Per- and Polyfluoroalkyl Substances and Twin Growth Discordance: New Insights from a Twin Birth Cohort Study

Prenatal exposure to per- and polyfluoroalkyl substances (PFASs) has been linked to adverse fetal growth and development. However, most evidence was generated based on the singleton pregnancy studies, whereas potential impact on twin fetuses remains largely unknown. This study aimed to explore the associations of prenatal PFAS exposure with the growth and developmental differences within twin pairs by investigating 162 twin newborns and their mothers and determining 19 PFASs in maternal serum during the first, second, and third trimesters and cord serum of twins. The results revealed that exposure to selected PFASs was significantly and positively associated with the within-pair differences in the birth weight or height. For example, maternal perfluorooctanoic acid (PFOA) exposure by a 1-unit increase was significantly associated with an increase of within-pair birth weight differences (% change = 40.57%, 95% CI: 28.58-53.68%). The negative impact of PFAS exposure on birth weight or height was more pronounced in the smaller fetuses as compared with the larger fetuses within each twin pair. The impact of PFAS exposure on within-pair growth and developmental differences also differed between those of the monozygotic (MZ) and dizygotic (DZ) twins. For example, the within-pair birth weight differences in the DZ twins (% change = 57.24%, 95% CI: 38.41-78.62%) attributable to intrauterine PFOA exposure exhibited a greater effect of percentage change than those in the MZ twins (% change = 21.27%, 95% CI: 5.13-39.89%). PFAS mixtures were found to be positively associated with birth weight and height differences within newborn twins with PFOA, perfluorodecanoic acid, perfluorooctanesulfonic acid, and perfluorononanoic acid as the major contributors to the outcomes. Our study provides epidemiological evidence for the first time on the potential influence of PFAS exposure on the within-pair growth and developmental differences.