Intellectual Disability In Children Research Articles

Pineal gland volume in children with intellectual disability.

Pineal gland volume (PGV), which is associated with sleep and circadian rhythm, is known to be changed in some psychiatric disorders such as major depression, mood disorders and schizophrenia. This study aimed to compare the PGV of children with mild and moderate intellectual disability (ID) and healthy children. This multicentre retrospective study included 40 children with ID (patient group), aged 6-12 years and 40 age- and sex-matched healthy children (control group). The children were examined for their sociodemographic characteristics and for PGV using magnetic resonance imaging. The PGV of the patient group was significantly larger than that of the controls (p = 0.023). There was no statistically significant difference in PGV between mild and moderate ID. A moderate and positive correlation was found between Weschler Intelligence Scale for Children-revised (WISC-R) performance score and PGV (p = 0.049, r = 0.313) only in the patient group. In the receiver operating characteristic analysis, the area under the curve was 0.648, and the sensitivity was 70.0%, and the specificity was 60.0%. In conclusion, this study demonstrated that the increased PGV levels were associated with autism spectrum disorder (ASD) and PGV could be a risk factor in the aetiology of ID. Further research with larger sample sizes is needed to clarify this issue.

The Correlation Between Odontogenic Infection and Total Spectrum of Dental Caries with Oral Health Related Quality of Life in Children with Intellectual Disabilities.

: Children with Intellectual Disabilities (ID) have a higher rate of untreated caries and often progress to caries with pulpal involvement or odontogenic infections. This can be assessed using the Caries Assessment Spectrum and Treatment (CAST) index and the Pulp Ulcer Fistula Abscess (PUFA) index. Dental problems often have an impact on quality of life, so Oral Health-Related Quality of Life (OHRQoL) assessment is needed for ID children. To identify and analyze the correlation between odontogenic infection, the total spectrum of caries, and OHRQoL in ID children. : The subjects of the research were 70 ID children who attended Special Needs Schools (SNS) Type D of the Foundation for the Development of Disabled Children (FDDC). This research uses an analytical survey using questionnaires and interviews to assess OHRQoL. The sampling technique, namely Total Sampling, obtained 43 ID child subjects who met the inclusion criteria. The data were tested statistically using the Spearman Correlation non-parametric test and the t-test. : The average value of odontogenic infection in the population was 1.79, including in the poor category, and the total spectrum of dental caries was 51.16%, including severe morbidity. Multivariate analysis showed a significant correlation between odontogenic infection, total spectrum of caries, and OHRQoL; odontogenic infection with total dental caries spectrum was significantly associated with each p-value = 0.0000, while the correlation between OHRQoL and both odontogenic infection and total caries spectrum had p-values > 0.05, respectively, so it is considered not significant. : Odontogenic infection in ID children is a poor category. The total spectrum of dental caries in ID children mostly includes severe morbidity. There is a correlation between odontogenic infections, the total spectrum of dental caries, and OHRQoL, as well as between odontogenic infections and the total spectrum of dental caries.

Evaluating the effectiveness of the CAIDS-Q for screening for intellectual disability in mainstream schools

Objectives The identification of intellectual disability in children can help them access targeted support and interventions. Research suggests that current methods of identifying intellectual disability in schools in the United Kingdom need to be improved. Screening tools can play a role in this. The study examined the performance of the Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) in mainstream schools as a means of facilitating identification of intellectual disability. Methods Parents and/or teachers of 70 children completed the CAIDS-Q and an assessment of adaptive functioning about them. Children who were indicated as having difficulties completed an intellectual assessment. The data were used to explore some psychometric properties of the CAIDS-Q. Results The CAIDS-Q had sensitivity and specificity values of 100% and 79% respectively when completed by teachers and 92% and 70% when completed by parents. CAIDS-Q scores correlated positively with intellectual and adaptive functioning scores, with large and medium effect sizes respectively. There was moderate agreement between parents and teachers on the outcome of the CAIDS-Q. Conclusions The CAIDS-Q, when used in mainstream schools, had psychometric properties consistent with those found in health service settings. It may offer a way of improving identification of intellectual disability in educational settings.

