxygen saturation. Information on cerebral blood flow autoregulatory capacity can be obtained from combining cerebral rStO 2 and invasive blood pressure monitoring by appropriate software. Cerebral rStO 2 provides real-time, end-organ information on perfusion-oxygenation, and when interpreted in the clinical context based on pathophysiological principles may be used as a help to guide interventions in the NICU. In this review we will discuss how to optimize NIRS monitoring for application in the NICU, with a particular focus on the preterm infant. IMPACT: Near-infrared spectroscopy (NIRS) provides cot-side, real-time information on blood and oxygen supply to the brain. Therefore, it is a valuable tool to better understand the pathophysiology underlaying disease processes. Current evidence suggests that NIRS-guided treatment in extremely preterm infants during transitional circulation does not improve clinical outcomes. Specific training is needed to maximize potential performance. Pathophysiological interpretation of cerebral NIRS data in the given clinical context may help in decision-making. Appropriate use of this monitoring technique, interpreted concurrently with other routine parameters, is a potential clinical tool to guide interventions in the NICU setting., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

PTEN hamartoma tumor syndrome (PHTS) has a broad clinical spectrum including various benign and malignant tumors at varying age of diagnosis. Many patients remain unrecognized, unaware of their increased cancer risk. We aimed to describe the cancer spectrum, age of onset and histopathological cancer characteristics to assess whether specific cancer characteristics could improve PHTS recognition. Genetic testing results and pathology reports were collected for patients tested for germline PTEN variants between 1997 and 2020 from the diagnostic laboratory and the Dutch nationwide pathology databank (Palga). The cancer spectrum and age of onset were assessed in patients with (PTENpos) and without (PTENneg) a germline PTEN variant. Histopathological cancer characteristics were assessed in a nested cohort. 341 PTENpos patients (56% females) and 2882 PTENneg patients (66% females) were included. PTENpos patients presented mostly with female breast (BC, 30%), endometrial (EC, 6%), thyroid (TC, 4%) or colorectal cancer (4%). PTENpos were significantly younger at cancer onset (43 vs. 47 years) and had more often (46% vs. 18%) a second BC than PTENneg. PTEN detection rates were highest for BC <40 years (9%), TC <20 years (15%) and EC <50 years (28%), and dropped to 6%, 4%, and 15% by age 60. Histopathological characteristics were similar between groups. No histopathological cancer characteristics were distinctive for PHTS. However, PTENpos were significantly younger at cancer onset. Therefore early-onset BC, EC, or TC warrants consideration of PHTS diagnostics either through a pre-screen for other PHTS features or direct germline testing., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Purpose: We aimed to develop and evaluate a population PK model of mycophenolic acid (MPA) in pediatric kidney transplant patients to aid MPA dose optimization., Methods: Data were collected from pediatric kidney transplant recipients from a Dutch academic hospital (Radboudumc, the Netherlands). Pharmacokinetic model-building and model-validation analyses were performed using NONMEM. Subsequently, we externally evaluated the final model using data from another academic hospital. The final model was used to develop an optimized dosing regimen., Results: Thirty pediatric patients were included of whom 266 measured MPA plasma concentrations, including 20 full pharmacokinetic (PK) curves and 24 limited sampling curves, were available. A two-compartment model with a transition compartment for Erlang-type absorption best described the data. The final population PK parameter estimates were K tr (1.48 h -1 ; 95% CI, 1.15-1.84), CL/F (16.0 L h -1 ; 95% CI, 10.3-20.4), V c /F (24.9 L; 95% CI, 93.0-6.71E25), V p /F (1590 L; 95% CI, 651-2994), and Q/F (36.2 L h -1 ; 95% CI, 9.63-74.7). The performance of the PK model in the external population was adequate. An optimized initial dose scheme based on bodyweight was developed. With the licensed initial dose, 35% of patients were predicted to achieve the target AUC, compared to 42% using the optimized scheme., Conclusion: We have successfully developed a pharmacokinetic model for MPA in pediatric renal transplant patients. The optimized dosing regimen is expected to result in better target attainment early in treatment. It can be used in combination with model-informed follow-up dosing to further individualize the dose when PK samples become available., (© 2024. The Author(s).)

Background: The aim of this study is to evaluate whether the parameters 'time' and 'distance', measured by SurgTrac, correlate with the assessment of the same skills by blinded experts., Methods: Basic open suturing tasks were executed by medical students. SurgTrac software measured objective parameters by tracking fingers. The executed tasks were recorded by a tablet and additionally assessed by a blinded expert with a Competency Assessment Tool-form (CAT-form). A Pearson's correlation was used to investigate the correlation between the parameters and the outcomes of the expert assessment., Results: A strong correlation between the measured parameters of SurgTrac and the expert-assessment was found for knot tying by hand (r ​= ​-0.703) and vertical mattress suture (r ​= ​-0.644) and a moderate correlation for transcutaneous suture (r ​= ​-0.555) and intracutaneous suture (r ​= ​-0.451)., Conclusion: The use of finger tracking by SurgTrac showed a good concurrent validity for the basic open suturing tasks knot tying by hand, transcutaneous suture and vertical mattress suture., Competing Interests: Declaration of competing interest No conflicts of interests have to be disclosed, other than the fact that dr. S. Botden is co-founder of PediatrickBoxx, a small non-for-profit cooperation, that has developed the wooden casing used in this study. The minimal profit on selling the models is used in the development and production of new models. Dr. S. Botden is no owner of this non-profit company and does not receive any endorsement for the use of this model. The models for this study were owned by the department., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Noonan syndrome (NS) is an autosomal dominant condition characterized by facial dysmorphism, congenital heart disease, development delay, growth retardation and lymphatic disease. It is caused by germline pathogenic variants in genes encoding proteins in the Ras/mitogen-activated protein kinase signaling pathway. Nerve enlargement is not generally considered as a feature of NS, although some cases have been reported. High-resolution nerve ultrasound enables detailed anatomical assessment of peripheral nerves and can show enlarged nerves. This retrospective cohort study aims to describe the sonographic findings of patients with NS performed during a 1-year time period. Data on the degree of enlargement, the relation to increasing age, pain in extremities, genotype on the gene level and clinical features were collected. Twenty-nine of 93 patients visiting the NS Center of Expertise of the Radboud University Medical Center Nijmegen underwent high-resolution ultrasound. In 24 patients (83%) nerve enlargement was found. Most of them experienced pain. We observed a weak correlation with increasing age and the degree of nerve enlargement but no association with pain, genotype at the gene level or clinical features. This study shows that patients with NS have a high predisposition for sonographic nerve enlargement and that the majority experience pain., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

