Pediatric Research最新文献

Background: Very early onset inflammatory bowel disease presents a rare condition with an enrichment of monogenic disorders. This cohort study aims to investigate the prevalence of IBD-like monogenic disorders as well as genotypic and phenotypic characteristics in an Iranian cohort of VEO-IBD patients.

Methods: Patients with VEO-IBD diagnosed between September 2019 and May 2023 were evaluated retrospectively. Clinical data were collected, and whole exome sequencing (WES) was performed on patients. Biological therapy was given to 10 patients (52%), and three underwent intestinal surgery.

Results: Among the 19 patients, 7 (36%) had Crohn's disease, 3 (15%) had ulcerative colitis, and 9 (47%) had unclassified IBD. Monogenic disorders were identified in 8 patients (42%), including variants in IL10RB, DKC1, FERMT1, GUCY2C, NLRC4, and a susceptibility gene variant in the MEFV gene. We identified a novel heterozygous duplication on chromosome 6 by karyotype and SNP-array analysis but the relevance of the genetic findings remains elusive and further functional testing is required. Four patients were considered for HSCT, and the patient with the MEFV variant responded well to colchicine.

Conclusions: The study revealed that 42% of VEO-IBD patients had underlying monogenic disorders. Early identification of causative mutations is crucial for improving prognosis and treatment strategies.

Impact: VEO-IBD is a rare condition with a high prevalence of monogenic disorders. Early detection of causal mutations is crucial for improving prognosis and selecting optimal treatment strategies. In our cohort study, eight patients were found to have five known and three novel pathogenic variants in five different genes. We also identified a de novo duplication of the 6q22 region. Allogeneic HSCT provides a curative treatment for IL-10R-deficient patients, while colchicine treatment resulted in sustained remission in a patient with an MEFV mutation. Our study indicates that early genetic diagnosis of immune-related IBD-like monogenic disorders is essential for effective patient management.

Background: Acute pancreatitis (AP) is one of the serious complications among patients with hematopoietic stem cell transplantation (HSCT). We aimed to evaluate the impact of AP on hospitalization outcomes in pediatric HSCT recipients.

Methods: We retrospectively queried the PHIS database to include all pediatric patients who underwent HSCT between 2005-2024. The study population was divided into those with and without AP, and compared for various demographic and clinical variables. The primary outcome was in-hospital mortality, and secondary outcomes included healthcare resource utilization.

Results: A total of 33,439 HSCT recipients were identified, and the prevalence rate of AP was 1.1%. The AP group had a significantly higher in-hospital mortality rate (22.7% vs. 4.6%), higher median hospitalization costs (USD 698,372 vs. 187,583), and higher median length of stay (138.5 vs. 60 days) (all p < 0.001). Our risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88).

Conclusion: AP in HSCT prognosticates adverse outcomes with increased in-hospital mortality, prolonged length of stay, and higher hospitalization costs. Clinicians need to be vigilant in preventing and aggressively managing AP in HSCT.

Category of study: Population study IMPACT: Acute pancreatitis (AP) in pediatric hemopoietic stem cell transplant (HSCT) recipients prognosticates adverse outcomes with increased mortality, prolonged length of stay, and higher hospitalization costs. The risk stratification model predicted a 2.7 (95% CI: 2.2 to 3.4) times increased risk of AP for a score of >10, with an AUC of 0.85 (95% CI: 0.84 to 0.88). Multivariable analysis showed AP was associated with 1.5 (CI:1.2 to 2, p = 0.001) times increased risk of mortality in pediatric population.

Background: Autism spectrum disorder (autism) describes a heterogeneous neurodevelopmental phenotype arising from the interplay of environmental and genetic factors in early life.

Methods: In a general population birth cohort, we employed a scoping approach to identify prospective associations between prenatal and birth factors and a subsequent autism diagnosis.

Results: Factors associated with increased likelihood of autism included those related to i) maternal health (maternal pre-pregnancy body mass index, pre-existing maternal mental health conditions, maternal use of selective serotonin reuptake inhibitors) ii) environmental exposures (maternal passive tobacco smoke exposure, and exposure to vinyl floors) iii) demographic factors (socioeconomic disadvantage). Factors associated with a decreased likelihood of autism included maternal dietary nutrition and supplementation (higher folic acid, magnesium, and iron, as well as adherence to the Australian Dietary Guidelines).

Conclusion: Our findings extend the evidence that autism may have a multifactorial origin in early life. Further studies should explore the composite effects of these prenatal and birth factors on autism outcomes via shared biological pathways, such as inflammation, and oxidative stress, in concert with genetic predisposition.

