Abstract
Given the rapidly expanding marketplace for Electronic Nicotine Delivery Systems (ENDS), it is important to monitor patterns of use, particularly among vulnerable populations. This study examined ENDS prevalence, reasons for use (i.e., to help quit smoking and for appealing flavors), and toxin exposure among U.S. women of reproductive age using data from the Population Assessment of Tobacco and Health (PATH) Study (2013–17). Exclusive ENDS users, dual users of ENDS and cigarettes, and exclusive cigarette smokers were compared within and between pregnant and not-pregnant women. Among pregnant women, prevalence of exclusive ENDS and dual use was similar (0.8%; 95%CI=0.4–1.2% vs. 1.4%; 95%CI=0.9–2.0%, respectively), but exclusive ENDS use was less prevalent than dual use among not-pregnant women (1.1%; 95%CI=0.9–1.4% vs. 3.7%; 95%CI=3.3–4.0%, respectively). Most women reported ENDs were used to help quit smoking (66.5–90.0%) and for appealing flavors (57.6–87.4%), and endorsement rates did not differ by use pattern or pregnancy status. Except for metals, toxin exposure was substantially lower for exclusive ENDS users relative to dual users and exclusive cigarette smokers regardless of pregnancy status (ps<0.0001). Pregnant and not-pregnant U.S. women regularly report using ENDS for help with quitting smoking and for appealing flavors. Although no type or pattern of tobacco/nicotine use is safe, especially during pregnancy, using ENDS exclusively is consistent with lower overall toxin exposure for pregnant and not-pregnant women. This study advances understanding of ENDS use and toxin exposure in women of reproductive age, a population highly vulnerable to the effects of nicotine/tobacco consumption.
Keywords: e-cigarettes, ENDS, combusted cigarettes, women of reproductive age, pregnancy, toxin exposure
1. Introduction
Cigarette smoking prevalence has steadily declined over time in the U.S. population. However, smoking prevalence remains as high as 20% among women of reproductive age (Lopez et al., 2018), which is roughly 5% higher than the U.S. national average (Jamal et al., 2018). For women of reproductive age, cigarette smoking is associated with risks to reproductive health such as early menopause and cervical cancer (Haverkos et al., 2003; Hayatbakhsh et al., 2012), and it is well known that pregnant women who smoke face greater risk of pregnancy complications and adverse birth outcomes such as ectopic pregnancy, fetal growth retardation, premature delivery, stillbirth, and sudden unexpected infant death (Cnattingius, 2004; Dietz et al., 2010; Higgins et al., 2020; Pauly and Slotkin, 2008). Electronic Nicotine Delivery Systems (ENDS) such as e-cigarettes and vaporizers have recently gained notable popularity among adolescents, young adults, and current cigarette smokers (Brandon et al., 2015; Chaffee et al., 2017; Evans-Polce et al., 2020; Hammond, 2019; McMillen et al., 2014; Rezk-Hanna et al., 2019). Given the ongoing expansion of ENDS product diversity and prevalence of use in certain subgroups, there is a need to regularly examine patterns and correlates of ENDS use among women of reproductive age, particularly pregnant women, as these populations are especially vulnerable to the adverse effects of nicotine and tobacco consumption.
Prevalence of ENDS use among U.S. women of reproductive age appears to vary by the pattern of use with other tobacco products (Liu et al., 2019; Obisesan et al., 2020). For example, between 2014–2017, according to the National Health Interview Survey, the prevalence of ENDS use ranged from 1.3–2.3% among former smokers to as high as 29–39% among current smokers (Liu et al., 2019). Importantly, women who are unable or unwilling to quit using nicotine may start using ENDS in an effort to transition away from combusted cigarettes to reduce smokingrelated health risks (Desai, 2020; Kurti et al, 2018; Kurti et al., 2020). Research is needed to continue monitoring how interests in reducing or quitting smoking and other factors, particularly the availability of appealing flavors (Soneji et al., 2019), may drive ENDS use among women of reproductive age. Furthermore, the debate over the efficacy of ENDS for harm reduction is ongoing. Although some evidence has demonstrated that pregnant women who smoke cigarettes exclusively and those who dual use ENDS and combusted cigarettes have similar levels of nicotine exposure (Clemens et al., 2019), additional research is needed to examine toxin exposure more generally in both pregnant and not-pregnant women. The purpose of this study was to characterize ENDS use among U.S. women of reproductive age, including pregnant and not-pregnant women, by examining prevalence, reasons for use, and levels of toxin exposure using the Population Assessment of Tobacco and Health (PATH) Study (detailed below; see also https://pathstudyinfo.nih.gov/UI/HomeMobile.aspx).
