Special issue on “Developmental effects of smoking, vaping, and cannabis use”

Despite many years and dollars spent on public education to expose the dangers of tobacco smoking and second-hand smoke, smoking persists. Not only that, we now worry about the potential dangers of third-hand smoke (the residue left on surfaces where smoking has occurred), devices offering new ways to smoke (vaping) and the legalization and resultant expansion of the many ways to use cannabis. New research is expanding the vast literature on, and revealing new adverse effects of exposure to tobacco smoke during pregnancy, while nascent research on vaping and cannabis use in pregnancy is just beginning to emerge. Vaping and cannabis are perceived by many to be safe for use in pregnancy, but public health and medical organizations have issued strong warnings against both. This special issue presents focused reviews that lay out what we know about some of the effects of these exposures during pregnancy and the vulnerable adolescent years (Figure 1), and the diverse approaches used to elucidate these effects.

FIGURE 1.

Old, new, and growing habits present known and potential hazards to prenatal and postnatal human development. Our understanding of the wide range of adverse effects of tobacco smoke and nicotine continues to grow, while the full risks of vaping and cannabis use remain to be elucidated

We have known for decades that tobacco smoke is a human developmental toxicant and teratogen, and new knowledge continues to emerge about the adverse effects of tobacco smoke on the outcome of pregnancy. We now understand that, in addition to maternal smoking, exposure of pregnant women to second-hand smoke is also developmentally toxic, as is periconceptual paternal smoking. Seven U.S. Surgeon General’s Reports since 1964 have addressed the effects of tobacco smoke on pregnancy, the latest of which finds a causal link between maternal smoking and orofacial clefts in offspring and suggestive causal links to clubfoot, gastroschisis and atrial septal defects (USDHHS, 2014). The range of known adverse effects and targets of tobacco smoke exposure during development continues to expand. Surprising links between maternal tobacco smoke exposure during pregnancy and elevated risk of obesity in adolescent offspring (Rogers, in this issue) probably represent the strongest evidence in humans that developmental exposure to environmental chemicals can raise the risk of obesity later in life, and such chemicals have been termed “obesogens” (Janesick & Blumberg, 2016).

Nicotine, one of the thousands of chemicals present in tobacco smoke as well as an active ingredient in most electronic cigarettes (also known as Electronic Nicotine Delivery Systems or ENDS) is known to be toxic to the developing brain from studies in both humans and laboratory animals (Hawkey et al., in this issue). Nicotine is also toxic to other developing organs including the lung. Strikingly, studies in rodents suggest that the effects of nicotine can be passed on to future generations even without continued exposure (Kuniyoshi & Rehan, in this issue).

The use of ENDS is increasing rapidly with new devices, flavors, and formulations being introduced to the market. Initially appearing around 2007, ENDS have been the most commonly used tobacco-related product among young people in the United States since 2014. Usage increased 78% among high school students between 2017 and 2018. New ENDS products look like USB thumb drives, the most popular brand being JUUL, which always contains nicotine, and which has increased in sales by 600% in 1 year (https://www.cdc.gov/tobacco/basic_information/e-cigarettes/surgeon-general-advisory/index.html). The level of nicotine in electronic cigarette fluids is variable and can be zero or quite high. Fluids are available that have only flavorings and carrier liquid, but recent reports indicate that these can still cause serious health effects. A new study in human volunteers demonstrates that vaping e-liquids, even those that do not contain nicotine, can have acute effects on the vascular endothelium, reducing peak blood flow velocity and luminal flow-mediated dilation in the superficial femoral artery and vein (Caporale et al., 2019). If such changes were to occur in the uteroplacental circulation of pregnant women, dangerous hypoxic conditions could occur for the embryo/fetus. Further, there have been several recent reports of serious lung damage among young ENDS users, prompting an investigation by CDC: https://www.huffpost.com/entry/severe-lung-illness-vaping-nicotine-thc-cdc_n_5d5b6ec4e4b0f667ed679101. The JUUL brand ENDS has among the highest concentrations of nicotine, with one JUUL pod estimated to contain as much nicotine as a pack of tobacco cigarettes. Breland, McCubbin, and Ashford (in this issue) discuss the current products available and patterns of usage, especially among adolescents and perceptions about safety for use in pregnancy. Then, what is currently known about the developmental toxicity of ENDS is reviewed by Greene and Pisano (in this issue).

Cannabis legalization continues to expand in the U.S., providing legal and easy access to a growing proportion of the population, including pregnant women. While possession of cannabis is illegal under U.S. federal law, medical use of cannabis is legal in 33 states, four of five U.S. territories and Washington, DC. Recreational use of cannabis is now legal in 11 states and Washington, DC, Guam and the Mariana Islands, and another 15 states have decriminalized use (https://en.wikipedia.org/wiki/Legality_of_cannabis_by_U.S._jurisdiction). The self-reported use of cannabis during pregnancy is estimated at 2–5% in most studies but rises to 15–28% in young, urban, socioeconomically disadvantaged women, and 34–60% of cannabis users continue use during pregnancy (https://www.drugabuse.gov/publications/drugfacts/marijuana). The American College of Obstetrics and Gynecology has issued a committee opinion strongly discouraging cannabis use during pregnancy and by women contemplating pregnancy (ACOG, 2017). Cannabis use during pregnancy is poorly studied and there is a paucity of dose–response data, which is difficult to assess given the increasing and widely variable potency of legal cannabis products. The developing nervous system is a primary target during both the prenatal brain growth spurt and during adolescent maturation. Jacobus, Courtney, and Hodgdon (in this issue) review their work on the effects of cannabis use on the still-developing adolescent human brain as revealed by neuroimaging and neurocognitive assessments.

Noncoding RNAs (ncRNAs) are RNAs that do not code for proteins and include microRNAs (miRNAs), long noncoding RNAs (lnRNAs), small interfering RNAs (siRNAs), pseudogenes, and circular RNAs (circRNAs). While ncRNAs do not code for proteins, they can strongly affect the expression of target genes. Expression of ncRNAs has been studied for its potential as a biomarker of diseases including many types of cancer and, during pregnancy, preeclampsia (Wang et al., 2018), and gestational diabetes (Guarino et al., 2018). MicroRNAs are known to regulate gene expression critical to placental development (Hayder, O’Brien, Nadeem, & Peng, 2018). In this issue, this cuttingedge approach is applied to understand the developmental toxicity of drugs of abuse (Pinson & Miranda, in this issue). These authors demonstrate that expression of ncRNAs is sensitive to developmental toxicants including cannabis and nicotine.

Social and marketplace forces are driving rapid increases in the use of ENDS and cannabis, and tobacco smoking among pregnant women remains a persistent public health issue. We hope that this special issue of Birth Defects Research helps bring needed increases in research and public policy attention to bear on these widespread exposures.