Pregnancy Planning and its Association with Autism Spectrum Disorder: Findings from the Study to Explore Early Development.

OBJECTIVES: To examine associations between pregnancy planning and autism spectrum disorder (ASD) in offspring. METHODS: The Study to Explore Early Development (SEED), a multi-site case-control study, enrolled preschool-aged children with ASD, other DDs, and from the general population (POP). Some children with DDs had ASD symptoms but did not meet the ASD case definition. We examined associations between mother's report of trying to get pregnant (pregnancy planning) and (1) ASD and (2) ASD symptomatology (ASD group, plus DD with ASD symptoms group combined) (each vs. POP group). We computed odds ratios adjusted for demographic, maternal, health, and perinatal health factors (aORs) via logistic regression. Due to differential associations by race-ethnicity, final analyses were stratified by race-ethnicity. RESULTS: Pregnancy planning was reported by 66.4%, 64.8%, and 76.6% of non-Hispanic White (NHW) mothers in the ASD, ASD symptomatology, and POP groups, respectively. Among NHW mother-child pairs, pregnancy planning was inversely associated with ASD (aOR = 0.71 [95% confidence interval 0.56-0.91]) and ASD symptomatology (aOR = 0.67 [0.54-0.84]). Pregnancy planning was much less common among non-Hispanic Black mothers (28-32% depending on study group) and Hispanic mothers (49-56%) and was not associated with ASD or ASD symptomatology in these two race-ethnicity groups. CONCLUSION: Pregnancy planning was inversely associated with ASD and ASD symptomatology in NHW mother-child pairs. The findings were not explained by several adverse maternal or perinatal health factors. The associations observed in NHW mother-child pairs did not extend to other race-ethnicity groups, for whom pregnancy planning was lower overall.

Genetic liability for gastrointestinal inflammation disorders and association with gastrointestinal symptoms in children with and without autism.

Children with autism spectrum disorder (ASD) have a greater prevalence of gastrointestinal (GI) symptoms than children without ASD. We tested whether polygenic scores for each of three GI disorders (ulcerative colitis, inflammatory bowel disease, and Crohn's disease) were related to GI symptoms in children with and without ASD. Using genotyping data (564 ASD cases and 715 controls) and external genome-wide association study summary statistics, we computed GI polygenic scores for ulcerative colitis (UC-PGS), inflammatory bowel disease (IDB-PGS), and Crohn's disease (CD-PGS). Multivariable logistic regression models, adjusted for genetic ancestry, were used to estimate associations between each GI-PGS and (1) ASD case-control status, and (2) specific GI symptoms in neurotypical children and separately in ASD children. In children without ASD, polygenic scores for ulcerative colitis were significantly associated with experiencing any GI symptom (adjusted odds ratio (aOR) = 1.36, 95% confidence interval (CI) = 1.03-1.81, p = 0.03) and diarrhea specifically (aOR = 5.35, 95% CI = 1.77-26.20, p = 0.01). Among children without ASD, IBD-PGS, and Crohn's PGS were significantly associated with diarrhea (aOR = 3.55, 95% CI = 1.25-12.34, p = 0.02) and loose stools alternating with constipation (aOR = 2.57, 95% CI = 1.13-6.55, p = 0.03), respectively. However, the three PGS were not associated with GI symptoms in the ASD case group. Furthermore, polygenic scores for ulcerative colitis significantly interacted with ASD status on presentation of any GI symptom within a European ancestry subset (aOR = 0.42, 95% CI = 0.19-0.88, p = 0.02). Genetic risk factors for some GI symptoms differ between children with and without ASD. Furthermore, our finding that increased genetic risks for GI inflammatory disorders are associated with GI symptoms in children without ASD informs future work on the early detection of GI disorders.

DSM-5 criteria for autism spectrum disorder maximizes diagnostic sensitivity and specificity in preschool children.

PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.

2020 Ebola virus disease outbreak in Équateur Province, Democratic Republic of the Congo: a retrospective genomic characterisation.

BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention.

Peri-Pregnancy Cannabis Use and Autism Spectrum Disorder in the Offspring: Findings from the Study to Explore Early Development.

The association of autism spectrum disorder (ASD) with self-reported maternal cannabis use from 3 months pre-conception to delivery ("peri-pregnancy") was assessed in children aged 30-68 months, born 2003 to 2011. Children with ASD (N = 1428) were compared to children with other developmental delays/disorders (DD, N = 1198) and population controls (POP, N = 1628). Peri-pregnancy cannabis use was reported for 5.2% of ASD, 3.2% of DD and 4.4% of POP children. Adjusted odds of peri-pregnancy cannabis use did not differ significantly between ASD cases and DD or POP controls. Results were similar for any use during pregnancy. However, given potential risks suggested by underlying neurobiology and animal models, further studies in more recent cohorts, in which cannabis use and perception may have changed, are needed.

Association between pica and gastrointestinal symptoms in preschoolers with and without autism spectrum disorder: Study to Explore Early Development.

BACKGROUND: Pica, the repeated ingestion of nonfood items, can result in gastrointestinal (GI) outcomes. Children with autism spectrum disorder (ASD) and other developmental disabilities (DDs) are disproportionately affected by both pica and GI symptoms. Study of the inter-relationship between pica, GI symptoms, and ASD/DD is limited. OBJECTIVE/HYPOTHESIS: We assessed associations between pica and GI symptoms in preschool-aged children with and without ASD and other (non-ASD) DDs in the Study to Explore Early Development. METHODS: Our sample included children with ASD (n = 1244), other DDs (n = 1593), and population (POP) controls (n = 1487). Data to define final case-control status, pica, and GI symptoms were from standardized developmental assessments/questionnaires. Prevalence ratios, adjusted for sociodemographic factors (aPRs), and 95% confidence intervals were derived from modified Poisson regression. RESULTS: Within each group (ASD, DD, POP) and for the total sample, pica was associated with vomiting (aPR for total sample 2.6 [1.7, 4.0]), diarrhea (1.8 [1.4, 2.2]), and loose stools (1.8 [1.4, 2.2]). In the DD group, pica was associated with constipation (1.4 [1.03, 1.9]) and pain on stooling (1.8 [1.2, 2.6]). In analyses of the subgroup without pica, increases in GI symptoms were still evident in the ASD and DD groups compared to POP group. CONCLUSION: These findings highlight an important adverse effect of pica, GI symptoms, in children with and without ASD and DDs; nonetheless, pica does not fully explain the increased risk for GI symptoms among children with ASD and DDs. These findings inform the specialized healthcare needs of children with ASD and other DDs.

Pica, Autism, and Other Disabilities.

BACKGROUND AND OBJECTIVES: Pica, the repeated ingestion of nonfood items, can be life-threatening. Although case reports describe pica in children with autism spectrum disorder (ASD) or intellectual disability (ID), there has been little systematic study of pica prevalence. We assessed pica in children 30 to 68 months of age (median = 55.4 months) with and without ASD. METHODS: Our sample from the Study to Explore Early Development, a multisite case-control study, included children with ASD (n = 1426), children with other developmental disabilities (DDs) (n = 1735), and general population-based controls (POPs) (n = 1578). We subdivided the ASD group according to whether children had ID and the DD group according to whether they had ID and/or some ASD characteristics. Standardized developmental assessments and/or questionnaires were used to define final study groups, subgroups, and pica. We examined pica prevalence in each group and compared ASD and DD groups and subgroups to the POP group using prevalence ratios adjusted for sociodemographic factors. RESULTS: Compared with the prevalence of pica among POPs (3.5%), pica was higher in children with ASD (23.2%) and DD (8.4%), and in the following subgroups: ASD with ID (28.1%), ASD without ID (14.0%), DD with ID (9.7%), DD with ASD characteristics (12.0%), and DD with both ID and ASD characteristics (26.3%); however, pica prevalence was not elevated in children with DD with neither ID nor ASD characteristics (3.2%). Between-group differences remained after adjustment (adjusted prevalence ratio range 1.9-8.0, all P <.05). CONCLUSIONS: Pica may be common in young children with ASD, ASD characteristics, and ID. These findings inform the specialized health care needs of these children.