2. Methods
2.1. Data Source
Data were obtained from the PATH Study – an ongoing national longitudinal cohort study that comprehensively examines nicotine and tobacco consumption in the U.S. noninstitutionalized population (for details on study methods, see Hayland et al., 2017). At the time of the analyses, the available waves included Waves 1–4 of the public-use files (N = 32,822) and Waves 1–3 of the biomarker restricted-use files (N = 11,522). This study focused on women between the ages of 18–49 years who reported using ENDS and/or conventional cigarettes and no other tobacco products (N=2,341; N=251 pregnant women; see Table 1 for sample characteristics). Wave 1 (W1) data were collected between September 2013 and December 2014; Wave 2 (W2) between October 2014 and October 2015; Wave 3 (W3) between October 2015 and October 2016; and Wave 4 (W4) between December 2016 and January 2018. The overall weighted response rates were 74.0%, 83.2%, 78.4%, and 73.5% for Waves 1–4, respectively. The University of Vermont IRB granted this study a non-human subjects designation.
Table 1.
Sociodemographic characteristics and frequency of tobacco product use among women of reproductive age by pregnancy status and tobacco product use category, Population Assessment of Tobacco and Health.
| Pregnant | Not-Pregnant | |||||
|---|---|---|---|---|---|---|
| Sample characteristics | ENDS Exclusively (n=15) | Dual Users (n=31) | Cigarettes Exclusively (n=205) | ENDS Exclusively (n=129) | Dual Users (n=416) | Cigarettes Exclusively (n=1,796) |
| Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted% (95% CI) | |
| Age | ||||||
| 18–24 years | 16.4 (0.0, 34.8) | 43.8 (23.5, 64.0) | 34.7 (27.9, 41.5) | 8.0 (3.5, 12.5) | 5.2 (3.4, 7.0) | 9.1 (8.0, 10.3) |
| 25–34 years | 59.1 (35.3, 82.8) | 44.7 (18.9, 70.5) | 53.5 (45.4, 61.6) | 32.5 (22.5, 42.5) | 34.4 (29.7, 39.1) | 33.2 (30.8, 35.7) |
| 35–49 years | 24.5 (12.2, 36.8) | 11.6 (0.0, 25.7) | 11.8 (7.6, 16.0) | 59.5 (48.4, 70.6) | 60.4 (55.1, 65.8) | 57.6 (55.2, 60.0) |
| Race Ethnicity | ||||||
| White, Non-Hispanic | 78.4 (53.9, 100.0) | 78.9 (66.5, 91.4) | 81.2 (75.9, 86.5) | 79.8 (73.3, 86.3) | 81.1 (77.4, 84.7) | 71.5 (68.9, 74.2) |
| Black, Non-Hispanic | 3.4 (0.0, 11.3) | 0.0 (0.0, 0.0) | 10.7 (6.9, 14.5) | 9.4 (4.3, 14.5) | 4.4 (2.2, 6.6) | 12.8 (10.9, 14.8) |
| Hispanic | 11.3 (0.0, 27.9) | 14.0 (4.5, 23.4) | 3.2 (0.8, 5.6) | 7.7 (3.4, 11.9) | 10.1 (7.2, 13.1) | 11.2 (9.3, 13.1) |
| Other | 7.0 (0.0, 19.3) | 7.1 (0.0, 15.8) | 4.9 (2.4, 7.4) | 3.1 (0.8, 5.5) | 4.4 (2.2, 6.7) | 4.4 (3.3, 5.6) |
| Education | ||||||
| Less than High School/GED | 10.7 (0.0, 25.1) | 36.2 (15.8, 56.7) | 29.7 (21.7, 37.8) | 13.9 (8.0, 19.8) | 22.2 (17.7, 26.7) | 25.2 (23.1, 27.3) |
| High School Diploma | 11.6 (0.0, 28.5) | 27.3 (1.1, 53.5) | 31.5 (23.5, 39.5) | 19.9 (10.1, 29.8) | 22.8 (18.1, 27.5) | 27.6 (25.1, 30.1) |
| Some College/Associate’s Degree | 31.5 (0.0, 64.1) | 33.1 (12.1, 54.0) | 30.8 (22.5, 39.1) | 51.5 (41.2, 61.8) | 44.5 (38.5, 50.6) | 38.9 (36.4, 41.5) |
| Bachelor’s/Advanced degree | 46.2 (1.6, 90.7) | 3.4 (0.0, 9.9) | 7.9 (3.4, 12.5) | 14.7 (8.6, 20.7) | 10.5 (7.5, 13.5) | 8.3 (6.7, 9.8) |
| Frequency of product use | ||||||
| Cigarettes Per Day | N/A | 9.59 (7.35, 11.83) | 9.29 (8.32, 10.25) | N/A | 12.81 (11.77, 13.86) | 14.16 (12.54, 15.78) |
| Number of Days of ENDS Use (past month) | 17.11 (11.64, 22.59) | 4.74 (2.16, 7.32) | N/A | 19.48 (17.23, 21.73) | 7.37 (6.22, 8.52) | N/A |
