scholarly journals Maternal Androgen-Related Conditions, Mediation by Cardiovascular, Metabolic and Fertility Factors, and Risk of Autism Spectrum Disorder in Progeny

2020 ◽  
Author(s):  
Ran S Rotem ◽  
Vy T Nguyen ◽  
Gabriel Chodick ◽  
Michael Davidovitch ◽  
Varda Shalev ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
In Utero ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Fetal Exposure ◽  
Multiple Mediation ◽  
Mediation Analyses ◽  
Etiologic Role ◽  
Ovarian Syndrome ◽  
Shared Genetic

Abstract Fetal exposure to elevated androgens is thought to contribute to Autism Spectrum Disorder (ASD) risk. However, data rely heavily on in utero androgens measurements, which also reflect fetal secretions. Thus, in utero hyperandrogenemia may indicate adverse autism-related neurogenesis that had already occurred affecting fetal androgen homeostasis, rather than a cause of the disorder. Associations between maternal androgen-related conditions and ASD could more directly implicate androgens’ etiologic role. We examined the association between maternal hyperandrogenemia-related conditions, focusing primarily on polycystic ovarian syndrome (PCOS), and progeny ASD, in an Israeli cohort of 437,222 children born in 1999-2013. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using generalized estimating equations. Multiple mediation analyses using natural effect models were conducted to evaluate combined mediation of the PCOS effect by androgen-related cardiovascular, metabolic, and fertility factors. Results indicated that children of mothers with PCOS had higher ASD odds compared with children of mothers without PCOS (OR=1.42, 95%CI:1.24,1.64), and this effect was not substantially mediated by the factors considered. Elevated odds were also observed for other hyperandrogenemia-related conditions. Findings provide support for direct involvement of maternal hyperandrogenemia in ASD etiology. Alternatively, findings may reflect shared genetic and/or environmental factors independently affecting maternal androgen homeostasis and fetal neurodevelopment.

scholarly journals Prenatal Risk for Autism Spectrum Disorder (ASD): Fetal Cortisol Exposure Predicts Child ASD Symptoms

2018 ◽  
Vol 7 (2) ◽  
pp. 349-361 ◽  
Author(s):  
Sheena Ram ◽  
Mariann A. Howland ◽  
Curt A. Sandman ◽  
Elysia Poggi Davis ◽  
Laura M. Glynn
Keyword(s):  
Autism Spectrum Disorder ◽  
Developmental Disorder ◽  
Maternal Plasma ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Sexually Dimorphic ◽  
Fetal Exposure ◽  
Prospective Longitudinal Study ◽  
The Social ◽  
Prospective Longitudinal

The etiology of autism spectrum disorder (ASD) is multifactorial, complex, and likely involves interactions among genetic, epigenetic, and environmental factors. With respect to environmental influences, a growing literature implicates intrauterine experiences in the origin of this pervasive developmental disorder. In this prospective longitudinal study, we examined the hypothesis that fetal exposure to maternal cortisol may confer ASD risk. In addition, because ASD is four times more prevalent in males than in females, and because sexually dimorphic responses to intrauterine experiences are commonly observed, we examined whether or not any associations differ by fetal sex. Maternal plasma cortisol was measured at 15, 19, 25, 31, and 37 weeks’ gestation in a sample of 84 pregnant women. ASD symptoms were assessed in their 5-year-old children with the Social Communication Questionnaire (SCQ). Fetal exposure to lower levels of maternal cortisol was associated with higher levels of ASD symptoms only among boys. The observed hypocortisolemic profile exhibited by these mothers may indicate a risk factor that precedes the stress of caregiving for a child with ASD and may not be solely a consequence of the stress of caregiving, as previously thought. These findings confirm the value of examining prenatal hormone exposures as predictors of ASD risk and support the premise that altered prenatal steroid exposures may play a role in the etiology of ASD.

scholarly journals In-Utero SSRI and SNRI Exposure and the Risk of Neurodevelopmental Disorders in Children: A Population-Based Retrospective Cohort Study Utilizing Linked Administrative Data

2018 ◽  
Vol 3 (4) ◽  
Author(s):  
Deepa Singal ◽  
Dan Chateau ◽  
Matthew Dahl ◽  
Shelley Derksen ◽  
Chelsea Ruth ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Anxiety Disorder ◽  
Disease Severity ◽  
Administrative Data ◽  
Neurodevelopmental Disorders ◽  
Population Based ◽  
In Utero ◽  
Autism Spectrum ◽  
Hazard Ratio ◽  
Spectrum Disorder

IntroductionMany studies demonstrating an association between in utero exposure to serotonergic antidepressants and higher risk of neurodevelopmental disorders in children are confounded by history of maternal depression and disease severity. We conducted a population-based analysis of women diagnosed with mood/anxiety disorder, a patient population for whom pharmacotherapy is clearly indicated. Objectives and ApproachUsing linked population-based administrative data, we identified all mother-newborn pairs in Manitoba (born 1996 to 2009, with follow-up through 2014). High dimensional propensity scores and inverse probability treatment weighting were used to address confounding by indication and disease severity. The final trimmed cohort consisted of mothers who were diagnosed with a mood/anxiety disorder from 90 days prior to conception until delivery (n=4995). Cox Proportional Hazard Regression models were used to estimate risk of Autism Spectrum Disorder, epilepsy and attention deficit hyperactivity disorder (ADHD) in offspring. In addition to clinical data, we used novel education data to define outcomes in children. ResultsAmong the cohort of mothers diagnosed with a mood/anxiety disorder during pregnancy or up to 90 days before, 16.8% received at least two dispensations of an SSRI or SNRI during pregnancy. We did not observe an association between use of SSRIs/SNRIs during pregnancy and increased risk of Autism Spectrum Disorder (hazard ratio 0.92; 95% CI 0.42 to 2.03), epilepsy (hazard ratio 1.21; 95% CI 0.48 to 3.05), or ADHD (hazard ratio 1.13, 95% CI 0.78 to 1.64) among offspring. Conclusion/ImplicationsIn the absence of randomized control trials, large observation studies using sophisticated data analysis are the gold standard of evidence to help patients and clinicians making the decision to continue antidepressant use during pregnancy. Results of this study reassure women for whom the medication is clinically indicated.

Maternal polycystic ovarian syndrome in autism spectrum disorder: a systematic review and meta-analysis

2019 ◽  
Vol 24 (12) ◽  
pp. 1787-1797 ◽  
Author(s):  
Maria Katsigianni ◽  
Vasilios Karageorgiou ◽  
Irene Lambrinoudaki ◽  
Charalampos Siristatidis
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Polycystic Ovarian Syndrome ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Ovarian Syndrome
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