Gastrointestinal Symptoms in 2- to 5-Year-Old Children in the Study to Explore Early Development.

Gastrointestinal symptoms (GIS) are commonly reported in children with autism spectrum disorder (ASD). This multi-site study evaluated the prevalence of GIS in preschool-aged children with ASD/(n = 672), with other developmental delays (DD)/(n = 938), and children in the general population (POP)/(n = 851). After adjusting for covariates, children in the ASD group were over 3 times more likely to have parent-reported GIS than the POP group, and almost 2 times more likely than the DD group. Children with GIS from all groups had more behavioral and sleep problems. Within the ASD group, children with developmental regression had more GIS than those without; however, there were no differences in autism severity scores between children with and without GIS. These findings have implications for clinical management.

Injury-related treatments and outcomes in preschool children with autism spectrum disorder: Study to Explore Early Development (SEED).

BACKGROUND: Evidence about injury management and outcomes in children with autism spectrum disorder (ASD) is limited. METHOD: Cross-sectional analyses included children aged 30-68 months with at least one medically attended injury. Standardized diagnostic instruments determined ASD cases. Parent-reported injury treatments and outcomes were examined in ASD cases (n = 224) versus developmental delays/disorders (DD) (n = 188) and population (POP) (n = 267) controls, adjusting for child and family characteristics using logistic regression. RESULTS: Injury characteristics were similar between groups. Most children (82.5%) had emergency care (EC) or hospitalization after injury. Nearly half (46.4%) ever received a medication or injection, mostly analgesics (53.4%) and local anesthetics (23.8%), while 9.4% ever received surgery, most often for open wound (47.0%) or fracture (16.7%). ASD group children were less likely than DD group children to receive medication/injection (41.1% vs. 53.2%, adjusted odds ratio [aOR] = 0.60 [0.40, 0.90]); receipt of EC/hospitalization and surgery were comparable. Children with ASD more often had surgery than POP children (14.3% vs. 4.9%, aOR = 2.62 [1.31, 5.25]); receipt of EC/hospitalization and medication/injection were similar. Loss of consciousness was uncommon (ASD = 6.3%, DD = 5.3%, POP = 3.4%), as was long-term or significant behavior change (ASD = 5.4%, DD = 3.2%, POP = 3.2%); differences were not significant. CONCLUSIONS: Injured children with ASD received fewer medications/injections than children with non-ASD developmental delays/disorders and more surgical treatments than general population children. Injury management was otherwise similar between groups. Understanding whether these results reflect child or injury characteristics or provider perceptions about behaviors and pain thresholds of children with ASD, and how these may influence care, requires further study.

Association Between Breastfeeding Initiation and Duration and Autism Spectrum Disorder in Preschool Children Enrolled in the Study to Explore Early Development.

