BACKGROUND AND AIM: Prenatal exposure to endocrine disrupting chemicals, including polychlorinated dibenzo-p-dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and dioxin-like polychlorinated biphenyls (DL-PCBs), has been hypothesized to have detrimental impact on neurodevelopment. However, the effect of prenatal exposure to dioxin and DL-PCB mixtures on neurodevelopment remains largely inconclusive. Therefore, we aimed to elucidate the associations of in utero exposure to a dioxin and DL-PCB mixture with infant neurodevelopment by applying novel multi-pollutant methods. METHODS: The concentrations of individual dioxin and DL-PCB isomers were measured in maternal peripheral blood during pregnancy in the Sapporo cohort, Hokkaido Study on Environment and Children’s Health. The mental and psychomotor development of the study participants’ six-month-old infants were assessed using the Bayley Scales of Infant Development-2nd Edition (n=210). To determine both the joint and individual associations of prenatal exposure to dioxin and DL-PCB mixtures with infant neurodevelopment, Bayesian Kernel Machine Regression (BKMR) and quantile-based g-computation models were performed. RESULTS:Suggestive, but not significant, inverse associations were observed between prenatal exposure to a dioxin and DL-PCB mixture, and infant psychomotor development in the both BKMR and quantile g-computation models. In contrast, we found no association of dioxin and DL-PCB mixtures with mental development. These mixture methods consistently indicated 2,3,7,8-TCDD and 23'44'55'-HxCB(#167) as the most influential dioxin and DL-PCB congener on mental and psychomotor development, respectively. When group-specific posterior inclusion probabilities were evaluated, BKMR revealed in utero exposure to PCDFs and mono-ortho DL-PCBs as the more important contributing factors to early mental and psychomotor development, respectively, compared with the other dioxin or DL-PCB groups. No evidence of non-linear relationships or interactions among the chemical mixtures was detected. CONCLUSIONS:Employing the novel statistical methods for chemical mixture analysis, we demonstrated limited evidence of inverse associations of prenatal exposure to dioxins and DL-PCBs with infant psychomotor development, but not with mental development. KEYWORDS: Chemical mixtures, Dioxins, Polychlorinated biphenyls, Neurological development, Bayesian Kernel Machine Regression, Quantile g-computation