European Journal of Pediatrics最新文献

To evaluate the effects of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) polymorphisms on the plasma concentrations, efficacy, and safety of lacosamide (LCM) among pediatric patients with epilepsy. This prospective study was conducted at two institutions. It included 215 pediatric patients with epilepsy who were under LCM. LCM plasma concentrations were quantified using validated ultra-performance liquid chromatography. CYP2C9 and CYP2C19 polymorphisms were analyzed in all pediatric patients in our hospital's Institute of Clinical Pharmacy research laboratory through polymerase chain reaction, agarose gel electrophoresis detection, gel recovery, and other steps. Seizure frequencies were recorded 3, 6, and 12 months after initiating LCM therapy and compared with the baseline monthly frequency. Clinical information, including efficacy, toxicity, and concomitant drugs, was collected. A total of 158 pediatric patients (73.5%) responded to LCM therapy. Of them, 77 patients reported adverse events while under LCM. The LCM plasma concentration was linearly correlated with its daily dose (r = 0.26, p < 0.001). Patients with adverse events reported higher LCM plasma concentrations (7.9 ± 4.0 µg/mL) than patients without adverse events (6.8 ± 3.0 µg/mL; p < 0.05). The poor metabolizer (PM) group demonstrated the highest concentration-to-dose ratio (1.7 ± 0.7 μg·mL^-1·kg·mg^-1) than the extensive metabolizer, intermediate metabolizer, and ultra-rapid metabolizer groups (0.8 ± 0.4, 1.0 ± 0.5, and 0.8 ± 0.4 μg·mL^-1·kg·mg^-1, respectively). The PM group comprised the highest proportion of patients with effective LCM (9/11, 81.8%) and adverse events (7/11, 63.6%).

Conclusion: LCM plasma concentrations were strongly associated with its clinical efficacy and toxicity. CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in pediatric patients with epilepsy. CYP2C19 PMs with two no-function alleles are likely to have higher LCM plasma concentrations.

What is known: • LCM is metabolized by CYP2C19, CYP2C9, and CYP3A4 into pharmacologically inactive O-desmethyl-lacosamide; it primarily undergoes renal elimination. • Plasma LCM concentrations in patients treated with the recommended dose vary widely between and within individuals variability.

What is new: • CYP2C19 polymorphisms affect the plasma concentration and treatment efficacy in Chinese pediatric patients with epilepsy. • CYP2C19 PMs with two no-function alleles are likely to have higher plasma LCM concentrations.

Glutaric aciduria type 1 (GA1) is a rare metabolic disorder characterized by a deficiency in the enzyme glutaryl-CoA dehydrogenase. This study aims to present the clinical, biochemical, genetic, and neuroimaging findings of GA1 patients, emphasizing the importance of early detection and the potential benefits of incorporating GA1 into NBS programs. The demographic, clinical, and laboratory findings of GA1 patients were reviewed retrospectively. This study presents the clinical, biochemical, genetic, and neuroimaging findings of 15 patients (six males, nine females) from 13 families diagnosed with GA1. The median age at diagnosis was 20 months, and the median follow-up period was 72 months. Developmental delay was observed in 66.7% of patients, with 46.7% experiencing seizures and 33.3% suffering from encephalopathic crises. Biochemical analyses showed elevated levels of glutaric acid and 3-hydroxyglutaric acid in 93.3% and 80% of patients, respectively. Genetic testing identified the p.Arg402Trp variant in 53.3% of patients. Neurological evaluations revealed delays in motor and speech development, with 66.7% of patients never achieving the ability to walk. Cranial MRI indicated white matter changes in all patients and basal ganglia involvement in 93.3%. Despite significant biochemical improvements with treatment in glutaric acid levels and head circumference over time, neurological deficits remain unchanged. Growth parameters such as body weight showed significant decreases due to poor neurological outcomes.

Conclusion: The study underscores the importance of early diagnosis and intervention to mitigate severe neurological outcomes. Our findings highlight the need for incorporating GA1 into newborn screening programs to ensure timely diagnosis and treatment.

What is known: • Glutaric aciduria type 1 (GA1) is a rare metabolic disorder caused by a deficiency of glutaryl-CoA dehydrogenase. If untreated, it often leads to severe neurological complications. Early diagnosis and treatment are crucial for improving clinical outcomes in GA1 patients.

