Can exposure to insecticide during pregnancy link to autism in children ?

Association of Maternal Insecticide Levels With Autism in Offspring From a National Birth Cohort

New research published in the American Journal of Psychiatry says that exposure to the notorious pesticide dichlorodiphenyltrichloroethane (DDT) during pregnancy could raise the risk of a child developing autism, ScienceAlert reports.

2018 Abstract

Objective
Autism is a complex neurodevelopmental disorder with a largely unknown etiology. To date, few studies have investigated prenatal exposure to toxins and risk of autism by using maternal biomarkers of exposure. Persistent organic pollutants are lipophilic halogenated organic compounds and include the insecticide dichlorodiphenyltrichloroethane (DDT), as well as its metabolite p,p′-dichlorodiphenyl dichloroethylene (p,p′-DDE), and polychlorinated biphenyls (PCBs). The objective of this study was to test whether elevated maternal levels of persistent organic pollutants are associated with autism among offspring.

Method
The investigation was derived from the Finnish Prenatal Study of Autism, a national birth cohort study based on a nested case-control design. Cases of autism among children born between 1987 and 2005 were ascertained by national registry linkages. In cases of childhood autism and matched control subjects (778 matched case-control pairs), maternal serum specimens from early pregnancy were assayed for levels of p,p′-DDE and total levels of PCBs.

Results
The odds of autism among offspring were significantly increased with maternal p,p′-DDE levels that were in the highest 75th percentile, with adjustment for maternal age, parity, and history of psychiatric disorders (odds ratio=1.32, 95% CI=1.02, 1.71). The odds of autism with intellectual disability were increased by greater than twofold with maternal p,p′-DDE levels above this threshold (odds ratio=2.21, 95% CI=1.32, 3.69). There was no association between total levels of maternal PCBs and autism.

Conclusions
These findings provide the first biomarker-based evidence that maternal exposure to insecticides is associated with autism among offspring. Although further research is necessary to replicate this finding, this study has implications for the prevention of autism and may provide a better understanding of its pathogenesis.

Behavioral effects of prenatal and postnatal PBDE exposures

Exposure to polybrominated diphenyl ethers (PBDEs) and child behavior: Current findings and future directions

2018 Study Highlights

  • Prenatal PBDEs are associated with executive function impairments and inattention.
  • Prenatal and postnatal PBDE exposures increase externalizing problems in children.
  • PBDEs’ association with internalizing, adaptive, and social behaviors is not clear.
  • PBDE exposure adversely affects behavioral development in children.

Abstract

Polybrominated diphenyl ethers (PBDEs) are recognized neurotoxicants, but the extent to which PBDEs influence various domains of behavior in children is not fully understood.

As such, we reviewed epidemiologic studies published to date to provide an overview of the current state of knowledge on PBDEs’ potential role in behavioral development.

We identified 19 epidemiologic studies reporting on associations of prenatal and childhood concentrations of PBDEs with behaviors assessed in children from 1 to 12 years, including executive function, attention, externalizing and internalizing behaviors, adaptive skills, and social behaviors/Autism Spectrum Disorder (ASD).

While the mechanisms of PBDE neurotoxicity in humans are still not clearly elucidated, findings from this review indicate that PBDE exposure during fetal development is associated with impairments in executive function and poorer attentional control in children. Results from large prospective cohorts demonstrate that prenatal and postnatal PBDE exposure adversely impacts externalizing behavior (e.g., hyperactivity and conduct problems). Additional studies are needed to determine whether PBDEs are associated with internalizing problems, adaptive skills, and social behaviors/ASD in children.

Future studies will help better understand the potential neurotoxic effects of PBDE exposures during adolescence, possible sex-dependent effects, and the impact of exposure to BDE-209 and alternative flame retardants. Future studies should also examine chemical mixtures to capture real-world exposures when examining PBDEs and their impact on various behavioral domains in the context of multiple chemical exposures.

Antidepressant use during pregnancy and psychiatric disorders in offspring

Danish nationwide register based cohort study, 2017

What is already known on this topic

  • Several studies have linked selective serotonin reuptake inhibitor use during pregnancy to autism spectrum disorder in offspring, although results have been conflicting
  • The potential explanation for this association is that selective serotonin reuptake inhibitors cross the placental barrier and affect the development of the fetal brain
  • If this holds true, in utero exposure to selective serotonin reuptake inhibitor and other classes of antidepressants may increase risk for various psychiatric disorders besides autism spectrum disorder

What this study adds

  • Antidepressant use during pregnancy was associated with increased risk for various diagnostic groups of psychiatric disorders in offspring
  • The observed associations may be attributable to the severity of underlying maternal psychiatric disorders in combination with in utero antidepressant exposure

Study Abstract

Objective
To investigate the association between in utero exposure to antidepressants and risk of psychiatric disorders.

