The Intrauterine Exposome: A Scoping Review of the Evidence Chain from Maternal Exposure to Foetal Effect and Later-Life Health

The intrauterine exposome includes the external conditions and internal biological environment that influence the mother, placenta and foetus during pregnancy. It includes chemical, physical, biological, nutritional, psychosocial and social exposures, as well as the chemicals, metabolites, hormones, cytokines, immune signals and redox changes produced within the maternal-placental-fetal system. Although maternal exposure is a critical component, it does not inevitably result in fetal exposure since maternal metabolism, storage, clearance, placental transport, and chemical transformation all influence whether a substance reaches the foetus and in what form. Similarly, presence of a chemical in cord blood or fetal tissue does not prove that it has caused a fetal effect since the fetal response may depend on the dose, duration, timing, developmental stage, target tissue and genetic susceptibility. This review presents a two-domain framework consisting of the external intrauterine exposome and the internal intrauterine exposome as it follows a sequential evidence chain from maternal exposure to maternal internal dose, placental transfer, fetal internal exposure, fetal biological response and later developmental outcome. The review also examines how short-term, repeated and persistent exposures may act differently during implantation, organogenesis, mid-gestation, late gestation and the perinatal period. Evidence from tobacco smoke, per- and polyfluoroalkyl substances, air pollution, psychosocial stress, nutrition, maternal metabolic disease and microplastics is compared using the same framework. Human observational, interventional, and experimental evidence accessed, while molecular signatures, functional changes, and disease mechanisms should be distinguished. This method avoids conflating maternal exposure with fetal exposure or fetal effects and provides a clearer basis for assessing developmental programming within the intrauterine exposome. Maternal gut dysbiosis is also studied as a probable modifier through microbial metabolites, endotoxaemia and immune signalling. A decisive next study can address substantial evidence gaps and interpret whether maternal exposures directly cause biological changes and health outcomes. These studies can appropriately measure exposure timing and intensity, identify critical windows of risks, and guide clinical interventions.