Per- and polyfluoroalkyl substances (PFAS) and organochlorines (OC) have been classified by the International Agency for Research on Cancer (IARC) as possible human carcinogens and human carcinogens, respectively (IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, 2017). Furthermore, they have been categorized as endocrine disrupters (Kar et al., 2017; Mnif et al., 2011) and linked to numerous adverse health outcomes (Meneguzzi et al., 2021; Perkins et al., 2016; Tang et al., 2014). Even though their use has been regulated in large parts of the world or banned for certain compounds (Commission Regulation (EU) no. EU/2020/784; U.S. Environmental Protection Agency (EPA), 1979; United Nations Environment Programme (UNEP)), the long half-lives of legacy PFAS and OC enable them to persist in the environment and humans.

Experimental (Kummu et al., 2015; Meerts et al., 2002) and epidemiological studies (Lu et al., 2021; Zhang et al., 2018b) showed that PFAS and OC can cross the placental barrier and reach the fetus. Prenatal exposure to PFAS and OC during the sensitive fetal period can result in adverse health outcomes later in life (Grandjean and Landrigan, 2006; Lau et al., 2004) and affect neurodevelopment, resulting in long-lasting cognitive changes (Gao et al., 2023; Saeedi Saravi and Dehpour, 2016). Information on the cognitive and neurodevelopmental effects of prenatal exposures to PFAS and OC at adolescence is scarce, with only a few studies investigating associations at this age for PFAS (Tillaut et al., 2023) or OC (Oppenheimer et al., 2021; Rokoff et al., 2022) and most studies reporting findings for younger children with inconsistent results. Regarding prenatal exposure to PFAS, some studies found a decrease in cognitive performance in toddlers (Luo et al., 2022), preschool children (Goodman et al., 2023), and school children (Vuong et al., 2021), while others found no associations in school children (Zhang et al., 2018a) or increases in cognitive or neurodevelopmental measures in preschool children (Spratlen et al., 2020) and school children (Harris et al., 2018; Zhang et al., 2018a). While some studies reported null-findings for the association between cognition and OC in children and adolescents (Oppenheimer et al., 2021; Rokoff et al., 2022; Zhang et al., 2017), neurobehavioral deficits at a young age have been described after higher prenatal OC exposure (Jacobson and Jacobson, 2003; Lynch et al., 2012; Vermeir et al., 2021; Yamazaki et al., 2018).

Assessment of mixture effects of highly correlated chemical exposures may contribute to the unbiased evaluation and understanding of dose-response associations in real-life exposure scenarios (Robinson et al., 2015; Rosofsky et al., 2017), as different chemicals could trigger the same biological pathways. While combined effects have been considered for different groups of persistent chemicals (Dingemans et al., 2016), the correlations with other chemical classes have not yet been exhaustively investigated for PFAS.

Most studies examined the effect of prenatal PFAS and OC exposure on childhood cognition for individual congeners. Only a few studies investigated the potential mixture effects of the two groups of chemicals on these outcomes separately (Goodman et al., 2023; Luo et al., 2022; Rokoff et al., 2022; Zhou et al., 2023) or combined (Kalloo et al., 2021); however, the latter study did not include postnatal exposure to these chemicals, which is important, as the exposure at the timepoint of outcome assessment could influence the association between prenatal exposure and outcome and therefore bias the results. Therefore, within the Flemish Environment and Health Studies (FLEHS) framework, the current study assesses the cognitive effects of prenatal exposure to mixtures of legacy PFAS and OC in adolescence while correcting for exposure levels measured at the time of the cognitive tests.