2.2. Measures
2.2.1. Pregnancy status.
All women < 50 years of age were queried regarding pregnancy status. W1 participants were first asked if they had ever been pregnant and W2, W3, and W4 participants were first asked about pregnancy in the past 12 months. Across all waves, those who responded affirmatively to the first pregnancy question received a second question asking if they were currently pregnant. Those responding affirmatively to the second question were treated as pregnant in the current study. For women pregnant during multiple waves, only their first pregnancy was considered in this report.
2.2.2. Tobacco product use categories.
Exclusive ENDS users included current established users (i.e., those who reported using any ENDS, such as an e-cigarette/cigar/pipe/hookah, vape or hookah pens, personal vaporizers, or modifiable tank systems regularly in the past and some days or every day at the time of survey completion) and current experimental users (respondents who reported not using ENDS regularly in the past, but using some days or every day at the time of survey completion) who did not also use cigarettes. Exclusive cigarette smokers included current established (respondents who reported smoking ≥ 100 cigarettes lifetime and smoking some days or every day at the time of survey completion) and current experimental smokers (respondents who reported smoking < 100 cigarettes lifetime, but smoking some days or every day at the time of survey completion) who did not also use ENDS. Dual users included respondents who endorsed (1) current established or experimental ENDS use and (2) current established or experimental cigarette smoking. Given the high percentage of women who reported using tobacco products other than ENDS or conventional cigarettes (i.e., 8.3% pregnant and 24.1% not-pregnant), toxin exposure analyses (described below) were conducted with and without users of other tobacco products. Results presented in the tables pertain to the sample without users of other products. Any differences in toxin exposure between the samples with and without users of other products are noted in the text of the Results section.
2.2.3. Reasons for ENDS use.
The two reported reasons for ENDS use examined in PATH included (1) Used e-cigs/ENDS because it helps people to quit smoking and (2) Used e-cigs/ENDS because it comes in flavors I like. These items included dichotomous response options 1 (“yes”) and 2 (“no”), as well as non-response options, which were coded as missing (e.g., “Refused”, “Don’t know”, “Inapplicable”).
2.2.4. Toxin exposure.
PATH participants who consented to providing biological specimens, self-collected urine samples at Waves 1–3 (N=1,613 overall; N=109 pregnant women), which were assayed for biomarkers of tobacco consumption. This study focuses on specific biomarkers that have been previously associated with pregnancy complications or adverse birth outcomes and known or likely carcinogens, including: (1) nicotine metabolites (i.e., total nicotine equivalents 2 [TNE2], consisting of the molar sum of cotinine and trans-3’-hydroxycotinine), (2) tobacco specific nitrosamines (i.e., NNAL), polycyclic aromatic hydrocarbon (PAH) metabolites (i.e., 1-PYR, 2-FLU), (3) volatile organic compound (VOC) metabolites (i.e., HPMA, CYMA), and (4) heavy metals (i.e., lead, cadmium). To control for variation in renal function, urinary biomarkers were creatinine-adjusted by dividing the biomarker value by the urinary creatinine value. Given pregnancy-related changes in creatinine clearance rate, urinary biomarkers were also examined without the creatinine correction (Lopes van Balen et al., 2019). Detailed information for each assay (including analytes not reported on in the current study), laboratory methods, scientific rationale, and literature references can be obtained at https://www.icpsr.umich.edu/icpsrweb/NAHDAP/studies/36840/summary.
