Postpartum depression (PPD) is a common complication associated with childbirth (Meltzer-Brody et al., 2017). Globally, approximately one in five perinatal women are affected by PPD (Wang et al., 2021), and its prevalence is higher in countries with lower socio-economic status (Roddy Mitchell et al., 2023). Women who experience depressive symptoms during the postpartum period may face many issues, including marital conflict (Asselmann et al., 2016), suicide (Johannsen et al., 2020), sleep disturbances (Park et al., 2013), and unhealthy habits and behaviors (e.g., alcohol and drug abuse) (Stewart et al., 2023). Moreover, maternal PPD can have negative impacts on their offspring. Children of depressed mothers are at increased risks for atypical development (Rogers et al., 2020), cognitive impairment (Sanger et al., 2015), emotional and behavioral problems (Dachew et al., 2021; Orri et al., 2021), as well as impaired interactions with their peers and family members (Burtchen et al., 2022). Therefore, recognizing and understanding the risk factors associated with PPD is a crucial priority in public health.

While the exact causes of PPD remain largely unclear, hormonal fluctuations during and after pregnancy have been widely acknowledged to play a significant role in the pathophysiology of depression (Payne and Maguire, 2019). Environmental chemicals that act as endocrine disruptors may contribute to the development of PPD by disrupting the dopamine system and hypothalamic-pituitary-adrenal (HPA) axis (Vuong et al., 2020). Environmental endocrine disruptor poly- and perfluoroalkyl substances (PFAS) are commonly used in various industrial and commercial products (Glenn et al., 2021). Humans are widely exposed to PFAS through ingestion of contaminated water and food, as well as inhalation of indoor dust (Poothong et al., 2020). Despite PFAS (e.g., perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS)) gradually being phased out worldwide, they can still be detected in all blood samples from pregnant women (Manzano-Salgado et al., 2017; Ouidir et al., 2020; Tian et al., 2018). Increasing concerns are thus arising about the potential toxic effects of PFAS exposure during the vulnerable time period prior to the onset of affective illness.

Toxicological studies suggest that PFAS can disrupt neuro-dopamine and steroid hormone homeostasis, interfere with the activities of tyrosine hydroxylase, and alter expression of dopamine transporter and receptor (Di Nisio et al., 2022; Grønnestad et al., 2021a, 2021b). However, the associations between prenatal exposure to PFAS and PPD have not yet been thoroughly investigated in epidemiological studies. To date, only two cohort studies of women delivering singletons have examined the associations of prenatal exposure to PFAS on maternal PPD, but the results are mixed due to the differences in study population and depression assessment scales (Vuong et al., 2020; Wang et al., 2023). Comparing to delivering singletons, women delivering twins are more likely to experience preterm delivery, neonatal intensive care unit (NICU) admission, higher rates of maternal, fetal, and infant mortality and morbidity (Committee on Practice Bulletins—Obstetrics; Society for Maternal–Fetal Medicine, 2016; Lewkowitz et al., 2021). Mothers with twin pregnancies therefore have a higher rate of PPD compared to those with singleton pregnancies (Wenze et al., 2015). Singleton studies conducted in Japan, Brazil and the USA have observed adverse effects of prenatal PFAS exposure on fetal growth (Kashino et al., 2020; Souza et al., 2020; Starling et al., 2019). We hypothesize that twin pregnancies may increase maternal vulnerability to various risk factors, including environmental endocrine disruptors such as PFAS.

However, no study has investigated the associations between prenatal PFAS exposure and PPD risk in this specific population of women pregnant with twins. Moreover, while several PFAS have relatively long half-lives, maternal PFAS concentrations during pregnancy were found to vary greatly, with the highest concentrations observed at early pregnancy (Fisher et al., 2016; Mamsen et al., 2019). Few studies have determined PFAS concentrations in different trimesters. Therefore, we determined the concentrations of PFAS in plasma samples collected in each trimester from women pregnant with twins and estimated the associations between prenatal PFAS exposure, either individually or in mixture, and the risk of PPD in women with twin pregnancies.