The influence of loss to follow-up in autism screening research: Taking stock and moving forward.

BACKGROUND: How best to improve the early detection of autism spectrum disorder (ASD) is the subject of significant controversy. Some argue that universal ASD screeners are highly accurate, whereas others argue that evidence for this claim is insufficient. Relatedly, there is no clear consensus as to the optimal role of screening for making referral decisions for evaluation and treatment. Published screening research can meaningfully inform these questions-but only through careful consideration of children who do not complete diagnostic follow-up. METHODS: We developed two simulation models that re-analyze the results of a large-scale validation study of the M-CHAT-R/F by Robins et al. (2014, Pediatrics, 133, 37). Model #1 re-analyzes screener accuracy across six scenarios, each reflecting different assumptions regarding loss to follow-up. Model #2 builds on this by closely examining differential attrition at each point of the multi-step detection process. RESULTS: Estimates of sensitivity ranged from 40% to 94% across scenarios, demonstrating that estimates of accuracy depend on assumptions regarding the diagnostic status of children who were lost to follow-up. Across a range of plausible assumptions, data also suggest that children with undiagnosed ASD may be more likely to complete follow-up than children without ASD, highlighting the role of clinicians and caregivers in the detection process. CONCLUSIONS: Using simulation modeling as a quantitative method to examine potential bias in screening studies, analyses suggest that ASD screening tools may be less accurate than is often reported. Models also demonstrate the critical importance of every step in a detection process-including steps that determine whether children should complete an additional evaluation. We conclude that parent and clinician decision-making regarding follow-up may contribute more to detection than is widely assumed.

Mother-Infant Interaction and Maternal Postnatal Psychological Distress Associate with Child's Social-Emotional Development During Early Childhood: A FinnBrain Birth Cohort Study.

We studied the effects of mother-infant interaction and maternal pre- and postnatal psychological distress on children's social-emotional problems and competences, as well as whether interaction quality moderates the association between distress and children's outcomes. Maternal pre- and postnatal psychological distress were measured using the SCL and EPDS questionnaires, whereas mother-infant interaction was measured when the child was 8 months old using the EA Scales. Children's social-emotional development was measured using the BITSEA questionnaire at 2 years old and using the SDQ questionnaire at 4 years old, where higher maternal structuring was associated with fewer social-emotional problems in children and higher maternal sensitivity was associated with greater social-emotional competence in children at 2 years old. Further, higher postnatal distress was found associated with greater social-emotional problems at 2 years old, though neither these effects nor moderating effects at 4 years old were observed after multiple-comparison corrections. Our findings support direct associations of both mother-infant interaction and maternal postnatal psychological distress with children's social-emotional development during toddlerhood.

Child social-emotional and behavioral problems and competencies contribute to changes in developmental functioning during Early Intervention.

This study examined how social-emotional and behavioral (SEB) problems and competencies contribute to changes in developmental functioning among children enrolled in Part C Early Intervention (EI), a U.S. program supporting young children with developmental delays and disabilities. The sample included 1,055 children enrolled in EI from 2011-2019 (mean age at EI entry = 17 months; 64% male; 72% marginalized racial and ethnic backgrounds). Standardized developmental assessments, drawn from administrative records, characterized developmental functioning at EI entry and exit and parents reported SEB functioning. Hierarchical regression analyses revealed that SEB problems and competencies interacted in predicting change in developmental functioning from EI entry to exit. Monitoring, identifying, and addressing SEB problems and competencies may optimize developmental outcomes for young children with developmental delays and disabilities.

Developmental Outcomes in Early-Identified Children Who Are Hard of Hearing at 2 to 3 Years of Age.