2.3. Statistical Analysis
Frequencies, percentages, and associated 95% confidence intervals (CIs) were generated across all respondents in SAS 9.4 (SAS Institute Inc., 2013). In order to prevent counting cases multiple times given the longitudinal design of PATH, prevalence estimates for not-pregnant women were based on Wave 1 data only, with anyone pregnant during any of the subsequent waves removed. Prevalence estimates for pregnant women were collapsed across waves (2013–17) and, as noted above, only the first pregnancy was examined in those with multiple pregnancies across waves. Values were weighted using census data as well as person-level data collected during the household-screening interview. Weighting accounts for the complex study design of the PATH Study and adjusts for varying selection probabilities and differential non-response rates (see Hyland et al. 2017 for additional details on the PATH weighting procedure). Variance estimation was conducted as a variant of balanced repeated replication (Fay’s method) using a predetermined value ε set to 0.3, as recommended for PATH (Judkins, 1990; McCarthy, 1969). Potential demographic differences between product user groups among the pregnant and not-pregnant women were examined using a χ2 Test of Independence. Between-group differences were examined using Logistic Regression for reasons for ENDS use and ANCOVA for toxin exposure, followed by post-hoc tests, using Bonferroni corrections, to examine pair-wise differences. Covariates included age, race/ethnicity, education in the Logistic Regression for reasons for ENDS use, plus secondhand smoke exposure, and marijuana use in the ANCOVAs for toxin exposure. Significance was set at p<.05.
3. RESULTS
3.1. Sample Characteristics
Sample characteristics are reported in Table 1. There were no significant age differences between exclusive ENDS, dual users, and exclusive cigarette smokers among pregnant (χ2(4)=4.44, p=0.35) or not-pregnant (χ2(4)=7.13, p=0.13) women, although pregnant women in every use category were younger than not-pregnant women. There were significant differences in use patterns by educational attainment in the pregnant (χ2(6)=20.21, p=0.003) and not-pregnant women (χ2(6)=20.16, p=0.003). Among the pregnant women, exclusive ENDS users attained greater education than dual users and exclusive cigarette smokers, and among the not-pregnant women, exclusive ENDS users attained more education than exclusive cigarette smokers but not dual users. Given the small sample, it was not possible to examine racial/ethnic differences in product use among the pregnant women. Among not-pregnant women, a higher percentage of Black Non-Hispanic women were exclusive cigarette smokers vs. dual users, whereas a higher percentage of White Non-Hispanic women were dual users vs. exclusive cigarette smokers (χ2(6)=28.97, p=0.001). There were no other sociodemographic differences between pregnant and not-pregnant women.
3.2. Prevalence
Among pregnant women, prevalence of exclusive ENDS use was lower than dual use, which was lower than exclusive cigarette smoking (Table 2). Not-pregnant women exhibited a similar pattern but with prevalence rates shifted upward. Among current ENDS users (Figure 1), a smaller percentage of women reported exclusive ENDS use (36.2% pregnant; 95% CI=21.2–51.2% and 23.7% not-pregnant; 95% CI=19.9–27.4%) compared to dual use (63.8% pregnant; 95% CI=48.8–78.8% and 76.3% not-pregnant; 95% CI=72.6–80.1%). Rates of exclusive ENDS and dual use did not vary by pregnancy status.
Table 2.
Prevalence of exclusive ENDS, dual, and exclusive cigarette use among women of reproductive age by pregnancy status, and reported reasons for ENDS use by pregnancy status and tobacco product use category, Population Assessment of Tobacco and Health.
