Maternal serum persistent organic pollutants in the Finnish Prenatal Study of Autism: A pilot study

Highlights

• Studies on associations between chemical exposures and autism have been limited.

• We conducted a pilot case–control study in the Finnish Prenatal Study of Autism.

• Persistent organic pollutants were measured in prenatal maternal serum samples.

• 6 PCB congeners and DDE were detected in all samples.

• Non-statistically significant positive associations with autism were observed.

Abstract

Recent research emphasizes the contribution of environmental as well as genetic factors to the etiology of autism but studies testing associations between chemical exposures and autism have been limited. Prenatal exposure to persistent organic pollutants (POPs) has previously been associated with decrements in cognitive and developmental performance. We conducted a pilot study in the Finnish Prenatal Study of Autism (FiPS-A). Seventy-five cases with autism and 75 controls matched on sex, birth year, urbanization and maternal age were sampled from first-born children in the Finnish Maternity Cohort, which includes over 1 million births. The study sample included births occurring from 1991 to 2000. Subjects were followed up for autism through 2007. DDT, DDE, PCB-118, PCB-138, PCB-153, PCB-156, PCB-170, PCB-180, hexachlorobenzene, and BDE-47 were measured in archived maternal serum samples taken during pregnancy using gas chromatography–high resolution mass spectrometry. Correlations between pollutant measures were assessed and mechanistically-related weighting schemes for summarizing PCB levels were compared. Case and control differences were assessed using graphical and statistical methods. All analytes, with the exception of DDT and BDE-47, were detected above the limit of quantification in all samples. The correlation between levels of individual PCB congeners and weighted summary measures was high (0.71–1.00). Paired t-tests revealed no significant differences between cases and controls for log-transformed mean values of any analyte; however, in an adjusted model the odds ratios for autism were 1.91 (p = 0.29) and 1.79 (p = 0.36) respectively, for subjects with total PCBs and DDE above the 90th percentile of control values. Levels of prenatal PCB exposure in FIPS-A were similar to the levels which previously correlated with poorer neurodevelopmental measures in other populations. Further study in a larger sample will be required to fully determine whether exposure to high POP levels is associated with autism diagnosis in the population.

Introduction

Autism is a developmental disorder involving impairments in language and social interaction; repetitive behaviors and restricted interests; and with an onset before age three. The developmentally dependent nature of the deficits involved in autism means that diagnosis is not typically made until after the first year of life. However, evidence suggests that neurodevelopmental events underlying the behavioral characteristics of autism have roots in the prenatal period (Arndt et al., 2005, Patterson, 2009), while recent heritability estimates suggest that environmental factors, in concert with genetics, play a substantial role in risk for the disorder (Hallmayer et al., 2011). Studies are limited in number that have addressed potential associations between autism spectrum disorders (ASDs) and prenatal exposure to chemicals in the environment, primarily focusing on exposure via air (Windham et al., 2006, Kalkbrenner et al., 2010, Roberts et al., 2007, Larsson et al., 2009, Volk et al., 2011).

Persistent organic pollutants (POPs) such as polychlorinated biphenyls (PCBs), polybrominated diphenyl ether (PBDE), the pesticide dichlorodiphenyltrichloroethane (DDT), and its metabolite dichlorodiphenyldichloroethylene (DDE), are lipophilic and bioaccumulate in the food chain. Associations between prenatal PCB or DDT/DDE exposure and lower scores on neurodevelopmental measures in humans have been reported in some (i.e. Eskenazi et al., 2006, Jacobson and Jacobson, 1996, Jacobson and Jacobson, 2003, Jacobson et al., 1985, Park et al., 2010, Patandin et al., 1999, Stewart et al., 2000, Stewart et al., 2008, Torres-Sanchez et al., 2007), though not all (i.e. Bahena-Medina et al., 2011, Fenster et al., 2007, Gray et al., 2005, Winneke et al., 1998) studies. While associations reported have primarily focused on general developmental or cognitive measures, studies examining the biomarkers of exposure to PCBs, DDT or PBDE, specifically, and autism have not to our knowledge been reported. Roberts et al. reported an increased risk of ASD among children whose mothers lived near sites where organochlorine pesticides as a group had been applied to fields in California during gestation (Roberts et al., 2007). Dicofol and endosulfan were the two pesticides primarily accounting for applications in this category. Dicofol in particular is chemically similar to DDT but is cleared from the body more quickly with lower bioaccumulation (Roberts et al., 2007). It may be hypothesized, therefore, that DDT could have a similar, and perhaps stronger, association with autism.

The Finnish Prenatal Study of Autism (FiPS-A) is based on a national birth cohort including the approximately 1.2 million births in Finland occurring from 1987 to 2005. A unique feature is the availability of archived maternal serum samples taken during early gestation. A study of 112 placentae from male infants born between 1997 and 2001 in Finland found detectable levels of p,p′-DDE in 100% of samples, as well as a high prevalence of additional organochlorinated pesticides (Shen et al., 2005), suggesting that prenatal exposure to these substances is relevant for the Finnish population. We conducted a pilot study with the following aims: 1) to establish the feasibility of measuring POPs in prenatal maternal serum samples from the FiPS-A; 2) to evaluate associations of POPs with covariates in the general population; 3) to compare alternative weighting schemes for PCB congeners; and 4) to assess preliminary evidence for a relationship between exposure to prenatal POPs and autism.