Early Prediction of Autistic Spectrum Disorder Using Developmental Surveillance Data.

Importance: With the continuous increase in the prevalence of autistic spectrum disorder (ASD), effective early screening is crucial for initiating timely interventions and improving outcomes. Objective: To develop predictive models for ASD using routinely collected developmental surveillance data and to assess their performance in predicting ASD at different ages and in different clinical scenarios. Design, Setting, and Participants: This retrospective cohort study used nationwide data of developmental assessments conducted between January 1, 2014, and January 17, 2023, with minimal follow-up of 4 years and outcome collection in March 2023. Data were from a national program of approximately 1000 maternal child health clinics that perform routine developmental surveillance of children from birth to 6 years of age, serving 70% of children in Israel. The study included all children who were assessed at the maternal child health clinics (N = 1 187 397). Children were excluded if they were born at a gestational age of 33 weeks or earlier, had no record of gestational age, or were followed up for less than 4 years without an ASD outcome. The data set was partitioned at random into a development set (80% of the children) and a holdout evaluation set (20% of the children), both with the same prevalence of ASD outcome. Exposures: For each child, demographic and birth-related covariates were extracted, as were per-visit growth measurements, quantified developmental milestone assessments, and referral summary covariates. Only information that was available before the prediction age was used for training and evaluating the models. Main Outcome and Measure: The main outcome was eligibility for a governmental disabled child allowance due to ASD, according to administrative data of the National Insurance Institute of Israel. The performance of the models that predict the outcome was evaluated and compared with previous work on the Modified Checklist for Autism in Toddlers (M-CHAT). Results: The study included 1 187 397 children (610 588 [51.4%] male). The performance of the ASD prediction models improved with prediction age, with fair accuracy already at 12 months of age. A model that combined longitudinal measures of developmental milestone assessments with a minimal set of demographic variables, which was applied at 18 to 24 months of age, achieved an area under the receiver operating characteristic curve of 0.83, with a sensitivity of 45.1% at a specificity of 95.0%. A model using single-visit assessments achieved an area under the receiver operating characteristic curve of 0.81 and a sensitivity of 41.2% at a specificity of 95.0%. The best performing prediction models surpassed the pooled performance of M-CHAT (sensitivity, 40%; specificity, 95%) reported in studies with a similar design. Conclusions and Relevance: This cohort study found that ASD can be predicted from routine developmental surveillance data at an accuracy surpassing M-CHAT screening. This tool may be seamlessly integrated in the clinical workflow to improve early identification of children who may benefit from timely interventions.

Sex-Specific Developmental Scales for Surveillance.

BACKGROUND: Developmental surveillance, conducted routinely worldwide, is fundamental for early detection of children at risk for developmental delay. We aimed to explore sex-related difference in attainment rates of developmental milestones and to evaluate the clinical need for separate sex-specific scales. METHODS: This is a cross-sectional, natiowide retrospective study, utilizing data from a national child surveillance program of ∼1000 maternal child health clinics. The main cohort, used for constructing sex-specific developmental scales, included all children born between January 2014 to September 2020, who visited maternal child health clinics from birth to 6 years of age (n = 839 574). Children with abnormal developmental potential were excluded (n = 195 616). A validation cohort included all visits between 2020 and 2021 (n = 309 181). The sex-differences in normative attainment age of 59 developmental milestones from 4 domains were evaluated. The milestones with a significant gap between males and females were identified, and the projected error rates when conducting unified versus sex-specific surveillance were calculated. RESULTS: A new sex-specific developmental scale was constructed. In total, females preceded males in most milestones of all developmental domains, mainly at older ages. Conducting routine developmental surveillance using a unified scale, compared with sex-specific scales, resulted in potential missing of females at risk for developmental delay (19.3% of failed assessments) and over-diagnosis of males not requiring further evaluation (5.9% of failed assessments). CONCLUSIONS: There are sex-related differences in the normative attainment rates of developmental milestones, indicating possible distortion of the currently used unified scales. These findings suggest that using sex-specific scales may improve the accuracy of early childhood developmental surveillance.

A Developmental Surveillance Score for Quantitative Monitoring of Early Childhood Milestone Attainment: Algorithm Development and Validation.

BACKGROUND: Developmental surveillance, conducted routinely worldwide, is fundamental for timely identification of children at risk of developmental delays. It is typically executed by assessing age-appropriate milestone attainment and applying clinical judgment during health supervision visits. Unlike developmental screening and evaluation tools, surveillance typically lacks standardized quantitative measures, and consequently, its interpretation is often qualitative and subjective. OBJECTIVE: Herein, we suggested a novel method for aggregating developmental surveillance assessments into a single score that coherently depicts and monitors child development. We described the procedure for calculating the score and demonstrated its ability to effectively capture known population-level associations. Additionally, we showed that the score can be used to describe longitudinal patterns of development that may facilitate tracking and classifying developmental trajectories of children. METHODS: We described the Developmental Surveillance Score (DSS), a simple-to-use tool that quantifies the age-dependent severity level of a failure at attaining developmental milestones based on the recently introduced Israeli developmental surveillance program. We evaluated the DSS using a nationwide cohort of >1 million Israeli children from birth to 36 months of age, assessed between July 1, 2014, and September 1, 2021. We measured the score's ability to capture known associations between developmental delays and characteristics of the mother and child. Additionally, we computed series of the DSS in consecutive visits to describe a child's longitudinal development and applied cluster analysis to identify distinct patterns of these developmental trajectories. RESULTS: The analyzed cohort included 1,130,005 children. The evaluation of the DSS on subpopulations of the cohort, stratified by known risk factors of developmental delays, revealed expected relations between developmental delay and characteristics of the child and mother, including demographics and obstetrics-related variables. On average, the score was worse for preterm children compared to full-term children and for male children compared to female children, and it was correspondingly worse for lower levels of maternal education. The trajectories of scores in 6 consecutive visits were available for 294,000 children. The clustering of these trajectories revealed 3 main types of developmental patterns that are consistent with clinical experience: children who successfully attain milestones, children who initially tend to fail but improve over time, and children whose failures tend to increase over time. CONCLUSIONS: The suggested score is straightforward to compute in its basic form and can be easily implemented as a web-based tool in its more elaborate form. It highlights known and novel relations between developmental delay and characteristics of the mother and child, demonstrating its potential usefulness for surveillance and research. Additionally, it can monitor the developmental trajectory of a child and characterize it. Future work is needed to calibrate the score vis-a-vis other screening tools, validate it worldwide, and integrate it into the clinical workflow of developmental surveillance.