Purpose: Selection for postgraduate medical training is high-stakes and complex. The learning value of assessments for selection has, thus far, been underexplored, limiting their uptake as potentially meaningful learning experiences. The aim of this study was to explore the learning value residency applicants derive from an intelligence, personality, motivation and competency selection assessment and what factors influence the experienced learning value., Methods: In Autumn 2020 and Spring 2021, we conducted individual semi-structured interviews with sixteen applicants for pediatric residency training. Selection outcomes were unknown at the time of the interview. Interviews were transcribed verbatim and thematically analyzed., Results: Participants reported that the assessment was valuable in fostering self-reflection and self-awareness, embracing self-acceptance, pursuing development goals, assessing professional fit, and harnessing motivational drivers in work. The experienced learning value was influenced by applicants' ability to interpret its results, their focus on the high-stakes selection process and concerns regarding the acceptability and credibility of the selection tool., Conclusions: While the selection assessment showed learning potential, its learning value was impeded by a preoccupation with the high-stakes nature of the selection procedure. Intentional integration of the selection assessment in the learning curriculum may play a pivotal role in realizing its learning potential.

Unexplainable gastrointestinal complaints occasionally occur after Roux-en-Y Gastric Bypass (RYGB) surgery. We therefor investigated the impact of microbiota composition and metabolites on gastrointestinal complaints after RYGB. In the BARICO study (Bariatric surgery Rijnstate and Radboudumc neuroimaging and Cognition in Obesity), microbiota and metabolites were measured before surgery, and 6, and 24 months after surgery. Gastrointestinal complaints were assessed with the Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) questionnaire 24 months after surgery. 65 participants (86.2 % female) with a mean age of 46.2 ± 6.0 years, and mean BMI of 41.2 ± 3.6 kg/m 2 were included. According to the IBS-SSS questionnaire, 32.3 % had moderate/severe gastrointestinal complaints 24 months after surgery. Microbiota alpha diversity remained stable, while beta diversity significantly changed over time. Bile acids and short-chain fatty acids were significantly higher, and inflammatory markers significantly lower after surgery. Barnesiella sp., Escherichia / Shigella sp., and Faecalibacterium prausnitzii correlated positively, while Akkermansia sp correlated inversely with gastrointestinal complaints. Patients with mild and moderate/severe gastrointestinal complaints showed higher levels of GLC-3S. These findings suggest involvement of microbiota and metabolite changes in gastrointestinal complaints after surgery. However, it remains unclear whether bacteria influence gastrointestinal complaints directly or indirectly. Further exploration is required for development of interventions against gastrointestinal symptoms after surgery., 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.)

Aim: To evaluate negative effects on oral motor function after concurrent submandibular and parotid (four-gland) botulinum neurotoxin A (BoNT-A) injections as a treatment for paediatric drooling., Method: This was a retrospective cohort study of 125 children (median age 7 years 7 months [interquartile range 4 years 5 months]) with developmental disabilities, including cerebral palsy, treated with four-gland injections. Most children (90.4%) were previously exposed to submandibular injections. Frequency, severity, and duration of negative effects on oral motor function (i.e. saliva swallowing, eating, drinking, articulation) were evaluated and compared to a reference cohort treated with submandibular injections., Results: Negative effects on oral motor function were reported in 45 children (36.0%), predominantly manifesting as eating-related problems (64.4%). Most negative effects (62.2%) were classified as mild and resolved within 4-weeks post-injunction (53.3%). Compared to the reference cohort, frequency (36.0% vs 33.0%) and duration (53.3% vs 53.6% resolving within 4 weeks) of negative effects were comparable, although problems were more often moderately severe (33.3% vs 10.1%)., Interpretation: While negative effects on oral motor function were relatively common after four-gland BoNT-A injections, most problems were mild and resolved promptly. No substantial differences to a reference cohort treated with submandibular injections were observed, although further research should establish the generalizability of these findings in a treatment-naive population. Nevertheless, when submandibular injections prove ineffective, clinicians can confidently consider four-gland injections., (© 2024 The Author(s). Developmental Medicine & Child Neurology published by John Wiley & Sons Ltd on behalf of Mac Keith Press.)

Background: SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG)., Methods: The Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient's age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed., Discussion: This study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines., Trial Registration: This study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee ('METC Oost-Nederland'; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland , file number: 2023-16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15)., (© 2024. The Author(s).)