Parenti–Migno neurodevelopmental disorder: a case associated with a new variant in the <i>CHD5</i> gene

Parenti–Migno neurodevelopmental disorder is a rare syndromal form of intellectual disability in children, associated with the CHD5 gene, the prevalence of which is not established. Currently, 16 patients with this pathology have been described. CHD5 belongs to the conservative family of chromatin remodeler proteins, is part of the histone deacetylase NuRD complex, and is crucial for the early differentiation of neurons in the central nervous system and acts as a tumor suppressor. Recently, thanks to the application of whole-exome sequencing, the association of this gene with Parenti–Migno neurodevelopmental disorder was first described in patients with developmental delay, psycho-neurological disturbances, facial phenotype features, and skull pathology. We present a unique case of the disease associated with a new variant p.Arg1521Thr in the CHD5 gene, in a girl with intellectual and neurological impairments, craniofacial dysmorphism, as well as previously undescribed symptoms such as cleft lip and palate, hydrocephalus, and renal pathology. The cause of the disease was determined through whole-genome sequencing, which highlights the value of this method in the diagnosis of undifferentiated forms of intellectual disabilities.

Medication Adherence of Children with Congenital Hypothyroidism in Iran: A National Cross-Sectional Study

Background: Congenital hypothyroidism is the most common preventable and treatable cause of intellectual disability in children. A key component of the surveillance system for congenital hypothyroidism is ensuring a regular treatment program for affected children. Despite nearly 20 years since the successful implementation of the newborn screening program for hypothyroidism in Iran, a comprehensive evaluation of patients' adherence to treatment has not been conducted. Objectives: The aim of this study was to investigate the adherence to treatment among patients with congenital hypothyroidism in Iran. Methods: In this national cross-sectional study conducted in 2024, the adherence to treatment of 400 children with congenital hypothyroidism born between 2019 and 2023 in Iran was examined using the Morisky Medication Adherence Scale. The patients were randomly selected from national registry data. Data were analyzed using chi-squared tests, Fisher's exact test, and logistic regression in Stata software version 16. Results: The mean and standard deviation of medication adherence was 6.35 ± 1.41. Overall, adherence was good (≥ 6) in 284 (71.0%) of the study participants. In the univariate analysis, the most significant factors influencing adherence were place of residence, higher maternal education, lower paternal education, and type of congenital hypothyroidism (CH). In the multivariate analysis, children with permanent CH had good adherence, and parental education was not statistically significant (P > 0.05). Conclusions: The results of this study showed that medication compliance in more than two-thirds of hypothyroid children diagnosed by national newborn screening is good. Given the importance of treatment in these patients, it is recommended that intervention plans be implemented, including educational programs and active follow-up of patients to increase compliance.

Development And Content Validation Of An Indigenous Diagnostic Questionnaire Of Intellectual Disability

Even though in the last decade, there has been a considerable increase in the prevalence of intellectual disability in Pakistan, there is scarcity of indigenous standardized diagnostic questionnaire for intellectual disability. Thus, the present study aimed to evaluate the content validity of the Indigenous Diagnostic Questionnaire of Intellectual Disability (IDQID) [1]designed in accordance with the Pakistani society’s norms. IDQID was designed to diagnose intellectual disability for 6-18 years old. Mixed method research design was used in the development and content validation phase. Purposive sampling strategy was used to recruit participants for expert panel review (n=10). Content validity index was used to assess the relevance and representativeness of the questionnaire. The scale level content validity index by averaging calculation method and by universal agreement method was 0.87 and 0.209 respectively. A total of 168 items with I-CVI greater than or equal to 0.78 were retained. Given the time efficient, cost effective and multidimensional nature of the questionnaire, mental health practitioners should use this questionnaire to evaluate intellectual disability in children.