OBJECTIVES: This study examined the psychosocial, adaptive behavior, and language outcomes of young children who are hard of hearing (HH) without additional disabilities or neurocognitive impairments. Relations between early developmental outcomes and child and parent demographic variables, and parenting stress and self-efficacy were also explored. DESIGN: Participants were 39 children with early identified, permanent mild to severe hearing loss, between the ages of 2 and 3 years, and a comparison group of 47 children with normal hearing (NH). Developmental outcomes were measured using clinician-administered standardized tests and parent-completed behavior rating instruments specific to language, psychosocial functioning, and adaptive behavior. Mothers completed self-report measures that assess parenting stress and maternal self-efficacy. RESULTS: The children who are HH were similar to the children with NH in terms of their psychosocial functioning and adaptive behavior, with the exception of their socialization skills. As a group, the children who are HH performed significantly worse than their peers with NH on all measures of language ability. Among the children who are HH, maternal self-efficacy showed a strong positive correlation with adaptive behavior outcomes; however, it failed to contribute unique variance above that explained by language ability and gender. Maternal self-efficacy was also significantly correlated with better psychosocial outcomes, but only parenting stress proved to be a significant predictor of child behavioral problems once other variables considered were in the model. CONCLUSIONS: Early-identified young children who are HH can demonstrate age-appropriate development in multiple domains, including language, psychosocial, and adaptive behavior. However, mild to severe hearing loss places young children with no additional disabilities or neurocognitive impairments at risk for language delays. Although the children who are HH demonstrated no more emotional or behavioral problems than their same-age peers with NH, results suggest that language delays increase their vulnerability for delays in various aspects of social competence.

How well are DSM-5 diagnostic criteria for ASD represented in standardized diagnostic instruments?

Five years after the publication of DSM-5 in 2013, three widely used diagnostic instruments have published algorithms designed to represent its (sub-)criteria for Autism Spectrum Disorder (ASD) in children and adolescents. This study aimed to: (1) establish the content validity of these three DSM-5-adapted algorithms, and (2) identify problems with the operationalization of DSM-5 diagnostic criteria in measurable and observable behaviors. Algorithm items of the Autism Diagnostic Observation Schedule-Second Edition (ADOS-2), Developmental, Dimensional and Diagnostic Interview (3di) and Diagnostic Interview for Social and Communication Disorders-11th edition (DISCO-11) were mapped onto DSM-5 sub-criteria. The development and decision-making rules integrated in their algorithms were then compared with DSM-5. Results demonstrated significant variability in the number and nature of sub-criteria covered by the ADOS-2, 3di and DISCO-11. In addition to differences in the development of algorithms and cut-off scores, instruments also differed in the extent to which they follow DSM-5 decision-making rules for diagnostic classification. We conclude that such differences in interpretation of DSM-5 criteria provide a challenge for symptom operationalization which will be most effectively overcome by consensus, testing and reformulation.

Introducing Typhoid Conjugate Vaccine in South Asia: Lessons From the Surveillance for Enteric Fever in Asia Project.

Enteric fever remains a public health concern in communities lacking sanitation infrastructure to separate sewage from drinking water. To bridge the gap until large-scale civil-engineering projects are implemented in high-burden countries, typhoid conjugate vaccine presents a promising disease-prevention technology. A new typhoid conjugate vaccine was prequalified by the World Health Organization in 2017 and is beginning to be introduced in countries around the world. To help inform vaccine introduction, the Surveillance for Enteric Fever in Asia Project (SEAP) conducts prospective enteric fever surveillance in Bangladesh, Nepal, and Pakistan. This supplement presents findings from Phase II of the study (2016-2019) on burden of disease, clinical presentation, the growing spread of drug-resistant strains, and policy and economic ramifications. These findings are delivered to support policymakers in their deliberations on strategies to introduce typhoid conjugate vaccine as a preventive tool against enteric fever.

Investigating the importance of individual mitochondrial genotype in susceptibility to drug-induced toxicity.

The mitochondrion is an essential organelle responsible for generating cellular energy. Additionally, mitochondria are a source of inter-individual variation as they contain their own genome. Evidence has revealed that mitochondrial DNA (mtDNA) variation can confer differences in mitochondrial function and importantly, these differences may be a factor underlying the idiosyncrasies associated with unpredictable drug-induced toxicities. Thus far, preclinical and clinical data are limited but have revealed evidence in support of an association between mitochondrial haplogroup and susceptibility to specific adverse drug reactions. In particular, clinical studies have reported associations between mitochondrial haplogroup and antiretroviral therapy, chemotherapy and antibiotic-induced toxicity, although study limitations and conflicting findings mean that the importance of mtDNA variation to toxicity remains unclear. Several studies have used transmitochondrial cybrid cells as personalised models with which to study the impact of mitochondrial genetic variation. Cybrids allow the effects of mtDNA to be assessed against a stable nuclear background and thus the in vitro elucidation of the fundamental mechanistic basis of such differences. Overall, the current evidence supports the tenet that mitochondrial genetics represent an exciting area within the field of personalised medicine and drug toxicity. However, further research effort is required to confirm its importance. In particular, efforts should focus upon translational research to connect preclinical and clinical data that can inform whether mitochondrial genetics can be useful to identify at risk individuals or inform risk assessment during drug development.