Objectives: This survey was conducted to describe current European postnatal prophylaxis (PNP) and infant feeding policies with the aim of informing future harmonized guidelines., Methods: A total of 32 senior clinicians with relevant expertise, working in 20 countries within the European Region, were invited to complete a REDCap questionnaire between July and September 2023., Results: Twenty-three of the 32 invited paediatricians responded, representing 16/20 countries. There were multiple respondents from the same country for Italy (n = 5), the UK (n = 2), Germany (n = 2) and France (n = 2). All countries use risk stratification to guide PNP regimen selection. Nine out of 16 countries reported three risk categories, six out of 16 reported two, and one country reported differences in categorization. Criteria used to stratify risk varied between and within countries. For the lowest risk category, the PNP regimen reported ranged from no PNP to up to four weeks of one drug; the drug of choice reported was zidovudine, apart from one country which reported nevirapine. For the highest risk category, the most common regimen was zidovudine/lamivudine/nevirapine (20/23 respondents); regimen duration varied from two to six weeks with variation in recommended dosing. Guidelines support breastfeeding for infants born to people living with HIV in eight out of 16 countries; in the other eight, guidelines do not support/specify., Conclusions: Guidelines and practice for PNP and infant feeding vary substantially across Europe and within some countries, reflecting the lack of robust evidence. Effort is needed to align policies and practice to reflect up-to-date knowledge to ensure the vertical transmission risk is minimized and unnecessary infant HIV testing and PNP avoided, while simultaneously supporting families to make informed decisions on infant feeding choice., (© 2024 The Author(s). HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Objective: To study the impact of unilateral ovariectomy for ovarian tissue cryopreservation (OTC) on the function of the remaining ovary in girls with Turner syndrome., Design: A prospective cohort study as a follow-up of OTC in a research setting (the TurnerFertility trial, NCT03381300)., Setting: University Hospital., Patient(s): A total of 28 girls with Turner syndrome with follicles in their cryopreserved ovarian cortex tissue, aged 5-19 years. Of the 28 girls, 21 had a 45,X/46,XX mosaic karyotype; 5 had structural aberrations of the X chromosome; 1 had a 45,X monosomy; and 1 had a 45,X/47,XXX karyotype., Intervention(s): Girls were monitored annually after OTC for pubertal development and levels of antimüllerian hormone (AMH), follicle-stimulating hormone, luteinizing hormone, estradiol, and inhibin B., Main Outcome Measure(s): Thelarche, menarche, and onset of premature ovarian insufficiency., Result(s): The girls were monitored for a median duration of 3.4 years (maximum 6.6 years). The pubertal development of five prepubertal girls is still unknown; all were aged <10 years and had low gonadotropin and estradiol levels at the end of the follow-up. Seven of the eight girls of approximately pubertal age (10-12 years) experienced spontaneous thelarche, although one received medication to induce puberty. Eleven of the 14 girls between the ages of 14-17 years experienced spontaneous menarche; three other girls with thelarche still had ongoing puberty at the end of follow-up with normal gonadotropins and AMH levels above the detection limit. Approximately 6-12 months after OTC, a decline in AMH concentration was observed in 57% (16/28) of girls, followed by an increase in AMH concentration in the following years. Six of the total 28 girls started hormone replacement therapy because of symptoms of premature ovarian insufficiency, and all had AMH levels <0.50 μg/L before OTC., Conclusion(s): Pubertal development progressed after unilateral ovariectomy for OTC in most girls with Turner syndrome. Hormone replacement therapy was required within a few years for girls with unfavorable parameters before OTC, such as AMH levels <0.50 μg/L. Decisions regarding OTC should be personalized, considering the girl's preferences and specific characteristics., Clinical Trial Registration Number: NCT03381300-Preservation of ovarian cortex tissue in girls with Turner syndrome-Full Text View-ClinicalTrials.gov. Registered on: December 21, 2017. The first patient was recruited on January 1, 2018., Competing Interests: Declaration of Interests S.v.d.C. has nothing to disclose. S.N. has nothing to disclose. R.P. has nothing to disclose. D.B. has nothing to disclose. G.B. has nothing to disclose. M.F. has nothing to disclose. S.H. has nothing to disclose. S.d.K. has nothing to disclose. T.S. has nothing to disclose. S.S. has nothing to disclose. V.v.T. has nothing to disclose. A.V.S. has nothing to disclose. K.F. has nothing to disclose. J.v.d.V. has nothing to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction:  Anorectal malformations (ARMs) are rare congenital anomalies that involve the anus, rectum, and oftentimes the genitourinary tract. The management of ARM patients is complex, and many controversies exist. To address this issue, the European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM., Methods:  The Dutch Quality Standard for ARM served as the basis for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected, and recommendations were formed considering current evidence and/or expert consensus., Results:  Prenatal and neonatal diagnostic workup as well as postsurgical follow-up of anorectal, genitourinary tract, and neurologic system were reviewed. Seven new studies were identified. The panel adapted 13 recommendations, adopted 7, and developed 8 de novo. The availability of high-quality evidence was limited, and most recommendations were based on retrospective studies, case series, or expert opinion., Conclusion:  Patients with ARM and their families require highly specialized and comprehensive care from the prenatal period to adulthood. This guideline provides recommendations for a comprehensive diagnostic workup of children with ARM throughout their life that is applicable on a European level., Competing Interests: We would like to disclose that two of the authors of this adaptation report (I.D.B., C.E.J.S.) were also authors of the Dutch Quality Standard. However, it is important to note that neither I.D.B. nor C.E.J.S. has any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Introduction:  Being born with an anorectal malformation (ARM) can have profound and lifelong implications for patients and parents. Organization of care and communication between health care providers is an overlooked area of patient care. The European Reference Network eUROGEN for rare and complex urogenital conditions assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM., Methods:  The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering all available evidence, expert consensus, and the European context., Results:  Aspects pertaining to organization of care, patient/parent/health care provider communication, and referral and collaboration between providers caring for ARM patients were assessed. Two new studies were identified. In total, the panel adapted 12 recommendations, adopted 7, and developed 2 de novo. The overall level of newly found evidence was considered low and most recommendations were based on expert opinion., Conclusion:  Collaborative care and organization of care are gaining importance in the field of ARM. This guideline gives practical guidance on how to achieve better communication and collaboration between all involved parties, applicable at the European level., Competing Interests: We would like to disclose that two of the authors of this adaptation report (I.D.B., C.S.) were also authors of the Dutch Quality Standard. However, it is important to note that neither I.D.B. nor C.S. has any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Background: Recurrent respiratory tract infections (rRTIs) are a common reason for immunodiagnostic testing in children, which relies on serum antibody level measurements. However, because RTIs predominantly affect the respiratory mucosa, serum antibodies may inaccurately reflect local immune defences. We investigated antibody responses in saliva and their interplay with the respiratory microbiota in relation to RTI severity and burden in young children with rRTIs., Methods: We conducted a prospective cohort study including 100 children aged <10 years with rRTIs, their family members and healthy healthcare professionals. Total and polyreactive antibody concentrations were determined in serum and saliva (ELISA); respiratory microbiota composition (16S rRNA sequencing) and respiratory viruses (quantitative PCR) were characterised in nasopharyngeal swabs. Proteomic analysis (Olink) was performed on saliva and serum samples. RTI symptoms were monitored with a daily mobile phone application and assessed using latent class analysis and negative binomial mixed models., Results: Serum antibody levels were not associated with RTI severity. Strikingly, 28% of salivary antibodies and only 2% of serum antibodies displayed polyreactivity (p<0.001). Salivary polyreactive IgA was negatively associated with recurrent lower RTIs (adjusted OR 0.80, 95% CI 0.67-0.94) and detection of multiple respiratory viruses (adjusted OR 0.76, 95% CI 0.61-0.96). Haemophilus influenzae abundance was positively associated with RTI symptom burden (regression coefficient 0.05, 95% CI 0.02-0.08)., Conclusion: These results highlight the importance of mucosal immunity in RTI severity and burden, and suggest that the level of salivary polyreactive IgA and H. influenzae abundance may serve as indicators of infection severity and burden in young children with rRTIs., Competing Interests: Conflict of interest: D. Bogaert reports grants from GSK and OM Pharma, speaker fees from MedImmune, and a leadership role as Treasurer of the International Society of Pneumonia and Pneumococcal Diseases, all outside the submitted work. The authors have no other conflicts of interest to disclose., (Copyright ©The authors 2024.)

