# Maternal-Foetal Effects of Exposure to Bisphenol A: Outcomes and Long-Term Consequences
## 5 Maternal-Foetal Effects of BPA
### Foetal Immune System  
A study attempted to understand prenatal exposure to BPA, the cytokine response induced by toll-like receptors (involved in the innate immune system in newborns), and the association with infectious diseases in the first year of life [35]. The authors demonstrated a significant association between the concentration of BPA (0.33 ng/mL) in the umbilical cord blood and the response of tumour necrosis factor alpha (TNF-\(\alpha\)) and interleukin 6 (IL-6) stimulated by toll-like receptors. Although this exposure has been shown to play a role in the innate immune response in neonates, it has not been concluded that the risk of infection during the first-year increases [35]. To analyse BPA exposure and oxidative stress and inflammation in pregnancy, [PERSON] et al. recruited 482 pregnant women, from whom urine and blood samples were collected at four different timepoints [36]. Urine samples were  
Figure 3: Main changes caused by exposure to BPA in pregnant women and in foetal and post-natal development. The figure was created on PowerPoint version 2204 using pictures from BioRender. used to quantify BPA levels and biomarkers of oxidative stress (8-hydroxydeoxyguanosine and 8-isoprostane), while inflammatory biomarkers (C-reactive protein, IL-18, IL-6, IL-10 and TNF-\(\alpha\)) were measured in plasma. The results showed an association between maternal BPA exposure (1.32-1.38 ng/mL) and both oxidative stress and inflammation, considering the increased levels of 8-hydroxydeoxyguanosine, 8-isoprostane and IL-6 [36]. On the other hand, in a Canadian birth cohort gathering 1258 mother-child pairs, different biomarkers related to childhood allergy measured in umbilical cord blood were inversely related to maternal urinary BPA levels (mean 0.8-1.0 ug/L) [37]. Considering the increased prevalence of asthma and allergies in children over the last decades, several studies have investigated the possible role of EDCs in the development of these diseases. Specifically, maternal BPA exposure has been linked to an increased risk of asthma and respiratory diseases in children. Different epidemiological studies analysed BPA concentration in maternal urine during pregnancy and compared them with spirometry, cytokine detection and questionnaires data on respiratory and allergy status in children from 6 months to 22 years. Overall, although one of the studies was not in agreement, with no association found [38], the majority showed a positive association between maternal BPA levels (median 2.4 ug/g creatinine [39]; mean 1.5 ug/mL [40]; median 2.3 ug/mL [41]; 0.001-12.58 ug/L [42]) and asthma, wheeze and respiratory tract infections in children [39; 40; 41; 42]. Additionally, a sex-specific association is also demonstrated; however, [PERSON] et al. found this association for girls, while [PERSON] et al. found it for boys [41; 42]. These differences may be due to the age and origin of the participants, given that the study from [PERSON] et al. followed an Australian population up to the age of 22 years old, whereas [PERSON] and co-workers used data from eight European birth cohorts covering the ages of 7-11 years [41; 42]. In addition, other studies have shown no differences, so more studies are needed on this subject to clarify the sex-specific differences. Several in vitro studies have also been carried out. In 2014, [PERSON] and co-workers performed a culture of human placental chorionic villous explants to understand the role of BPA exposure on the placenta [43]. These were exposed directly to BPA and ethanol as control or to conditioned media from endometrial stromal cells from healthy human endometrium either exposed to BPA or control. Then, the culture medium was quantified for the proinflammatory cytokine macrophage migration inhibitory factor (MIF) and \(\beta\) subunit of human chorionic gonadotropin (\(\beta\)-hCG).