Design
Population based cohort study.

Setting
Danish national registers.

Participants
905 383 liveborn singletons born during 1998-2012 in Denmark and followed from birth until July 2014, death, emigration, or date of first psychiatric diagnosis, whichever came first. The children were followed for a maximum of 16.5 years and contributed 8.1×106 person years at risk.

Exposures for observational studies
Children were categorised into four groups according to maternal antidepressant use within two years before and during pregnancy: unexposed, antidepressant discontinuation (use before but not during pregnancy), antidepressant continuation (use both before and during pregnancy), and new user (use only during pregnancy).

Main outcome measure
First psychiatric diagnosis in children, defined as first day of inpatient or outpatient treatment for psychiatric disorders. Hazard ratios of psychiatric disorders were estimated using Cox regression models.

Results
Overall, psychiatric disorders were diagnosed in 32 400 children. The adjusted 15 year cumulative incidence of psychiatric disorders was 8.0% (95% confidence interval 7.9% to 8.2%) in the unexposed group, 11.5% (10.3% to 12.9%) in the antidepressant discontinuation group, 13.6% (11.3% to 16.3%) in the continuation group, and 14.5% (10.5% to 19.8%) in the new user group. The antidepressant continuation group had an increased risk of psychiatric disorders (hazard ratio 1.27, 1.17 to 1.38), compared with the discontinuation group.

Conclusions
In utero exposure to antidepressants was associated with increased risk of psychiatric disorders. The association may be attributable to the severity of underlying maternal disorders in combination with antidepressant exposure in utero. The findings suggest that focusing solely on a single psychiatric disorder among offspring in studies of in utero antidepressant exposure may be too restrictive.

  • Antidepressant use during pregnancy and psychiatric disorders in offspring: Danish nationwide register based cohort study, BMJ 2017;358:j3668, 06 September 2017.
  • Characteristics of study population according to maternal antidepressant use before and during pregnancy. Values are numbers (percentages) unless stated otherwise, featured image credit bmj.

New method to diagnose ASD children for anxiety symptoms shown to be effective

Anxiety Disorders Interview Schedule–Autism Addendum: Reliability and Validity in Children With Autism Spectrum Disorder

In children on the spectrum, anxiety is often masked by the symptoms of autism. But a new variant to a standard anxiety screening method has now proven effective in separating the two and it is leading to important diagnoses.

Abstract

Assessing anxiety in autism spectrum disorder (ASD) is inherently challenging due to overlapping (e.g., social avoidance) and ambiguous symptoms (e.g., fears of change).

An ASD addendum to the Anxiety Disorders Interview Schedule–Child/Parent, Parent Version (ADIS/ASA) was developed to provide a systematic approach for differentiating traditional anxiety disorders from symptoms of ASD and more ambiguous, ASD-related anxiety symptoms.

Interrater reliability and convergent and discriminant validity were examined in a sample of 69 youth with ASD (8–13 years, 75% male, IQ = 68–143) seeking treatment for anxiety. The parents of participants completed the ADIS/ASA and a battery of behavioral measures. A second rater independently observed and scored recordings of the original interviews.

Treating anxiety is important in autism spectrum disorder because anxiety is associated with significantly more impairment for the child and their family.

Findings suggest reliable measurement of comorbid (intraclass correlation = 0.85–0.98, κ = 0.67–0.91) as well as ambiguous anxiety-like symptoms (intraclass correlation = 0.87–95, κ = 0.77–0.90) in children with ASD. Convergent and discriminant validity were supported for the traditional anxiety symptoms on the ADIS/ASA, whereas convergent and discriminant validity were partially supported for the ambiguous anxiety-like symptoms. Results provide evidence for the reliability and validity of the ADIS/ASA as a measure of traditional anxiety categories in youth with ASD, with partial support for the validity of the ambiguous anxiety-like categories. Unlike other measures, the ADIS/ASA differentiates comorbid anxiety disorders from overlapping and ambiguous anxiety-like symptoms in ASD, allowing for more precise measurement and clinical conceptualization. Ambiguous anxiety-like symptoms appear phenomenologically distinct from comorbid anxiety disorders and may reflect either symptoms of ASD or a novel variant of anxiety in ASD.

