Association Between Antenatal Antimicrobial Therapy and Autism Spectrum Disorder-A Nested Case-Control Study.
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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.
| S-EPMC7214718 | biostudies-literature
Project description:The insulin-like growth factor (IGF) pathway is thought to play an important role in brain development. Altered levels of IGFs and their signaling regulators have been shown in autism spectrum disorder (ASD) patients. In this study, we investigated whether coding region single-nucleotide polymorphisms (cSNPs) of the insulin receptor substrates (IRS1 and IRS2), key mediators of the IGF pathway, were associated with ASD in Korean males. Two cSNPs (rs1801123 of IRS1, and rs4773092 of IRS2) were genotyped using direct sequencing in 180 male ASD patients and 147 male control subjects. A significant association between rs1801123 of IRS1 and ASD was shown in additive (p = 0.022, odds ratio (OR) = 0.66, 95% confidence interval (CI) = 0.46-0.95) and dominant models (p = 0.013, OR = 0.57, 95% CI = 0.37-0.89). Allele frequency analysis also showed an association between rs1801123 and ASD (p = 0.022, OR = 0.66, 95% CI = 0.46-0.94). These results suggest that IRS1 may contribute to the susceptibility of ASD in Korean males.
| S-EPMC5000625 | biostudies-literature
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.
| S-EPMC7217425 | biostudies-literature
Project description:The 'extreme male brain theory of autism' describes an extreme male pattern of cognitive traits defined as strong systemising abilities paired with empathising weaknesses in autism spectrum disorder. However, beyond these cognitive traits, clinical observations have suggested an ambiguous gender-typed pattern regarding several sexually dimorphic traits. The aim of the present study was to investigate if patterns of non-cognitive sexually dimorphic traits differed between the autism spectrum disorder and control groups. Fifty adults with autism spectrum disorder and intelligence within the normal range, and 53 neurotypical controls responded to questions on gender role, self-perceived gender typicality and gender identity, as well as sexuality. Measures used were a Swedish modification of the Bem Sex Role Inventory and questions on sexuality and gender designed for the purpose of this study. Our results showed that one common gender role emerged in the autism spectrum disorder group. Masculinity (e.g. assertiveness, leadership and competitiveness) was weaker in the autism spectrum disorder group than in the controls, across men and women. Self-perceived gender typicality did not differ between the groups but tomboyism and bisexuality were overrepresented amongst women with autism spectrum disorder. Lower libido was reported amongst both male and female participants with autism spectrum disorder compared with controls. We conclude that the extreme male patterns of cognitive functions in the autistic brain do not seem to extend to gender role and sexuality. A gender-atypical pattern for these types of characteristics is suggested in autism spectrum disorder.
| S-EPMC3909328 | biostudies-literature
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.
| S-EPMC6022498 | biostudies-literature
Project description:Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by challenges in social communication as well as repetitive or restrictive behaviors. Many genetic associations with ASD have been identified, but most associations occur in a fraction of the ASD population. Here, we searched for eQTL-associated DNA variants with significantly different allele distributions between ASD-affected and control. Thirty significant DNA variants associated with 174 tissue-specific eQTLs from ASD individuals in the SPARK project were identified. Several significant variants fell within brain-specific regulatory regions or had been associated with a significant change in gene expression in the brain. These eQTLs are a new class of biomarkers that could control the myriad of brain and non-brain phenotypic traits seen in ASD-affected individuals.
| S-EPMC10465380 | biostudies-literature
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.
| S-EPMC7363534 | biostudies-literature
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.