What is new: • This study presents comprehensive data from a cohort of 15 Glutaric aciduria type 1 (GA1) patients, detailing their biochemical, genetic, clinical, and neuroimaging findings. Drawing attention to the severe neurological findings in late-diagnosed patients underscores the critical importance of including GA1 in newborn screening programs to enhance early diagnosis and prevent severe outcomes.

Health care disruptions associated with the COVID-19 pandemic have caused persistent decreases in human papillomavirus (HPV) vaccination uptake in Germany. The objective of this study was to estimate the cumulative deficit in first doses of the HPV vaccine administered to girls in Germany since the beginning of the pandemic and the projected time to recover from this deficit at different catch-up vaccination uptake levels, focusing on girls 9-14 years of age. This study used a published HPV vaccination modeling tool. Retrospective vaccination data from 2019 were used to calculate the baseline vaccination rate, while data from 1 January 2020 to 31 December 2023 were used to estimate the size and duration of the HPV vaccination deficit accrued since the beginning of the COVID-19 pandemic. We modeled scenarios in which the rate of monthly vaccinations increased from the 2023 average to 5%, 10%, or 15% above the baseline 2019 level. The average monthly number of first doses of HPV vaccine administered to girls 9-14 years of age was 7.4% below the 2019 baseline level in 2020, 21.2% below baseline in 2021, 21.0% below baseline in 2022, and 19.5% below baseline in 2023. At a catch-up vaccination uptake of 5-15% above the 2019 baseline, there would be an estimated accumulated deficit of 267,052-285,798 first doses by 31 December 2024 that would clear between October 2029-April 2040. A catch-up vaccination uptake of 12.3% (11.9-12.7%) every month above baseline would be needed to clear the accumulated deficit by the end of 2030. Conclusions: Significant HPV vaccination deficits have accrued in Germany since the beginning of the COVID-19 pandemic. Sustained efforts to vaccinate the affected cohorts are now needed to mitigate the long-term impacts of the vaccination deficit. What is known: • Health care disruptions associated with the COVID-19 pandemic have caused persistent decreases in human papillomavirus (HPV) vaccination uptake in Germany. What is new: • Our model projected that the HPV vaccination deficit would be cleared between October 2029 (15% above the 2019 baseline level) and April 2040 (5% above the 2019 baseline level). • A catch-up rate of 12.3% (11.9-12.7%) above the 2019 baseline level would be needed to clear the HPV vaccination deficit by 31 December 2030. • Sustained efforts to vaccinate the affected cohorts are now needed to mitigate the long-term impacts of the accrued vaccination deficit on mortality, morbidity, and health care costs from HPV-associated diseases.

3 M syndrome is a well-known autosomal recessive skeletal genetic disorder caused by biallelic pathogenic variants in the CUL7, OBSL1, and CCDC8 genes. Affected individuals exhibit profound pre- and postnatal growth retardation, distinctive facial features with normal intelligence. This study aims to provide insight into the comprehensive evaluation of clinical, laboratory, and radiological findings, expand the mutational spectrum of the disease, and establish a genotype-phenotype correlation in the present cases. A total of 25 patients from 19 unrelated families were included in the study. Genetic etiology was determined in probands through the utilization of Sanger sequencing and/or targeted gene panel analysis. The clinical, laboratory, and genetic features of all patients at admission and during follow-up were documented. Genotype-phenotype correlation was carried out in the CUL7 and OBSL1 groups. The genetic etiology was established in all patients (n = 25/25, 100%). We identified 15 distinct variants in CUL7, OBSL1, and CCDC8 genes, with eleven being novel. CUL7 variants were present in 13 patients (n = 13/25, 52%), while OBSL1 variants were found in 11 patients (n = 11/25, 44%). No notable distinctions were found in mean birth weight, height, and standard deviation scores between the CUL7 and OBSL1 mutation groups (p > 0.05). Patients with CUL7 variants exhibited significantly lower height standard deviation scores both at admission and at the last examination, as well as lower weight standard deviation scores at the last examination, compared to those with OBSL1 variants (p < 0.05).

Conclusion: To date, genotype-phenotype correlations have been identified in a limited number of studies. Further research involving larger cohorts is necessary to solidify these correlations.

What is known: • 3M syndrome is a well-known skeletal dysplasia caused by biallelic pathogenic variants in CUL7, OBSL1, and CCDC8 genes. • Despite genetic heterogeneity, clinical, and radiologic features show homogeneity in affected individuals.