Development and validation of a nomogram for predicting intellectual disability in children with cerebral palsy

ObjectiveIntellectual disability (ID) is a prevalent comorbidity in children with cerebral palsy (CP), presenting significant challenges to individuals, families and society. This study aims to develop a predictive model to assess the risk of ID in children with CP. MethodsWe analyzed data from 885 children diagnosed with CP, among whom 377 had ID. Using least absolute shrinkage and selection operator regression, along with univariate and multivariate logistic regression, we identified key predictors for ID. Model performance was evaluated through receiver operating characteristic curves, calibration plots, and decision curve analysis (DCA). Bootstrapping validation was also employed. ResultsThe predictive nomogram included variables such as preterm birth, CP subtypes, Gross Motor Function Classification System level, MRI classification category, epilepsy status and hearing loss. The model demonstrated strong discrimination with an area under the receiver operating characteristic curve (AUC) of 0.781 (95% CI: 0.7504-0.8116) and a bootstrapped AUC of 0.7624 (95% CI: 0.7216-0.8032). Calibration plots and the Hosmer-Lemeshow test indicated a good fit (χ2= 7.9061, p = 0.4427). DCA confirmed the model's clinical utility. The cases were randomly divided into test group and validation group at a 7:3 ratio, demonstrating strong discrimination, good fit and clinical utility; similar results were found when stratified by sex. ConclusionsThis predictive model effectively identifies children with CP at a high risk for ID, facilitating early intervention strategies. Stratified risk categories provide precise guidance for clinical management, aiming to optimize outcomes for children with CP by leveraging neuroplasticity during early childhood.

How do Children with Intellectual Disabilities Empathize in Comparison to Typically Developing Children?

Two studies were conducted to better understand how children with intellectual disabilities (ID) empathize with the feelings of others during social interactions. The first study tested hypotheses of developmental delay or difference regarding empathy in 79 children with ID by comparing them with typically developing (TD) children, matched for developmental age or chronological age. The second study examined specific aspects of empathy in 23 children with Down syndrome (DS), compared with 23 nonspecific ID children, matched for developmental age, and TD children, matched for developmental age or chronological age. An empathy task was administered to the children while their parents completed the French versions of the Empathy Questionnaire and the Griffith Empathy Measure. The first study showed that ID children showed delayed empathy development but were perceived by their parents as deficient in cognitive empathy. The second study showed that DS children were perceived as being more attentive to the feelings of others than TD children and non-specific ID children, matched for developmental age, and as having affective empathy that was similar to that of TD children matched for chronological age. These studies have drawn attention to delays or differences in different dimensions of empathy in children with ID and DS, which need to be taken into account in interventions.

Persistent Narratives: Intellectual Disability in Canadian Children’s Literature

Canadian children’s literature rarely depicts characters labelled with intellectual disabilities, yet when it does it often remains mired in stereotypes that recycle prevalent myths and misconceptions. Even as more recent literature attempts to push back against such stereotypes, it nevertheless predominantly remains caught in these dangerous representational repertoires. This article offers a brief history of Canadian literary depictions of intellectual disability and a critique of the Canadian publishing spheres. Through a critical analysis of Lorna Schultz Nicholson’s book Fragile Bones, we discuss the limits of representation of intellectual disability in children’s fiction. We also offer a critique of the ableist publishing climate in Canada and suggest that structural barriers prevent disabled writers from entering the literary marketplace on an equal playing field. These barriers to publishing lead to the vast underrepresentation of disabled authors and the misrepresentation of disability in general and intellectual disability in particular in Canadian children’s literature.

The Cognitive Styles as Predictive with Behavior Problems in Intellectual disabilities Children

The Cognitive Styles as Predictive with Behavior Problems in Intellectual disabilities Children

Serum brain-derived neurotrophic factor concentration is different between autism spectrum disorders and intellectual disability children and adolescents

PurposeRecent studies showed that mature brain-derived neurotrophic factor (mBDNF) and its precursor proBDNF are associated with autism spectrum disorders (ASD). Whether their levels are different between ASD and intellectual disability (ID) subjects is not clear. The aim of this study is to compare the serum mBDNF and proBDNF concentration, and mBNDF/proBDNF ratio in ASD and ID volunteers. MethodsChildren and adolescents with ASD or ID between the ages of 4 and 22 were recruited in Tianjin, China. Serum mBDNF and proBDNF level were tested and Wechsler Preschool and Primary Scale of Intelligence (WPPSI), Wechsler Intelligence Scale for Children (WISC), and Childhood Autism Rating Scale (CARS) evaluations were conducted. ResultsSerum mBDNF concentration and the ratio of mBDNF to proBDNF was higher in ASD subjects than that in ID subjects (P = 0.035 and P < 0.001, respectively), while serum proBDNF of ASD participants was lower compared to that of ID participants (P < 0.001). CARS score was positively correlated with serum mBDNF level (r = 0.33, P = 0.004) and m/p ratio (r = 0.39, P < 0.001), and negatively correlated with serum proBDNF level (r = −0.39, <0.001) after adjusting for age and IQ. The AUC of mBDNF, proBDNF, and m/p ratio were 0.741, 0.790, and 0.854, respectively, after adjusted for age and IQ. ConclusionSerum mBDNF, proBDNF and m/p ratio were different between ASD and ID group. The three biomarkers displayed good diagnostic values for classification of ASD and ID subjects.