The Family Life Impairment Scale: Factor Structure and Clinical Utility with Young Children.

Although it is well-established that young children experience significant psychopathology, diagnostic decisions continue to be challenging, in part due to the way impairment is understood, defined, and measured. Most existing clinical tools assess impairment in an individualized manner, whereas for many young children, impairment is more accurately conceptualized as a family-oriented, multidimensional construct, impacting various parental and family activities. Two studies were completed using the Family Life Impairment Scale (FLIS), a multidimensional parent-report measure of family and associated impairment designed for young children. In Study 1, factor analysis was used in a large (n = 945) representative sample (23-48 months of age). FLIS associations with measures of parent and child well-being were explored to investigate convergent validity. Study 2 was completed in a sample (n = 174) of young children (18-33 months of age) diagnosed with autism spectrum disorders to explore factorial consistency in a clinical sample. Study 1 yielded evidence of a four-factor solution, including parent impairment (affecting parental well-being), family impairment (affecting family activities and routines), childcare impairment (affecting challenges with childcare), and positive growth (parental learning and growth associated with the child's problem). Evidence of convergent validity was also found, as factors were differentially associated with established measures of child symptoms and parent stress. Factor structure was supported in the clinical sample. Results support both the factorial structure and clinical utility of the FLIS for use across clinical and nonclinical populations of young children.

Parental insightfulness and parenting behavior: a two-dimensional analysis of parent contributions to child cognitive outcomes.

Utilizing a two-dimensional model of parenting emphasizing both (1) proximity seeking and (2) exploration, consistent with a conceptual framework rooted in attachment theory, the relations between parental insightfulness, observed parenting, and child cognitive outcomes were investigated in a low-income sample of 64 of caregivers and their young 3-5-year-old children. Specifically, observed parental sensitivity (proximity seeking) and intrusiveness (exploration) and parental insightfulness assessed dimensionally to capture Positive Insight and Focus on Child were examined in relation to child cognitive outcomes. Parental intrusiveness was negatively correlated with cognitive performance; however, parental sensitivity was not associated with child cognitive outcomes. Parents' capacity to remain child-focused during the Insightfulness Assessment was negatively correlated with observed intrusiveness and was associated with child cognitive performance. These results suggest unique contributions of dimensions of parental insightfulness and parenting behaviors to child cognitive outcomes - specifically, parents' capacity to remain focused on children's experience during the Insightfulness Assessment and nonintrusive parenting behavior, which may reflect strategies to support children's exploration.

Do child healthcare professionals and parents recognize social-emotional and behavioral problems in 1-year-old infants?

Growing evidence supports the existence of clinically significant social-emotional/behavioral (SEB) problems among as young as 1-year-old infants. However, a substantial proportion of early SEB problems remain unidentified during contacts with child healthcare professionals. In this study, child healthcare nurse (CHCN; N = 1008) and parental (N = 518) reports about SEB worries were gathered, along with the maternal and paternal Brief Infant-Toddler Social and Emotional Assessment (BITSEA) ratings, for 12-month-old infants randomly recruited through Finnish child health centers. Only 1.4-1.8 % of CHCNs, 3.9 % of mothers, and 3.2 % of fathers reported of being worried about the assessed child's SEB development. When the CHCNs' and parental reports were combined, 7.7 % (33/428) of the infants assessed each by all three adults had one (7.0 %), two (0.7 %) or three (0 %) worry reports. Even the combination of the CHCN's and parental worry reports identified only 7.0-13.8 % of the infants with the maternal and/or paternal BITSEA Problem or Competence rating in the of-concern range. Identified associations across the three informants' worry reports, parental BITSEA ratings and sociodemographic factors are discussed in the paper. Routine and frequent use of developmentally appropriate screening measures, such as the BITSEA, might enhance identification and intervening of early SEB problems in preventive child healthcare by guiding both professionals and parents to pay more attention to substantial aspects of young children's SEB development and encouraging them to discuss possible problems and worries.