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.

OBJECTIVES: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. DESIGN: Retrospective nationwide cohort study. SETTING: Electronic medical records from an Israeli nationwide healthcare organisation. POPULATION: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. MAIN OUTCOME MEASURES: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. RESULTS: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. CONCLUSIONS: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Assessing the Attainment Rates of Updated CDC Milestones Using a New Israeli Developmental Scale.

OBJECTIVES: Developmental milestones norms are widely used worldwide and are fundamental for early childhood developmental surveillance. We compared a new Israeli evidence-based national developmental scale with the recently updated Centers for Disease Control and Prevention (CDC) checklists. METHODS: We used a cohort of nearly 4.5 million developmental assessments of 758 300 full-term born children aged 0 to 6 years (ALL-FT cohort), who visited maternal child health clinics in Israel for routine developmental surveillance. Among the assessed milestones of 4 developmental domains (gross motor, fine motor, language, and personal-social) we identified milestones that had equivalents on the CDC checklists and assessed the attainment rates of the Israeli children at the ages recommended by the CDC, at which ≥75% of the children would be expected to achieve the milestone. The analysis was repeated on a subgroup of 658 958 children who were considered healthy, typically developing by their birth and growth characteristics (NORMAL-FT cohort). RESULTS: There were 29 milestones, across all developmental domains and assessment ages, whose definitions by both tools were compatible, and could be compared. The attainment rate at the CDC-recommended age was >90% for 22 (76%) and 23 (79%) milestones, and the median attainment rates were 95.2% and 96.3% in the ALL-FT and NORMAL-FT cohorts, respectively. CONCLUSIONS: For almost all comparable milestones of all domains and all ages, children of the Israeli cohorts achieved the milestones earlier than expected by the CDC-defined threshold age. Evidence-based analysis of milestone norms among different populations may enable adjustments of developmental scales and facilitate more personalized developmental surveillance.

Standardization of a Developmental Milestone Scale Using Data From Children in Israel.

Importance: Routine developmental screening tests for children are used worldwide for early detection of developmental delays. However, assessment of developmental milestone norms lacks strong normative data, and there are inconsistencies among different screening tools. Objective: To establish milestone norms and build an updated developmental scale. Design, Setting, and Participants: This is a cross-sectional, population-based study conducted between 2014 and 2020. Developmental assessments were conducted by trained public health nurses, documented in national maternal child health clinics, known as Tipat Halav, which serve all children in Israel. Participants included all children born between January 2014 and September 2020, who were followed at the maternal child health clinics from birth to age 6 years. Exclusion criteria were preterm birth, missing gestational age, low birth weight (<2.5 kg), abnormal weight measurement (<3% according to standardized child growth charts), abnormal head circumference measurement (<3% or >97% according to standardized child growth charts), and visits without developmental data or without the child's age. Data analysis was performed from September 2020 to June 2021. Exposures: In total, 59 milestones in 4 developmental domains were evaluated, and the achievement rate per child's age was calculated for each milestone. Main Outcomes and Measures: A contemporary developmental scale, the Tipat Halav Israel Screening (THIS) Developmental Scale, was built, presenting the 75%, 90%, and 95% achievement rates for each milestone. The THIS scale was compared with other commonly used screening tests, including the Denver Developmental Screening Test II (Denver II), the Alberta Infant Motor Scale (AIMS), and the Centers for Disease Control and Prevention (CDC) Developmental Assessment. Results: A total of 839 574 children were followed in the maternal child health clinics between January 2014 and September 2020 in Israel, and 195 616 children were excluded. A total of 3 774 517 developmental assessments were performed for the remaining 643 958 children aged 0 to 6 years (319 562 female children [49.6%]), resulting in the establishment of new developmental norms. In terms of the comparable milestones, THIS milestones had a match of 18 of 27 (67%) with the Denver II, 7 of 7 (100%) with AIMS, and 10 of 19 (53%) with the CDC Developmental Assessment. The remaining unmatched milestones were achieved earlier in the THIS scale compared with other screening tools. Conclusions and Relevance: The THIS developmental scale is based on the largest population evaluated to date for developmental performance, representing the heterogeneous, multicultural population comprising this cohort. It is recommended for further evaluation worldwide.