Pediatric Investigation最新文献

Importance: Although macrolides combined with glucocorticoid therapy have demonstrated efficacy in preventing long-term pulmonary lesions of severe Mycoplasma pneumoniae pneumonia (MPP), evidence regarding glucocorticoid dose is lacking.

Objective: To evaluate the effects of low- and high-dose methylprednisolone on the risk of long-term pulmonary lesions for children with severe MPP when combined with azithromycin.

Methods: This randomized, parallel-controlled, multicenter clinical trial was conducted in mainland China and enrolled pediatric patients hospitalized with severe MPP. A total of 424 enrolled patients were randomized (allocation ratio of 1:1) to azithromycin combined with either a low-dose [2 mg/(kg·d)] or a high-dose [10 mg/(kg·d)] methylprednisolone treatment for 3 d followed by tapering over 12 d. The primary outcome was the incidence of composite adverse outcomes, including atelectasis, bronchiectasis, or bronchiolitis obliterans 6 months after treatment.

Results: A total of 118 (27.8%) developed adverse pulmonary lesions at 6 months after treatment; 66 of 211 (31.3%) in the high-dose methylprednisolone group and 52 of 213 (24.4%) in the low-dose group, respectively. The risk ratio of long-term pulmonary lesions in a high-dose group to those in a low-dose group was 1.28 (95% confidence interval [95% CI]: 0.94-1.75). In addition, the risk of hypertension in the high-dose group (8.1%, 17 of 211) was higher than that in the low-dose group (1.4%, three of 213), with a risk ratio of 5.72 (95% CI: 1.70-19.23).

Interpretation: Azithromycin combined with low-dose methylprednisolone demonstrates non-inferior efficacy in reducing pulmonary lesions at 6-month follow-up compared to combined with high-dose methylprednisolone while exhibiting a more favorable safety profile.

Importance: Hypertensive disorders in pregnancy (HDPs) are common and increase the risk of maternal and fetal morbidity and mortality. HDPs may impact fetal growth; however, sex-specific effects have been understudied.

Objective: To examine whether sex-specific differences exist in the association between HDPs and birthweight and placental weight.

Methods: A birth cohort based in Detroit, Michigan, was utilized (n = 1258). HDPs and birthweight were abstracted from medical records; placental weight was obtained from placental pathology reports. Linear regression was used to model sex-specific associations, after multiple imputation, confounder adjustment, and inverse probability weighting to account for selection bias.

Results: The primary analysis included all pregnancies (n = 853), while the secondary analysis included those sent for placental pathology, reflective of complicated pregnancies (n = 165). In the primary analysis subset, males of mothers with gestational hypertension had birthweight Z-scores that were on average 0.90 standard deviations higher, but this association was not found among females (interaction P = 0.019; male β [95% confidence interval {CI}]: 0.90 [0.28, 1.52]; female β [95% CI]: -0.12 [-0.65, 0.41]). However, in the subset of complicated pregnancies, female mothers with gestational hypertension also had reduced birthweight (interaction P = 0.013; male β [95% CI]: 1.50 [0.15, 2.86]; female β [95% CI]: -1.14 [-2.13, -0.16]). For fetoplacental weight ratio, any HDP was associated with a lower ratio among females only (interaction P = 0.028; male β [95% CI]: -0.04 [-0.71, 0.64]; female β [95% CI]: -0.95 [-1.57, -0.33]).

Interpretation: Male fetuses may prioritize growth, whereas females may prioritize placental development when exposed to HDPs.

Importance: Cornelia de Lange syndrome (CdLS) is a rare genetic disorder characterized by a spectrum of developmental and physical anomalies. Understanding the clinical and genetic landscape of CdLS in pediatric patients is crucial for improving diagnosis and management.

Objective: To investigate the clinical and genetic characteristics of 19 pediatric patients with CdLS in China, with a focus on identifying the association between genetic variants and clinical severity.

Methods: We performed whole exome sequencing on 19 patients with CdLS and compared their clinical characteristics based on the presence of null variants.

Results: Among the 19 patients, 16 (84.2%) showed global developmental delays and 14 (73.7%) experienced prenatal growth retardation and short stature. Craniofacial anomalies-short noses and anteverted nares were observed in 94.7% (18/19) of patients. Small hands and/or feet were present in 16 patients, skin manifestations (hirsutism or mottled skin) in six, and hearing loss in four. Genetic testing identified 19 variants in NIPBL (78.9%, 15/19), SMC1A (10.5%, 2/19), and RAD21 (10.5%, 2/19), including 13 novel variants. NIPBL null variants correlated significantly with more severe growth impairments (P = 0.016) and microcephaly (P = 0.004). Although complete protein function loss often correlated with more severe clinical presentations, no significant difference in clinical scoring was observed (P = 0.600). Three patients treated with recombinant human growth hormone showed heterogeneous responses.