What is new: • Genotype-phenotype correlations have been established in limited studies. • The CUL7 group exhibited significantly lower height SDS at both admission and the final evaluation and lower weight SDS at the final examination compared to the OBSL1 group. • The frequency of variants in the OBSL1 gene among Turkish patients exceeds the rates reported in the literature. • Gradenigo syndrome is being reported for the first time in a patient with 3M syndrome.

Ankle sprains are common injuries in pediatric populations, yet current literature lacks consensus on optimal management strategies. This study aimed to compare the effectiveness of non-restraint treatment versus bandaging in children with mild ankle sprains, focusing on functional recovery and pain management.A single-center, open-label, non-inferiority randomized clinical trial was conducted at a pediatric emergency service. Patients aged 5-16 years with mild ankle sprains were included. Participants were randomized in a 1:1 ratio to receive either a standardized functional bandage or only general measures with non-restraint. The primary endpoints were a 10-point difference in the OXAFQ-C and a 2-point difference in pain intensity at day 5 after discharge. A total of 113 participants were randomly assigned to receive a functional bandage (n = 51) or non-restraint measures (n = 62). At day 5, the OXAFQ-C score in the non-restraint group was 76.59 (SD 15.51) and 69.71 (SD 15.24) in the restraint group, with a mean difference of 6.295 (90% CI - 0.058 to 12.647). The mean difference in pain intensity was 0.048 (90% CI - 0.741 to 0.838). No differences were observed in the OXAFQ-C scores or pain intensity at 14 and 30 days. Conclusions: This single-center, randomized clinical trial demonstrates that non-restraint is non-inferior to bandaging for functional recovery and short- to medium-term pain management in pediatric patients with mild ankle sprains. The treatment was very well accepted among patients and no adverse effects were reported.Trial registration: Retrospectively registered in January 2024 on clinicaltrials.org with identifier: NCT06189625. What is Known • Current literature lacks consensus on optimal ankle sprain management, with no evidence supporting non-restraint approaches. Guidelines recommend immobilization despite insufficient comparative data on different restraint systems. Some studies seem to demonstrate that early mobilization may offer better outcomes. What is New • This study contributes novel evidence by demonstrating the non-inferiority of non-restraint treatment compared to bandaging in pediatric ankle sprains. It highlights the safety and efficacy of early mobilization without restraint, suggesting a potential shift in standard management practices.

The diagnosis of suspected physical abuse (SPA) remains a continuous challenge to paediatric healthcare. Several studies have reported that computed tomography (CT) improves the evaluation of SPA. This study aims to systematically review the diagnostic performance of CT compared to radiography in investigating skull and chest fractures for SPA. Multiple databases were searched, using PRISMA methods, from 2008 to August 2024 for relevant studies in English. Two reviewers independently screened and selected relevant studies using Covidence software. The QUADAS-2 tool was used for the quality assessment of the included papers. Sensitivity, specificity and the effective radiation dose of CT and radiography from the included studies were extracted. Pooled sensitivity and specificity were calculated with their respective 95% confidence intervals (CI). GRADE criteria were used to appraise the overall quality of the synthesis. Of the 4057 identified papers, 10 met the inclusion criteria; all 10 included skull and/or chest. The overall sensitivity and specificity of CT were 96.5% (95% CI, 94.9-97.7%) and 99.5% (95% CI, 99.1-99.8%), respectively. Compared to the sensitivity and specificity of radiography, 59.8% (95% CI, 56.2-63.3%) and 99.7% (95% CI, 99.3-99.8%), respectively. Conclusion: CT sensitivity is significantly higher than radiography in detecting rib and skull fractures for SPA. The effective dose for chest LDCT is comparable to that of radiography. Therefore, LDCT should be considered a potential replacement to radiography in SPA investigations for the chest and skull. What is Known • CT shows higher diagnostic performance than radiography in detecting skull and rib fractures in the diagnosis of SPA. What is New • When a head CT scan is acquired for SPA diagnosis at any age, the two-view skull radiograph can be safely eliminated from the Skeletal Survey protocol, likewise, Chest CT can replace chest radiography for SPA diagnosis of rib fractures. • The effective dose and image quality of low-dose chest CT is comparable to that of two-view chest radiography for SPA diagnosis.

