Association between prenatal antibiotic exposure and autism spectrum disorder among term births: A population-based cohort study.

BACKGROUND: Prenatal antibiotic exposure induces changes in the maternal microbiome, which could influence the development of the infant's microbiome-gut-brain axis. OBJECTIVES: We assessed whether prenatal antibiotic exposure is associated with an increased risk of autism spectrum disorder (ASD) in offspring born at term. METHODS: This population-based retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada between April 2000 and December 2014. Exposure was defined as filling antibiotic prescriptions during pregnancy. The outcome was an ASD diagnosis from the British Columbia Autism Assessment Network, with a follow-up to December 2016. To examine the association among pregnant individuals treated for the same indication, we studied a sub-cohort diagnosed with urinary tract infections. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios (HR). The analysis was stratified by sex, trimester, cumulative duration of exposure, class of antibiotic, and mode of delivery. We ran a conditional logistic regression of discordant sibling pairs to control for unmeasured environmental and genetic confounding. RESULTS: Of the 569,953 children included in the cohort, 8729 were diagnosed with ASD (1.5%) and 169,922 were exposed to prenatal antibiotics (29.8%). Prenatal antibiotic exposure was associated with an increased risk of ASD (HR 1.10, 95% confidence interval [CI] 1.05, 1.15), particularly for exposure during the first and second trimesters (HR 1.11, 95% CI 1.04, 1.18 and HR 1.09, 95% CI 1.03, 1.16, respectively), and exposure lasting ≥15 days (HR 1.13, 95% CI 1.04, 1.23). No sex differences were observed. The association was attenuated in the sibling analysis (adjusted odds ratio 1.04, 95% CI 0.92, 1.17). CONCLUSIONS: Prenatal antibiotic exposure was associated with a small increase in the risk of ASD in offspring. Given the possibility of residual confounding, these results should not influence clinical decisions regarding antibiotic use during pregnancy.

Rethinking diagnosis-based service models for childhood neurodevelopmental disabilities in Canada: a question of equity.

Neurodevelopmental disability in children covers a vast array of congenital and acquired long-term conditions associated with brain or neuromuscular impairments that impact function. While some presentations of neurodevelopmental disability align with diagnostic labels, many do not, leaving children whose conditions don't fit neatly under diagnostic labels struggling to access services or families and professionals feeling pressured to assign a diagnostic label in order to access services. In this paper, we (1) discuss the evidence showing that there is often a mismatch between a child's neurodevelopmental diagnosis, or lack of diagnosis, and function, (2) comment on the inequities exacerbated by diagnosis-based approaches for services, and (3) highlight the potential benefits of using a function and participation-based approach for providing services to children with neurodevelopmental disabilities. We close with three calls to action for function and participation-based approaches that could better support equitable services for children with neurodevelopmental disabilities.

Medicinal cannabis in children and adolescents with autism spectrum disorder: A scoping review.

BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition estimated to affect 1 in 66 children in Canada and 1 in 270 individuals worldwide. As effective therapies for the management of ASD core and associated symptoms are limited, parents are increasingly turning to clinicians for advice regarding the use of medicinal cannabis to manage behavioural disturbances. OBJECTIVE: The objective of this scoping review was to identify and map symptoms, outcomes and adverse events related to medicinal cannabis treatment for ASD-related behaviours. METHODS: Ovid MEDLINE, Embase, CINAHL, PsycInfo, Web of Science Core Collection, Google Scholar and grey literature sources were searched up to 5 January 2020 for studies. Included studies met the following criteria: (1) investigate the use of medicinal cannabis, (2) at least 50% participants had ASD, (3) at least 50% of the study population was 0-18 years old and (4) any study design (published or unpublished). RESULTS: We identified eight completed and five ongoing studies meeting the inclusion criteria. All studies reported substantial behaviour and symptom improvement on medicinal cannabis, with 61% to 93% of subjects showing benefit. In the three studies reporting on concomitant psychotropic medication usage and with cannabis use, up to 80% of participants observed a reduction in concurrent medication use. Adverse events related to cannabis use were reported in up to 27% of participants related, and two participants had psychotic events. CONCLUSIONS: Early reports regarding medicinal cannabis in paediatric ASD symptom management are presented as positive; the evidence, however, is limited to very few retrospective cohort and observational studies. Evidence of safety and efficacy from prospective clinical trials is needed.

Association of Epidural Analgesia During Labor and Delivery With Autism Spectrum Disorder in Offspring.