Impact: Autism spectrum disorder (autism) is a multifactorial condition. Here we report on multiple prenatal environmental, demographic, maternal and pregnancy factors that are associated with an increased likelihood of an autism diagnosis. For example, adherence to the Australian Dietary Guidelines during pregnancy is linked to a reduced likelihood of autism in the offspring, consistent with mounting evidence that prenatal nutrition impacts brain development. We examine how the multiple risk factors, identified by our comprehensive approach, may be linked to shared biological mechanisms. Future work should examine composite exposure measures acting through shared mechanisms as a more productive approach to understanding aetiology than focusing solely on individual exposures.

Background: Many preterm infants need nutrition beyond 24 kcal/oz (standard fortification) to support growth. Individualized targeted fortification improves growth but is labor-intensive. Universal enhanced fortification to presumed 26 kcal/oz for very low birth weight infants was clinically implemented. We determined how often donor breast milk (DBM) and preterm maternal breast milk (MBM) met nutritional targets with enhanced fortification.

Methods: MBM/DBM samples were collected for a prospective cohort study of infants born <1500 g and <33 weeks. Macronutrients were measured using a mid-infrared analyzer. The frequency at which MBM/DBM samples met intake goals (4.8-8.1 g/kg/day fat, 11.6-13.2 g/kg/day carbohydrate, 3.5-4.5 g/kg/day protein) with enhanced and standard fortification was compared.

Results: Among 198 MBM samples and 168 DBM samples, MBM had higher protein, fat, and energy (p < 0.0001). Regardless of fortification method, MBM samples met lower and mid-range fat goals more often (p < 0.01 and p = 0.03, respectively). Collectively, more samples achieved protein targets with enhanced fortification: all samples reached 3.5 and 4 g/kg/day, 56% (147 MBM, 58 DBM) attained 4.5 g/kg/day. With standard fortification, 11% achieved 4 g/kg/day protein; none attained 4.5 g/kg/day.

Conclusions: Enhanced fortification is an efficient method that meets enteral nutrition goals for preterm infants and delivers desired protein intake more consistently.

Impact: Enhanced fortification is a feasible and efficient alternative to targeted fortification that can also achieve enteral nutrition goals for preterm infants. Enhanced fortification delivers desired protein intake more consistently than standard fortification, especially with donor breast milk. Regardless of fortification strategy, maternal breast milk is more likely to reach fat intake goals, although additional enrichment may be needed, depending on the fortifier product.

Survival rates of preterm infants have been steadily increasing over the last few decades. This has drawn long-term outcomes in this population to the forefront of scientific attention. Caffeine is a pharmacological agent that is available to neonatologists in the treatment of apnoea of prematurity. Its use for this condition has been well researched; however, less focus has been directed towards its neuroprotective capabilities. Long-term follow-up from the landmark 'Caffeine Therapy for Apnoea of Prematurity' trial suggested that caffeine may confer benefits in neurodevelopmental outcomes. The indirect ways in which caffeine could confer these benefits have been extensively discussed; however, the direct molecular mechanisms by which this is achieved are poorly understood. This article reviews the putative mechanisms through which caffeine acts as a neuroprotectant in the preterm infant. Caffeine may directly confer neuroprotective benefits through altering white matter structures, reducing inflammation, preventing cell death and conferring neuromodulatory benefits. With the rise in preterm birth and the need for effective neuroprotective therapies, caffeine's multifaceted mechanisms offer promising avenues for future research and clinical application. IMPACT: This article adds to the existing literature by which it: reviews the putative mechanisms through which caffeine acts as a neuroprotectant hypotheses that caffeine confers neuroprotective benefits through altering white matter structures, reducing inflammation, preventing cell death, and conferring neuromodulatory benefits, and consolidates evidence regarding caffeine's impact on neurodevelopmental outcomes.

Background: Elevated pre-pregnancy body mass index (BMI) and perinatal depressive symptoms have been linked to neonatal alterations in brain structure and function. This study examined associations between neonatal functional brain dynamics, maternal BMI, and perinatal depressive symptoms measured by the Edinburgh Postnatal Depression Scale (EPDS) in a community-based, largely low-risk cohort.