| S-EPMC7434090 | biostudies-literature
Project description:Polyunsaturated fatty acids (PUFAs) are critical for brain development and have been linked with neurodevelopmental outcomes. We conducted a population-based case-control study in California to examine the association between PUFAs measured in midpregnancy serum samples and autism spectrum disorder (ASD) in offspring. ASD cases (n = 499) were identified through the California Department of Developmental Services and matched to live-birth population controls (n = 502) on birth month, year (2010 or 2011), and sex. Logistic regression models were used to examine crude and adjusted associations. In secondary analyses, we examined ASD with and without co-occurring intellectual disability (ID; n = 67 and n = 432, respectively) and effect modification by sex and ethnicity. No clear patterns emerged, though there was a modest inverse association with the top quartile of linoleic acid level (highest quartile vs. lowest: adjusted odds ratio = 0.74, 95% confidence interval: 0.49, 1.11; P for trend = 0.10). Lower levels of total and ω-3 PUFAs were associated with ASD with ID (lowest decile of total PUFAs vs. deciles 4-7: adjusted odds ratio = 2.78, 95% confidence interval: 1.13, 6.82) but not ASD without ID. We did not observe evidence of effect modification by the factors examined. These findings do not suggest a strong association between midpregnancy PUFA levels and ASD. In further work, researchers should consider associations with ASD with ID and in other time windows.
| S-EPMC8086417 | biostudies-literature
Project description:ImportanceThe prevalence of autism spectrum disorder (ASD) has been increasing rapidly, with current estimates of 1 in 68 children affected. Simultaneously, use of prenatal ultrasonography has increased substantially, with limited investigation into its safety and effects on brain development. Animal studies have demonstrated that prenatal ultrasonography can adversely affect neuronal migration.ObjectiveTo quantify prenatal ultrasound exposure by the frequency, timing, duration, and strength of ultrasonographic scans in children with later ASD, developmental delay, and typical development.Design, setting, and participantsThis case-control study included 107 patients with ASD, 104 control individuals with developmental delay, and 209 controls with typical development. Participants were identified from medical records based on prenatal care and delivery at Boston Medical Center, a diverse, academic, safety-net medical center, from July 1, 2006, through December 31, 2014, with a gestational age at birth of at least 37 weeks. Data were analyzed from May 1, 2015, through November 30, 2017.ExposuresUltrasonographic exposure was quantified by the number and timing of scans, duration of exposure, mean strength (depth, frame rate, mechanical index, and thermal index), and time of Doppler and 3- and 4-dimensional imaging.Main outcomes and measuresAmong participants with ASD and controls with developmental delay and typical development, ultrasound exposure was quantified and compared per trimester and for the entire pregnancy, with adjustment for infant sex, gestational age at birth, and maternal age.ResultsA total of 420 participants were included in the study (328 boys [78.1%] and 92 girls [21.9%]; mean age as of January 1, 2016, 6.6 years; 95% CI, 6.5-6.8 years). The ASD group received a mean of 5.9 scans (95% CI, 5.2-6.6), which was not significantly different from the 6.1 scans (95% CI, 5.4-6.8) in the developmental delay group or the 6.3 scans (95% CI, 5.8-6.8) in the typical development group. Compared with the typical development group, the ASD group had shorter duration of ultrasound exposure during the first (290.4 seconds [95% CI, 212.8-368.0 seconds] vs 406.4 seconds [95% CI, 349.5-463.3 seconds]) and second (1687.6 seconds [95% CI, 1493.8-1881.4 seconds] vs 2011.0 seconds [95% CI, 1868.9-2153.1 seconds]) trimesters but no difference in the number of scans. The ASD group had greater mean depth of ultrasonographic penetration than the developmental delay group in the first trimester (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.1-12.1 cm]). The ASD group had greater mean depth than the typical development group during the first (12.5 cm [95% CI, 12.0-13.0 cm] vs 11.6 cm [95% CI, 11.3-12.0 cm]) and the second (12.9 cm [95% CI, 12.6-13.3 cm] vs 12.5 cm [95% CI, 12.2-12.7 cm]) trimesters.Conclusions and relevanceThis study found significantly greater mean depth of ultrasonographic penetration in the ASD group compared with the developmental delay group in the first trimester and compared with the typical development group in the first and second trimesters. Further research is needed to determine whether other variables of ultrasound exposure also have adverse effects on the developing fetus.
| S-EPMC5875374 | biostudies-literature