Study and Press Release
  • Anxiety Disorders Interview Schedule–Autism Addendum: Reliability and Validity in Children With Autism Spectrum Disorder, Journal of Clinical Child & Adolescent Psychology, doi/full/10.1080/15374416.2016.1233501, 07 December 2016.
  • Anxiety measure for children with autism proven reliable, Drexel University, December 8, 2016.

Autism outcomes in DES grandchildren : support the first study !

Help Fund Research into Neurodevelopment and Behavioral Impacts of DES

” My name is Jill Escher. I’m a science philanthropist who kickstarts pioneering research projects investigating the generational toxicity of certain potent exposures, including DES, tobacco and other drugs. While I’m not a DES daughter, I was exposed to a multitude of other synthetic steroid hormones in utero as part of a then-popular, if ineffective, “anti-miscarriage” practice. You can read my story here. You can see my science website at GermlineExposures.org.

Based on human, animal, and in vitro studies, as well as family interviews, I hypothesize that diethylstilbestrol DES, along with several other toxic substances, can damage the genomic information in early fetal-stage gametes. For a variety of reasons, the early gamete is probably the single most vulnerable stage of the human lifecycle. Damage during that phase, which could be genetic or epigenetic in nature, can manifest as abnormal development in the subsequent offspring.

For example, I hypothesize that the intensive synthetic steroid hormone drug regimen to which I was subjected as a fetus subtly deranged the molecular programming of my early eggs. This derangement I believe resulted in the starkly abnormal neurodevelopment — autism — of my children. I have met many other families with the same story.

Support Research into the Far-Reaching Generational Toxicity of DES, germline exposures, 10/10/2016.

Autism by pycik.

I am pleased to announce that I am funding the world’s first research study into the grandchild effects of DES (3d gen), looking specifically at neurodevelopment and behavioral impacts. This work will be done in collaboration with Harvard University, based on the Nurses’ Health Study II.

Thank you for your support! If you have any questions, please do not hesitate to email me. “

Jill Escher, President of Autism Society San Francisco Bay Area, 10/10/2016.

More DES DiEthylStilbestrol Resources

Old Exposures, Heritable Effects, and Emerging Concepts for Autism Research

Out of the past – heritable effects of endocrine disruptors

Video published on 27 May 2016 by FSUMedMedia channel.

Presentation given by Jill Escher on April 8, 2016 at Florida State University’s Symposium on the Developing Brain.

More DES DiEthylStilbestrol Resources

Are autism genes in all of us?

Genetic risk for autism spectrum disorders and neuropsychiatric variation in the general population

New light has been shed on the genetic relationship between autistic spectrum disorders (ASD) and ASD-related traits in the wider population, by a team of international researchers including academics from the University of Bristol, the Broad Institute of Harvard and MIT, and Massachusetts General Hospital (MGH).

Summary

Almost all genetic risk factors for autism spectrum disorders (ASDs) can be found in the general population, but the effects of this risk are unclear in people not ascertained for neuropsychiatric symptoms.

Using several large ASD consortium and population-based resources (total n > 38,000), we find genome-wide genetic links between ASDs and typical variation in social behavior and adaptive functioning.

Autism genes are in all of us, new research reveals, University of Bristol, 21 March 2016.

This finding is evidenced through both LD score correlation and de novo variant analysis, indicating that multiple types of genetic risk for ASDs influence a continuum of behavioral and developmental traits, the severe tail of which can result in diagnosis with an ASD or other neuropsychiatric disorder.

A continuum model should inform the design and interpretation of studies of neuropsychiatric disease biology.

Premature mortality risk about 2.5 times higher in autism spectrum disorder

Autism: early death risk a ‘hidden crisis’

Abstract

A registry study conducted at Karolinska Institutet shows that the risk of premature death is about 2.5 times higher for people with autism spectrum disorder than for the rest of the population.

Background
Mortality has been suggested to be increased in autism spectrum disorder (ASD).

Aims
To examine both all-cause and cause-specific mortality in ASD, as well as investigate moderating role of gender and intellectual ability.

