Early environmental risk factors for neurodevelopmental disorders – a systematic review of twin and sibling studies

Carlsson, Torkel; Molander, Felix; Taylor, Mark J.; Jönsson, Ulf; Bölte, Sven

doi:10.1017/s0954579420000620

Cited by 100 publications

(85 citation statements)

References 206 publications

(203 reference statements)

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“…Identifying specific environmental factors that influence risk for ASD may suggest rational approaches for the primary prevention of the symptoms associated with the disorder. Progress has been made in identifying environmental risk factors for ASD, including advanced paternal age at conception, complications during pregnancy, maternal diet, and prenatal exposure to psychotropic drugs [24,25]. While environmental chemicals are widely posited to also contribute to ASD risk [14,[26][27][28], it has been difficult to demonstrate this in human studies.…”

Section: Introductionmentioning

confidence: 99%

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Panesar

Kennedy

Stietz

et al. 2020

Toxics

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Autism spectrum disorder (ASD) includes a group of multifactorial neurodevelopmental disorders defined clinically by core deficits in social reciprocity and communication, restrictive interests and repetitive behaviors. ASD affects one in 54 children in the United States, one in 89 children in Europe, and one in 277 children in Asia, with an estimated worldwide prevalence of 1–2%. While there is increasing consensus that ASD results from complex gene x environment interactions, the identity of specific environmental risk factors and the mechanisms by which environmental and genetic factors interact to determine individual risk remain critical gaps in our understanding of ASD etiology. Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants that have been linked to altered neurodevelopment in humans. Preclinical studies demonstrate that PCBs modulate signaling pathways implicated in ASD and phenocopy the effects of ASD risk genes on critical morphometric determinants of neuronal connectivity, such as dendritic arborization. Here, we review human and experimental evidence identifying PCBs as potential risk factors for ASD and discuss the potential for PCBs to influence not only core symptoms of ASD, but also comorbidities commonly associated with ASD, via effects on the central and peripheral nervous systems, and/or peripheral target tissues, using bladder dysfunction as an example. We also discuss critical data gaps in the literature implicating PCBs as ASD risk factors. Unlike genetic factors, which are currently irreversible, environmental factors are modifiable risks. Therefore, data confirming PCBs as risk factors for ASD may suggest rational approaches for the primary prevention of ASD in genetically susceptible individuals.

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Section: Introductionmentioning

confidence: 99%

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Panesar

Kennedy

Stietz

et al. 2020

Toxics

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“…The perturbation produced by external agents during the prenatal and perinatal periods has been widely reported for NDDs in general and for ASD in particular. The environmental factors that have been consistently associated with NDDs include paternal age, gestational age, low birth weight, birth defects and perinatal hypoxia and respiratory stress, lower socioeconomic status and prenatal or childhood exposure to certain environmental chemicals (ACE, 2019; Carlsson et al., 2020; Cheroni et al., 2020). Serious infection and exposure to psychoactive or addictive drugs during early development are well‐known environmental factors relevant to NDDs (Hsueh, 2019).…”

Section: Assessmentmentioning

confidence: 99%

Development of Integrated Approaches to Testing and Assessment (IATA) case studies on developmental neurotoxicity (DNT) risk assessment

