Environmental Factors (2017) Reading Guide

Ng et al. 2017 Environmental Factors Guide

Ng, M., de Montigny, J. G., Ofner, M., & Do, M. T. (2017). Environmental factors associated with

autism spectrum disorder: A scoping review for the years 2003-2013. Health Promotion

and Chronic Disease Prevention in Canada, 37(1), 1-23.

The purpose of this article is to provide a review of research that has been conducted over the period from 2003 -2013 that have investigated possible environmental factors that might contribute to ASD. Chemical, physiological, nutritional, and social factors were included in this review. As you read this article, take note of the evidence for each factor. 

Environmental Factors What is the evidence that this factor contribute to ASD?

Chemical Dimension

Heavy metals - mercury

• Biomarkers of mercury exposure in children with autism were examined by testing hair, blood, urine, teeth, and nails. The findings were largely inconsistent due to Mercury’s short half-life

• Elevated porphyrins have been found in children with autism compared to allistic children but needs more study with larger sample sizes

Other heavy metals

• Lead, cadmium, aluminum, and arsenic were the most-studied with conflicting findings

• Most studies found no significant association, none investigated possible exposure sources      

Air pollution

• Relatively consistent evidence for an association between traffic-related air pollutant exposures and ASD. Exposure to traffic-related air pollution can result in respiratory, cardiovascular disease, and certain neurological outcomes by triggering inflammation and oxidative stress, which are common physiological abnormalities observed in children with ASD

MMR Vaccine

• Wakefield case series study found an increased prevalence of a new variant of ASD characterized by gastrointestinal disorders and developmental regression. ← later retracted due to false data

• Other studies found no significant association between the MMR vaccine or MMR itself and ASD      

Thimerosal-containing vaccines

• Preservative that contains 50% ethylmercury and is used for multi-vial vaccines such as diphtheria-tetanus-pertussis vaccine

• Widely researched because of concerns about mercury overexposure stemming from the expansion of childhood vaccination schedules in the past several decades

• Thimerosal in Rh immune globulins given to pregnant women with Rh incompatibility issues has also been investigated as a source of prenatal mercury exposure      

Medications (acetaminophen, SSRI’s, Valproic acid)      

• The increasing use of antidepressants, antibiotics, and acetaminophen has sparken hypotheses of possible links with the use of these medications and synchronous rising ASD prevalence in the 1980s

• Prenatal use of SSRIs (Selective Serotonin Reuptake Inhibitors, a class of antidepressants) can be connected to 1% of ASD cases

• A large prospective cohort study showed that prenatal valpoate exposure was associated with an absolute risk of ASD

Substance abuse – tobacco smoke      

• Meta-analysis and other studies have indicated no significant association between smoking during pregnancy and ASD

• Maternal secondhand tobacco exposure may be associated with ASD

Alcohol

• Only heavy prenatal consumption of alcohol has shown a significant association with ASD

Physiological Dimension

Advanced parental age

• There is no evidence for a synergistic effect

• Multicollinearity of maternal and paternal ages found that advanced maternal age was the primary independent contributor of the parental age effect      

Assisted conception (like in-vitro)      

• Connected to high rate of prematurity and low birth weight

• Methodological limitations are the source of inconsistent findings

• Significant positive correlations were found among subgroups such as woman over age 34, multiple births, and those exposed to specific assisted conception methods

Prenatal testosterone

• An association between elevated prenatal testosterone levels and ASD has been implicated in three meta-analyses and a case-control study, however, no significant correlation was found with neonatal testosterone levels in a cohort study    

Thyroid hormone      

• Can be due to prenatal or early-life exposure to the anti-thyroid effects of heavy metals, to endocrine-disrupting chemicals or to dietary deficiencies

• May affect neurodevelopment

• Evidence for the association between neonatal or maternal levels of thyroid hormone and ASD is limited and inconsistent

Birthweight and gestational age      

• Low birth weight found to be a significant risk factor for ASD in children

• Significant association between small for gestational age and ASD

Clustering of pregnancy complications      

• Composite measures of compromised prenatal, perinatal and neonatal health overall → optimality scores

