Vaping for two: unravelling the mysteries of E‐cigarettes and fetal vascular health

The negative impact of cigarettes on the health of the developing fetus was first recognized by Simpson (1957). Since then, our understanding of the adverse impacts of smoking on fetal health has grown to include fetal growth restriction and preterm birth, in addition to organ-specific pathology in the lungs (chronic bronchitis and asthma), heart (hypertension and atherosclerosis) and brain (increased risk of poor neurodevelopmental outcomes). Cigarette smoking during pregnancy causes profound neuropathology, including abnormalities in brain structure, reduced cortical thickness and altered neurotransmitter release that are evident from birth (Slotkin et al., 2011). Awareness of the overwhelmingly devastating impacts of cigarettes on the health of an individual and for both the mother and fetus during pregnancy has led to the implementation of regulations, health warnings, advertising restrictions and taxation to reduce smoking rates for the first time in history. In turn, the highly regulated consumption of cigarettes has prompted the tobacco industry to diversify into smokeless tobacco products. The emergence of E-cigarette devices occurred in 2003, initially intended for use as a product to help quit smoking. E-cigarettes, which deliver nicotine through aerosolized vapour rather than smoke, were then marketed as a smoking cessation aid and rapidly gained popularity. Since then, the uptake of E-cigarettes has increased rapidly, particularly for a younger demographic of previous non-smokers looking for a less harmful alternative to smoking. Current data indicate that 19−32% of people of reproductive age are using E-cigarettes and, in women of reproductive age, between 4 and 10% are daily users (Scully et al., 2023). Worryingly, the highest prevalence of individuals who use E-cigarettes are those of childbearing age. Unsurprisingly and concerningly, data are now emerging that E-cigarettes are as harmful, if not more harmful, than their cigarette predecessor. Conventional cigarettes contain tobacco and ≤600 other ingredients, whereas E-cigarettes have a unique composition of propylene glycol, vegetable glycerine, formaldehyde, acrolein, flavouring chemicals, heavy metals and other trace elements. They may or may not contain nicotine. In this issue of The Journal of Physiology, Mills et al. (2024) report a significant step forwards in our understanding of the potential harm of E-cigarettes on the developing fetus. Using a model of rat pregnancy, Mills and colleagues exposed female rats to a whole-body chamber containing the base mixture upon which flavourings or tobacco are typically added to E-cigarettes, i.e. vegetable glycerol and propylene glycol. The study aimed to examine the timing of E-cigarette exposure on vascular and behavioural outcomes. The different periods of exposure examined included preconception, the first third of gestation, the second third of gestation, the final third of gestation or exposure throughout gestation, and different wattages of E-cigarettes. The different wattages of E-cigarette used refer to the heat generated to produce the vapour, with low wattage delivering less intense flavour and using less power. In contrast, high wattage uses high power and creates an intense flavour. In this study, the authors chose to test only the impact of the base liquid products in the absence of nicotine. A recent study showed that 66% of E-cigarette use was nicotine free in those approaching reproductive age (Tokle et al., 2022). Therefore, the authors of this study assessed an essential demographic of E-cigarette users. Exposure to E-cigarettes throughout gestation impacted fetal weight, pup survival and cerebral vascular function. Mills et al. (2024) showed worsening effects in the following conditions: (i) when exposure occurred later in pregnancy; (ii) with longer exposure; and (iii) with increased wattage of the E-cigarette. The researchers expanded the findings to explore postnatal neurological outcomes, finding increased anxiety-like behaviours and poor locomotor activity of the offspring at 3 and 6 months postnatal age (the latter time point being of particular importance, given that this is when rats are considered socially mature), suggesting long-term implications for neurological function following non-nicotine E-cigarette use. An early narrative review of neuropathological outcomes of E-cigarette use (Sailer et al., 2019) showed evidence in in vitro experimentation that vapour fluid was neurotoxic, while preclinical studies showed altered gene expression, poor memory and cognition and hyperactive behaviours. Mills et al. (2024) also provide the first evidence that E-cigarette exposure in the preconception era does not appear to impact fetal growth, middle cerebral vascular function or behavioural outcomes. The findings of Mills et al. (2024) add growing weight to the calls to recommend cessation of E-cigarette use before conception. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. No competing interests declared. Sole author. DHAC | National Health and Medical Research Council (NHMRC): Beth J. Allison, 1175843. Open access publishing facilitated by Monash University, as part of the Wiley - Monash University agreement via the Council of Australian University Librarians.