A Ray of New Hope for the Parents of Children with Intellectual Disability

ABSTRACT “Everything has its wonders, including darkness and stillness, and I learn to be satisfied in whatever situation I am in.” Research literature illustrates that parents of children with intellectual impairments are exposed to a variety of stressful life events while caring for their children with intellectual disabilities. The pivotal aim is to determine that the parenting intervention has a meaningful impact on parents’ care of their intellectual disabled child and also to improve the parenting abilities of intellectual developmentally disabled children. It is indeed crucial to strengthen parenting skills through various means or strategies. Thus, the researcher examined numerous parenting practices that can help the parents in instilling positive attitudes to improve their parenting skills so that they can modify their intellectual and developmental disabilities (IDDs) child’s behavioral issues. Researcher has also identified the various strategies and principles to change the inappropriate behavior of IDD child such as acceptance, positive self-beliefs, positive reinforcement, self-efficacy, endurance, consistency, remain calm and be respectful, learn to stand and assertively explore out their feelings, nonjudgmental, and nonpunitive toward their disabled child. Apart from this, behavioral techniques for problematic behavior management such as changing the antecedent, extinction/ignoring, time out, response cost, and overcorrection prove beneficial in making modifications and improvement in child’s behavior. It has been found that parenting skill program brings positive motivation, guidance, and zeal in parents and also enhances personal and parental self-efficacy which further helps to improve the family functioning. In addition to this, parenting intervention helps the parents to realize their own potential to manage their daily life stress, thereby living a happy and successful life with the intellectual disability child. It is estimated that disabilities will cross 10 million by 2022 if appropriate skills are not imparted through training programs.

EFFECT OF MANIPULATION OF BASE OF SUPPORT ON CENTER OF PRESSURE: COMPARISON OF CHILDREN WITH AND WITHOUT INTELLECTUAL DISABILITY

The postural control (PC) of children with intellectual disabilities (ID) have been extensively studied; however, there is limited information available on the role of PC strategies during manipulated balance conditions. The aim of this study is to investigate the effect of manipulation of the base of support on the center of pressure in the children with and without intellectual disabilities. This study included 34 girls with mild intellectual disabilities and 30 typically developing children of the same sex and age (7-13 years old). The participants as stood as still on a platform and completed four tasks: feet-together on a firm surface, feet-together on a foam surface, tandem stance on a firm surface, and tandem stance on a foam surface. The displacement, sway, amplitude, root mean square (RMS), velocity, and acceleration of the center of pressure (CoP) were calculated. The results indicate significant differences between the two groups in spatial variables of CoP movement (p &lt; 0.05). Moreover, sway and amplitude were found to be sensitive to changes in surface factors (p &lt; 0.05) and all variables to be sensitive to changes in stance position. There was significant interaction of stance*group in CoP velocity (p &lt; 0.05). Based on the results, children with intellectual disabilities demonstrated poorer postural control than the control group, particularly in more demanding PC tasks. However, the quantitative variables of CoP were less impacted by ID characteristics compared to spatial variables. Accordingly, it is suggested that the role of effective balance training on improving postural control strategies in ID children be investigated in future studies.

