Two recently published reviews and two research studies have analyzed the effects of exposure to different endocrine disrupting chemicals (EDCs) during pregnancy. The two review articles focused on bisphenol A (BPA, CAS 80-05-07) in epidemiological studies, and the two research studies, presented at the ENDO 2021 conference, investigated the impacts of synthetic progesterone 17-alpha hydroxyprogesterone caproate (17-OHPC, CAS 630-56-8) and propylparaben (CAS 94-13-3) exposure.
The article published on June 8, 2021, in the peer-reviewed journal Ecotoxicology and Environmental Safety by Asmagvl Namat from the Huazhong University of Science and Technology, Wuhan, China, and colleagues evaluated the relationship between BPA exposure during pregnancy and preterm birth as well as changes in gestational age by combining a systematic review with a meta-analysis.
The scientists searched PubMed, OVID, and Web of Science for human biomonitoring studies on BPA and preterm birth and/or gestational age published between 2008 and June 2020. Of the 668 found references, seven studies on preterm birth and nine on gestational age were identified that fulfilled the set of pre-defined criteria for inclusion, were rated as high quality, and were used for subsequent meta- and subgroup analyses. The studies on preterm birth and gestational age included 3565 and 4983 pregnant women, respectively. Maternal urinary BPA (median or geometric mean) measured in the included studies was between 0.48 and 6.44 ng/mL. The meta-analysis identified that the risk of preterm birth increases and length of gestational age decreases (by 0.5 days) with higher BPA exposure of pregnant women. A significant association between maternal urinary BPA and premature birth was only found for women assessed in the third trimester of pregnancy. Exposure in that period also led to the strongest decrease in gestational age by 1.36 days. This suggests that women pregnant in the third trimester might be most susceptible to BPA exposure. The findings “may help researchers identify women at risk of preterm birth during pregnancy to provide targeted interventions.” The motivation of Namat et al. to conduct the study was to shed light on the controversial associations between BPA exposure of pregnant women and the risk of preterm birth (FPF reported and here) and changes in gestational age.
In a systematic review published on July 15, 2021, in the journal Nutrients, Nikolaos Vrachnis from the National and Kapodistrian University of Athens, Greece, and co-authors investigated the association of BPA exposure during pregnancy and fetal growth. They searched the PubMed and Cochrane databases for epidemiological studies that measured BPA during pregnancy or delivery in at least one biological sample and provided birth weight, and they identified 25 relevant studies published until September 2019. While three studies associated BPA exposure with increased fetal growth, nine associated it with reduced fetal growth. The findings of another two studies were contradicting (FPF reported), and eleven did not show any relationship. The authors conclude that “there is mounting evidence that combined exposure to BPA from dietary and non-dietary sources during pregnancy may contribute to abnormal fetal growth; a tendency towards fetal growth restriction was shown, especially when exposure occurs during the first half” of pregnancy. However, they also highlighted that due to the contradicting results of the evaluated studies further research is necessary to fully evaluate the role of BPA in fetal growth.
Caitlin Murphy, assistant professor at the University of Texas Southwestern Medical Center in Dallas, US, and their team studied the relationship between exposure to the synthetic progesterone 17-OHPC and pregnancy and presented their results at the ENDO 2021 conference, as Endocrine News reported. For their analysis, Murphy and colleagues used the data from the Child Health and Development Studies conducted between 1959 and 1967 with women receiving prenatal care and linked it to cancers diagnosed in the adult children of the study as identified by the California Cancer Registry in 2018. The researchers found that intake of the drug 17-OHCP by pregnant women to prevent miscarriage can double the cancer risk of their offspring by causing endocrine disruption during early fetal development. Many different cancers can occur, but the risk for colorectal cancer and prostate cancers are particularly elevated by being five- and three-times higher in exposed compared to non-exposed individuals, respectively. Murphy said that their study “presents really compelling evidence that events and exposures that happen during critical periods of growth and development really matter for your risk of developing cancer many decades later.”