PARENTAL REPORTS OF EARLY SOCIOEMOTIONAL AND BEHAVIORAL PROBLEMS: DOES THE FATHER'S VIEW MAKE A DIFFERENCE?

Although both mothers and fathers are essential sources of information to address early socioemotional/behavioral (SEB) problems, there continues to be a dearth of studies considering both parental views. A sample of 208 toddlers (Mage = 19.3 months) was recruited through public child health centers. Both parents of 172 toddlers (76 boys, 96 girls) completed the Child Behavior Checklist (CBCL) 1-5 (T.M. Achenbach & L.A. Rescorla, 2000; Finnish translation by F. Almqvist, ). Correspondence (intraclass correlation coefficients; ICCs) between the maternal and paternal CBCL ratings was good (.64) for the Internalizing and excellent (.76) for the Externalizing and Total Problems scores whereas ICCs varied from .45 for the Withdrawn to .76 for the Sleep Problems and Aggressive Behavior syndrome scores. Regarding discrepancies, mothers consistently reported higher CBCL scale scores than did fathers. Most significant differences between the parental ratings were found on the Aggressive Behavior syndrome, Externalizing, and Total Problems scales. Interparental rating discrepancies increased with elevations in the corresponding CBCL scale scores. Positive correlations were found between maternal, but not paternal, parenting stress and interparental rating discrepancies on the CBCL. The observed differences between maternal and paternal ratings highlight the importance of gathering reports from both parents when assessing early SEB problems. The findings are more profoundly discussed in the article.

Unimpaired attentional disengagement in toddlers with autism spectrum disorder.

A prominent hypothesis holds that 'sticky' attention early in life in children with autism spectrum disorder (ASD) limits their ability to explore and learn about the world. Under this hypothesis, the core clinical symptoms of ASD - restricted interests, repetitive behaviors and impaired social/communication abilities - could all result from impaired attentional disengagement during development. However, the existence of disengagement deficits in children with ASD is controversial, and a recent study found no deficit in 5- to 12-year-olds with ASD. Nonetheless, the possibility remains that disengagement is impaired earlier in development in children with ASD, altering their developmental trajectory even if the attentional deficit itself is remediated or compensated for by the time children with ASD reach school age. Here, we tested this possibility by characterizing attentional disengagement in a group of toddlers just diagnosed with ASD (age 21 to 37 months). We found strikingly similar performance between the ASD and age-matched typically developing (TD) toddlers, and no evidence of impaired attentional disengagement. These results show that even at a young age when the clinical symptoms of ASD are first emerging, disengagement abilities are intact. Sticky attention is not a fundamental characteristic of ASD, and probably does not play a causal role in its etiology.

Prevention Services for Externalizing and Anxiety Symptoms in Low-Income Children: the Role of Parent Preferences in Early Childhood.

Dissemination of prevention programs targeting young children is impeded by challenges with parent engagement. Matching program characteristics to parent preferences is associated with increased retention in clinical/intervention settings, but little is known about the types of prevention programs that interest parents. The objectives of this study were to better understand parents' preferences for services designed to prevent externalizing and anxiety disorders and to identify factors associated with preferences. Ethnically diverse, low-income caregivers (n = 485) of young children (11-60 months) completed surveys on child anxiety and externalizing symptoms, parental worry about their children, parent anxiety symptoms, and preferences for prevention group topics. Parents were more likely to prefer a group targeting externalizing behaviors compared to anxiety. Cluster analysis revealed four groups of children: low symptoms, moderate anxiety-low externalizing, moderate externalizing-low anxiety, and high anxiety and externalizing. Parents' preferences varied according to co-occurrence of child anxiety and externalizing symptoms; interest in a program targeting externalizing problems was associated with elevated externalizing problems (regardless of anxiety symptom level), parent anxiety symptoms, and parent worry about their child. Only parent anxiety symptoms predicted parents' interest in an anxiety-focused program, and preference for an anxiety-focused program was actually reduced if children had co-occurring anxiety and externalizing symptoms versus only anxiety symptoms. Results suggest that parents' interest in a program to prevent externalizing problems was well-aligned with the presenting problem, whereas preferences for anxiety programming suggest a more complex interplay among factors. Parent preferences for targeted programming are discussed within a broader framework of parent engagement.

