Search

Previous studies indicate a role of immune disturbances during early development in the etiology of autism spectrum disorders (ASD). Any potential disturbances during fetal development are best addressed by prospective evaluation of maternal markers of inflammation. Previous studies have investigated maternal cytokines, a group of powerful effectors of the immune system, with inconsistent results. In this study, we aimed to clarify the relationship between maternal cytokines and ASD by evaluating levels of 17 cytokines in first trimester maternal serum samples, from 318 mothers to ASD-cases and 429 mothers to ASD-unaffected controls, nested within the register-based Stockholm Youth Cohort. Overall, we observed no consistent associations between levels of maternal cytokines and ASD. While we observed a number of individual associations, the patterns varied across the diagnostic sub-groups. Levels above the 90th percentile of IL-1β (OR = 2.31, 95% CI 1.16-4.60), IL-7 (OR = 2.28, 95% CI 1.20-4.33), IL-13 (OR = 2.42, 95% CI 1.29-4.55), and MCP-1 (OR = 2.09, 95% CI 1.03-4.24) were associated with increased odds of ASD with co-occurring intellectual disability (ID), whereas GMCSF (OR = 2.06, 95% CI 1.03-4.11) and TNF-α (OR = 2.31, 95% CI 1.18-4.50) were associated with increased odds of ASD with ADHD but none survived correction for multiple comparisons. Also, none of the measured maternal cytokines were associated with ASD without co-occurring ID or ADHD. Implementing a data-driven approach using machine learning (Random Forest's Variable Importance measurement), we found no evidence to suggest that adding these cytokines and other markers of maternal immunity, to register-based maternal factors (e.g., psychiatric history) improves prediction of ASD. In summary, we found no robust evidence of an association between maternal immune markers during early pregnancy and ASD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Brynge, Gardner, Sjöqvist, Lee, Dalman and Karlsson.)

Background: The objectives of this study were to examine the independent and dependent associations of maternal and paternal age and risk of offspring autism spectrum disorders (ASD), with and without intellectual disability (ID).Methods: The sample consisted of 417 303 Swedish children born 1984–2003. ASD case status (N = 4746) was ascertained using national and regional registers. Smoothing splines in generalized additive models were used to estimate associations of parental age with ASD.Results: Whereas advancing parental age increased the risk of child ASD, maternal age effects were non-linear and paternal age effects were linear. Compared with mothers at the median age 29 years, those <29 had similar risk, whereas risk increased after age 30, with an odds ratio (OR) of 1.75 [95% (CI): 1.63–1.89] at ages 40–45. For fathers, compared with the median age of 32 years, the OR for ages 55–59 was 1.39 (1.29–1.50). The risk of ASD was greater for older mothers as compared with older fathers. For example, mothers aged 40–45 (&geq;97.2th percentile) had an estimated 18.63 (95% CI: 17.25–20.01) ASD cases per 1000 births, whereas fathers aged 55–59 (&geq;99.7th percentile) had 16.35 (95% CI: 15.11–17.58) ASD cases per 1000 births. In analyses stratified by co-parental age, increased risk due to advancing paternal age was evident only with mothers &leq;35 years. In contrast, advancing maternal age increased risk regardless of paternal age. Advancing parental age was more strongly associated with ASD with ID, compared with ASD without ID.Conclusions: We confirm prior findings that advancing parental age increases risk of ASD, particularly for ASD with ID, in a manner dependent on co-parental age. Although recent attention has emphasized the effects of older fathers on ASD risk, an increase of n years in maternal age has greater implications for ASD risk than a similar increase in paternal age. [ABSTRACT FROM PUBLISHER]