Research Abstract | Flavored E-Cigarettes Disrupt Placental Development and Pregnancy Outcomes Regardless of Nicotine Content

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2Firsts, August 29, 2025 —— Communications Medicine, a prestigious journal under Nature Portfolio, has published a new study entitled “Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine”. The paper was a collaborative effort between the Department of Obstetrics and Gynecology at Duke University School of Medicine and the Department of Cell Biology and Physiology at the University of North Carolina at Chapel Hill School of Medicine. It was co-authored by Margeaux W. Marbrey, Samuel M. Cripps, Rennica Huang, Bryan M. Kistner, Aanvi Somany, Elizabeth S. Douglas, and Kathleen M. Caron, and was released online on August 28, 2025.

The study examined the potential health risks of e-cigarette use during pregnancy. In recent years, approximately 15% of pregnant women in the United States and the United Kingdom have reported using e-cigarettes, often believing them to be safer alternatives to traditional cigarettes. However, besides nicotine, flavorings and other components in e-cigarettes may also affect pregnancy outcomes, an area where research remains limited. This study aimed to investigate how flavored e-cigarettes influence embryo implantation, fetal growth, and placental development during early pregnancy.

Researchers used a mouse model, exposing pregnant female mice to flavored e-cigarette aerosols with or without nicotine, and conducted assessments on gestational day 6.5 and 12.5. They examined embryo elongation, placental weight, gene expression changes, and indicators of early fetal demise, differentiating the effects of nicotine during pregnancy.

The experiment utilized the SciReq inExpose system with a Joyetech Mini device (65W, 250°C). The e-liquid used was a strawberry custard flavor (VapeTasia Killer Kustard Strawberry).

Main Findings and Conclusions

Nicotine-free flavored e-cigarettes:

• Abnormal accumulation of red blood cells at implantation sites was observed in the mouse model, signaling early fetal death or pregnancy disruption.
• Embryo elongation range was reduced, suggesting developmental delays or irregularities.

Nicotine-containing flavored e-cigarettes:

• The embryo-to-placenta weight ratio decreased significantly, indicating inadequate nutrient supply and increased risk of fetal growth restriction.
• Compared with the nicotine-free group, the nicotine group showed a lower embryo resorption rate (miscarriage rate), which may offer some protection but at the cost of restricted fetal development.

Sex-dependent changes in placental gene expression:

• Key developmental and stress-related genes (Hif1a, Ptgs2, Gpx2/3, Txnrd1, Mapk1) were downregulated differently depending on the sex of the placenta.
• Male and female fetuses exhibited different placental responses to e-cigarette exposure, suggesting varying levels of health risk based on fetal sex.

Study Conclusions

• Flavored e-cigarettes pose risks during pregnancy: nicotine-free versions may increase early miscarriage, while nicotine-containing versions may restrict fetal growth.
• Regardless of nicotine content, flavored e-cigarettes can adversely affect pregnancy.
• Flavoring agents themselves carry potential toxicity, comparable to nicotine.
• Multiple critical placental genes showed sex-specific downregulation under exposure, suggesting long-term health risks.
• E-cigarette exposure during pregnancy should not be considered a safe alternative.

Study Limitations

The paper noted several limitations:

• Findings were based on a mouse model and may not fully represent human pregnancy.
• The nicotine concentration used (6 mg/mL) was lower than that found in widely available disposable e-cigarettes (often up to 50 mg/mL), which means risks may have been underestimated.
• Long-term studies on human pregnancy outcomes are still needed.

Article Information

• Title: Flavored e-cigarettes modulate embryo development, fetal growth, and potentiate early fetal demise without nicotine
• Authors: Margeaux W. Marbrey, Samuel M. Cripps, Rennica Huang, Bryan M. Kistner, Aanvi Somany, Elizabeth S. Douglas, Kathleen M. Caron
• Publication Date: August 28, 2025
• Journal: Communications Medicine (Nature Portfolio)

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