| Pregnant | Not Pregnant | |||||
|---|---|---|---|---|---|---|
| ENDS Exclusively (n=15) | Dual Users (n=31) | Cigarettes Exclusively (n=205) | ENDS Exclusively (n=129) | Dual Users (n=416) | Cigarettes Exclusively (n=1,796) | |
| Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | |
| Overall Prevalence | 0.8 (0.4, 1.2) | 1.4 (0.9, 2.0) | 9.6 (8.0, 11.1) | 1.1 (0.9, 1.4) | 3.7 (3.3, 4.0) | 15.4 (14.4, 16.4) |
| Reasons for ENDS use | ||||||
| Used ENDS because they help people quit smoking | 90.0 (39.5, 99.2) | 73.6 (46.1, 90.1) | N/A | 73.1 (62.3, 81.7) | 66.5 (56.2, 75.4) | N/A |
| Used ENDS because they came in flavors I like/d | 87.4 (30.0, 99.1) | 78.4 (52.6, 92.3) | N/A | 65.2 (53.7, 75.2) | 57.6 (48.3, 66.4) | N/A |
Figure 1.

Prevalence of exclusive ENDS vs. dual use among U.S. women of reproductive age who reported current ENDS use.
3.3. Reasons for ENDS Use
Among pregnant women, the majority of exclusive ENDS and dual users reported using ENDS to quit smoking and/or because they came in appealing flavors (Table 2), with no notable differences between exclusive ENDS and dual users in that regard; this pattern of endorsement was similar among the not-pregnant women. Compared to pregnant women, rates of endorsement shifted downward for the not-pregnant women, although the differences were not statistically significant: 79.0%; 95% CI=54.2–92.3% vs. 68.2%; 95% CI=59.3–76.0% (χ2(1)=0.97, p=0.33) for quitting smoking and 82.2%; 95% CI=56.3–94.3% vs. 59.6%; 95% CI=51.2–67.5% (χ2(1)=2.79, p=0.09) for appealing flavors.
3.4. Toxin exposure
For pregnant and not-pregnant women, levels of TNE2, NNAL, 1-PYR, 2-FLU, HPMA, and CYMA exposure were lower for exclusive ENDS users compared to dual users and exclusive cigarette smokers (ts(100)>5.46, ps<0.001) (see “Creatinine-adjusted biomarkers” in Table 3). Regardless of pregnancy status, exposure to lead (F(2,100)=2.88, p=.06) and cadmium (F(2,100)=1.13, p=.33) was similar for exclusive ENDS, dual users, and exclusive cigarette smokers. In general, there were no differences in toxin exposure between dual users and exclusive cigarette smokers (ts(100)<2.26, ps≥.08), save for TNE2 levels which were higher among dual users (t(100)=3.04, p=.009). Compared to not-pregnant women, pregnant women had higher levels of NNAL, 1-PYR, 2-FLU, HPMA, cadmium, and lead (Fs(1,100)>5.75, ps≤0.02). Repeating the toxin exposure analyses without the creatinine correction yielded similar results (see “Unadjusted biomarkers” in Table 3); however, differences between pregnant and not-pregnant women remained significant only for NNAL, 1-PYR, and HPMA (Fs(1,100)>4.10; p<.05).
Table 3.
Geometric means (95% Confidence Intervals) for creatinine-adjusted urinary biomarkers of tobacco toxin exposure by pregnancy status and tobacco product use category, adjusting for age, race/ethnicity, education, cigarettes per day, number of days of ENDS use (past month), exposure to second hand smoke, and past-30-day marijuana use, Population Assessment of Tobacco and Health Study.
