Organophosphate esters (OPEs) are a class of synthetic chemicals and extensively used as flame retardants (FRs) and plasticizers in furniture (polyurethane foam), textiles, electronics, building materials, and baby products (nursing pillows and car seats) (Cooper et al., 2016; Du et al., 2019; Hoffman et al., 2015). Due to the progressive phase-out of polychlorinated biphenyls and polybrominated diphenyl ethers, OPEs have been among the most commonly used alternative FRs in recent years. Global consumption of OPEs accounted for 11% of the total consumption of FRs in 2008 and increasingly over 30% in 2017 (Wang et al., 2020). Most OPEs are additives and are not chemically bound to the products in which they are used; thus, they can easily migrate into the surrounding environment (Hou et al., 2016). Humans can be exposed to OPEs through ingestion (contaminated foodstuff and dust), inhalation (dust), and skin contact (Mäkinen et al., 2009; Poma et al., 2017; Yang et al., 2014). Recent studies have reported the ubiquitous detection of OPEs in human samples, such as blood, urine, and breast milk (Kim et al., 2014; Wang et al., 2021; Zhao et al., 2016). Particularly, OPEs have been detected in human deciduae and chronic villi, suggesting that OPEs may undergo maternal-fetal transfer during pregnancy (Zhao et al., 2017), which raises concerns about the adverse effects of gestational OPEs exposure.

Gestational OPEs exposure may have adverse effects on the growth and development of offspring, especially with regard to the risk of obesity (Crawford et al., 2020; Wang et al., 2019). OPEs may act as metabolic disruptors given their potential to disrupt lipid and glucose metabolism (Wade et al., 2019; Wang et al., 2019) and sex steroid activities (Liu et al., 2013) in animals, and thyroid functions in humans (Preston et al., 2017); thus, may disrupt energy homeostasis. Animal studies have revealed that perinatal OPEs exposure can result in increased body mass, fat mass, fasting leptin levels, and total energy intake in rats (Green et al., 2017; Moser et al., 2015; Patisaul et al., 2013). Several epidemiological studies investigating the associations of gestational OPEs exposure with birth size (Feng et al., 2016; Hoffman et al., 2018; Kuiper et al., 2020; Luo et al. 2020, 2021) have yielded inconsistent results. Gestational exposure to individual OPE metabolites or their mixtures was shown to be associated with lower birth weight and the risk of being large-for-gestational age (Bommarito et al., 2021; Luo et al. 2020, 2021). Another study found that gestational OPEs exposure could affect infants’ weight and waist circumference (WC) during the first 6 weeks of life, and the effects were sex-specific (Crawford et al., 2020). However, null associations of OPEs exposure with birth weight have also been reported (Crawford et al., 2020; Hoffman et al., 2018; Kuiper et al., 2020). To our knowledge, no studies have investigated the long-term effects of gestational OPEs exposure on childhood adiposity measures.

Maternal nutritional resources play an important role in the growth and development of offspring in early life. Accumulating evidence suggested that the effects of gestational environmental pollutants exposure may be modified by maternal dietary factors (e.g. fruit and vegetable intake, fat intake, fish consumption, and vitamin D intake) (Gennings et al., 2020; Guxens et al., 2012; Somm et al., 2009). Breast milk represents the optimal nutritional form of feeding for infants and contains high levels of macronutrients, micronutrients, and bioactive factors, which may reduce oxidative stress and inflammation that may be associated with the development of obesity (Andreas et al., 2015). Additionally, breastfeeding is a key factor that may drive the transition of infants' gut microbiota in the first months of life, which can modulate energy homeostasis and adiposity (Petraroli et al., 2021). Furthermore, previous studies have shown that gestational OPEs exposure can induce oxidative stress (Wang et al., 2015) and disturb gut microbiota (Wang et al., 2019) in animals. Thus, breastfeeding may confer developmental benefits and act as a potential effect modifier. While previous studies have shown that adequate breastfeeding may protect against the adverse impacts of gestational environmental pollutants exposure on children's health (Guxens et al., 2012; Lertxundi et al., 2015), no study has investigated the potential effect modification by breastfeeding on the associations of OPEs exposure with childhood obesity.

This study aimed to investigate the associations of gestational OPEs exposure with adiposity measures in children from birth to 6 years of age, and the potential effect modification by breastfeeding on these associations in a birth cohort study.