Nemaline myopathy (NM) is a congenital myopathy with generalised muscle weakness, most pronounced in neck flexor, bulbar and respiratory muscles. The aim of this cross-sectional study was to assess the Dutch NM patient cohort. We assessed medical history, physical examination, quality of life (QoL), fatigue severity, motor function (MFM), and respiratory muscle function. We included 18 of the 28 identified patients (13 females (11-67 years old); five males (31-74 years old)) with typical or mild NM and eight different genotypes. Nine patients (50 %) used a wheelchair, eight patients (44 %) used mechanical ventilation, and four patients (22 %) were on tube feeding. Spinal deformities were found in 14 patients (78 %). The median Medical Research Council (MRC) sum score was 38/60 [interquartile range 32-51] in typical and 48/60 [44-50] in mild NM. The experienced QoL was lower and fatigue severity was higher than reference values of the healthy population. The total MFM score was 55 % [49-94] in typical and 88 % [72-93] in mild NM. Most of the patients who performed spirometry had a restrictive lung function pattern (11/15). This identification and characterisation of the Dutch NM patient cohort is important for international collaboration and can guide the design of future clinical trials., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

In this narrative review, we summarize the current knowledge and applications of somatic near-infrared spectroscopy (NIRS), with a focus on intestinal, renal, limb, and multi-site applications in neonates. Assessing somatic oxygenation at various body locations in neonates may aid in the understanding of underlying pathophysiology of organ injury. Considering cerebral autoregulation may be active to protect the brain during systemic circulatory failure, peripheral somatic oxygenation may potentially provide an early indication of neonatal cardiovascular failure and ultimate hypoxemic injury to vital organs including the brain. Certain intestinal oxygenation patterns appear to be associated with the onset and course of necrotizing enterocolitis, whereas impaired renal oxygenation may indicate the onset of acute kidney injury after various types of hypoxic events. Peripheral muscle oxygenation measured at a limb may be particularly effective in the early prediction of shock in neonates. Using multi-site NIRS may complement current approaches and clinical investigations to alert for neonatal tissue hypoxemia, and potentially even guide management. However, somatic NIRS has its inherent limitations in regard to accuracy. Interpretation of organ-specific values can also be challenging. Last, currently there are limited prospective intervention studies, and clinical benefits need to be examined further, after the clarification of critical threshold-values. IMPACT: The assessment of somatic oxygenation using NIRS may contribute to the prediction of specific diseases in hemodynamically challenged neonates. Furthermore, it may give early warning signs for impending cardiovascular failure, and impaired cerebral circulation and oxygenation. We present a comprehensive overview of the literature on applications of NIRS to various somatic areas, with a focus on its potential clinical applicability, including future research directions. This paper will enable prospective standardized studies, and multicenter collaboration to obtain statistical power, likely to advance the field., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Drug metabolism in the intestinal wall affects bioavailability of orally administered drugs and is influenced by age. Hence, it is important to fully understand the drug metabolizing capacity of the gut to predict systemic exposure. The aim of this study was to investigate the potential of enteroids as a tool to study CYP3A4/5 -mediated metabolism in both children and adults. Bioconversion of midazolam, a CYP3A4/5 model substrate, was studied using enteroid monolayers as well as tissue explants in the Ussing chamber, both derived from pediatric [median (range age): 54 weeks (2 days - 13 years), n = 21] and adult (n = 5) tissue. Caco-2 cellular monolayers were employed as controls. In addition, mRNA expression of CYP3A4 was determined in enteroid monolayers (n = 11), tissue (n = 23) and Caco-2 using RT-qPCR. Midazolam metabolism was successfully detected in all enteroid monolayers, as well as in all tissue explants studied in the Ussing chamber, whereas Caco-2 showed no significant metabolite formation. The extracted fraction of midazolam was similar between enteroid monolayers and tissue. The fraction of midazolam extracted increased with age in enteroid monolayers derived from 0 to 70 week old donors. No statistically significant correlation was observed in tissue likely due to high variability observed and the smaller donor numbers included in the study. At the level of gene expression, CYP3A4 increased with age in tissues (n = 32), while this was not reflected in enteroid monolayers (n = 16). Notably, asymmetric metabolite formation was observed in enteroids and tissue, with higher metabolite formation on the luminal side of the barrier. In summary, we demonstrated that enteroids can be used to measure CYP3A4/5 midazolam metabolism, which we show is similar as observed in fresh isolated tissue. This was the case both in children and adults, indicating the potential of enteroids to predict intestinal metabolism. This study provides promising data to further develop enteroids to study drug metabolism in vitro and potentially predict oral absorption for special populations as an alternative to using fresh tissue., Competing Interests: Declaration of competing interest All authors declared no competing interests for this work., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: White blood cell count (WBC) is a widely used marker for the prediction of serious bacterial infection (SBI); however, previous research has shown poor performance. This study aims to assess the value of WBC in the prediction of SBI in children at the emergency department (ED) and compare its value with C reactive protein (CRP) and absolute neutrophil count (ANC)., Methods: This study is an observational multicentre study including febrile children aged 0-18 years attending 1 of 12 EDs in 8 European countries. The association between WBC and SBI was assessed by multivariable logistic regression, adjusting for age, CRP and duration of fever. Additionally, diagnostic performance was assessed by sensitivity and specificity. Results were compared with CRP and ANC., Results: We included 17 082 children with WBC measurements, of which 1854 (10.9%) had an SBI. WBC >15 had an adjusted OR of 1.9 (95% CI 1.7 to 2.1) for prediction of SBI, after adjusting for