| Pregnant | Not Pregnant | |||||
|---|---|---|---|---|---|---|
| ENDS Exclusively (n=7) | Dual Users (n=18) | Cigarettes Exclusively (n=84) | ENDS Exclusively (n=111) | Dual Users (n=370) | Cigarettes Exclusively (n=1,023) | |
| Geometric Mean (95% CI) | Geometric Mean (95% CI) | Geometric Mean (95% CI) | Geometric Mean (95% CI) | Geometric Mean (95% CI) | Geometric Mean (95% CI) | |
| Nicotine | ||||||
| TNE2 nmol/mg creatinine | 0.51 (0.08, 3.49) | 24.88 (14.67, 42.22) | 25.08 (13.69, 45.95) | 0.44 (0.16, 1.19) | 11.62 (7.80, 19.50) | 12.33 (7.80, 19.50) |
| TSNA | ||||||
| NNAL pg/mg creatinine | 14.90 (2.04, 108.67) | 136.80 (80.43, 232.70) | 196.79 (130.32, 297.10) | 6.12 (3.59, 10.41) | 125.92 (96.61, 164.17) | 90.91 (71.58, 115.45) |
| PAHs | ||||||
| 1-PYR ng/mg creatinine | 0.25 (0.14, 0.43) | 0.37 (0.24, 0.55) | 0.38 (0.32, 0.45) | 0.18 (0.14, 0.23) | 0.34 (0.30, 0.39) | 0.29 (0.27, 0.32) |
| 2-FLU ng/mg creatinine | 0.22 (0.15, 0.33) | 0.77 (0.54, 1.09) | 0.88 (0.71, 1.07) | 0.23 (0.17, 0.30) | 0.83 (0.70, 0.98) | 0.68 (0.58, 0.78) |
| VOCs | ||||||
| HPMA ng/mg creatinine | 223.67 (157.69, 317.25) | 1,331.07 (974.09, 1,818.86) | 1,020.94 (783.61, 1,330.15) | 296.48 (207.92, 422.67) | 861.19 (726.78, 1,020.47) | 697.75 (601.87, 809.10) |
| CYMA ng/mg creatinine | 8.48 (3.36, 21.40) | 96.74 (66.67, 140.38) | 73.98 (51.20, 106.88) | 4.36 (2.54, 7.50) | 82.05 (60.97, 110.43) | 63.07 (47.96, 82.93) |
| Metals | ||||||
| Lead ng/mg creatinine | 0.42 (0.17, 1.00) | 0.50 (0.35, 0.71) | 0.49 (0.42, 0.57) | 0.34 (0.29, 0.39) | 0.40 (0.35, 0.45) | 0.38 (0.35, 0.41) |
| Cadmium ng/mg creatinine | 0.17 (0.04, 0.67) | 0.15 (0.09, 0.22) | 0.22 (0.18, 0.28) | 0.15 (0.11, 0.19) | 0.17 (0.15, 0.18) | 0.17 (0.15, 0.18) |
Note: TNE2 = Total Nicotine Equivalents (molar sum of cotinine + 3-hydroxycotinine); TSNA = Tobacco Specific Nitrosamine; NNAL = 4-(methylnitrosamino)-1-(3-pyridyl)-1butanol; PAH = Polycyclic Aromatic Hydrocarbon; 1-PYR = 1-hydroxypyrene; 2-FLU = 2hydroxyfluorene; VOC = Volatile Organic Compound; HMPA = N-Acetyl-S-(3hydroxypropyl)-L-cysteine; CYMA = N-Acetyl-S-(2-cyanoethyl)-L-cysteine.
Including the women who used other tobacco products into the sample and rerunning the above analyses, toxin exposure remained lowest among exclusive ENDS users compared to dual users and exclusive cigarette smokers (ts(100)>6.91, ps<0.001), save for lead (F(2,100)=3.08, p=.05) and cadmium exposure (F(2,100)=2.63, p=.08), and TNE2 levels remained higher among dual users compared to exclusive cigarette smokers (t(100)=2.78, p=.02). Compared to not-pregnant women, pregnant women had higher levels of TNE2, NNAL, 1-PYR, cadmium, and lead (Fs(1,100)>5.17, ps≤0.03). Additionally, there was a significant pregnancy by product use interaction on HPMA exposure, indicating that compared to not-pregnant exclusive cigarette smokers, pregnant exclusive cigarette smokers had higher levels of HPMA (F(2,100)=5.62, p<.01). Removing the creatinine correction yielded similar results; however, differences between pregnant and not-pregnant women were no longer significant, save for NNAL which remained higher among pregnant women (F(1,100)=9.46; p>.01).
4. Discussion
The purpose of this study was to characterize ENDS use among U.S. women of reproductive age by examining prevalence of ENDS use, reasons for use, and levels of toxin exposure using the PATH Study. Prevalence of exclusive ENDS use was considerably lower than dual use regardless of pregnancy status. Reasons for use, including using ENDS to help quit smoking conventional cigarettes and liking the flavors, were comparable among exclusive ENDS and dual users regardless of pregnancy status, although a somewhat (yet not significantly) larger percentage of pregnant than not-pregnant women endorsed using ENDS for those reasons. Toxin exposure was significantly lower among exclusive ENDS than dual or exclusive cigarette smokers save for metals, which were comparable across the three use categories, and this pattern of toxin exposure was consistent across pregnant and not-pregnant women. In light of the rapidly expanding ENDS marketplace, these findings may be helpful to developing effective policy to regulate ENDS, and may also help inform efforts to further reduce harm associated with tobacco and nicotine consumption.