Although in October 2020 the US Food and Drug Administration (FDA) proposed to withdraw 17-OHCP from the market, the chemical is still prescribed to women susceptible for preterm birth under the trade name Mekana. “There’s controversy in that some people are observing that this drug does have a benefit,” Murphy stated, “but when we look at the randomized trials, clearly there is none. Something needs to be done to reconcile the mixed evidence.”
Another presenter at ENDO 2021, Laura N. Vandenberg from the University of Massachusetts, Amherst, US, shared the findings from the research she and her co-authors conducted on pregnant mice to examine impacts of propylparaben (e.g., used in personal care and baby products) exposure during pregnancy and lactation. The study, with Joshua P. Mogus as the lead author, was published in the peer-reviewed journal Endocrinology in March 2021. The researchers exposed mouse dams from day 0 of pregnancy to day 21 of lactation to 0, 20, 100, or 10 000 µg propylparaben/kg/day and assessed mammary glands five weeks post-involution. Propylparaben exposure affected the thickness of periductal collagen and immune cell populations, increased epithelial cell proliferation, and reduced the volume of mammary epithelium. The study outcomes “suggest that propylparaben, at levels relevant to human exposure, can interfere with the effects of parity on the mouse mammary gland and induce long-term alterations to mammary gland structure.” According to the authors, further research is needed “to understand whether propylparaben can undermine the protective effects of parity against breast cancer.” In March 2020, the Canadian government published a draft screening assessment for seven parabens and found propylparaben to be at present a danger to human health or the environment at current levels of exposure (FPF reported).
Ann M. Vuong from the University of Nevada Las Vegas, US, and co-authors also investigated the effects of EDCs on pregnant women but with a focus on cardiometabolic indices. The study was published on June 28, 2021, in Environment International. For their analyses, the researchers used urine levels of BPA and phthalate metabolites at 16 and 26 weeks’ gestation and the polybrominated diphenyl ethers (PBDEs) and per- and polyfluoroalkyl substances (PFAS) levels in serum at 16 weeks’ gestation of 388 pregnant women from the Health Outcomes and Measures of the Environment (HOME) study (FPF reported). They performed regression analyses to estimate associations with cardiometabolic indices including blood pressure, lipids, and glucose. The authors reported that PBDEs were associated with higher glucose and cholesterol levels during pregnancy, while with increasing concentrations of some phthalate metabolites cholesterol levels were lower. For BPA and PFAS, they did not observe any relationship with the assessed cardiometabolic indices. During pregnancy, women are considered particularly sensitive to cardiometabolic health impacts since metabolic changes, epigenetic programming, and marketed cellular proliferation occur in that period.
Recently, scientists of another research study considered that a web-based behavioral intervention can reduce exposure of mothers with young children to BPA, propylparaben, and other EDCs (FPF reported).
Namat, A. et al. (2021). „Association of BPA exposure during pregnancy with risk of preterm birth and changes in gestational age: A meta-analysis and systematic review.” Ecotoxicology and Environmental Safety. DOI: 10.1016/j.ecoenv.2021.112400
Vrachnis, N. et al. (2021). “A Systematic Review of Bisphenol A from Dietary and Non-Dietary Sources during Pregnancy and Its Possible Connection with Fetal Growth Restriction: Investigating Its Potential Effects and the Window of Fetal Vulnerability.” Nutrients. DOI: 10.3390/nu13072426
Mogus, J. P. et al. (2021). „Exposure to Propylparaben During Pregnancy and Lactation Induces Long-Term Alterations to the Mammary Gland in Mice.” Endocrinology. DOI: 10.1210/endocr/bqab041
Vuong A. M. et al. (2021): “Exposure to endocrine disrupting chemicals (EDCs) and cardiometabolic indices during pregnancy: The HOME Study.” Environment International. DOI: 10.1016/j.envint.2021.106747
Kelly Horvath (July 2021). “Mother and Child: Pregnancy Exposures Can Have Unintended Effects in Later Life for Both Offspring and Mother.” Endocrine News
Lee, Y. et al. (2021). “Early postnatal exposure to di(2-ethylhexyl) phthalate causes sex-specific disruption of gonadal development in pigs.” Reproductive Toxicity. DOI: 10.1016/j.reprotox.2021.08.004