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Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study.

ABSTRACT: Background: Multiple prenatal factors have been associated with autism spectrum disorder (ASD) risk. However, current data about the association between antimicrobial use during pregnancy and ASD is limited. Methods: A nested matched case-control study of children with ASD (cases), and children without ASD or other psychiatric or genetic disorders (controls). We compared the use of antimicrobial therapy during the 3 months before conception or during pregnancy between mothers of cases and controls and used multivariate conditional logistic regression models to assess the independent association between maternal use of antimicrobials during pregnancy and the risk of ASD in their offspring. Results: More than half of the mothers in the study (54.1%) used antimicrobial drugs during the 3 months before conception or during pregnancy. Rates of antimicrobial use were lower for mothers of children with ASD compared to mothers of controls (49.0 vs. 55.1%, respectively; p = 0.02), especially during the third trimester of pregnancy (18.8 vs. 22.9%, respectively; p = 0.03), and for the use of penicillins (15.7 vs. 19.7%, respectively; p = 0.06). These case-control differences suggest that antimicrobial administration during pregnancy was associated with a reduced risk of ASD in the offspring (aOR = 0.75, 95% CI = 0.61-0.92). Interestingly, this association was seen only among Jewish but not for the Bedouin mothers (aOR = 0.62, 95% CI = 0.48-0.79 and aOR = 1.21, 95% CI = 0.82-1.79). Conclusions: The reduced risk of ASD associated with prenatal antimicrobials use only in the Jewish population suggest the involvement of other ethnic differences in healthcare services utilization in this association.

SUBMITTER: Abelson N

PROVIDER: S-EPMC8639519 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:AIMS:Children with autism spectrum disorder (ASD) tend to suffer from various medical comorbidities. We studied the comorbidity burden and health services' utilisation of children with ASD to highlight potential aetiologies and to better understand the medical needs of these children. METHODS:In this nested case-control study, ASD cases and controls - matched by age, sex and ethnicity in a 1:5 ratio - were sampled from all children born between 2009 and 2016 at a tertiary medical centre. Data were obtained from the hospital's electronic database. Comorbid diagnoses were classified according to pathophysiological aetiology and anatomical/systemic classification of disease. Standard univariate and multivariate statistics were used to demonstrate comorbidities and health services' utilisation patterns that are significantly associated with ASD. RESULTS:ASD children had higher rates of comorbidities according to both pathophysiological and anatomical/systemic classifications (p < 0.001). The most marked significant differences were observed for: hearing impairments (OR = 4.728; 95% CI 2.207-10.127) and other auricular conditions (OR = 5.040; 95% CI 1.759-14.438); neurological (OR = 8.198; 95% CI 5.690-11.813) and ophthalmological (OR = 3.381; 95% CI 1.617-7.068) conditions; and ADD/ADHD (OR = 3.246; 95% CI 1.811-5.818). A subgroup analysis revealed a more profound case-control difference in anaemia rates among girls than in boys (OR = 3.25; 95% CI 1.04-10.19 v. OR = 0.74; 95% CI 0.33-1.64 respectively) and an opposite trend (larger differences in males than in females in cardiovascular diseases (OR = 1.99; 95% CI 1.23-3.23 v. OR = 0.76; 95% CI 0.17-3.45, respectively)). In addition, larger case-control differences were seen among Bedouin children than in Jewish children in a number of medical comorbidities (Breslow-Day test for homogeneity of odds ratio p-value <0.05). Finally, we found that children with ASD tended to be referred to the emergency department and to be admitted to the hospital more frequently than children without ASD, even after adjusting for their comorbidity burden (aOR = 1.28; 95% CI 1.08-1.50 and aOR = 1.28; 95% CI 1.11-1.47 for >1 referrals and admissions per year, respectively). CONCLUSIONS:The findings of this study contribute to the overall understanding of comorbid conditions and health services' utilisation for children with ASD. The higher prevalences of comorbidities and healthcare services' utilisation for children with ASD highlight the additional medical burden associated with this condition.