Interpretation: This study highlights the clinical heterogeneity of CdLS and suggests a potential link between specific genetic variants and disease severity. These findings warrant further research to optimize treatments and better understand the functional impact of these genetic variants.

Importance: Preterm birth is a leading cause of perinatal morbidity and mortality and a priority area for care improvement globally, including in Aotearoa New Zealand. To improve the efficiency and impact of preterm birth research and clinical care advancement, it is important to use standardized outcomes across studies and clinical sites.

Objective: To identify existing core outcome sets related to preterm birth and use consensus methodology to develop a national core outcome set applicable for use in Aotearoa New Zealand.

Methods: A systematic search identified established core outcome sets relevant to preterm birth. The core outcomes were reviewed, similar terms were merged, and outcomes irrelevant to preterm birth were excluded. The resultant outcomes were included in a three-round online Delphi survey involving people with lived experience, healthcare professionals, and researchers, with focussed recruitment of Māori, Pacific, and Indian participants. Outcomes were included if >70% of participants in each stakeholder group scored the outcome as critically important.

Results: Eighteen established core outcome sets, containing 348 outcomes, were identified. Seventy-three distinct relevant outcomes were included for prioritization. Fifty-two participants, including 25 with lived experience, completed all rounds of the Delphi survey, with 15 outcomes included in a resultant preterm birth core outcome set.

Interpretation: Core outcomes relevant to preterm birth were systematically identified. A national preterm birth core outcome set, informed by people with lived experience and perinatal healthcare professionals and researchers, was developed and will allow meaningful comparisons over time and across groups.

Respiratory syncytial virus (RSV) is one of the most common respiratory pathogens in children under 5 years of age worldwide and it seriously threatens children's health. In recent years, great progress has been made in the field of RSV-related diseases. To better guide and standardize the clinical diagnosis and treatment of RSV infection and to improve the prevention and control of RSV infection in children in China, a guideline development group was established by experts in children's respiratory infections and neonatal health care, clinical epidemiology, health statistics, virology, evidence-based medicine, health economics, and other related fields. Following the standard methodology for developing clinical practice guidelines, 12 clinical questions concerning the detection, diagnosis, treatment, and prevention of RSV infection were proposed from the perspective of clinical practice. Finally, the "Guideline for the diagnosis, treatment, and prevention of RSV infection in children in China" was formulated to improve the clinical diagnosis, treatment, prevention, and control of RSV infection-related diseases in children in China.

Importance: Myopia of Marfan syndrome (MFS) may be ascribed to crystalline lens subluxation, abnormal corneal curvature, and increased globe axial length. Few studies have reported these measures in MFS children who did or did not have ectopia lentis (EL).

Objective: To measure eye findings longitudinally in MFS children with and without EL.

Methods: A prospective, comparative case study was conducted on 24 MFS children (48 eyes). EL necessitated lensectomy and intraocular lens implantation surgery in 16/24 children (mean age 5.6 ± 2.8 years). The remaining 8/24 MFS children (mean age 11.2 ± 4.2 years) had no EL and were phakic. Follow-up was a mean of 3.1 ± 0.5 years. At follow-up visits, visual acuity, tonometry, refractive error, central corneal thickness (CCT), biomicroscopic examination, axial length, anterior chamber depth, endothelial cell density (ECD), and corneal curvature were monitored.

Results: At the initial visit, before EL surgery, MFS children with EL had greater myopia (P < 0.01), corneal cylinder (P = 0.04), and CCT (P = 0.01) compared to children with no EL. Over the follow-up interval, EL children had a progressive increase in CCT (P = 0.02) and a reduction in ECD (P = 0.02). EL children also showed: progressive flattening of corneal curvature (P = 0.01); reduction of corneal cylinder (P = 0.02); and increase in axial length (P < 0.01). MFS children with no EL exhibited a smaller increase in CCT (P < 0.01) and a milder flattening of corneal curvature (P < 0.01). The no EL children showed no change in ECD (P = 0.09), corneal cylinder (P = 0.80), or axial length (P = 0.27).

Interpretation: MFS children who have EL exhibit differences in corneal structure and axial length when compared to MFS children with no EL. Children with EL have thicker CCT, more corneal cylinder, lower ECD, and longer axial lengths compared to children with no EL. The differences imply that the fibrillin defect of MFS is more severe in children with EL. The ocular defect is manifested chiefly as zonular hyperextension but has effects also on corneal and scleral integrity.

