Potential Sex Differences Relative to Autism Spectrum Disorder and Metals

Abstract

Sex differences in ASD diagnosis and mutagenic effects of toxic exposures indicate that sex differences may play a major part in the causal relationship of any potential associations seen; however, we were only able to find three studies that reported on sex differences in observed associations with toxic metals exposure and ASD. We also found several studies investigating associations between ASD and metals exposures, including 11 on aluminum, 6 on antimony, 15 on arsenic, 5 on beryllium, 17 on cadmium, 11 on chromium, 25 on lead, 14 on manganese, and 13 on nickel with markers of exposure in hair, urine, blood, teeth, fingernails, and air pollution. Results for each metal were conflicting, but studies on cadmium and lead yielded the highest proportion of studies with positive results (72% and 36%, respectively). Based on our examination of existing literature, the current evidence warrants a considerable need for evaluations of sex differences in future studies assessing the association between metals exposures and ASD. Additionally, failure to account for potential sex differences could result in bias and misinterpretation of exposure-disease relationships.

Age‐SpecificTime Trends in Incidence Rates of Autism Spectrum Disorder Following Adaptation ofDSM‐5 and OtherASD‐RelatedRegulatory Changes in Israel

“…That said, we did not see evidence that the implementation of stricter NII eligibility requirements or the expansion of access to health‐related services substantially affected the observed trends. Importantly, our results may reflect real changes in the occurrence of ASD symptoms in the population, possibly due to effects of environmental factors [Dickerson, Rotem, Christian, Nguyen, & Specht, 2017; Grandjean & Landrigan, 2014; Rotem et al, 2018; Sandin et al, 2014; Tordjman et al, 2014]. Previous analyzes associated exposure to several environmental toxicants, including endocrine disrupting chemicals, air pollution, pesticides, and certain pharmaceuticals, with ASD risk, although a secular rising trend in these exposures that parallels the rise in ASD incidence has not always been established [Grabrucker, 2012; Raz et al, 2015; Raz et al, 2017; Roberts et al, 2013; Rotem et al, 2018].…”

Periconceptional and prenatal exposure to metal mixtures in relation to behavioral development at 3 years of age

“… 1 , 49 , 50 Our observation of potential modification of the metals–neurodevelopment associations by sex accords with available evidence indicating sexually differential susceptibility to metals. 40 – 42 Metals may exert physiological impacts that are differential by sex through several mechanisms, including disruption of sexually differential properties of the endocrine system 40 , 41 , 51 , 52 and disruption of neurotransmitters with sexually differential distributions. 42 However, our findings regarding specific sex–metal interactions were limited and inconsistent, 42 , 47 , 53 partially owing to decreased precision from modest sample sizes in sex-stratified analyses.…”

“…These analyses were repeated stratified by sex of the child to investigate effect measure modification by sex, as sex may modify the physiological effects of metal exposure, resulting in sexually differential metal–neurodevelopment relations. 40 – 42 …”

Mercury and autism spectrum disorders

“…В частности, было установлено, что на результаты исследований могут влиять гендерные различия выборок. Так, в одном из исследований [54] положительная ассоциация между уровнем ртути и РАС была выявлена у мальчиков и отсутствовала у девочек. Оказалось также, что на полученные данные могут оказывать влияние экономическое развитие страны [39] и потенциальные конфликты интересов исследователей [55].…”