Regarding sociodemographic characteristics, educational attainment was significantly related to ENDS use among both pregnant and not-pregnant women. Exclusive ENDS users were more educated than exclusive cigarette smokers regardless of pregnancy status, and among the pregnant women, exclusive ENDS users were also more educated than dual users. Prior studies have reported similar findings (Chivers et al., 2016; Glover et al., 2018; Nayak et al., 2016). For example, one study demonstrated that the prevalence of current ENDS use increased with higher educational attainment (Glover et al., 2018), and another study comparing dual users to exclusive cigarette smokers demonstrated that educational attainment was greater among dual users than exclusive cigarette smokers (Nayak et al., 2016). Furthermore, educational attainment is a known protective factor against cigarette smoking (Coleman et al., 2019; Gaalema et al., 2018; Park et al., 2017). For example, in one study, smokers attempting to quit who had a Bachelor’s degree or higher were more likely to report having switched from conventional cigarettes to exclusive ENDS rather than dual use, but individuals with less than a high school diploma were less likely to report transitioning from conventional cigarettes to exclusive ENDS over dual use (Park et al., 2017). The current findings provide further evidence that individuals with greater educational attainment are more likely to engage in behaviors perceived to be health protective including exclusive ENDS use relative to use patterns involving conventional cigarettes, especially during pregnancy. This pattern is consistent with concerns that ENDS may increase racial health disparities because those with fewer barriers to educational attainment are more likely to substitute ENDS for conventional cigarettes (Friedman and Horn, 2019; Harlow et al., 2019). In line with this concern, the current study demonstrated that within the not-pregnant women, a higher percentage of Black, Non-Hispanic women were exclusive cigarette smokers than dual users, whereas the opposite pattern was true of White Non-Hispanic women, and this finding is consistent with prior research (Assari et al., 2020; Lopez et al., 2018).
With respect to prevalence of ENDS use, pregnant and not-pregnant women reported comparable levels of exclusive ENDS use, and in both groups rates of exclusive ENDS use were lower than those of dual use. Reducing tobacco consumption in women of reproductive age, especially during pregnancy, is a public health priority. In light of evidence that women who use ENDS exclusively or in combination with conventional cigarettes may be less likely to quit using nicotine entirely (Kim, 2020; Kurti et al., 2020), clearer messaging may be needed to inform women regarding the risks of nicotine and other constituents in ENDS and conventional cigarettes to the fetus. Clearer messaging in this regard is particularly important as pregnant women may be aware that ENDS contain harmful substances, but exclusive ENDS users and dual users may feel confident in their decision to use ENDS based on strong beliefs that ENDS will help them to gradually wean off cigarettes and/or nicotine (Bowker et al., 2020).
In general, the results of the current study may also prove useful in efforts to regulate ENDS. For example, the majority of exclusive ENDS and dual users endorsed using ENDS because they came in appealing flavors, which is concerning in light of recent findings that those who use multiple flavors of ENDS may smoke cigarettes and vape more frequently (Lanza et al., 2020). This evidence underscores the importance of regulatory policies that target flavors not only to protect youth, but also other vulnerable populations such as women of reproductive age. Furthermore, it is worth noting that a somewhat higher percentage of pregnant than not-pregnant women endorsed using ENDS for flavors. Although rates of endorsement were not significantly different between pregnant and not-pregnant women, the possibility that availability of appealing flavors may be of special interest to pregnant women warrants further investigation. Additionally, more research would be useful for determining whether use of ENDS containing flavors makes quitting nicotine use more difficult for those who report using ENDS to help quit smoking. Interestingly, the majority of women in this study who reported using ENDS endorsed doing so to help quit smoking, with exclusive ENDS and dual users endorsing that rationale at similar rates. Although ENDS may facilitate quitting cigarette smoking, there is mixed evidence of ENDS as a smoking cessation aid to date (Hajek et al., 2019; Jackson et al., 2020; Neisler et al., 2018). It may be helpful for health care providers to convey the mixed evidence on the efficacy of using ENDS as a smoking cessation aid to their patients.