Method
Odds ratios (ORs) were calculated for a population-based cohort of ASD probands (n = 27 122, diagnosed between 1987 and 2009) compared with gender-, age- and county of residence-matched controls (n = 2 672 185).

People with autism run a higher risk of premature death, Karolinska Institutet, 21 March 2016.

Results
During the observed period, 24 358 (0.91%) individuals in the general population died, whereas the corresponding figure for individuals with ASD was 706 (2.60%; OR = 2.56; 95% CI 2.38–2.76). Cause-specific analyses showed elevated mortality in ASD for almost all analysed diagnostic categories. Mortality and patterns for cause-specific mortality were partly moderated by gender and general intellectual ability.

Conclusions
Premature mortality was markedly increased in ASD owing to a multitude of medical conditions.

Children with Autism Spectrum Disorder: Survey of Parents in the UK

Report highlights problems faced by parents of children with Autism

2014 Survey Conclusion

Parents of children with Autism Spectrum Disorder (ASD) face severe challenges in accessing adequate services, according to a survey of hundreds of parents in the United Kingdom.

This report has highlighted the scale of the challenges faced by parents and children with ASD both in relation to the behaviours and health problems encountered but also in relation to accessing adequate services for support. The survey data indicated that a minority of respondents were struggling to access services from the NHS for basic support with challenges such as diet, nutrition, gut problems and sleep difficulties. In addition, even those who had managed to access the professional services available did not have their problems resolved.

Only 11% of respondents felt that the NHS professionals they encountered understood their concerns about the behaviour and healthcare issues of their child, and the majority (70%) felt that their child’s symptoms were attributed to ASD, rather than being worthy of investigation with the potential for treatment. Indeed, having a label of autism seemed to get in the way of accessing services and potential treatments that would ordinarily be available on the NHS. This diagnostic overshadowing meant that children’s symptoms were often left untreated and when parents sought help privately, they were often able to get at least some of these problems resolved. Many of the comments exposed what might best be called a ‘perception gap’ between parents’ experiences of looking after their children– and trying to deal with the wide range of health and behavioural problems they face – and the official health system that still classifies autism as a developmental disability. The official diagnosis is based upon the observation of cognitive, social and other behavioural and communication problems (the so-called ‘triad of impairments’) rather than any recognition of the wide range of co-morbid conditions that are commonly associated with the condition, many of which can be treated. As a result, parents struggled to access treatment, and what was provided was often inadequate.

Report highlights problems faced by parents of children with Autism, Queen Mary University of London, News story, 15 March 2016.

Given this, it is hardly surprising that almost all respondents (80%) had sought help privately. Parents had paid to see a range of health professionals that included doctors, nutritionists, speech and language and occupational therapists. In addition, however, and often in consultation with privately-accessed professionals, parents were experimenting with diet, nutritional supplementation and safe alternative therapies to see if they could help relieve some of the challenging problems faced by their children. In the vast majority of cases, these experiences had been positive, and for a sizeable number, the changes were reported to be life-changing.

The collective experiences of these parents are a reservoir of valuable testimony about the impact of relatively easy, low-cost, interventions that can improve the lives of children with ASD and their families, sometimes dramatically. Much more could be done to document these experiences and develop a more helpful dialogue between parents and clinical practitioners. It would also be possible to foster wider debate and education about these possibilities amongst NHS staff and thereby help many more families to improve the well-being of their children.

Health and service provision for people with Autism Spectrum Disorder: A survey of parents in the United Kingdom, 2014, Queen Mary University of London, ISBN: 978-1-910195-17-8, March 2016.

In this regard, many respondents argued that they would like to see improved relationships with NHS staff, along with a new approach to training and service provision. There were also calls for specialist teams to be set up, including a range of professionals, who could then fully investigate the range of challenges faced by children with ASD and identify possible areas for treatment and support. This has the potential to be life-changing for children with ASD and their families, and in the long-run, it could also save the wider community from at least some of the financial and emotional costs associated with the condition. New forms of best practice that incorporate routine medical checks for treatable comorbid conditions are now being developed for people with ASD in other parts of the world, and there is scope for extending this learning to the UK. As Perrin (2016, 1; see also McElhanon et al 2014) and his co-authors from the Autism Intervention Network on Physical Health and the Autism Speaks Autism Treatment Network (AIR-P/ATN) explain:

“Whereas, until recently, medical complaints (eg, abdominal pain, poor sleep, or disruptive behaviors) were typically considered part of the disorder and therefore not requiring specific attention, today clinicians throughout the country directly assess and treat these associated conditions. The combined AIR-P/ATN network has developed systematic ways to assess and treat coexisting conditions, focusing on those for which management was previously highly variable or sporadic and has shared those methods broadly with the larger parent and professional communities. The active involvement of families and young people with ASD has helped the network identify key issues for individuals and families and focus its attention accordingly. Although clinicians may have limited new, evidence-based options for treating autism directly, they now have systematic ways to evaluate and manage coexisting conditions. In turn, families have learned about new ways to help their children and improve their functioning and outcomes.”