Project description:Autism spectrum disorder (ASD) trends have been gaining a great deal of focus in recent decades, as many studies worldwide show a continued rise in incidence rates. Many researchers have begun analyzing socioeconomic data in relation to ASD in an effort to understand the source of these changing rates and the role of awareness and access to resources. In this study, we aim to contribute to this body of knowledge by examining incidence time trends of ASD in Israel according to socioeconomic factors. While similar studies have been conducted in Israel, this study is the first of its kind to include the total population. Individual-level data from the Israeli National Insurance Institute were used to determine cumulative incidence of ASD, first for the total population, and then stratified by population group and income categories. Multivariable logistic regression models were fit to analyze associations between income category and both risk of ASD and risk of ASD diagnosis in later age. A total of 431,348 children were examined in this study, with 13,841 cases of ASD. The cumulative incidence of all children aged 8 in 2015 was 0.64%, marking an increase compared to previous literature from Israel. Within our study period, ASD incidence followed this increase until the 2009 birth cohort, where it began to stabilize. Our initial findings from regression models showed strong positive associations between household income and ASD incidence, as expected. After factoring in population group, however, the elevated ASD incidence rates in the highest income bracket decreased. Autism Res 2019, 12: 1870-1879. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study contributes comprehensive and current data on ASD trends overtime in Israel and introduces crucial insights regarding the impact of socioeconomic factors on ASD diagnoses. We found a rise in ASD that began leveling off in 2009. We identified more ASD diagnoses occurring in families with higher incomes and in the General Population, pointing to the important role of sociodemographic factors on ASD diagnoses.

Project description:BackgroundSeveral reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies.MethodsDNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample.FindingsIn this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 × 10- 7. Seven CpGs showed differences at p < 1 × 10- 5 and 48 at 1 × 10- 4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds.ConclusionsNo single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.

Project description:Background/objectivePer- and polyfluoroalkyl substances (PFAS) display neurobehavioral toxicity in laboratory animal studies. We examined associations of modeled prenatal maternal exposure to PFAS with child diagnosis of autism spectrum disorder (ASD).MethodsParticipants were 453 mother-child pairs from CHARGE (CHildhood Autism Risk from Genetics and Environment), a population-based case-control study. Children underwent psychometric testing and were clinically confirmed for ASD (n = 239) or typical development (TD, n = 214). At the end of the clinic visit, maternal blood specimens were collected. We quantified nine PFAS in maternal serum samples collected when their child was 2-5 years old. As surrogate in utero exposure, we used a model built from external prospective data in pregnancy and 24 months post-partum and then reconstructed maternal PFAS serum concentrations during pregnancy in this case-control sample. We used logistic regression to evaluate associations of modeled prenatal maternal PFAS concentrations with child ASD.ResultsModeled prenatal maternal perfluorohexane sulfonate (PFHxS) and perfluorooctane sulfonate (PFOS) were borderline associated with increased odds of child diagnosis of ASD (per nanogram per milliliter increase: odds ratio [OR] = 1.46; 95% confidence interval [CI]: 0.98, 2.18 for PFHxS, OR = 1.03; 95% CI: 0.99, 1.08 for PFOS). When compared to the lowest quartile (reference category), the highest quartile of modeled prenatal maternal PFHxS was associated with increased odds of child diagnosis of ASD (OR = 1.95; 95% CI: 1.02, 3.72).ConclusionsIn analyses where modeled prenatal maternal PFAS serum concentrations served as in utero exposure, we observed that prenatal PFHxS and PFOS exposure, but not other PFAS, were borderline associated with increased odds of child diagnosis of ASD. Further studies in which PFAS concentrations are prospectively measured in mothers and children at a range of developmental stages are needed to confirm these findings.

Project description:BackgroundPostprescription review and feedback (PPRF) is one of the most common strategies in antimicrobial stewardship program (ASP) intervention. However, disagreements between the prescribers and ASP personnel can occur. The aim of the present study was to identify the factors associated with nonadherence to PPRF intervention.MethodsThe present retrospective nested case-control study was performed at a tertiary care center, which has been conducting a once-weekly PPRF for carbapenems and piperacillin/tazobactam since 2014. Nonadherence to ASP recommendations was defined as the failure of the primary care team to modify or stop antimicrobial therapy 72 hours after the issuance of PPRF recommendations. Factors associated with nonadherence to PPRF intervention were identified using multivariate logistic regression analysis.ResultsIn total, 2466 instances of PPRF in 1714 cases between April 2014 and September 2019 were found. The nonadherence rate was 5.9%, and 44 cases were found in which carbapenems or piperacillin/tazobactam continued to be used against PPRF recommendations. Factors associated with nonadherence to PPRF recommendations were a previous history of hospitalization within 90 days (adjusted odds ratio [aOR], 2.62; 95% confidence interval [CI], 1.18-5.81) and a rapidly fatal McCabe score at the time of PPRF intervention (aOR, 2.87; 95% CI, 1.18-6.98). A review of the narrative comments in the electronic medical records indicated that common reasons for nonadherence were "the patient was sick" (n = 12; 27.3%) and "the antimicrobial seemed to be clinically effective" (n = 9; 20.5%).ConclusionsNonadherence to PPRF recommendations was relatively uncommon at the study institution. However, patients with a severe disease condition frequently continued to receive broad-spectrum antimicrobials against PPRF recommendations. Understanding physicians' cognitive process in nonadherence to ASP recommendations and ASP interventions targeting medical subspecialties caring for severely ill patients is needed to improve ASP.

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Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study.

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