Importance: Evidence from studies investigating the association of epidural analgesia use during labor and delivery with risk of autism spectrum disorder (ASD) in offspring is conflicting. Objective: To assess the association of maternal use of epidural analgesia during labor and delivery with ASD in offspring using a large population-based data set with clinical data on ASD case status. Design, Setting, and Participants: This population-based retrospective cohort study included term singleton children born in British Columbia, Canada, between April 1, 2000, and December 31, 2014. Stillbirths and cesarean deliveries were excluded. Clinical ASD diagnostic data were obtained from the British Columbia Autism Assessment Network and the British Columbia Ministry of Education. All children were followed up until clinical diagnosis of ASD, death, or the study end date of December 31, 2016. Exposures: Use of epidural analgesia during labor and delivery. Main Outcomes and Measures: A clinical diagnosis of ASD made by pediatricians, psychiatrists, and psychologists with specialty training to assess ASD. Cox proportional hazards models were used to estimate the hazard ratio of epidural analgesia use and ASD. Models were adjusted for maternal sociodemographics; maternal conditions during pregnancy; labor, delivery, and antenatal care characteristics; infant sex; gestational age; and status of small or large for gestational age. A conditional logistic regression model matching women with 2 births or more and discordance in ASD status of the offspring also was performed. Results: Of the 388 254 children included in the cohort (49.8% female; mean gestational age, 39.2 [SD, 1.2] weeks; mean follow-up, 9.05 [SD, 4.3] years), 5192 were diagnosed with ASD (1.34%) and 111 480 (28.7%) were exposed to epidural analgesia. A diagnosis of ASD was made for 1710 children (1.53%) among the 111 480 deliveries exposed to epidural analgesia (94 157 women) vs a diagnosis of ASD in 3482 children (1.26%) among the 276 774 deliveries not exposed to epidural analgesia (192 510 women) (absolute risk difference, 0.28% [95% CI, 0.19%-0.36%]). The unadjusted hazard ratio was 1.32 (95% CI, 1.24-1.40) and the fully adjusted hazard ratio was 1.09 (95% CI, 1.00-1.15). There was no statistically significant association of epidural analgesia use during labor and delivery with ASD in the within-woman matched conditional logistic regression (839/1659 [50.6%] in the exposed group vs 1905/4587 [41.5%] in the unexposed group; fully adjusted hazard ratio, 1.07 [95% CI, 0.87-1.30]). Conclusions and Relevance: In this population-based study, maternal epidural analgesia use during labor and delivery was associated with a small increase in the risk of autism spectrum disorder in offspring that met the threshold for statistical significance. However, given the likelihood of residual confounding that may account for the results, these findings do not provide strong supporting evidence for this association.

Assessment, diagnosis, and management of developmental coordination disorder.

Developmental coordination disorder (DCD) is a neurodevelopmental condition that affects 5% to 6% of school-aged children. DCD can significantly impact early development and life-long functioning. Evidence supports promising interventions for DCD, but the disorder continues to be under-recognized and under-diagnosed. Paediatricians play an important role in the identification and management of DCD. This practice point, with accompanying tables, assists and supports paediatricians in diagnosing and managing uncomplicated cases of DCD.

L'évaluation, le diagnostic et la prise en charge du trouble développemental de la coordination.

Le trouble développemental de la coordination est une affection neurodéveloppementale qui touche de 5 % à 6 % des enfants d'âge scolaire. Il peut avoir des effets considérables sur le début du développement et le fonctionnement tout au long de la vie. Les données probantes appuient des interventions prometteuses, mais ce trouble continue d'être sous-estimé et sous-diagnostiqué. Les pédiatres jouent un rôle important dans son diagnostic et sa prise en charge. Le présent point de pratique et les tableaux qui l'accompagnent visent à aider les pédiatres à diagnostiquer et prendre en charge les cas de trouble développemental de la coordination non compliqué.

General paediatric practice in autism spectrum disorder screening in Ontario, Canada: Opportunities for improvement.

BACKGROUND: Screening is important for early identification of children with autism spectrum disorder (ASD), potentially leading to earlier intervention. Research has identified some barriers to early identification of ASD, however, information about ASD screening in Canadian general paediatric practice is lacking. OBJECTIVES: The aim of the study is to better understand ASD screening practice patterns by examining the use of ASD and general developmental screening tools by general paediatricians. METHODS: The research team conducted a cross-sectional survey of general paediatricians. RESULTS: Two-hundred and sixty-seven paediatricians responded and 132 were eligible for the study. Ninety-three per cent of the responders used a developmental screening tool. Eighty-five per cent of the responders used an ASD screening tool when there were concerns for ASD, and 15% never used one. The most commonly used ASD screening tool was the M-CHAT. Children suspected of having ASD were referred to specialists not only to confirm the diagnosis but also to facilitate access to resources. General paediatricians were keen to incorporate formal ASD screening tools in their practice but identified the need for clearer guidelines. CONCLUSION: Previous studies have shown that children at risk of ASD continue to be missed through developmental surveillance and targeted screening. Paediatricians are interested in implementing an ASD screening tool and cite brevity and forms that can be completed by parents as factors that would support the use of a screening tool. Clearer guidelines and tools to support ASD screening and access to resources are needed.