confounders. Sensitivity and specificity were 0.56 (95% CI 0.54 to 0.58) and 0.74 (0.73 to 0.75) for WBC >15, and 0.32 (0.30 to 0.34) and 0.91 (0.91 to 0.91) for WBC >20, respectively. In comparison, CRP >20 mg/L had a sensitivity of 0.87 (95% CI 0.85 to 0.88) and a specificity of 0.59 (0.58 to 059). For CRP >80 mg/L, the sensitivity was 0.55 (95% CI 0.52 to 057) and the specificity was 0.91 (0.90 to 0.91). Additionally, for ANC >10, the sensitivity was 0.55 (95% CI 0.53 to 0.58) and the specificity was 0.75 (0.75 to 0.76). The combination of WBC and CRP did not improve performance compared with CRP alone., Conclusion: WBC does not have diagnostic benefit in identifying children with an SBI compared with CRP and should only be measured for specific indications., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Epicutaneo-caval catheters (ECC) are vital in neonatal intensive care units (NICU) in enabling prolonged venous access. Despite their benefits, central line-associated bloodstream infections (CLABSI) pose a potential risk. The ECC removal procedure may contribute to an increased risk of post removal sepsis through biofilm release. Antimicrobial-impregnated ECCs have been proposed as a potential solution to prevent this complication, but research on their effectiveness in neonates is limited., Objective: To compare post-ECC or neonatal peripherally inserted central catheter (n-PICCs) removal sepsis rates when using conventional or antimicrobial-impregnated catheters in neonates., Methods: A retrospective, single center cohort analysis using 2019 data from 421 neonates after successful ECC insertion at the Women's Wellness and Research Center, a large tertiary level NICU in Qatar. The study systematically collected data on demographics, insertion, and removal as well as microbiology, and infection data. Statistical analyses compared conventional and antimicrobial ECCs, with a focus on the incidence of sepsis within 72 hr post-removal., Results: After excluding non-eligible, 349 cases were included in the analysis (138 conventional, 211 antimicrobial-impregnated). There were no significant demographic differences between the two groups. The CLABSI incidence was higher amongst the antimicrobial ECC group (4% vs 0.6%, p  = 0.031). Among the included neonates, the confirmed post-removal sepsis incidence was 4.3% (6 cases) for the conventional and 10% (21 cases) for the antimicrobial ECC groups, which was not statistically significant ( p  = 0.055)., Conclusion: The study noted a higher, but statistically insignificant, incidence of post removal sepsis when using antimicrobial-impregnated ECCs. This finding raises questions about the effectiveness of antimicrobial ECCs in preventing post-removal sepsis in this patient population. Further randomized trials are needed to assess the role of antimicrobial ECCs amongst neonates and to refine neonatal ECC care strategies., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction:  Anorectal malformations (ARMs) are rare birth defects affecting the anorectum and oftentimes the genitourinary region. The management of ARM patients is complex and requires highly specialized surgical and medical care. The European Reference Network eUROGEN for rare and complex urogenital conditions aimed to develop comprehensive guidelines for the management of ARM applicable on a European level., Methods:  The Dutch Quality Standard for ARM served as the basis for the development of guidelines. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from seven European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence, expert opinion, and the European context., Results:  Surgical and medical treatment of ARM, postoperative instructions, toilet training, and management of fecal and urinary incontinence were addressed. Seven new studies were identified. The panel adapted 23 recommendations, adopted 3, and developed 8 de novo. The overall level of newly found evidence was considered low., Conclusion:  Treatment of ARM patients requires a multidisciplinary team and expertise about anatomical and surgical aspects of the disease, as well as long-term follow-up. This guideline offers recommendations for surgical and medical treatment of ARM and associated complications, according to the best available evidence and applicable on a European level., Competing Interests: The authors would like to disclose that two of the authors of this adaptation report (I.D.B., C.S.) were also authors of the Dutch Quality Standard. However, it is important to note that neither I.D.B. nor C.S. has any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Introduction:  Anorectal malformations (ARMs) are complex congenital anomalies of the anorectal region, oftentimes also affecting the genitourinary system. Although successful surgical correction can often be achieved in the neonatal period, many children will experience functional problems in the long term. The European Reference Network for rare and complex urogenital conditions (eUROGEN) assembled a panel of experts to address these challenges and develop comprehensive guidelines for the management of ARM., Methods:  The Dutch Quality Standard for ARM served as the foundation for the development of guidelines applicable on a European level. Literature was searched in Medline, Embase, and Cochrane. The ADAPTE method was utilized to incorporate the newest available evidence. A panel of 15 experts from 7 European countries assessed currency, acceptability, and applicability of recommendations. Recommendations from the Dutch Quality Standard were adapted, adopted, or rejected and recommendations were formed considering the current evidence and/or expert consensus., Results:  Lifelong follow-up, integration, and transition of care were assessed. A total of eight new studies were identified. The panel adapted 18 recommendations, adopted 6, and developed 6 de novo. Overall, the level of evidence was considered low., Conclusion:  Successful lifelong follow-up and transition of care require a dedicated team of pediatric and adult specialist and an individually tailored patient-centered approach. This guideline summarizes the best available evidence on follow-up of ARM patients and provides guidance for the development of structured transition programs., Competing Interests: We would like to disclose that two of the authors of this adaptation report (IDB, CEJS) were also authors of the Dutch Quality Standard. However, it is important to note that neither IDB nor CEJS have any conflict of interest to declare and they did not advocate for any particular viewpoints or positions in relation to the content of the Dutch Quality Standard. No conflicting interests were declared from the other authors., (Thieme. All rights reserved.)

