In a case-control study, researchers measured levels of bisphenol A (BPA) in 2 sets of pregnant women—those with a diagnosis of fetal malformation and those without. Surprisingly, the women with healthy fetuses demonstrated higher rates of conjugated BPA, which may indicate that women who metabolize BPA poorly are more likely to have fetuses with developmental defects.
This paper is part of our Environmental Medicine Special Issue. Read the entire issue below.
Reference
Guida M, Troisi J, Ciccone C, et al. Bisphenol A and congenital developmental defects in humans. Mutat Res. 2015 Apr;774:33-39. Epub 2015 Mar 6.
Design
Case-control study
Participants
One hundred fifty-one pregnant women were divided into 2 groups: the case group (n=101) consisted of women with established diagnosis of fetal malformation and the control group (n=50) consisted of women who visited the hospital during routine evaluations.
Study Intervention
Total, free, and conjugated bisphenol A (BPA) levels were measured in participants’ blood using gas chromatography–mass spectrometry with isotropic dilution.
Key Findings
The average value of free BPA was nearly 3 times greater in the cases of chromosomal malformations and nearly 2 times greater in cases of central and peripheral nervous system nonchromosomal malformations compared to controls. Conjugated BPA levels, which were higher in the control group, support the hypothesis that a reduced ability to metabolize the chemical in the mother can lead to the occurrence of malformation in the fetus.
Practice Implications
Various studies point to BPA as an endocrine-disruptor that interferes with the programming of complex endocrine pathways during in utero and early childhood development.1-3 This is one of the first studies conducted in humans to explore the correlation between maternal blood BPA and fetal malformations. The most interesting observation from the study is that the control group with normally developed fetuses had higher levels of BPA conjugate compared to the case group of women with malformed fetuses. This finding reflects the ability of the control group to metabolize BPA to its inert form. The conjugated forms of BPA do not have endocrine-like activity and do not alter the biological processes of fetal development. Nonconjugated BPA binds to plasma proteins and interferes with the endocrine system, leading to fetal malformations.
A study conducted by Matsumoto et al in 2002 on BPA pharmacokinetics demonstrated that the end result of BPA metabolism is eliminated via the kidneys as a water-soluble formation of BPA-glucuronide occurring via hepatic glucuronosyltransferase (GT).4 Another metabolite of BPA can occur, to a lesser degree, by sulfotransferase, resulting in the formation of BPA-sulfate. Hepatic GT activity is dependent on age and is much lower in fetuses and neonates.5 The major route of BPA metabolism in fetuses and neonates is via sulfation.6,7
Another focus in preconception care and infertility evaluation needs to be placed on identifying how well a woman can adequately clear toxicant exposures.
This study clearly illustrates the environmental medicine concept of total body burden. The accumulation of toxicant load over time predisposes individuals to be more susceptible to chronic illnesses and diseases. Reports of decreased fertility over the last decade can be attributed to long-term exposure to BPA, which has been linked to decreases in the percentage of oocytes that develop during meiosis II.8,9 The mechanism of action of BPA on oocytes remains unknown. From the study’s findings, the authors hypothesize the reduced ability to metabolize BPA may predispose a woman to pregnancies with fetal chromosomal abnormalities. These women can be classified as “poor metabolizers” who were more susceptible to the endocrine disruption of BPA. The results of the study also confirm the correlation between blood concentrations of total BPA in women with fetuses that had chromosomal abnormality compared to women with normally developed fetuses, as demonstrated by Yamada et al.10
It is imperative that clinicians educate patients on sources of BPA exposure to reduce or eliminate exposure for potential harm. Exposure to BPA is ubiquitous: the substance is found in plastics, linings of cans for food and beverages, thermal receipts, dental sealants, and self-adhesive labels, among several sources.11 A significant finding of this study highlights that those with normal biotransformation processes or ability to detoxify do not seem to exhibit the same deleterious effects of BPA as those who do are not able to clear exogenous compounds as well. Another focus in preconception care and infertility evaluation needs to be placed on identifying how well a woman can adequately clear toxicant exposures.
Nutrients provided to patients prior to conception should focus on all aspects of biotransformation, especially on hepatic GT activity to improve clearance of BPA to its nonactive forms and prevent harm to the developing fetus. Another note to emphasize is that BPA substitutes bisphenol-S (BPS) and bisphenol-F (BPF) can also have the same endocrine-disrupting effects as BPA since they are as hormonally active.12 BPS and BPF can be found in the same sources as BPA—personal care products, paper products, and food.
This study is a wake-up call to the role of BPA exposure on fetal development and human reproduction. Further exploration is warranted to determine its effects, if any, on male fertility and contribution to fetal malformation.