Methods: Funcitonal MRI and Leading Eigenvector Analysis (LEiDA) were applied in a neonatal cohort (N = 437; 236 males; mean gestational age 39.6 weeks) from the developing Human Connectome Project. We assessed whether neonatal brain-state probabilities related to maternal BMI and EPDS scores (M = 5.6, SD = 4.3), testing main effects and, separately, their interaction. The sample included 291 healthy-weight (BMI < 25), 98 overweight (25 BMI < 30), and 48 obese (BMI 30) mothers.

Results: EPDS scores were low in this cohort and did not demonstrate associations with brain states or a significant BMI × EPDS interaction. Higher maternal pre-pregnancy BMI was negatively associated with the stability of a functional network encompassing superior frontal, superior parietal, and temporal regions (ß = -0.129, p = 0.006).

Conclusion: As this network is normally recruited more with age, reduced stability suggests slowed maturation of fronto-parieto-temporal systems and may signal early risk for later behavioral challenges.

Impact: Higher maternal pre-pregnancy BMI is associated with reduced stability in a neonatal frontoparietal brain state, characterized by coordinated activity in frontal, parietal, and temporal regions. This state is one of six distinct dynamic connectivity patterns identified, reflecting core neonatal resting-state networks. The association was robust across multiple analytic models and clustering solutions. No significant effects were found for maternal depressive symptoms. These findings underscore the selective impact of maternal metabolic health on early brain organization, suggesting prenatal influences on the functional architecture of the newborn brain that may shape long-term neurodevelopmental trajectories.

Background: Exposure to unconventional hydraulically fractured oil and gas wells during pregnancy is associated with a higher risk of structural birth defects. These associations have not been examined in California, where most operators use conventional methods that do not use enhanced techniques.

Objectives: Determine whether residing near oil and gas wells during early pregnancy was associated with birth defect risks among San Joaquin Valley, California, residents.

Methods: We conducted a case-control study with data from the California Center of the National Birth Defects Prevention Study for births delivered from 1997-2011. We considered 16 structural birth defect phenotypes. We assessed exposure to active wells within 3 km of the maternal residence or inactive wells within 1 km. We fit adjusted logistic regression models for each exposure and birth defect phenotype.

Results: Exposure to active wells was associated with elevated odds of some CHDs and significantly lower odds of atrial septal defect secundum and gastroschisis. Exposure to inactive wells was associated with significantly elevated odds of cleft palate.

Conclusions: Among San Joaquin Valley residents, living near active and inactive wells was associated with risks of birth defects. The estimates were imprecise and, given the number of statistical tests we conducted, may be spurious.

Impact: Researchers have not yet characterized structural birth defect-related potential risks associated with living near conventional wells in California, and there is little understanding of the hazards associated with inactive wells. We found that living near active wells in the San Joaquin Valley, California, was associated with risk of some structural birth defects, but findings were imprecise. Living near inactive wells was associated with an elevated risk of cleft lip and cleft palate. Further research could help determine whether findings were valid and explicate plausible etiological pathways.

Neuroplasticity, the brain's adaptive ability to restructure and reorganize itself, represents one of the most fascinating aspects of the developing brain. Neuroplasticity is maximal during the "first 1000 days" (conception through two years of life), presenting both unique opportunities and vulnerabilities. While neonatal neurology often focuses on the "symptomatic minority" presenting early after birth, there remains an "unrecognized majority" of children who will present with disorders later in childhood. For clinicians working with newborns and young infants, a comprehensive understanding of developmental principles provides the foundation for knowledge to optimize early intervention strategies. This review focuses on the biological basis of neuroplasticity and metaplasticity in the neonatal brain, as well as their role in neurodevelopment. We examine how the "dynamic neural exposome" (the full mix of biological and environmental influences the brain is exposed to over time) and "toxic stressor interplay" (the combined effect of multiple stressors such as pain, infection, and inflammation) influence these processes, often leading to "ontogenetic adaptations" (short-term survival-driven changes in brain wiring that may have long-term consequences). We outline mechanisms shaping early brain development, describe how early experiences and interventions influence outcomes, and emphasize prioritizing prevention over later rescue to improve neurodevelopmental outcomes. IMPACT: The article provides a high-level framework that links the brain's response to experience and injury directly to clinical implications in neonatology, expanding the focus to the "first 1000 days". The effectiveness of interventions hinges on their timing relative to developmental critical and sensitive periods, alongside the dynamic interplay between genetic and environmental influences (including the Maternal-Placental-Fetal triad) on brain development. Neuroplasticity presents both a window for recovery and adaptation, and a susceptibility to adverse experiences, emphasizing the need for evidence-based neuroprotective and neurodevelopmental care that prioritizes preventive approaches to improve long-term outcomes.