Two cases of neonatal splenic hemorrhage with acute cardiorespiratory failure are described in this report. The first case involves a full-term neonate who was found unresponsive without any witnesses and could not be successfully resuscitated. A postmortem diagnosis revealed a splenic hemorrhage. Second case is an extremely premature neonate who experienced a witnessed cardiovascular collapse on the 14th day of life. Rapid cardiovascular support was administered, resulting in a positive outcome. While splenic hemorrhage is commonly associated with traumatic events, these cases highlight the need of considering spontaneous splenic hemorrhages as a potential cause of acute neonatal compromise, even in the absence of birth-related trauma (e.g., asphyxia, prolonged labor, clavicle fractures, brachial plexus injuries). This report emphasizes the importance of including splenic hemorrhage timely in the differential diagnosis of neonatal cardiorespiratory instability, especially in the absence of more common diagnoses, and discusses the challenges associated with its recognition and treatment., (© 2024. The Author(s).)

Background: The aim of this systematic qualitative review was to give an overview of reference ranges defined as normal values or centile charts of regional tissue oxygen saturation measured by near-infrared spectroscopy (NIRS) in term and preterm neonates., Methods: A systematic search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials was performed. Additional articles were identified by manual search of cited references. Only human studies in neonates were included., Results: Nineteen studies were identified. Eight described regional tissue oxygen saturation during fetal-to-neonatal transition, six during the first 3 days after birth, four during the first 7 days after birth, and one during the first 8 weeks after birth. Nine described regional tissue oxygen saturation in term, nine in preterm neonates, and one in both. Eight studies published centile charts for cerebral regional tissue oxygen saturation, and only five included large cohorts of infants. Eleven studies described normal values for cerebral, muscle, renal, and abdominal regional tissue oxygen saturation, the majority with small sample sizes. Four studies of good methodological quality were identified describing centile charts of cerebral regional tissue oxygen saturation., Conclusions: In clinical settings, quality centile charts are available and should be the preferred method when using NIRS monitoring., Impact: Near-infrared spectroscopy (NIRS) enables a bed-side non-invasive continuous monitoring of tissue oxygenation. When using NIRS monitoring in a clinical setting, centile charts with good quality are available and should be preferred to normal values. High-quality reference ranges of regional tissue oxygenation in term and preterm born neonates are an important step toward routine clinical application of NIRS., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: Cerebral oxygenation monitoring utilising near-infrared spectroscopy (NIRS) is increasingly used to guide interventions in clinical care. The objective of this systematic review with meta-analysis and Trial Sequential Analysis is to evaluate the effects of clinical care with access to cerebral NIRS monitoring in children and adults versus care without., Methods: This review conforms to PRISMA guidelines and was registered in PROSPERO (CRD42020202986). Methods are outlined in our protocol (doi: 10.1186/s13643-021-01660-2)., Results: Twenty-five randomised clinical trials were included (2606 participants). All trials were at a high risk of bias. Two trials assessed the effects of NIRS during neonatal intensive care, 13 during cardiac surgery, 9 during non-cardiac surgery and 1 during neurocritical care. Meta-analyses showed no significant difference for all-cause mortality (RR 0.75, 95% CI 0.51-1.10; 1489 participants; I 2  = 0; 11 trials; very low certainty of evidence); moderate or severe, persistent cognitive or neurological deficit (RR 0.74, 95% CI 0.42-1.32; 1135 participants; I 2  = 39.6; 9 trials; very low certainty of evidence); and serious adverse events (RR 0.82; 95% CI 0.67-1.01; 2132 participants; I 2  = 68.4; 17 trials; very low certainty of evidence)., Conclusion: The evidence on the effects of clinical care with access to cerebral NIRS monitoring is very uncertain., Impact: The evidence of the effects of cerebral NIRS versus no NIRS monitoring are very uncertain for mortality, neuroprotection, and serious adverse events. Additional trials to obtain sufficient information size, focusing on lowering bias risk, are required. The first attempt to systematically review randomised clinical trials with meta-analysis to evaluate the effects of cerebral NIRS monitoring by pooling data across various clinical settings. Despite pooling data across clinical settings, study interpretation was not substantially impacted by heterogeneity. We have insufficient evidence to support or reject the clinical use of cerebral NIRS monitoring., (© 2022. The Author(s).)

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.)

