Bisphenols and Preterm Birth: What a New Study Shows and Why Doctors Should Consider Anemia

Environment International published a study by a Chinese cohort that linked prenatal exposure to bisphenols (BPs) to the risk of preterm birth (PTB) and specifically tested whether maternal anemia increased this risk. Unlike many previous papers, the authors measured BPA levels in each trimester and analyzed not only single substances but also mixtures (q-gcomp, WQS, BKMR), and also identified critical windows of vulnerability using GEE models. The results: certain BPA analogs are associated with increased odds of PTB, with anemia in the third trimester significantly enhancing this effect.

Background of the study

Bisphenols (BPA and its "replacements"—BPAF, BPB, BPP, etc.)—are a class of ubiquitous monomers used in polycarbonates and epoxy resins, which are used to make food packaging, can linings, bottles, and thermal paper. These compounds can migrate into food and drink and are almost universally detected in the urine of pregnant women, so the focus of research is shifting from BPA alone to a mixture of analogs and to the sensitive windows of fetal development. Against this backdrop, the European Food Safety Authority (EFSA) in 2023 sharply tightened the permissible daily intake of BPA to 0.2 ng/kg body weight per day, citing concerns about typical dietary exposure levels; this has intensified the debate about the risks of BPA "analogs," which often come packaged together.

Preterm birth remains a "silent emergency" globally: according to WHO and partners, approximately 13.4 million babies were born preterm in 2020 (approximately one in ten newborns), and complications of preterm birth are the leading cause of death in children under five. Global rates have shown little decline since the 2010s, prompting a search for manageable risk factors, including chemical exposures during pregnancy and their combination with maternal conditions that can increase vulnerability.

One such risk modifier is anemia. According to WHO global monitoring, approximately 35% of pregnant women worldwide suffer from anemia (2023), with iron deficiency contributing significantly, but mixed causes (inflammation, vitamin deficiencies, and infections) are also common. Anemia is associated with tissue hypoxemia, oxidative stress, and impaired placental perfusion—mechanisms that could theoretically enhance the adverse effects of endocrine-active impurities, including bisphenols. Therefore, modern cohort studies are increasingly testing not only the direct association between chemicals and outcomes, but also their interactions with the mother's condition.

Finally, an important methodological shift in recent years has been the move away from single BPA measurements to repeated trimester-by-trimester analyses and mixture models (WQS, q-gcomp, BKMR), which allows for capturing real "windows of vulnerability" and accounting for the multi-chemical nature of exposures. Against this backdrop, a new study in Environment International examines prenatal exposure to a panel of bisphenols at different periods of pregnancy and tests whether maternal anemia modifies the strength of the association with preterm birth—a step toward a more practical, clinically relevant risk profile.

What exactly was found: "dangerous windows" and synergy with anemia

The study demonstrated a statistically significant association between exposure to certain BPs and the risk of preterm birth. In early pregnancy, BPAF (OR 1.222; 95% CI 1.006-1.486) and BPP (OR 1.454; 95% CI 1.054-2.007) were associated with preterm birth. For mid- and late pregnancy, BPB provided a "signal" (OR 1.651 and 1.952, respectively). Mixture analyses confirmed that higher total BP levels during these periods increased the odds of preterm birth. Most importantly, in the third trimester, a significant interaction was observed between BPB exposure and maternal anemia, both additively and multiplicatively, suggesting that anemia may synergistically increase the risk of preterm birth in the setting of BPB exposure.

Why this matters for clinical and policy

Preterm birth is a leading cause of neonatal morbidity and mortality; even small shifts in risk at the population level translate into large "tails" of complications. The new study adds two practical insights: 1) it is necessary to look at trimesters individually rather than averaging pregnancy; 2) the mother's condition (here, anemia) can modify the effect of pollutants, and this should be taken into account when managing pregnancy and planning preventive measures. At the regulatory level, the context is also changing: in 2023, EFSA radically reduced the tolerable daily intake of BPA to 0.2 ng/kg body weight/day and recognized that current food contact poses a safety concern; in 2024, the European Commission supported a ban on BPA in food contact materials. The study on preterm births is not directly related to regulations, but it shows that, in addition to BPA, BPA analogs (BPAF, BPP, BPB) and mixtures require attention.

How it was done and where are the limits of confidence

This is a prospective cohort with multiple (by trimester) urine collections for bisphenol A panel and subsequent analysis of birth outcomes. For "single" associations, the authors used GLM, for the "window of vulnerability" - GEE, and for mixtures - q-gcomp, WQS, and BKMR, which increases the robustness of the results to the intercorrelation of BPs. However, this is an observational study: it identifies associations, not proves causality; residual confounding (diet, social factors, other endocrine disruptors) is possible. However, the overlapping signals across multiple methods and the identified effect modification by anemia make the findings clinically significant and fully applicable to risk counseling.

Key facts of the study

• Early trimester: PR association with BPAF (OR 1.222; CI 1.006-1.486) and BPP (OR 1.454; CI 1.054-2.007). Middle/late - with BPB (OR 1.651 and 1.952). Critical windows of the early and late periods were identified.
• Mixtures and synergy: Higher levels of BP mixtures increased the odds of PTD; in the third trimester, BPB × anemia interactions were observed on an additive and multiplicative scale.

What does this mean in practice (emphasis for doctors and pregnant women)

• Routine anemia screening and correction is not only about the mother's well-being: in the context of exposure to BPs, anemia can increase the risk of preterm delivery, especially in the third trimester.
• When counseling pregnant women, it's helpful to discuss ways to reduce exposure to bisphenols (containers/thermal paper/can varnish, etc.), especially in the early and late trimesters—periods of increased sensitivity. Context: EFSA's harsh conclusions on BPA and the EU's commitment to restrictions.

Next on the list: what scientists should check and what regulators should change

The authors carefully raise the bar for field studies: consider exposure time windows, mixtures, and modifying factors (anemia, micronutrient deficiencies, inflammatory conditions). For regulators and the industry, this is an argument to expand the scope from BPA to include analogs and real mixtures: consumers are often exposed not to a single substance, but to a whole "cocktail" of BPs, the sources of which range from packaging and thermal paper to household dust. In practice, this leads to stricter requirements for materials, labeling, and monitoring, as well as educational programs for expectant parents.

What can be done today (families and clinics)

• Diet and household: avoid heating food in plastic; prefer glass/steel/ceramic; do not store hot/fatty foods in plastic containers; minimize contact with thermal checks whenever possible; wash hands after handling paper/packaging; ventilate frequently and remove dust (some BPs migrate into the dust fraction). These measures should be especially strengthened in the first and third trimesters. (Risk-based recommendations in line with the conclusions of the article and the EFSA assessments on BPA.)
• Medical: Systematically identify and treat anemia; provide iron/folate supplementation as indicated, implement nutritional strategies, and monitor for intercurrent infections and conditions that may increase vulnerability to chemical exposure.

Result

A new article in Environment International shifts the conversation about "plastic" chemicals during pregnancy to a more precise language: which specific analogs, at what times, and under what maternal conditions pose the greatest risk. For clinicians, this means a dual focus: managing anemia and sensibly reducing exposure to BPs during the most sensitive windows. For regulators, this means paying attention to BPA analogs and formulas. And for expectant parents, this means a set of simple but effective solutions that fit into their daily routine and potentially reduce the risk of preterm birth. [*][*]

Source: Li Y.-L. etal. “Association between prenatal exposure to bisphenols and preterm birth: the interaction effect of anemia.” Environment International (online August 11, 2025), doi: 10.1016/j.envint.2025.109724.