Early detection for autism spectrum disorder in young children.

Autism spectrum disorder (ASD) is a life-long neurodevelopmental disorder, characterized by impairments in social communication, repetitive, restricted patterns of behaviour, and unusual sensory sensitivities or interests. ASD significantly impacts the lives of children and their families. Currently, the estimated prevalence of ASD is 1 in 66 Canadians aged 5 to 17 years. General paediatricians, family physicians, and other health care professionals are, therefore, seeing more children with ASD in their practices. The timely diagnosis of ASD, and referral for intensive behavioural and educational interventions at the earliest age possible, may lead to better long-term outcomes by capitalizing on the brain's neuroplasticity at younger ages. This statement provides clear, comprehensive, evidence-informed recommendations and tools to help community paediatricians and other primary care providers monitor for the earliest signs of ASD-an important step toward an accurate diagnosis and comprehensive needs assessment for intervention planning.

Standards of diagnostic assessment for autism spectrum disorder.

The rising prevalence of autism spectrum disorder (ASD) has created a need to expand ASD diagnostic capacity by community-based paediatricians and other primary care providers. Although evidence suggests that some children can be definitively diagnosed by 2 years of age, many are not diagnosed until 4 to 5 years of age. Most clinical guidelines recommend multidisciplinary team involvement in the ASD diagnostic process. Although a maximal wait time of 3 to 6 months has been recommended by three recent ASD guidelines, the time from referral to a team-based ASD diagnostic evaluation commonly takes more than a year in many Canadian communities. More paediatric health care providers should be trained to diagnose less complex cases of ASD. This statement provides community-based paediatric clinicians with recommendations, tools, and resources to perform or assist in the diagnostic evaluation of ASD. It also offers guidance on referral for a comprehensive needs assessment both for treatment and intervention planning, using a flexible, multilevel approach.

Post-diagnostic management and follow-up care for autism spectrum disorder.

Paediatricians and other primary care providers are well positioned to provide or coordinate ongoing medical and psychosocial care and support services for children with autism spectrum disorder (ASD). This statement provides recommendations and information on a range of interventions and resources, to help paediatric care providers optimize care for children with ASD and support their families. The management of ASD includes treating medical and psychiatric co-morbidities, behavioural and developmental interventions, and providing supportive social care services to enhance quality of life for affected children and families.

Exogenous oxytocin administration during labor and autism spectrum disorder.

BACKGROUND: Oxytocin is a neuropeptide hormone that plays a key role in social behavior, stress regulation, and mental health. Synthetic oxytocin administration is a common obstetrical practice, and importantly, previous research has suggested that intrapartum exposure may increase the risk of neurodevelopmental disorders, such as autism spectrum disorder. OBJECTIVE: This study aimed to examine the association between synthetic oxytocin exposure during labor and autism spectrum disorder diagnosis in the child. STUDY DESIGN: This population-based retrospective cohort study compared 2 cohorts of children: (1) all children born in British Columbia, Canada between April 1, 2000 and December 31, 2014 (n=414,336 births), and (2) all children delivered at Soroka University Medical Center in Be'er-Sheva, Israel between January 1, 2011 and December 31, 2019 (n=82,892 births). Nine different exposure groups were examined. Cox proportional hazards models were used to estimate crude and adjusted hazard ratios of autism spectrum disorder in both cohorts on the basis of induction and/or augmentation exposure status. To further control for confounding by indication, we conducted sensitivity analyses among a cohort of healthy, uncomplicated deliveries and among a group that was induced only for postdates. In addition, we stratified our analyses by infant sex to assess for potential sex differences. RESULTS: In the British Columbia cohort, 170,013 of 414,336 deliveries (41.0%) were not induced or augmented, 107,543 (26.0%) were exposed to oxytocin, and 136,780 (33.0%) were induced or augmented but not exposed to oxytocin. In the Israel cohort, 51,790 of 82,892 deliveries (62.5%) were not induced or augmented, 28,852 (34.8%) were exposed to oxytocin, and 2250 (2.7%) were induced or augmented but not exposed to oxytocin. On adjusting for covariates in the main analysis, significant associations were observed in the Israel cohort, including adjusted hazard ratios of 1.51 (95% confidence interval, 1.20-1.90) for oxytocin-augmented births and 2.18 (95% confidence interval, 1.32-3.57) for those induced by means other than oxytocin and not augmented. However, oxytocin induction was not significantly associated with autism spectrum disorder in the Israel cohort. In the Canadian cohort, there were no statistically significant adjusted hazard ratios. Further, no significant sex differences were observed in the fully adjusted models. CONCLUSION: This study supports that induction of labor through oxytocin administration does not increase the risk of autism spectrum disorder in the child. Our international comparison of 2 countries with differences in clinical practice regarding oxytocin administration for induction and/or augmentation suggests that previous studies reporting a significant association were likely confounded by the underlying indication for the induction.