Cerebrovascular reactivity defines the ability of the cerebral vasculature to regulate its resistance in response to both local and systemic factors to ensure an adequate cerebral blood flow to meet the metabolic demands of the brain. The increasing adoption of near-infrared spectroscopy (NIRS) for non-invasive monitoring of cerebral oxygenation and perfusion allowed investigation of the mechanisms underlying cerebrovascular reactivity in the neonatal population, confirming important associations with pathological conditions including the development of brain injury and adverse neurodevelopmental outcomes. However, the current literature on neonatal cerebrovascular reactivity is mainly still based on small, observational studies and is characterised by methodological heterogeneity; this has hindered the routine application of NIRS-based monitoring of cerebrovascular reactivity to identify infants most at risk of brain injury. This review aims (1) to provide an updated review on neonatal cerebrovascular reactivity, assessed using NIRS; (2) to identify critical points that need to be addressed with targeted research; and (3) to propose feasibility trials in order to fill the current knowledge gaps and to possibly develop a preventive or curative approach for preterm brain injury. IMPACT: NIRS monitoring has been largely applied in neonatal research to assess cerebrovascular reactivity in response to blood pressure, PaCO 2 and other biochemical or metabolic factors, providing novel insights into the pathophysiological mechanisms underlying cerebral blood flow regulation. Despite these insights, the current literature shows important pitfalls that would benefit to be addressed in a series of targeted trials, proposed in the present review, in order to translate the assessment of cerebrovascular reactivity into routine monitoring in neonatal clinical practice., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Perioperative applications of near-infrared spectroscopy (NIRS) to monitor regional tissue oxygenation and perfusion in cardiac and noncardiac surgery are of increasing interest in neonatal care. Complex neonatal surgery can impair adequate oxygen delivery and tissue oxygen consumption and increase the risk of neurodevelopmental delay. Coupled with conventional techniques, NIRS monitoring may enable targeted hemodynamic management of the circulation in both cardiac and noncardiac surgical procedures. In this narrative review, we discuss the application of perioperative NIRS in specific neonatal interventions, including surgical intervention for congenital heart defects, definitive closure of the patent ductus arteriosus, neurological and gastrointestinal disorders, and use of extracorporeal membrane oxygenation. We identified areas for future research within disease-specific indications and offer a roadmap to aid in developing evidence-based targeted diagnostic and management strategies in neonates. IMPACT: There is growing recognition that perioperative NIRS monitoring, used in conjunction with conventional monitoring, may provide critical hemodynamic information that either complements clinical impressions or delivers novel physiologic insight into the neonatal circulatory and perfusion pathways., (© 2021. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Objective: There is currently scarce data on the electroclinical characteristics of epilepsy associated with synapsin 1 (SYN1) pathogenic variations. We examined clinical and electro-encephalographic (EEG) features in patients with epilepsy and SYN1 variants, with the aim of identifying a distinctive electroclinical pattern., Methods: In this retrospective multicenter study, we collected and reviewed demographic, genetic, and epilepsy data of 19 male patients with SYN1 variants. Specifically, we analyzed interictal EEG data for all patients, and electro-clinical data from 10 epileptic seizures in 5 patients, using prolonged video-EEG monitoring recordings. Inter-ictal EEG functional connectivity parameters and frequency spectrum of the 10 patients over 12 years of age, were computed and compared with those of 56 age- and sex-matched controls., Results: The main electroclinical features of epilepsy in patients with SYN1 were (1) EEG background and organization mainly normal; (2) interictal abnormalities are often rare or not visible on EEG; (3) more than 60% of patients had reflex seizures (cutaneous contact with water and defecation being the main triggers) isolated or associated with spontaneous seizures; (4) electro-clinical semiology of seizures was mainly temporal or temporo-insulo/perisylvian with a notable autonomic component; and (5) ictal EEG showed a characteristic rhythmic theta/delta activity predominating in temporo-perisylvian regions at the beginning of most seizures. Comparing patients with SYN1 to healthy subjects, we observed a shift to lower frequency bands in power spectrum of interictal EEG and an increased connectivity in both temporal regions., Interpretation: A distinct epilepsy syndrome emerges in patients with SYN1, with a rather characteristic clinical and EEG pattern suggesting predominant temporo-insular involvement. ANN NEUROL 2024., (© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Objective: To investigate the perspectives of experienced parents regarding guidelines and personalisation for managing imminent extremely premature births (22-26 weeks gestational age (GA)) . The study examined four scenarios: no guideline, a guideline based on GA, a guideline based on GA plus other factors and a guideline based on a calculated prognosis., Design: Nineteen semistructured qualitative interviews were conducted with Dutch parents who experienced (imminent) extremely premature births between 23+5 and 26+2 weeks of gestation. Diversity was aimed for through purposive sampling from a database created prior to this study. Four of the parents opted for palliative care. Among the parents who chose intensive care, in nine cases the infant(s) survived., Results: All participants acknowledged the necessity of having a periviability guideline because it would provide valuable decision-making support, and counterbalance decisions solely based on parental instincts to save their infant. Parents preferred guidelines that considered multiple prognostic factors beyond GA alone, without overwhelming parents with information, because more information would not necessarily make the decision easier for parents. Personalisation was defined by parents mainly as 'being seen and heard' and associated with building relationships with healthcare professionals and effective communication between them and professionals., Conclusions: The results underscore the importance of having a periviability guideline including multiple prognostic factors to assist parents in making decisions at the limit of viability, and the importance of a personalised care approach to meet parental needs in the context of imminent extremely preterm birth., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: When extremely premature birth at the limits of viability is imminent, shared decision-making with parents regarding the infant's treatment is widely recommended. Aligning decisions with parental values can be challenging. So, this study aims to get insight into (1) what values parents considered important in their decision, (2) whether their decision was based on intuition and/or rational analysis and (3) parental suggestions on how to help explore and articulate values during prenatal counselling., Design: A qualitative study was performed among Dutch parents who experienced (imminent) extremely premature birth. Diversity was aimed for through purposive sampling. Semistructured interviews were conducted until saturation was achieved. Transcripts were coded and themes were derived from the data., Results: Nineteen interviews were performed. Results show what parents considered important in their decision, such as the infants' future, family life and 'giving a chance'. Most parents made their decision more intuitively rather than rationally, for others both coexisted. Particularly fathers and parents who opted for palliative comfort care experienced the decision as rational. Parents would have liked to explore values, but found it challenging. They suggested strategies and conditions to help explore and articulate their values during counselling, such as a multidisciplinary approach., Conclusions: Various considerations and underlying values were found to be important. Parents recognise the influence of emotions and intuition in decision-making and struggle to articulate their values, emphasising the need for guidance. Healthcare providers should engage in open, personalised discussions to facilitate value exploration, enabling informed decisions aligned with parental values., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Children with PTEN hamartoma tumor syndrome (PHTS) are at increased risk for developing thyroid abnormalities, including differentiated thyroid carcinoma (DTC). The Dutch PHTS guideline recommends ultrasound surveillance starting from age 18. Since the literature describes PHTS patients who developed DTC before age 18, the Dutch PHTS expertise centre has initiated annual ultrasound surveillance starting from age 12. The purpose of this study was to identify the yield of thyroid ultrasound surveillance in children., Methods: A retrospective single centre cohort study was conducted. Pediatric PHTS patients who received thyroid ultrasound surveillance before age 18 between 2016-2023 were included. Patients' medical records have been reviewed. Primary outcomes included prevalence and time to develop thyroid nodules ≥10mm, nodular growth, goiter, thyroiditis and DTC. Descriptive statistics and Kaplan-Meier analyses were performed., Results: Forty-three patients were included. Two patients (5%) were diagnosed with DTC at ages 12 and 17. Both DTCs were identified as minimally invasive follicular carcinoma at stages pT3NxMx and pT1NxMx respectively. A total of 84% were diagnosed with thyroid abnormalities at a median age of 12 years (range 9-18). Most common findings were benign, including nodular disease (74%), goiter (30%) and autoimmune thyroiditis (12%). Nodular growth was observed in 14 patients (33%) resulting in (hemi)thyroidectomy in 7 patients (16%)., Conclusion: Thyroid ultrasound surveillance resulted in the detection of DTC in 2/43 PHTS patients before age 18. These findings support the recommendation to initiate thyroid ultrasound surveillance in children at least from age 12, preferably within an expertise centre.