• Optimality scores have found that reduced prenatal and neonatal optimality is more evident than perinatal suboptimality in ASD cases

• Fetal hypoxia (intrauterine deprivation of oxygen) may be implicated in ASD etiology → low Apgar score, caesarean sections, and growth retardation

• Fetal hypoxia has been weakly associated with ASD according to a population-based cohort study

Birth order and spacing      

• First-born children are more likely to be diagnosed with ASD than 3rd or later

• Earlier birth order and greater parity appear to be conflicting risk factors because first-born children in sibship sizes of two, and later-bron children in families with larger sibship sizes are more likely to have ASD

• Interpregnancy intervals of less than 18 months have also been associated with autism in the second-born child

Autoimmune diseases      

• Antibody reactivity to human fetal brain protein is more prevalent in mothers of children who are not autistic

• Elevated autoantibodies were also present in at least one parent of children with autism; parental antibodies may contribute to autism etiology

Brain inflammation      

• Implicated in the etiology of ASD

• Food additives or stress may result in a cascade of excitotoxicity in the brain and may be related to dysregulation of glutamate neurotransmission, triggering production of proinflammatory cytokines resulting in chronic inflammation affecting neurodevelopment

Maternal infection      

• Infections may trigger the chronic inflammation of the CNNS, affecting brain development and maturation, which has been implicated in ASD etiology

• There was no significant association between maternal infection and ASD

Neonatal jaundice      

• An elevated serum bilirubin levels (hyperbilirubinemia) have been a concern

• Unconjugated bilirubin can be toxic to developing CNS

• Hyperbilirubinemia was associated with an increased risk of autism

Neonatal epileptic disorder      

• No significant relationship between neonatal seizures and ASD

• Small studies have found some evidence for a possible association

Oxidative stress

• One of the most-studied physiological abnormalities in ASD

• Case-controlled studies indicated a role for oxidative stress in ASD patients based on different biomarkers of oxidative stress and impaired antioxident systems

• Biomarkers include altered levels of oxidative stress defense systems (metallothioneins and antioxidant enzymes)      

Nutritional Dimension

Minerals and trace elements      

• Studies examining hair samples remain inconclusive

• Studies looking at associations between levels of zinc, iron, magnesium, copper, molybdenum, nickel, and selenium and ASD have conflicting results

• Calcium deficiencies have also been documented in association with ASD with some inconsistencies

• Differences in levels of cobalt, chromium, and manganese in children with or without ASD were mostly insignificant

Vitamin D      

• Plays a crucial role in various functions, such as neurodevelopment, the anti-inflammatory response, and the detoxification pathway

• Evidence for an association between vitamin D deficiency and ASD is limited and indirect

Infant feeding      

• Few studies on infant feeding methods concerning ASD

• Absence or late initiation of breastfeeding was significantly associated with ASD in contrast to findings of an ecological study

Folic acid

• Recent prospective cohort study found maternal folic acid intake to tbe protective against ASD → contrasted by an ecological study that found positive correlations between percentages of prescription prenatal vitamins and pediatric vitamins containing folic acid and ASD incidence      

Social Dimension

Socioeconomic status (SES)      

• No association with autism was found using case ascertainment only from school sources

• Other studies had different results

• In countries with universal healthcare programs, lower family or maternal income was associated with ASD, which suggests that ASD found mainly in the US studies may reflect inequalities in access to healthcare services

Ethnicity      

• Possible racial or ethnic disparities in ASD diagnosis

Immigrant status      

• Migrant mothers had a higher prevalence of offspring with ASD

Maternal stress

• Prenatal exposure to environmental stressors, including stress-related immunological and neuroinflammatory abnormalities and placental dysfunction that can affect fetal neurodevelopment, may play a role in ASD etiology      

What is your takeaway from reading this article? 

• My takeaway from this article is that there are millions of different possibilities for the cause of ASD and we may never truly know the answer, even with more research. All we can do it work toward making society a safer place for people who already have ASD.