The purpose of this study is to compare the effects of two different ways of stopping incubator humidification on episodes of hypothermia, hyperthermia, hyponatraemia, hypernatraemia, or skin injury. The design is a single site, two-armed, parallel, randomised, clinical trial conducted between April 2019 and March 2022. The setting was a quaternary referral and teaching hospital in Queensland, Australia. There were 140 extremely preterm infants, born < 28 weeks gestational age (GA). Intervention groups were (1) cease humidity: incubator humidification turned from 80% to off at 00.01am on day 8 of life (n = 70); or (2) gradually reduce humidity: incubator humidification reduced by 5% at 00:01 of each day from day 8 until ceased on day 14 (n = 70). The primary outcome was episodes of temperature instability: defined as either hypothermia < 36.5 °C or hyperthermia > 37.5 °C. Secondary outcomes included episodes of hyponatraemia: hypernatraemia or skin injury. One hundred forty infants were enrolled, 70 in each group. No statistically significant differences for any outcomes. Hyperthermia: 77% (n = 54) in the cease group and 73% (n = 51) in the gradual reduction group (P = 0.70). Hypothermia: 53% (n = 37) in the cease group and 37% (n = 26) in the gradual reduction group (P = 0.09). The number of hyponatraemic events was similar for both groups (P = 0.73), as for hypernatraemic events (P = 0.3). Skin injury in week 2 of life: 63% in the cease group and 67% in the gradual reduction group (P = 0.72).

Conclusions: Ceasing or gradually reducing incubator humidification after day 7 of life had no effect on the number of episodes of hypothermia or hyperthermia in this cohort of extremely preterm infants (EPTI). There was also no effect on the number of episodes of hyponatraemia or hypernatraemia.

Trial registration: ANZCTR.org.au (Australia New Zealand Clinical Trials Registry). ACTRN 1261 9000 266167 Registered 21/2/2019.

What is known: • Incubator humidification is a widely accepted and routine practice in the management of EPTI as it influences transepidermal water loss (TEWL) and supports thermoregulation. However, weaning practices remain varied and inconsistent across the globe. • There remains a paucity of data to inform specific evidenced-based humidification practices.

What is new: • Ceasing or gradually reducing incubator humidification after 7 days had no effect on temperature stability, serum sodium levels, or frequency of skin injury in this cohort of EPTI between day 8 and day 14. • There is no apparent benefit in prolonging incubator humidity beyond day 7 of life in these EPTI.

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.

Physical activity measured by accelerometry (PA-accelerometry) is used as an indicator of physical capacity in chronic diseases. Currently, only fragmented age ranges of reference percentile curves are available for European children and adolescents. This study aimed to provide age- and sex-specific percentiles for physical activity measured by hip-worn accelerometry derived throughout the full age range of European children and adolescents. Individual-level population-based PA data measured by accelerometry from HELENA and IDEFICS/I.Family studies were pooled and harmonized. Together these studies involved children and adolescents aged 2-18 years from 12 European countries. Primary outcomes included averaged counts per minute (CPM), sedentary time (SED), light PA (LPA) and moderate-to-vigorous PA (MVPA). Generalized Additive Models for Location, Scale and Shape were used to derive age- and sex-specific reference percentile curves for these outcomes. The combined cohort consisted of 11,645 children and adolescents aged 2 to 18 years who contributed 14,610 valid accelerometry recordings, with a median accelerometer wear time of 6 days. This dataset allowed for the construction of age- and sex-specific reference percentile curves for CPM, SED, LPA, and MVPA. The curves demonstrated varying trends and variability across age groups.

Conclusions: This study provides age- and sex-specific percentile curves for PA-accelerometry in European children and adolescents, addressing a current gap in the availability of full-age range reference data. These curves based on healthy children and adolescents can be used by clinicians, researchers, and policymakers to interpret PA-accelerometry measurements, track physical activity trends, and evaluate treatment responses and health interventions.

What is known: • Daily physical activity (PA) is considered an important measure in various paediatric conditions. Existing reference data for PA in European children based on hip-worn accelerometers are limited to specific age ranges, and comprehensive data covering the full age range are lacking.

What is new: • The study provides age- and sex-specific reference curves for PA derived by hip-worn accelerometers in European children and adolescents. These curves aid clinicians, researchers, and policymakers in interpreting PA measurements and tracking trends over time in European children.