Maternal DDT Metabolite Levels Associated with Autism in Offspring

by Ashley Jordan Ferira, PhD, RDN

Autism spectrum disorder (ASD) is an urgent public health concern affecting approximately 1 in 59 US children.^1-2 This complex neurodevelopmental syndrome is 4x more common in boys than girls and impacts all racial, ethnic, and socioeconomic backgrounds, although ASD is more common in white > black > Hispanic children.¹ Other developmental, psychiatric, neurologic, chromosomal, and genetic diagnoses are known to co-occur with ASD,^3-4 however, the genetic and epigenetic factors that impact autism pathogenesis are largely unknown.

To enlighten possible environmental etiologies of autism, a study in The American Journal of Psychiatry examined whether blood levels of specific toxins in pregnant Finnish mothers were associated with autism risk in offspring.⁵ The toxins in question included persistent organic pollutants: insecticide dichlorodiphenyltrichloroethane (DDT), its metabolite p,p’-dichlorodiphenyl dichloroethylene (p,p’-DDE), and polychlorinated biphenyls (PCBs) (total and 10 major congeners). Data from the Finnish Prenatal Study of Autism, a national birth cohort study using a nested case-control design, was utilized; cases of childhood autism were born between 1987 and 2005 and matched to control subjects (matched based on date of birth, gender, birthplace, and residence in Finland), yielding 778 matched case-control pairs.⁵ Maternal blood specimens were collected during early pregnancy (months 2-4), and associations (odds ratios) controlled for covariates (maternal age, parity, and history of psychiatric disorders).⁵

Results:

• Mothers of case subjects with autism had significantly higher levels of p,p’-DDE (1,032pg/mL) on average than mothers of control subjects without autism (811 pg/mL)
• Odds of autism in offspring was significantly increased (↑32%) with maternal p,p’-DDE levels in the top 75^th percentile: OR=1.32; CI:1.02-1.71; p=0.03
• Odds of autism with intellectual disability was increased >2-fold with maternal p,p’-DDE levels >75^th percentile: OR=2.21; CI:1.32-3.69; p=0.04
• No association was observed between total levels of maternal PCBs and autism

Persistent organic pollutants can be transferred across the placenta, and although DDT and PCBs were widely banned in many countries 30+ years ago (banned in US in 1972), their widespread use (DDT mainly in insecticides; PCBs mainly in transformers and electrical equipment), combined with their chemical characteristics (i.e., lipophilic and long half-lives) led to their persistence in the food chain and ubiquitous exposure, which has been observed in both US⁶ and Finnish⁷ populations.

Previous studies have also observed associations between autism-related behaviors and maternal exposure (assessed via interview and ecologic data) to persistent organic pollutants, including DDT and DDE, but this is the first study to provide biomarker-based evidence of maternal insecticide exposure being associated with autism in offspring.⁵ Possible mechanisms include: 1) maternal exposure to DDT and DDE is associated with premature birth and small-for-gestational age babies, 2) p,p’-DDE inhibition of androgen receptor expression and binding, as well as androgen action, which may be involved in autism pathogenesis, although current evidence is preclinical in nature (i.e., rodent studies).⁵ Further preclinical and clinical study are certainly warranted.

So what can we do? In addition to limiting incremental exposures (household and occupational) to insecticides and other chemicals whenever possible, supporting prenatal nutrition via healthful nutrition and targeted multivitamin/mineral supplementation is important to support a robust in utero environment. A 2017 study demonstrated that associations between pesticide exposures and ASD were lessened in mothers supplementing with ≥800 mcg/day of folic acid during their first month of pregnancy.⁸

Why is this Clinically Relevant?

• Autism etiology remains to be fully elucidated, but the in utero environment appears to play a pivotal role
• High maternal levels of the insecticide metabolite p,p’-DDE are associated with increased odds of autism in offspring⁵
• Although persistent organic pollutants are in fact “persistent” in the food chain, it is prudent to proactively limit incremental exposures to household and environmental chemicals and pesticides (e.g. sprays, foggers, etc.)
• Maternal folic acid supplementation ≥800 mcg/day during early pregnancy may attenuate the association between pesticide exposures and autism⁸

View the abstract

Citations

1. Baio J et al. Prevalence of autism spectrum disorder among children aged 8 years – Autism and Developmental Disabilities Monitoring Network, 11 sites, United States, 2014. MMWR Surveillance Summaries. 2018;67(6):1-23.
2. CDC. Autism Spectrum Disorder (ASD). https://www.cdc.gov/ncbddd/autism/data.html. Accessed August 27, 2018.
3. Levy SE et al. Autism spectrum disorder and co-occurring developmental, psychiatric, and medical conditions among children in multiple populations of the United States. J Dev Behav Pediatr. 2010;31(4):267-275.
4. Hallmayer J et al. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 2011;68(11):1095-1102.
5. Brown AS et al. Association of maternal insecticide levels with autism in offspring from a national birth cohort. Am J Psychiatry. 2018;175(11):1094-1101.
6. Woodruff TJ et al. Environmental chemicals in pregnant women in the United States: NHANES 2003-2004. Environ Health Perspect. 2011;119:878-885.
7. Kiviranta H, Tuomisto JT, Tuomisto J, et al. Polychlorinated dibenzo-p-dioxins, dibenzofurans, and biphenyls in the general population in Finland. Chemosphere. 2005;60:854-869.
8. Schmidt RJ et al. Combined prenatal pesticide exposure and folic acid intake in relation to autism spectrum disorder. Environ Health Perspect. 2017;126(9):097007.