Time-to-event estimation of birth prevalence trends: A method to enable investigating the etiology of childhood disorders including autism

An unbiased, widely accepted estimate of the rate of occurrence of new cases of autism over time would facilitate progress in understanding the causes of autism. The same may also apply to other disorders. While incidence is a widely used measure of occurrence, birth prevalence—the proportion of each birth year cohort with the disorder—is the appropriate measure for disorders and diseases of early childhood. Studies of autism epidemiology commonly speculate that estimates showing strong increases in rate of autism cases result from an increase in diagnosis rates rather than a true increase in cases. Unfortunately, current methods are not sufficient to provide a definitive resolution to this controversy. Prominent experts have written that it is virtually impossible to solve. This paper presents a novel method, time-to-event birth prevalence estimation (TTEPE), to provide accurate estimates of birth prevalence properly adjusted for changing diagnostic factors. It addresses the shortcomings of prior methods. TTEPE is based on well-known time-to-event (survival) analysis techniques. A discrete survival process models the rates of incident diagnoses by birth year and age. Diagnostic factors drive the probability of diagnosis as a function of the year of diagnosis. TTEPE models changes in diagnostic criteria, which can modify the effective birth prevalence when new criteria take effect. TTEPE incorporates the development of diagnosable symptoms with age. General-purpose optimization software estimates all parameters, forming a non-linear regression. The paper specifies all assumptions underlying the analysis and explores potential deviations from assumptions and optional additional analyses. A simulation study shows that TTEPE produces accurate parameter estimates, including trends in both birth prevalence and the probability of diagnosis in the presence of sampling effects from finite populations. TTEPE provides high power to resolve small differences in parameter values by utilizing all available data points.

Patient-Driven Findings of Genetic Associations for PANS and PANDAS

Background: There are presently very few genetic studies for PANS (Pediatric Acute-Onset Neuropsychiatric Syndrome) or PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections). More work in genetic associations for PANS and PANDAS (P/P) is needed to increase understanding of these debilitating childhood disorders that have a range of presentations.Objective: This work represents a novel approach that aims to determine genetic associations between P/P and other diseases, disorders and traits (hereafter referred to as phenotypes).Methods: Consumer genetic data (23andMe, AncestryDNA) for 155 patients with P/P were obtained from consenting parents over a period from 2018 to 2020. An analysis plan for this work was registered at Open Science Framework, additional genotypes imputed using Impute.me, and polygenic risk scores for 1,702 phenotypes calculated for each of the 155 P/P patients.Results: One-sample t-tests performed across the 155 individual risk scores revealed that P/P is statistically significantly associated with 21 different groups of Single Nucleotide Polymorphisms (SNPs) that are in turn associated with 21 phenotypes. Some of the 21 phenotypes (see Table 3) are previously known to be related to or associated with P/P: a group of SNPs associated with Tourette’s Syndrome, and another group associated with Autism Spectrum Disorder or Schizophrenia, and a third associated with “feeling nervous” yielded t-tests with p values of 1.2x10-5, 1.2x10-11 and 1.0x10-5 respectively for association with the P/P data. This validated our analysis methodology. Our analysis also revealed novel genetic associations such as between P/P and plasma anti-thyroglobulin levels (p=1.3x10-7), between P/P and triglycerides (p=5.6x10-6), and between P/P and Lewy body disease (p=7.8x10-6), inviting further investigation into the underlying etiology of P/P.Conclusion: P/P is associated with many phenotypes not previously recognized as being connected to P/P. Further work on these connections can lead to better understanding of P/P.

Role of Partial Splenectomy in Hematologic Childhood Disorders

The spleen is a secondary lymphoid organ that belongs to the reticular-endothelial system, directly connected to blood circulation. The spleen is greatly involved in the immune response, especially against capsulated bacteria. Splenectomy plays a fundamental role in the treatment of numerous pediatric hematologic disorders. Taking into account all the possible complications (especially infections) linked to this procedure, alternatives to total splenectomy have been sought. Partial splenectomy has been proposed as a treatment that allows the reduction of infectious risk. This approach has proven safe and feasible in most patients, but multicentric and prospective studies are necessary to more accurately define the indications for performing partial splenectomy. However, vaccinations and antibiotic prophylaxis remain fundamental for preventing serious infections, even in the case of partial splenectomy. We review anatomical and functional properties of the spleen, with a focus on medical or surgical indications to splenectomy, aiming to give practical educational information to patients and their families after splenectomy. Furthermore, we discuss the feasibility of partial splenectomy in children with hematologic diseases who require splenectomy.

Childhood Movement Disorders

The phenomenology and classification of movement disorders are similar for adults and children, but the causes and approach are distinct. In children, hyperkinetic disorders are more common than hypokinetic disorders. Furthermore, some disorders are present exclusively in infants and children; others may begin in childhood and persist into adulthood. This chapter focuses primarily on movement disorders that begin in childhood. Disorders that occur in children or adults without a specific predilection are covered in individual movement disorders sections.

Beneficial Effects of Plant Extracts and Bioactive Food Components in Childhood Supplementation

The pivotal role of childhood nutrition has always roused a growing interest from the scientific community. Plant extracts and bioactive dietary components play a significant role in the maintenance of human health and wellness, with the potential to modulate risk factors and manage symptoms for a large number of common childhood disorders such as memory impairment, respiratory illnesses, gastrointestinal disorders, metabolic derangements, and pathologies related to the oral cavity. This review is designed to highlight the health benefits of botanical extracts and bioactive dietary components in children as evidenced by clinical trials, considering their safety with regards to childhood sensibilities. The supplementation of children with the herbal extracts or bioactive components mentioned in this review leads to the conclusion that they are useful for treating various ailments, with no serious adverse events being reported. However, for the limited number of investigations specifically focused on the safety of such products in children, time is needed to expand the literature data covering the safety of childhood supplementation with botanical extract and bioactive food components.

Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

Exploring the evidence for epigenetic regulation of environmental influences on child health across generations

Environmental exposures, psychosocial stressors and nutrition are all potentially important influences that may impact health outcomes directly or via interactions with the genome or epigenome over generations. While there have been clear successes in large-scale human genetic studies in recent decades, there is still a substantial amount of missing heritability to be elucidated for complex childhood disorders. Mounting evidence, primarily in animals, suggests environmental exposures may generate or perpetuate altered health outcomes across one or more generations. One putative mechanism for these environmental health effects is via altered epigenetic regulation. This review highlights the current epidemiologic literature and supporting animal studies that describe intergenerational and transgenerational health effects of environmental exposures. Both maternal and paternal exposures and transmission patterns are considered, with attention paid to the attendant ethical, legal and social implications.

Skills and strategies used to manage aggression and conflict with children in residential settings

Residential settings are intended to address more serious problems which include childhood disorders, behavioural issues and emotional disturbance. Dealing with aggressive behaviours has begun to represent a multifaceted issue within residential settings indicating the need to examine the most frequently used skills and strategies of Child and Youth Workers when managing children and youth with aggressive tendencies. It is important to implement skills and strategies that will decrease the aggressive tendencies present in children and youth however the challenge is in determining whether these approaches are productive in residential settings to manage the daily conflict and aggression that occurs. This study is a secondary analysis of data from a study focused on Evidence-Based Practices in Group Care. The purpose of this analysis is to examine the interventions used by Child and Youth Workers to manage aggressive behavior within residential settings and determine what role if any education plays in the reported choice of the strategies they use.