Self – Advocacy Significance in Work Placement Adjustment of PwID

Self – Advocacy of differently abled adults living in Urban cities, Suburban and Rural areas were examined with respect to self - advocacy of their technical training, life skill development programs and social support systems. In the present situation based on applicability of scientific knowledge helping the Intellectual disabled adult children from positive psychology frameworks and from the strengths-based approach through which they can learn natural language and understanding language is currently focused by special education and vocational training centres for differently abled adult students. Under this framework, Self-determined, Self – advocacy action is including and able to implement practically by two following essential criteria’s: 1. Vocational training action, 2. Self - governing action. Vocational action refers to the extent to which a person makes intentional, conscious choices based on differently abled adult choice and interests. Self - governing action involves self-directing and managing actions in service of a chosen work area and implies identifying different ways and methods to solve their disable problem. This study paper focusing on the dedicated services of Vocational training centres rendering multiple roles in promoting technical skills and life skills based on identifying different abilities and preparing the differently abled adults to enter into suitable work places for self-earning with intellectual disabilities. The study was conducted with the purpose to identifying the role of Vocational instructors in development of assessment tool, need assessment of functional skills, programming, implementation, and evaluation of training program by involving even parents in all stages. Differently abled adults in DAIL section identified male and female students and their parents who showed their commitment to participate in the program were involved in the Work Placement Adjustment of PwID program. Need assessment of functional skills of each adult was done through technical and functional skills training programs were developed by implementing and evaluated with the support of parents. Data showed that Instructors played multiple roles were observed in the whole study; their teaching style, use of different behaviour modification technique and other were come forth and performance of differently abled adults was increased.

Parent Education Program about Dental Health Education for Intellectual Disability Children in Wetland

Background: Wetlands are swamps with a water pH of 3.5-4.5. There are also cariogenic bacteria, including Streptococcus sp. Parents living in wetlands have a habit of using wetland water for their daily routine, such as for gargling after toothbrushing. Oral health problems in intellectual disabilities children include gingivitis, periodontitis, and rapid dental caries. Dental Health Education can increase the awareness of people in wetlands.&#x0D; Purpose: to analyse the effectivity of parent education program about dental health education for intellectual disability children in Wetland&#x0D; Methods: A quasi-experiment study with pretest and posttest without control design that used a simple random sampling technique.&#x0D; Results: Thirty-eight parents of intellectual disabilities children filled questionnaires for pretest, then asked to watch an animated video of Dental Health Education for moderate intellectual disabilities children living in wetlands concerning dental caries prevention. As for the posttest, the samples were asked to fill the same questionnaire after 20 days. Data were analyzed using Wilcoxon statistical test. The results of the Wilcoxon test prove value = 0.000 (p &lt; 0.05).&#x0D; Conclusion: There is an effect of the parent education program through Dental Health Education video for intellectual disabilities children in wetlands on dental caries prevention. This video can be applied to parents of children with intellectual disabilities as promotive action for dental health education.

The association between maternal infection and intellectual disability in children: A systematic review and meta-analysis.

There is arguing evidence regarding the association between maternal infections during pregnancy and the risk of intellectual disability (ID) in children. This systematic review and meta-analysis are essential to determine and address inconsistent findings between maternal infections during pregnancy and the risk of ID in children. The MOOSE and PRISMA guidelines were followed to perform and report on this study. The Medline/PubMed, Web of Science, Embase, and Scopus databases were searched from inception up to March 15, 2023, to identify potentially eligible studies. Inclusion and exclusion criteria were applied, as well as the Newcastle-Ottawa Scale was used to assess the methodological quality of studies included. The included studies were divided into two types based on the participants: (1) ID-based studies, which involved children with ID as cases and healthy children as controls and evaluated maternal infection in these participants; (2) infection-based studies, which assessed the prevalence or incidence of ID in the follow-up of children with or without exposure to maternal infection. We used Random-effects models (REM) to estimate the overall pooled odds ratio (OR) and 95% confidence intervals (CIs). The between-studies heterogeneity was assessed with the χ2-based Q-test and I2 statistic. Subgroup and sensitivity analyses were applied to explore the source of heterogeneity and results consistency. A total of eight studies including 1,375,662 participants (60,479 cases and 1,315,183 controls) met the eligibility criteria. The REM found that maternal infection significantly increased the risk of ID in children (OR, 1.33; 95% CI, 1.21-1.46; I2 = 64.6). Subgroup analysis showed a significant association for both infection-based (OR, 1.27; 95%CI, 1.15-1.40; I2 = 51.2) and ID-based (OR, 1.44; 95%CI, 1.19-1.74; I2 = 77.1) studies. Furthermore, subgroup analysis based on diagnostic criteria revealed a significant association when maternal infection or ID were diagnosed using ICD codes (OR, 1.33; 95% CI, 1.20-1.48; I2 = 75.8). Our study suggests that maternal infection during pregnancy could be associated with an increased risk of ID in children. This finding is consistent across different types of studies and diagnostic criteria. However, due to the heterogeneity and limitations of the included studies, we recommend further longitudinal studies to confirm the causal relationship and the underlying mechanisms.

