Maternal serum dioxin-like activity and gestational age at birth and indices of foetal growth: The Aarhus birth cohort

Abstract

Human exposure to lipophilic persistent organic pollutants (lipPOP) is ubiquitous and life-long, beginning during foetal development. Exposure to lipPOP elicits a number of species and tissue specific responses including dioxin-like activity which involve the activation of aryl hydrocarbon receptor (AhR). This study aims i) to describe the combined dioxin-like activity in serum from Danish pregnant women collected during 2011-2013; ii) to assess the association between maternal serum dioxin-like activity, gestational age at birth and foetal growth indices. The serum lipPOP fraction was extracted using Solid Phase Extraction and cleaned-up on Supelco multi-layer silica and florisil columns. The combined dioxin-like activity of the extract was determined using the AhR reporter gene bioassay, expressed as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalent (TEQ) [AhR-TEQ (pg/g lipid)]. The associations of AhR-TEQ and foetal growth indices (birth weight, birth length and head circumference) and gestational age were assessed by linear regression models. We detected AhR-TEQ in 93.9 % of maternal first trimester serum samples, with a median level of 185 pg/g lipid. Each ln-unit increase in AhR-TEQ was associated with an increase in birth weight of 36 g (95 % CI: 5; 68), birth length of 0.2 cm (95 % CI: 0.01; 0.3) and pregnancy duration of 1 day (95 % CI: 0; 1.5). In women who never smoked, higher AhR-TEQ values were associated with higher birth weight and longer duration of gestation, while in smokers the association was the opposite. Mediation analyses suggested that gestational age may mediate the association of AhR-TEQ with foetal growth indices. We conclude that AhR activating substances are present in the bloodstream of almost all pregnant women in Denmark and the AhR-TEQ level was around four times higher than previously reported. The AhR-TEQ was associated with slightly longer gestational duration and thereby higher birth weight and birth length.

Keywords: Aryl hydrocarbon receptor; Foetal growth indices; Gestational age at birth; Persistent organic pollutants; Pregnant women.