Studies report inconsistent findings on the relationship between ASD and breastfeeding. We explored associations between ASD and breastfeeding initiation (yes/no) and duration (months categorized in tertiles) in the Study to Explore Early Development, a community-based case-control study in six sites in the Unites States. We adjusted for various child and mother demographic and pregnancy factors. Breastfeeding initiation was reported in 85.7% of mothers of children with ASD and 90.6% of mothers of controls. After adjustment, we found no significant difference in breastfeeding initiation (adjusted odds-ratio [aOR]: 0.88 and 95% confidence interval (CI) 0.60-1.28). However, mothers of children with ASD were less likely to report duration of breastfeeding in the high (≥12 months) versus low tertile (<6 months) (aOR and 95% CI: 0.61 [0.45-0.84]) or the middle (6-<12 months) versus low tertile (0.72: 0.54-0.98). The association of ASD and breastfeeding duration was slightly attenuated when the presence of the broader autism phenotype (BAP) in the mother was accounted for, but still remained for the highest tertile. This association does not appear to be totally explained by maternal BAP. We were unable to distinguish whether the difference in duration was due to difficulties breastfeeding children who later develop ASD, other factors not adjusted in our study, or greater ASD risk resulting from shorter breastfeeding duration. Longitudinal studies that compare reasons why mothers stop breastfeeding between ASD and controls and establish a temporal relation between ASD and breastfeeding are needed. Future studies should also evaluate interactions between ASD risk genes and breastfeeding. Autism Research 2019, 12: 816-829. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this study, we compared breastfeeding practices between mothers of children with and without autism spectrum disorder (ASD). We found that the percentage of mothers who started breastfeeding was similar between the two groups, but mothers of children with ASD breastfed for a shorter amount of time compared to mothers of children without ASD. Future studies are needed to evaluate the reasons why the duration of breastfeeding was shorter for mothers of children with ASD compared to those without ASD.

Community-based service use in preschool children with autism spectrum disorder and associations with insurance status.

BACKGROUND: ASD-related services can improve outcomes for children, but less is known about service outside of school settings during preschool age. We aimed to describe amount and category of community-based service use among 3-5-year-old children with ASD and examine differences by health insurance. METHODS: We used cross-sectional data on 792 children with ASD diagnoses in the Study to Explore Early Development, a community-based study of neurodevelopment with enrollment between 2012-2016. Mothers reported current child service use and insurance status at study entry. We used log-Poisson and logistic regression to compare service use by insurance group. RESULTS: Nearly 40% of children were not receiving community-based services at study entry. Children with public insurance had fewer total services than children with private or both insurances. After adjustment for sociodemographic confounders, insurance status was not associated with types of different categories of community-based services. However, children with public insurance alone were least likely to receive community-based behavioral therapy and most likely to receive psychotropic medication compared to other insurances. CONCLUSION: Many preschool-aged children do not receive community-based services, with receipt associated with insurance type. Increasing access and availability for evidence-based service, especially for beneficiaries of public insurance, may improve service use and outcomes.

Sleep Problems in 2- to 5-Year-Olds With Autism Spectrum Disorder and Other Developmental Delays.

: media-1vid110.1542/5984243260001PEDS-VA_2018-0492Video Abstract BACKGROUND: Sleep problems can impact daytime behavior, quality of life, and overall health. We compared sleep habits in young children with autism spectrum disorder (ASD) and other developmental delays and disorders and in children from the general population (POP). METHODS: We included 2- to 5-year-old children whose parent completed all items on the Children's Sleep Habits Questionnaire (CSHQ) in a multisite case-control study: 522 children with ASD; 228 children with other developmental delays and disorders with autism spectrum disorder characteristics (DD w/ASD); 534 children with other developmental delays and disorders without autism spectrum disorder characteristics (DD w/o ASD); and 703 POP. Multivariable analysis of variance compared CSHQ mean total score (TS) and subscale scores between groups. Logistic regression analysis examined group differences by using TS cutoffs of 41 and 48. Analyses were adjusted for covariates. RESULTS: Mean CSHQ TS for children in each group: ASD (48.5); DD w/ASD (50.4); DD w/o ASD (44.4); and POP (43.3). Differences between children with ASD and both children with DD w/o ASD and POP were statistically significant. Using a TS cutoff of 48, the proportion of children with sleep problems was significantly higher in children in the ASD group versus DD w/o ASD and POP groups (adjusted odds ratios [95% confidence intervals]: 2.12 [1.57 to 2.87] and 2.37 [1.75 to 3.22], respectively). CONCLUSIONS: Sleep problems are more than twice as common in young children with ASD and DD w/ASD. Screening for sleep problems is important in young children to facilitate provision of appropriate interventions.

Injuries in Children with Autism Spectrum Disorder: Study to Explore Early Development (SEED).