Background Research on how tools can support coaching of residents is lacking. We hypothesized that an electronic assessment (EA) tool presently applied in selection for residency training, which measures cognitive capacities, personality, motivational drivers, and competencies, could be a valuable tool to support coaching of residents. Objective This study explored the value and limitations, as perceived by residents and coaches, of using the EA to facilitate a single coaching session. Methods This qualitative study took place in the East-Netherlands Training District from August 2022 to April 2023. Volunteer residents and professionally trained coaches engaged in a single coaching session, using the EA. A purposive sample of 7 residents in different training years from 3 specialties were recruited via the training secretariats. Individual interviews with residents were conducted 1 week and 3 months after the coaching session. Data collection ceased when data sufficiency was considered reached. A focus group interview was held with the 3 participating coaches. Thematic analysis was employed to identify themes. Results Participants considered the EA a supportive tool, but not the core focus in the coaching process. Coaching sessions remained guided by residents' individual needs. The EA was considered supportive in fostering residents' self-reflection and awareness, accelerating the coaching process by enhancing preparedness and fostering familiarity among residents and coaches. The perceived value of the EA for the coaching process was affected by residents' and coaches' attitudes toward the tool. Conclusions The EA played a supportive but nonprominent role in the coaching of residents.

Background: Vesico-ureteral reflux (VUR) is a common associated urological anomaly in anorectal malformation (ARM)-patients. High-grade VUR requires antibiotic prophylaxis to prevent urinary tract infections (UTI's), renal scarring and -failure. The exact prevalence of high-grade VUR in ARM patients is unknown. Hence, the aim of this study was determining the incidence of high-grade VUR in ARM-patients, and its associated risk factors., Methods: A multicenter retrospective cohort study was performed using the ARM-Net registry, including data from 34 centers. Patient characteristics, screening for and presence of renal anomalies and VUR, sacral and spinal anomalies, and sacral ratio were registered. Phenotypes of ARM were grouped according to their complexity in complex and less complex. Multivariable analyses were performed to detect independent risk factors for high-grade (grade III-V) VUR., Results: This study included 2502 patients (50 % female). Renal screening was performed in 2250 patients (90 %), of whom 648 (29 %) had a renal anomaly documented. VUR-screening was performed in 789 patients (32 %), establishing high-grade VUR in 150 (19 %). In patients with a normal renal screening, high-grade VUR was still present in 10 % of patients. Independent risk factors for presence of high-grade VUR were a complex ARM (OR 2.6, 95 %CI 1.6-4.3), and any renal anomaly (OR 3.3, 95 %CI 2.1-5.3)., Conclusions: Although renal screening is performed in the vast majority of patients, only 32 % underwent VUR-screening. Complex ARM and any renal anomaly were independent risk factors for high-grade VUR. Remarkably, 10 % had high-grade VUR despite normal renal screening. Therefore, VUR-screening seems indicated in all ARM patients regardless of renal screening results, to prevent sequelae such as UTI's, renal scarring and ultimately renal failure., Type of Study: Observational Cohort-Study., Level of Evidence: III., Competing Interests: Conflict of interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: To deliver high-quality collaborative care, residents need to be trained across the boundaries of their medical specialty (intraprofessional learning). The current literature does not provide insights into the underlying processes that influence intraprofessional learning. The aim of this study was to gain insight into the processes that occur during intraprofessional workplace learning in residency training, by exploring everyday intraprofessional interactions experienced by residents, with the ultimate objective of improving collaborative practice., Method: We conducted a focused ethnography using field observations and in-depth interviews with residents at an academic children's hospital in the Netherlands. In 2022, nine residents from four different medical specialties were shadowed and/or interviewed. In total, >120 hours of observation and 10 interviews were conducted. Data collection and analysis were conducted iteratively and discussed in a research team with diverse perspectives, as well as with a sounding board group of stakeholders., Results: Residents were involved in numerous intraprofessional interactions as part of their daily work. We identified three themes that shed light on the underlying processes that occur during intraprofessional workplace learning: (1) residents' agency, (2) ingroups and outgroups and (3) communication about intraprofessional collaboration., Conclusions: Collaborative practice offers many intraprofessional learning opportunities but does not automatically result in learning from, with and about other specialties to improve intraprofessional collaborative care. Overarching the identified themes, we emphasise the pivotal role of the resident-supervisor dyad in facilitating residents' engagement in the learning opportunities of complex intraprofessional care. Furthermore, we propose that promoting deliberate practice and shared responsibility in collaborative care are crucial to better prepare residents for their roles and responsibilities in delivering high-quality collaborative patient care., (© 2023 The Authors. Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

We describe a premature hydropic infant with Noonan syndrome and a therapy refractory chylothorax. This was shown to be due to a central conducting lymphatic anomaly. After therapy with a MEK-inhibitor the infant recovered clinically and radiologically completely, possibly by restoring lymphatic valve function., Competing Interests: All authors have no conflict of interest to declare., (© 2024 The Author(s). Clinical Case Reports published by John Wiley & Sons Ltd.)