SYMPTOM PRESENTATIONS AND CLASSIFICATION OF AUTISM SPECTRUM DISORDER IN EARLY CHILDHOOD: APPLICATION TO THE DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD (DC:0-5).

Over the past 5 years, a great deal of information about the early course of autism spectrum disorder (ASD) has emerged from longitudinal prospective studies of infants at high risk for developing ASD based on a previously diagnosed older sibling. The current article describes early ASD symptom presentations and outlines the rationale for defining a new disorder, Early Atypical Autism Spectrum Disorder (EA-ASD) to accompany ASD in the new revision of the ZERO TO THREE Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5) (in press) alternative diagnostic classification manual. EA-ASD is designed to identify children who are 9 to 36 months of age presenting with a minimum of (a) two social-communication symptoms and (b) one repetitive and restricted behavior symptom as well as (c) evidence of impairment, with the intention of providing these children with appropriately tailored services and improving the likelihood of optimizing their development.

DIAGNOSTIC CLASSIFICATION OF MENTAL HEALTH AND DEVELOPMENTAL DISORDERS OF INFANCY AND EARLY CHILDHOOD DC:0-5: SELECTIVE REVIEWS FROM A NEW NOSOLOGY FOR EARLY CHILDHOOD PSYCHOPATHOLOGY.

The Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-5; ZERO TO THREE) is scheduled to be published in 2016. The articles in this section are selective reviews that have been undertaken as part of the process of refining and updating the nosology. They provide the rationales for new disorders, for disorders that had not been included previously in the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood: Revised Edition (DC:0-3R; ZERO TO THREE, 2005), and for changes in how certain types of disorders are conceptualized.

Thresholds and accuracy in screening tools for early detection of psychopathology.

BACKGROUND: The accuracy of any screening instrument designed to detect psychopathology among children is ideally assessed through rigorous comparison to 'gold standard' tests and interviews. Such comparisons typically yield estimates of what we refer to as 'standard indices of diagnostic accuracy', including sensitivity, specificity, positive predictive value (PPV), and negative predictive value. However, whereas these statistics were originally designed to detect binary signals (e.g., diagnosis present or absent), screening questionnaires commonly used in psychology, psychiatry, and pediatrics typically result in ordinal scores. Thus, a threshold or 'cut score' must be applied to these ordinal scores before accuracy can be evaluated using such standard indices. To better understand the tradeoffs inherent in choosing a particular threshold, we discuss the concept of 'threshold probability'. In contrast to PPV, which reflects the probability that a child whose score falls at or above the screening threshold has the condition of interest, threshold probability refers specifically to the likelihood that a child whose score is equal to a particular screening threshold has the condition of interest. METHOD: The diagnostic accuracy and threshold probability of two well-validated behavioral assessment instruments, the Child Behavior Checklist Total Problem Scale and the Strengths and Difficulties Questionnaire total scale were examined in relation to a structured psychiatric interview in three de-identified datasets. RESULTS: Although both screening measures were effective in identifying groups of children at elevated risk for psychopathology in all samples (odds ratios ranged from 5.2 to 9.7), children who scored at or near the clinical thresholds that optimized sensitivity and specificity were unlikely to meet criteria for psychopathology on gold standard interviews. CONCLUSIONS: Our results are consistent with the view that screening instruments should be interpreted probabilistically, with attention to where along the continuum of positive scores an individual falls.

Development of a novel observational measure for anxiety in young children: The Anxiety Dimensional Observation Scale.