Developmental profiles of children at risk for autism spectrum disorder at school entry.

Functional abilities in children with autism spectrum disorder (ASD) are highly heterogenous, and impairments can overlap with non-ASD neurodevelopmental disorders. We compared the profiles of children assessed for ASD with and without an ASD diagnosis using a retrospective cohort study of 101,739 children born in British Columbia (2000-2008). The children were grouped into the following five comparison groups: (1) ASD- (n = 1131), (2) ASD+ (n = 1583), (3) Ministry of Education designated ASD+ (n = 654), (4) special need other than ASD (n = 11,663), and (5) typically developing (n = 86,708). Five developmental domains were assessed using the Early Development Instrument. ANCOVA was used to control for covariates, Tukey's HSD test for multiple comparisons, and Cohen's d for effect size. The ASD- group had slightly higher scores than the ASD+ group with small to medium effect sizes in all domains (d = 0.20-0.48). The ASD- group had slightly higher scores than the Ministry of Education ASD+ group in only three domains with small effect sizes (d = 0.21-0.25). The ASD- group had lower scores in all domains compared to the typically developing group with large effect sizes in all domains (d = 1.12-1.77). The ASD- group received less education funding at school entry than both ASD+ groups. Overall, only small to medium differences in development were detected between the ASD- and ASD+ groups. While these children differ diagnostically, they share similar functional profiles and have substantially more difficulties than typically developing children. Therefore, differences in levels of support at school entry raise critical questions of equity. LAY SUMMARY: Comparison of children in British Columbia who have been referred for an autism assessment, with or without a diagnosis, shows similarities in their functional and developmental profiles in kindergarten. Furthermore, both groups of children have more difficulties than typically developing children. However, children who have been referred for assessment without an autism diagnosis receive less financial support at school entry, raising important questions on equity.

Autism Risk and Perinatal Antibiotic Use.

OBJECTIVES: Antibiotics are commonly administered during labor and delivery, and research has suggested that fetal exposure to antibiotics can increase risk for autism spectrum disorder (ASD). We assessed whether antibiotic exposure during labor and delivery increased the risk of ASD in the offspring. METHODS: This retrospective cohort study included everyone who delivered a live singleton-term infant in British Columbia, Canada, between April 1, 2000, and December 31, 2014. This cohort included 569 953 deliveries. To examine the association among pregnant individuals being treated for the same indication, we studied a subcohort of those who tested positive for group B Streptococcus. Cox proportional hazards models were used to estimate unadjusted and adjusted hazard ratios in both cohorts. A sensitivity analysis was conducted using length of first stage of labor as a proxy measure for dose to assess for a dose-response relationship. RESULTS: In this population-based study, antibiotic use during labor and delivery was not associated with an increased risk of ASD in offspring. The unadjusted and adjusted hazard ratios were 1.29 (95% confidence interval, 1.24-1.35) and 0.99 (0.94-1.04), respectively; and 1.07 (0.90-1.27) and 0.88 (0.74-1.05), respectively, in the group B Streptococcus-positive cohort. We observed no substantial difference in the association between antibiotic exposure and ASD depending on length of the first stage of labor. CONCLUSIONS: Our findings suggest that concern for ASD should not factor into the clinical decision on whether to administer antibiotics during labor and delivery. Future research is needed to examine longer durations of prenatal antibiotic exposure.

Symptoms, adverse events, and outcomes in the use of medicinal cannabis in children and adolescents with autism spectrum disorder: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map and identify the symptoms, adverse events, and outcomes in the use of medicinal cannabis in children and adolescents with autism spectrum disorder. INTRODUCTION: Autism spectrum disorder is a neurodevelopmental disorder that impacts social communication and social interaction, and is associated with restrictive and repetitive behaviors and interests. Medicinal cannabis has become a potential area of interest for parents for the treatment of autism spectrum disorder symptoms in their children. There is some evidence that cannabinoids may be involved in autism spectrum disorder, laying a potential foundation for medicinal cannabis utility; however, previous reviews did not identify any clinical research on this topic. INCLUSION CRITERIA: This scoping review will consider all published and unpublished studies that investigate the use of medicinal cannabis in autism spectrum disorder, where at least 50% of the participants have a diagnosis of autism spectrum disorder and at least 50% of the study population is 0 to 18 years of age, or where pediatric data are reported separately. Studies undertaken in any context (hospital or community) and in any geographic location will be included. METHODS: We will search MEDLINE, Embase, CINAHL, PsycINFO, Web of Science, and Google Scholar, and the gray literature sources for studies. Two independent team members will screen titles and abstracts, review full texts for potential inclusion, and extract data for all studies. The results will be presented as a narrative synthesis and in tabular form.