Importance: Early diagnosis of biliary atresia (BA) is important for advancing the Kasai operation time and improving the BA prognosis.

Objective: To develop machine learning (ML) models for neonatal BA diagnosis using clinical characteristics and serological data.

Methods: Neonates presenting with pathological jaundice between January 1, 2013, and December 31, 2023 were enrolled. Five ML models-logistic regression (LR), random forest (RF), support vector machine classifier (SVC), multilayer perceptron (MLP), and extreme gradient boosting (XGBoost)-were trained using neonatal clinical and laboratory data. The stacking classifier (SC) algorithm was employed to select the best-performing models for constructing the ensemble learning model.

Results: This study included 85 patients, 42 of whom were diagnosed with BA. Among the five ML models, XGBoost (area under the receiver operating characteristic curve [AUC] = 1.000; 95% confidence interval [CI]: 1.000-1.000) and the RF (AUC = 1.000; 95% CI: 1.000-1.000) demonstrated better diagnostic performance. All models showed acceptable consistency between the predicted and actual probabilities. The SC model, built on the LR, RF, and XGBoost models, also exhibited a strong generalization ability and diagnostic performance (AUC = 1.000; 95% CI: 1.000-1.000). Key diagnostic predictors included elevated gamma-glutamyl transpeptidase (GGT) (AUC = 0.837; 95% CI: 0.749-0.925), increased platelet (PLT) counts (AUC = 0.728; 95% CI: 0.618-0.838), and acholic stools (AUC = 0.765; 95% CI: 0.663-0.867). An XGBoost-based nomogram was also developed.

Interpretation: ML models demonstrate high diagnostic accuracy for BA in neonates, with GGT, PLT counts, and acholic stools as pivotal predictors. This approach may enable earlier BA identification and intervention during the neonatal period.

Introduction: Suprasellar cistern arachnoid cysts are rare non-neoplastic cystic lesions that represent nearly 1% of all intracranial arachnoid cysts. Symptomatology can vary; small cysts typically do not produce any symptoms, whereas larger cysts may lead to headaches, blurred vision, and other related issues. However, the etiology, pathogenesis, and natural history of this condition remain unclear.

Case presentation: This study includes four cases from our hospital from the year 2016 to 2021, first diagnosed with hydrocephalus received ventriculoperitoneal shunt treatments, the patients complicated with enlargement of the suprasellar cisterna arachnoid cyst occurred following ventriculoperitoneal shunt placement, leading to secondary obstructive hydrocephalus and received neuroendoscopic third ventriculostomy and cyst fenestration.

Conclusion: Suprasellar cisterna arachnoid cysts may be related to intracranial pressure dynamics. Fluctuations in intracranial pressure can lead to variations in cyst size and may result in associated symptoms. Monitoring imaging and symptoms before, during, and after surgery, along with comprehensive follow-up, is important.

Importance: Anti-neurofascin (anti-NF) 155 antibody-positive autoimmune nodopathy is a distinct subset of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Given the increase in pediatric cases, understanding this condition is crucial.

Objective: This study aimed to delineate the clinical features of children with anti-NF155 antibody-positive autoimmune nodopathy to enhance disease management strategies.

Methods: We conducted a retrospective cohort study of 34 CIDP patients admitted to Beijing Children's Hospital from January 2015 to December 2024, including six with confirmed anti-NF155-antibody positivity. Their clinical symptoms, laboratory results, neuroimaging findings, and therapeutic responses were retrospectively analyzed.

Results: Of the 34 patients, six (17.6%) were tested positive for anti-NF155 antibodies. The cohort was male-dominated (male-to-female ratio of 4:2) with symptoms starting primarily in school-aged children. The symptoms included progressive limb weakness, sensory ataxia, and tremors. Notably, cerebrospinal fluid (CSF) protein levels were significantly elevated in seropositive patients. Electrophysiological studies indicated sensorimotor polyneuropathy, and neuroimaging revealed nerve root thickening. While intravenous immunoglobulin (IVIG) therapy was not effective, a combination of glucocorticoids, rituximab, and plasma exchange showed promise. At the final follow-up, all patients experienced symptom relief and could perform daily activities without relapse.

Interpretation: Pediatric anti-NF155 antibody autoimmune nodopathy was uncommon, featuring male dominance, and distal weakness with sensory symptoms. Additionally, the CSF protein levels were significantly elevated in seropositive patients. As IVIG treatment was ineffective, early immunosuppressive therapy was recommended. Early diagnosis and treatment are critical in reducing myelin and axonal damage.