BACKGROUND: Identifying anxiety disorders in preschool-age children represents an important clinical challenge. Observation is essential to clinical assessment and can help differentiate normative variation from clinically significant anxiety. Yet, most anxiety assessment methods for young children rely on parent-reports. The goal of this article is to present and preliminarily test the reliability and validity of a novel observational paradigm for assessing a range of fearful and anxious behaviors in young children, the Anxiety Dimensional Observation Schedule (Anx-DOS). METHODS: A diverse sample of 403 children, aged 3 to 6 years, and their mothers was studied. Reliability and validity in relation to parent reports (Preschool Age Psychiatric Assessment) and known risk factors, including indicators of behavioral inhibition (latency to touch novel objects) and attention bias to threat (in the dot-probe task) were investigated. RESULTS: The Anx-DOS demonstrated good inter-rater reliability and internal consistency. Evidence for convergent validity was demonstrated relative to mother-reported separation anxiety, social anxiety, phobic avoidance, trauma symptoms, and past service use. Finally, fearfulness was associated with observed latency and attention bias toward threat. CONCLUSIONS: Findings support the Anx-DOS as a method for capturing early manifestations of fearfulness and anxiety in young children. Multimethod assessments incorporating standardized methods for assessing discrete, observable manifestations of anxiety may be beneficial for early identification and clinical intervention efforts.

Predicting externalizing and internalizing behavior in kindergarten: examining the buffering role of early social support.

This study tested an ecological model predicting children's behavior problems in kindergarten from risk and protective factors (parent psychological distress, parenting behavior, and social support) during early childhood. Study participants were 1,161 sociodemographically diverse mother-child pairs that participated in a longitudinal birth cohort study. The predictor variables were collected at two separate time points and based on parent reports; children were an average of 2 years old at Time 1 and 3 years old at Time 2. The outcome measures were collected when children reached kindergarten and were 6 years old on average. Our results show that early maternal psychological distress, mediated by suboptimal parenting behavior, predicts children's externalizing and internalizing behaviors in kindergarten. Moreover, early social support buffers the relations between psychological distress and later suboptimal parenting behavior and between suboptimal parenting behavior and later depressive/withdrawn behavior. Our findings have several implications for early intervention and prevention efforts. Of note, informal social support appears to play an important protective role in the development of externalizing and internalizing behavior problems, weakening the link between psychological distress and less optimal parenting behavior and between suboptimal parenting behavior and children's withdrawal/depression symptoms. Increasing social support may be a productive goal for family and community-level intervention.

Caregiver insightfulness and young children's violence exposure: testing a relational model of risk and resilience.

This study employed a relational post-traumatic stress frame to explore the co-contribution of young children's exposure to violence and caregiver insightfulness on child behavioral outcomes in a high-risk, non-referred sample of caregivers and preschoolers (n = 64; mean age 3.83 years, SD = .77). Caregiver insightfulness did not have a main effect on child outcomes but did moderate the relation between violence exposure and child behavior across all observed outcomes. Violence-exposed children with non-insightful caregivers demonstrated higher caregiver-rated internalizing and externalizing behaviors and observer-rated negative affect than all other groups. Among children not exposed to violence, insightfulness was not related to children's behavior problems or negative affect, suggesting violence-specific processes. Though cross-sectional, results suggest that the effects of violence and caregiver insightfulness on child outcomes are contingent on one another and that caregiver insightfulness may play a protective role in contexts of violence.

Targeted prevention of childhood anxiety: engaging parents in an underserved community.

Selective prevention programs hold the promise of alleviating child anxiety symptoms, decreasing the risk for emotional problems across the lifespan. Such programs have particular public health import for young children of poor, underserved communities. Identifying factors related to parent engagement, and methods to improve engagement, are paramount in the effort to develop anxiety-focused, community prevention programs. This feasibility study investigated the effect of an enhanced recruitment strategy to maximize parent engagement, as well as factors related to attendance in a single session focused on anxiety prevention. Participants were poor, ethnic minority parents of children aged 11-71 months (n = 256) who completed a survey that assessed anxiety risk according to trauma exposure, child anxiety, or parent anxiety, as well as preferences for preventive services (phase 1). Those meeting risk criteria (n = 101) were invited to a preventive group session (phase 2). Half of parents received enhanced recruitment (ER), which included personalized outreach, matching parent preferences, and community endorsement. Other parents were invited by mail. Chi square analyses indicated that ER was associated with planning to attend (49 vs. 6% of control). Parents receiving ER were 3.5 times more likely to attend. Higher sociodemographic risk was correlated with higher child anxiety symptoms but not attendance. Results highlight the need for improved strategies for engaging parents in preventive, community-based interventions.