This approach would greatly improve the lives of the families who took part in the survey reported here, as well as many thousands of others across the UK. In addition, the survey highlights the need for more scientific research into the causes and possible treatments of ASD and the range of co-morbid conditions associated with the condition. Parental experiences highlight the way in which diet and nutritional supplements can make a significant difference to the lives of children with ASD, and this is a vital area for further research.

In summary, this research report has highlighted the scale of the challenges faced by children with ASD and their families, the inadequacy of the current services provided by the NHS, the experiences of parents who are using changes in diet, nutritional supplements and a range of therapies to support their children, and the need for new thinking by those who are training health professionals and designing services for the twenty-first century.

Antidepressant use during Pregnancy and the Risk of Autism Spectrum Disorder in Children

Taking antidepressants during pregnancy increases risk of autism by 87 percent

Taking antidepressants during pregnancy increases risk of autism by 87 percent. Some classes of antidepressants work by inhibiting serotonin (SSRIs and some other antidepressant classes), which will have a negative impact on the ability of the brain to fully develop and adapt in utero, Scott Roberts.

2015 Study Abstract

Importance
The association between the use of antidepressants during gestation and the risk of autism spectrum disorder (ASD) in children is still controversial. The etiology of ASD remains unclear, although studies have implicated genetic predispositions, environmental risk factors, and maternal depression.

Objective
To examine the risk of ASD in children associated with antidepressant use during pregnancy according to trimester of exposure and taking into account maternal depression.

Design, Setting, and Participants
We conducted a register-based study of an ongoing population-based cohort, the Québec Pregnancy/Children Cohort, which includes data on all pregnancies and children in Québec from January 1, 1998, to December 31, 2009. A total of 145 456 singleton full-term infants born alive and whose mothers were covered by the Régie de l’assurance maladie du Québec drug plan for at least 12 months before and during pregnancy were included. Data analysis was conducted from October 1, 2014, to June 30, 2015.

Exposures
Antidepressant exposure during pregnancy was defined according to trimester and specific antidepressant classes.

Main Outcomes and Measures
Children with ASD were defined as those with at least 1 diagnosis of ASD between date of birth and last date of follow-up. Cox proportional hazards regression models were used to estimate crude and adjusted hazard ratios with 95% CIs.

Results
During 904 035.50 person-years of follow-up, 1054 children (0.7%) were diagnosed with ASD; boys with ASD outnumbered girls by a ratio of about 4:1. The mean (SD) age of children at the end of follow-up was 6.24 (3.19) years. Adjusting for potential confounders, use of antidepressants during the second and/or third trimester was associated with the risk of ASD (31 exposed infants; adjusted hazard ratio, 1.87; 95% CI, 1.15-3.04). Use of selective serotonin reuptake inhibitors during the second and/or third trimester was significantly associated with an increased risk of ASD (22 exposed infants; adjusted hazard ratio, 2.17; 95% CI, 1.20-3.93). The risk was persistent even after taking into account maternal history of depression (29 exposed infants; adjusted hazard ratio, 1.75; 95% CI, 1.03-2.97).

Conclusions and Relevance
Use of antidepressants, specifically selective serotonin reuptake inhibitors, during the second and/or third trimester increases the risk of ASD in children, even after considering maternal depression. Further research is needed to specifically assess the risk of ASD associated with antidepressant types and dosages during pregnancy.

Sources and more information
  • Antidepressant Use During Pregnancy and the Risk of Autism Spectrum Disorder in Children, JAMA Pediatrics, doi:10.1001/jamapediatrics.2015.3356, December 14, 2015.
  • Taking antidepressants during pregnancy increases risk of autism by 87 percent, medicalxpress, December 14, 2015.
  • Antidepressants during pregnancy linked to autism, medicalnewstoday, 14 December 2015.