Usefulness of interactive video-based instruction on learning performance in relation to cognitive development of children with moderate intellectual disability.

The usefulness of information and communication technology has been witnessed around the globe with the occurrence of rapid changes in the field of education i.e. through the formal or informal way. For this, the researchers have assessed Interactive video-based instruction (IVBI) on (N = 95; males = 47 & females = 48 age range between 12 and 15years) moderate intellectual disability children in Guwahati, Assam, India from three day-care rehabilitation centres. The main objective was to examine the effect of IVBI intervention (IIVBI & CIVBI) on academic performance in association with the cognitive development of children with moderate intellectual disability in a comfortable setting within working hours. The findings conclude that children in the CIVBI group performed more actively as compared to IIVBI and comparison group, and it was due to the involvement of video-based instruction that helped understand the topic more precisely and acts effectively for CIVBI children in an experimental setting.

Maternal hypertensive pregnancy disorders increase childhood intellectual disability hazards independently from preterm birth and small for gestational age

BackgroundChildren of mothers with hypertensive-disorders-of-pregnancy (HDP) have high rates of preterm-birth (<37 weeks' gestation) and small-for-gestational-age (SGA), both of which are risk factors of intellectual disability (ID). AimsTo test the multiple-hit hypothesis that preterm-birth and SGA in the neonatal period might potentiate the antenatal impact of HDP to increase childhood ID hazards, and HDP might not have independent effects. MethodsThis population-based cohort study enrolled 1,417,373 mother-child pairs between 2004 and 2011. A total of 19,457 pairs with HDP were identified and propensity-score-matched with 97,285 normotensive controls. Children were followed up for ID outcome until 6–13 years of age. HDP were classified into chronic-hypertension, gestational-hypertension, preeclampsia, and preeclampsia-with-chronic-hypertension. Using the normotensive group as the reference, the associations between HDP subgroups and ID hazards were assessed with adjusted hazard ratios (aHR) and 95 % confidence intervals (CI), and the effects of preterm-birth and SGA on the associations were examined. ResultsThe HDP group had higher cumulative rates of ID (1.6 %) than the normotensive group (0.9 %), particularly the subgroup of preeclampsia-with-chronic-hypertension (2.4 %), followed by preeclampsia (1.7 %), chronic-hypertension (1.5 %) and gestational hypertension (1.0 %). Preterm-birth and SGA exerted aggravating effects on ID hazards in children exposed to any HDP. After adjustments, maternal chronic-hypertension (aHR 1.59, 95 % CI 1.28–1.97), preeclampsia (1.52, 1.26–1.83), and preeclampsia-with-chronic-hypertension (1.86, 1.38–2.51) independently contributed to ID outcome. ConclusionsMaternal HDP other than gestational hypertension increased offspring's ID hazards independently from the potentiating hits of preterm-birth and SGA, implicating long-lasting influence of in-utero HDP exposure on children's cognitive development.

Antidepressants in pregnancy: applying causal epidemiological methods to understand service-use outcomes in women and long-term neurodevelopmental outcomes in exposed children.

