They float through the air—sweet-smelling, thick plumes of vapor rising from sleek devices clutched by young hands. To many, vaping feels like a modern escape, a cleaner alternative to smoking, a harmless habit. Especially when there’s no nicotine. Especially when it’s marketed as “safe.” But inside a quiet laboratory, far from public view, a series of tiny skulls told a different story.
At The Ohio State University College of Medicine, a team of developmental biology researchers, led by Professor James Cray, has uncovered startling evidence that even nicotine-free e-cigarette vapor can alter fetal development—specifically, the shape and size of the skull. Published in the journal PLOS One, this study is the first of its kind in Australia or the United States to examine how common vaping liquids, stripped of their addictive core, still leave lasting marks on unborn life.
And what they found was as unsettling as it was unexpected.
Not All That’s Missing Is Safe
To understand the implications, we must first understand the design of the experiment. Cray and his team weren’t trying to prove vaping was dangerous. In fact, they were designing a control group—a kind of scientific “baseline”—for comparison with other mice exposed to nicotine during pregnancy. To do this, they exposed pregnant mice not to nicotine, but to two chemical liquids used in nearly all e-cigarette solutions: propylene glycol (PG) and vegetable glycerin (VG).
These substances are not fringe additives. They are the very foundation of vaping’s signature appeal: the smooth smoke-like clouds and that characteristic “throat hit.” They are also widely used in processed foods, pharmaceuticals, and cosmetics, which is one reason they’ve long flown under the radar in discussions about vaping risks.
Cray’s team exposed groups of pregnant mice to different concentrations: one group inhaled clean air; another inhaled a 50/50 PG/VG mix; the third was exposed to a mixture more common in so-called “safer” vape products—30% PG and 70% VG. This latter mixture, now widely used by vaping companies in an effort to reduce perceived harm, was expected to show fewer effects.
But it didn’t.
It showed more.
Small Skulls, Subtle Warnings
Two weeks after birth, the mouse pups underwent digital scanning to analyze their skulls with extraordinary precision. The results were striking. Pups born to mothers exposed to the 30/70 PG/VG vapor had narrower facial structures, shorter skulls, and lower birth weights compared to both the clean air group and those exposed to the 50/50 vapor mix.
These changes, though measured in millimeters, were not trivial. Cray described the pups as “globally narrower”—the facial structures, eye sockets, and overall cranial width were all affected. The skulls were subtly but consistently different. And these changes were statistically significant across multiple litters and both biological sexes.
“The 50/50 mixture had no dramatic statistical changes—and that’s where we were looking for the difference,” Cray said. “We thought heavier propylene glycol should be causing more effects, and it was the exact opposite.”
This reversal surprised the team. It was the glycerin-heavy formula—the one increasingly promoted as the “safe” or “gentle” choice—that produced the more dramatic outcomes. The chemical balance that had been shifted to soothe throats may also be quietly reshaping faces.
Beyond the Smoke: A Story of Timing
One of the most crucial facts in fetal development is timing. The formation of the skull, face, and neck occurs early in pregnancy—often before many people even realize they’re expecting. That timing makes the presence of any environmental disruption particularly dangerous.
And as Cray points out, “The majority of users are young adults and teenagers, so we are talking about people who are in peak reproductive years.” In other words, a college freshman taking puffs from a flavored vape pen may unknowingly be affecting not only her own health, but the biological blueprint of a child not yet imagined.
With 3% of babies in the United States born with birth defects annually—many of them involving the skull and facial region—this research is a red flag in a cloud of vapor. While cleft lips and palates are among the more visible conditions, more subtle cranial changes may go unnoticed until developmental or neurological concerns arise later in childhood.
Why Vaping Without Nicotine Still Matters
Public conversations around vaping have long focused on nicotine—its addictive power, its role in the teen vaping epidemic, its regulation by the FDA. But this study asks a deeper question: What if the delivery system itself carries risks, even when the addictive compound is gone?
Most e-cigarette liquids use PG and VG as base ingredients, regardless of flavor or nicotine content. These humectants are generally recognized as safe for eating, but inhalation is an entirely different route of exposure. The lungs are not the stomach. And once inhaled, these chemicals can cross the placental barrier, entering the developing fetal bloodstream.
“This had no nicotine, and it’s still having effects on the development of the skull in our model,” Cray said. “Which was not anything we expected.”
If these findings hold true in humans—and more research is urgently needed—they could reshape how we think about vaping in pregnancy. The assumption that nicotine-free means risk-free may not just be misguided; it may be dangerously false.
The Regulatory Battle in the Background
As scientific discoveries emerge, the legal and political backdrop continues to shift. The U.S. Food and Drug Administration has attempted to curb the rapid rise of e-cigarettes, particularly among teens, but it faces legal resistance from powerful industry players. In June 2024, the Supreme Court made it easier for vape companies to sue the FDA over blocked products. A previous April ruling had upheld the FDA’s ban on sweet-flavored e-cigarettes, a major contributor to the surge in adolescent use.
But while the regulatory fights drag on, the chemicals continue to circulate.
And while headlines focus on nicotine’s addictive grip, studies like Cray’s illuminate a quieter threat: one that operates on a cellular level, before birth, altering the architecture of life before it even begins.
A Call for Caution, Not Panic
Cray is the first to caution against overgeneralizing from a single mouse study. Mice are not humans. Facial growth patterns, metabolism, and pregnancy timelines differ. But in developmental biology, mice are often the first clue—a whisper from nature that demands further listening.
“This is a small study that speaks to the possibility that nicotine-free vaping is not safe,” Cray emphasized. “And it’s a sign that we probably should study nicotine-free products as much as we study the nicotine-laden products.”
The findings don’t call for alarm, but they do demand curiosity. How many people vaping today are unknowingly taking risks tomorrow’s research will reveal? How many developing lives might be nudged, reshaped, or disrupted before their stories have even begun?
The Unseen Legacy of Vapor
It’s easy to think of vaping as an individual act. One person, one habit, one moment of stress relief or peer pressure. But when the plume fades, what remains?
In this study, it’s the subtle narrowing of a skull. The few grams missing from birth weight. The molecular traces of exposure, whispered through bone.
For the young and the unborn, for those making choices in their teens without knowing the consequences—it’s a reminder that our habits are not invisible. They carry forward. Into tissue. Into shape. Into future generations.
And if something as small as the ratio of two colorless liquids can bend the structure of a skull, then perhaps it’s time we reexamine what we call safe. Not based on flavor or throat feel, but on the truths our biology is beginning to reveal.
More information: Ethan Richlak et al, In utero exposure to electronic cigarette carriers alters craniofacial morphology, PLOS One (2025). DOI: 10.1371/journal.pone.0327190