Maternal serum bisphenol A levels and risk of pre-eclampsia: a nested case–control study

Abstract

BackgroundAlthough recent studies have indicated the potential adverse effects of maternal bisphenol A (BPA) exposure on pregnancy such as increasing the risk of pre-eclampsia, epidemiological evidence is limited. We aimed to evaluate the relationship between maternal BPA exposure and the risk of pre-eclampsia. MethodsWe conducted a nested case–control study among 173 women (74 cases of pre-eclampsia and 99 controls). BPA concentrations were measured using liquid chromatography-mass spectrometry in the maternal serum samples collected during 16–20 gestational weeks. Multivariate logistic models were used to examine the relationship between maternal serum BPA concentrations and the risk of pre-eclampsia. ResultsBPA was detectable (>0.1 µg/l) in 78.6% of the maternal serum samples at three levels: low (<2.24 µg/l), medium (2.24-4.44 µg/l), and high (>4.44 µg/l). BPA concentrations were significantly higher in the serum samples collected from the pre-eclampsia cases than those from controls (median: 3.40 vs. 1.50 µg/l, P < 0.01). With adjustment for maternal age, primiparous and BMI, the odds of developing pre-eclampsia were significantly elevated in subjects with high serum BPA levels compared with those with low levels (adjusted OR = 16.46, 95%CI = 5.42–49.85) regardless of subcategories of pre-eclampsia including severity and onset time. Among the pre-eclampsia subjects, the maternal serum concentration of BPA was not different between the early- and late-onset subjects (median: 3.09 vs. 3.50 µg/l, P = 0.57), but surprisingly higher in mild pre-eclampsia subjects compared with severe pre-eclampsia subjects (median: 5.20 vs. 1.80 µg/l, P < 0.01). ConclusionsThese results demonstrated that maternal exposure to high level of BPA could be associated with an increased risk of pre-eclampsia.

The role of epigenetic changes in preeclampsia

“…Previous studies showed that BPA exposure affects placental angiogenesis and morphology in mice . Studies have demonstrated a positive correlation between risk of PE‐like features such as disruption of the circulation or hypertension and maternal exposure to BPA and also studies have proven altered global DNA methylation levels in mice placentas of BPA exposed . WNTs signaling has an important role in trophoblast invasion but BPA exposure during pregnancy prevented placental spiral artery remodeling and trophoblast invasion .…”

Oestrogenic Endocrine Disruptors in the Placenta and the Fetus

“…During this period, hormone and protein levels will change and balance as cells begin to grow and differentiate. When EDCs are transferred into the fetus through the placenta, the equilibrium state of the hormonal environment will be broken, due to the sensitivity of the immature fetus to EDCs, resulting in miscarriage, fetal growth retardation, and preeclampsia [10][11][12].…”

Bisphenol A exposure alters placentation and causes preeclampsia‐like features in pregnant mice involved in reprogramming of DNA methylation ofWNT2

“…BPA is detectable in the urine, serum, and placental tissues of pregnant women (11). Epidemiologic studies have reported a positive association between maternal exposure to BPA and the risk of preeclampsia (9,10,13). BPA exposure also affects placental morphology and angiogenesis during early pregnancy in mice (7), and the WNT2 signaling pathway may be involved (7).…”

“…Epigenetic regulation is vital during placental development, and abnormal epigenetic regulation in the placenta is associated with preeclampsia (15). Although mounting data suggest a positive correlation between BPA exposure and preeclampsia (6,7,9,10,13), evidence confirming a causal relationship is currently unavailable.…”