Antidepressants are commonly prescribed during pregnancy, despite a lack of evidence from randomised trials on the benefits or risks. Some studies have reported associations of antidepressants during pregnancy with adverse offspring neurodevelopment, but whether or not such associations are causal is unclear. To study the associations of antidepressants for depression in pregnancy with outcomes using multiple methods to strengthen causal inference. This was an observational cohort design using multiple methods to strengthen causal inference, including multivariable regression, propensity score matching, instrumental variable analysis, negative control exposures, comparison across indications and exposure discordant pregnancies analysis. This took place in UK general practice. Participants were pregnant women with depression. The interventions were initiation of antidepressants in pregnancy compared with no initiation, and continuation of antidepressants in pregnancy compared with discontinuation. The maternal outcome measures were the use of primary care and secondary mental health services during pregnancy, and during four 6-month follow-up periods up to 24 months after pregnancy, and antidepressant prescription status 24 months following pregnancy. The child outcome measures were diagnosis of autism, diagnosis of attention deficit hyperactivity disorder and intellectual disability. UK Clinical Practice Research Datalink. Data on 80,103 pregnancies were used to study maternal primary care outcomes and were linked to 34,274 children with at least 4-year follow-up for neurodevelopmental outcomes. Women who initiated or continued antidepressants during pregnancy were more likely to have contact with primary and secondary health-care services during and after pregnancy and more likely to be prescribed an antidepressant 2 years following the end of pregnancy than women who did not initiate or continue antidepressants during pregnancy (odds ratioinitiation 2.16, 95% confidence interval 1.95 to 2.39; odds ratiocontinuation 2.40, 95% confidence interval 2.27 to 2.53). There was little evidence for any substantial association with autism (odds ratiomultivariableregression 1.10, 95% confidence interval 0.90 to 1.35; odds ratiopropensityscore 1.06, 95% confidence interval 0.84 to 1.32), attention deficit hyperactivity disorder (odds ratiomultivariableregression 1.02, 95% confidence interval 0.80 to 1.29; odds ratiopropensityscore 0.97, 95% confidence interval 0.75 to 1.25) or intellectual disability (odds ratiomultivariableregression 0.81, 95% confidence interval 0.55 to 1.19; odds ratiopropensityscore 0.89, 95% confidence interval 0.61 to 1.31) in children of women who continued antidepressants compared with those who discontinued antidepressants. There was inconsistent evidence of an association between initiation of antidepressants in pregnancy and diagnosis of autism in offspring (odds ratiomultivariableregression 1.23, 95% confidence interval 0.85 to 1.78; odds ratiopropensityscore 1.64, 95% confidence interval 1.01 to 2.66) but not attention deficit hyperactivity disorder or intellectual disability; however, but results were imprecise owing to smaller numbers. Several causal-inference analyses lacked precision owing to limited numbers. In addition, adherence to the prescribed treatment was not measured. Women prescribed antidepressants during pregnancy had greater service use during and after pregnancy than those not prescribed antidepressants. The evidence against any substantial association with autism, attention deficit hyperactivity disorder or intellectual disability in the children of women who continued compared with those who discontinued antidepressants in pregnancy is reassuring. Potential association of initiation of antidepressants during pregnancy with offspring autism needs further investigation. Further research on larger samples could increase the robustness and precision of these findings. These methods applied could be a template for future pharmaco-epidemiological investigation of other pregnancy-related prescribing safety concerns. This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (15/80/19) and will be published in full in Health Technology Assessment; Vol. 27, No. 15. See the NIHR Journals Library website for further project information.

De Novo Variants in RAB11B Cause Various Degrees of Global Developmental Delay and Intellectual Disability in Children

BackgroundRAB11B was described previously once with a severe form of intellectual disability. We aim at validation and delineation of the role of RAB11B in neurodevelopmental disorders. MethodsWe present seven novel individuals with disease-associated variants in RAB11B when compared with the six cases described in the literature. We performed a cross-sectional analysis to identify the clinical spectrum and the core phenotype. Additionally, structural effects of the variants were assessed by molecular modeling. ResultsSeven distinct de novo missense variants were identified, three of them recurrent (p.(Gly21Arg), p.(Val22Met), and p.(Ala68Thr)). Molecular modeling suggests that those variants either affect the nucleotide binding (at amino acid positions 21, 22, 33, 68) or the interaction with effector molecules (at positions 72 and 75). Our data confirmed the main manifestations as neurodevelopmental disorder with intellectual disability (85%), muscular hypotonia (83%), structural brain anomalies (77%), and visual impairment (70%). Combined analysis indicates a genotype-phenotype correlation; variants impacting the nucleotide binding cause a severe phenotype with intellectual disability, and variants outside the binding pocket lead to a milder phenotype with epilepsy. ConclusionsWe confirm that disease-associated missense variants in RAB11B cause a neurodevelopmental disorder and suggest a genotype-phenotype correlation based on the impact on nucleotide binding functionality of RAB11B.