Hernandez-Jerez¹,

Adriaanse²,

Aldrich³

et al. 2021

EFS2

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The EFSA Panel on Plant Protection Products and their Residues (PPR) has developed, as a self-task mandate (EFSA-Q-2019-00100), two adverse outcome pathway (AOP)-informed integrated approach to testing and assessment (IATA) case studies to answer a developmental neurotoxicity (DNT) hazard identification and characterisation problem formulation that could support the regulatory decisions for the pesticide active substances deltamethrin and flufenacet. The IATA were developed to assess the applicability of the DNT in vitro testing battery (IVB), designed to explore fundamental neurodevelopmental processes, in the regulatory risk assessment of pesticides. For this purpose, an evidence-based-approach methodology was applied: 1) systematic literature review and critical appraisal of all the evidence i.e. human observational studies, in vivo data from rodent models and new approach methodologies (NAMs, i.e. in vitro studies including high-throughput testing from IVB and zebrafish studies from the literature) for both case studies; 2) a quantitative uncertainty analysis of all the evidence using expert knowledge elicitation (EKE) and a probabilistic approach; 3) integration of all the evidence using the AOP conceptual framework. This stepwise approach resulted in the postulation of an evidencebased AOP network for one of the case studies. A probabilistic quantification of the weight of evidence (WoE) using Bayesian network analysis allowed the assessment and the quantification of the uncertainty in the postulated AOP. The approach taken allowed conclusions to be drawn with an acceptable level of certainty in DNT hazard identification and characterisation of deltamethrin and that flufenacet is not a developmental neurotoxicant, supporting the relevance of the mechanistic understanding. The case studies show the applicability of the DNT-IVB for hazard identification and characterisation and illustrate the usefulness of an AOP-informed IATA for regulatory decision making. The overall activity led to improved interpretation of human data by providing a plausible mechanistic link to adverse outcomes, which would support their contextualisation in the risk assessment process. This Scientific Opinion allows the PPR Panel to draft several recommendations for the implementation of the AOP-informed IATA methodology and of the DNT-IVB in the regulatory risk assessment of pesticides.

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“…Studies investigating the impacts of IPIs on child development outcomes have typically focused on neurodevelopmental morbidities and disabilities such as autism spectrum disorder or attention-deficit/hyperactivity problems. [10][11][12][13] In terms of school-based outcomes, studies have more readily examined the impact of adversities associated with suboptimal IPIs such as preterm birth and low birth weight. The available studies assessing the relationship between birth spacing and child development outcomes, beyond those observed at birth and in children without diagnosed developmental disabilities, have primarily examined the impact of birth intervals.…”

Section: Introductionmentioning

confidence: 99%

Interpregnancy intervals and child development at age 5: a population data linkage study

2021

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ObjectiveTo investigate the associations between interpregnancy intervals (IPIs) and developmental vulnerability in children’s first year of full-time school (age 5).DesignRetrospective cohort study using logistic regression. ORs were estimated for associations with IPIs with adjustment for child, parent and community sociodemographic variables.SettingWestern Australia (WA), 2002–2015.Participants34 574 WA born singletons with a 2009, 2012 or 2015 Australian Early Development Census (AEDC) record.Main outcome measureThe AEDC measures child development across five domains; Physical Health and Wellbeing, Social Competence, Emotional Maturity, Language and Cognitive Skills (school-based) and Communication Skills and General Knowledge. Children with scores <10th percentile were classified as developmentally vulnerable on, one or more domains (DV1), or two or more domains (DV2).Results22.8% and 11.5% of children were classified as DV1 and DV2, respectively. In the adjusted models (relative to the reference category, IPIs of 18–23 months), IPIs of <6 months were associated with an increased risk of children being classified as DV1 (adjusted OR (aOR) 1.17, 95% CI 1.08 to 1.34), DV2 (aOR 1.31, 95% CI 1.10 to 1.54) and an increased risk of developmental vulnerability for the domains of Physical Health and Wellbeing (aOR 1.25, 95% CI 1.06 to 1.48) and Emotional Maturity (aOR 1.36, 95% CI 1.12 to 1.66). All IPIs longer than the reference category were associated with and increased risk of children being classified as DV1 and DV2 (aOR >1.15). IPIs of 60–119 months and ≥120 months, were associated with an increased risk of developmental vulnerability on each of the five AEDC domains, with greater odds for each domain for the longer IPI category.ConclusionsIPIs showed independent J-shaped relationships with developmental vulnerability, with short (<6 months) and longer (≥24 months) associated with increased risks of developmental vulnerability.

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Early environmental risk factors for neurodevelopmental disorders – a systematic review of twin and sibling studies

Cited by 100 publications

References 206 publications

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Polychlorinated Biphenyls (PCBs): Risk Factors for Autism Spectrum Disorder?

Development of Integrated Approaches to Testing and Assessment (IATA) case studies on developmental neurotoxicity (DNT) risk assessment

Interpregnancy intervals and child development at age 5: a population data linkage study

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