This study examined caregiver-reported medically-attended injuries among 30-68 month old children with autism spectrum disorder (ASD) compared to general population (POP) and non-ASD developmental disorders (DD) controls in the Study to Explore Early Development. Injuries were common in ASD cases (32.3%) as well as POP (30.2%) and DD (27.8%) controls; most resulted in an emergency visit or hospitalization. After accounting for sociodemographic, health, IQ and behavior differences, odds of injury in ASD cases were significantly higher than DD controls but similar to POP controls. Attention problems mediated the relationships. Clinicians caring for children with both ASD and attention problems should consider providing targeted safety advice. Differences in injury risk between children with ASD vs. other developmental disorders need further study.

Brief Report: Estimated Prevalence of a Community Diagnosis of Autism Spectrum Disorder by Age 4 Years in Children from Selected Areas in the United States in 2010: Evaluation of Birth Cohort Effects.

We compared early-diagnosed autism spectrum disorder (ASD) (defined as diagnosis by age 4 years) between the 2002 and 2006 birth cohorts, in five sites of the Autism and Developmental Disabilities Monitoring Network. In the 2002 cohort, the prevalence/1000 of early-diagnosed ASD was half the 8-year-old prevalence (7.2 vs. 14.7, prevalence ratio [PR] 0.5 [0.4-0.6]). Overall, the prevalence of early-diagnosed ASD did not differ between birth cohorts (PR 1.1 [0.9-1.3]). However, in three sites with complete case ascertainment, the prevalence of early-diagnosed ASD was higher for those born in 2006 versus 2002 (PR 1.3 [1.1-1.5]), suggesting possible improvement in early identification. The lack of change in two sites may reflect less complete case ascertainment. Studies in more recent cohorts are needed.

Brief Report: Prevalence of Self-injurious Behaviors among Children with Autism Spectrum Disorder-A Population-Based Study.

Self-injurious behaviors (SIB) have been reported in more than 30 % of children with an autism spectrum disorder (ASD) in clinic-based studies. This study estimated the prevalence of SIB in a large population-based sample of children with ASD in the United States. A total of 8065 children who met the surveillance case definition for ASD in the Autism and Developmental Disabilities Monitoring (ADDM) Network during the 2000, 2006, and 2008 surveillance years were included. The presence of SIB was reported from available health and/or educational records by an expert clinician in ADDM Network. SIB prevalence averaged 27.7 % across all sites and surveillance years, with some variation between sites. Clinicians should inquire about SIB during assessments of children with ASD.

Demographic profile of families and children in the Study to Explore Early Development (SEED): Case-control study of autism spectrum disorder.

BACKGROUND: The Study to Explore Early Development (SEED) is designed to enhance knowledge of autism spectrum disorder characteristics and etiologies. OBJECTIVE: This paper describes the demographic profile of enrolled families and examines sociodemographic differences between children with autism spectrum disorder and children with other developmental problems or who are typically developing. METHODS: This multi-site case-control study used health, education, and birth certificate records to identify and enroll children aged 2-5 years into one of three groups: 1) cases (children with autism spectrum disorder), 2) developmental delay or disorder controls, or 3) general population controls. Study group classification was based on sampling source, prior diagnoses, and study screening tests and developmental evaluations. The child's primary caregiver provided demographic characteristics through a telephone (or occasionally face-to-face) interview. Groups were compared using ANOVA, chi-squared test, or multinomial logistic regression as appropriate. RESULTS: Of 2768 study children, sizeable proportions were born to mothers of non-White race (31.7%), Hispanic ethnicity (11.4%), and foreign birth (17.6%); 33.0% of households had incomes below the US median. The autism spectrum disorder and population control groups differed significantly on nearly all sociodemographic parameters. In contrast, the autism spectrum disorder and developmental delay or disorder groups had generally similar sociodemographic characteristics. CONCLUSIONS: SEED enrolled a sociodemographically diverse sample, which will allow further, in-depth exploration of sociodemographic differences between study groups and provide novel opportunities to explore sociodemographic influences on etiologic risk factor associations with autism spectrum disorder and phenotypic subtypes.