The present study provides clear evidence that overall toxin exposure was lowest for exclusive ENDS users, with dual users and exclusive cigarette smokers exhibiting comparable toxin exposures, findings consistent with recent evidence from the general population (Majeed et al., 2020). An unsettling exception to that pattern is that exclusive use of ENDS was not associated with reduced exposure to heavy metals such as lead and cadmium. This is no minor exception given substantial evidence that even low levels of exposure to lead and cadmium during pregnancy can adversely affect birth outcomes, particularly preterm delivery and low birthweight among term infants (Berkowitz et al., 2006; Guo et al., 2017; Perkins et al., 2014; Sun et al., 2014; Xie et al., 2013). Thus, while exclusive use of ENDS is associated with an overall reduction in toxin exposure, there is still clear potential for harm associated with ENDS use among pregnant women (Breland et al., 2019).
This study has at least five limitations that merit mention. First, analyses were cross-sectional with some aspects based largely on self-report data. Experimental studies or studies using intensive daily sampling (e.g., ecological momentary assessment) would be useful for examining biomarker exposure following the use of various tobacco products closer to the actual behavior. Second, the sample of pregnant women was small. Studies in larger samples would be helpful to confirm the accuracy of the prevalence estimates. Relatedly, pregnant women in this study exhibited higher toxin exposure levels than not-pregnant women, although differences in exposure levels for the majority of toxins were no longer significant after removing the creatinine correction. This suggests pregnancy-related differences in creatinine clearance may complicate interpretation of potential differences between pregnant and not-pregnant women in toxin exposure, as might the higher rates of nicotine metabolism, both oxidation and glucuronidation, during pregnancy (Arger et al., 2019; Taghavi et al., 2018). Third, there are other potentially important reasons for ENDS use that were not measured across all data collection waves, such as using ENDS because they are viewed as a “safer alternative” to cigarettes. Due to the small number of pregnant women at each wave it was not possible to make valid comparisons of exclusive ENDS users to dual users on items only available at one or two waves. Fourth, frequency of ENDS and conventional cigarette use are reported on different metrics, specifically puffs vs. cigarettes per day; as such, we were not able to adjust for frequency of use in comparisons involving ENDS and conventional cigarettes. Finally, given the rapid pace at which the ENDS marketplace is evolving, it will be important to reexamine the variables in the current study using data collected since 2017 (i.e., the last available wave of PATH). These limitations notwithstanding, we believe this study offers important new practical information that has the potential to enhance understanding of ENDS use among U.S. women of reproductive age and inform ENDS regulatory policies.
Supplementary Material
Table 4.
Frequency of tobacco product use among women of reproductive age by pregnancy status and tobacco product use category, adjusting for age, race/ethnicity, education, exposure to second hand smoke, and past-30-day marijuana use, Population Assessment of Tobacco and Health.
| Pregnant | Not-Pregnant | |||||
|---|---|---|---|---|---|---|
| Frequency of product use | ENDS Exclusively (n=7) | Dual Users (n=18) | Cigarettes Exclusively (n=84) | ENDS Exclusively (n=111) | Dual Users (n=370) | Cigarettes Exclusively (n=1,023) |
| Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | Weighted % (95% CI) | |
| Cigarettes Per Day | N/A | 8.75 (5.26, 12.24) | 9.80 (7.18, 12.42) | N/A | 9.44 (7.88, 11.00) | 9.48 (7.33, 11.63) |
| Number of Days of ENDS Use (past month) | 10.63 (3.41, 17.85) | 5.09 (0.80, 9.39) | N/A | 17.13 (13.62, 20.65) | 7.45 (5.09, 9.80) | N/A |
Highlights.
Nicotine/tobacco consumption poses unique health risks to women of reproductive age.
Monitoring use of Electronic Nicotine Delivery Systems (ENDS) is critical.
Exclusive ENDS and dual use (ENDS/cigarette) rates do not vary by pregnancy status.
Most women report using ENDS to help quit smoking and for appealing flavors.
Toxins are lowest among exclusive ENDS vs. dual and exclusive cigarette smokers.
Funding
This project was supported in part by Tobacco Centers of Regulatory Science (TCORS) Award U54DA036114 from the National Institute on Drug Abuse (NIDA) and Food and Drug Administration (FDA), Centers of Biomedical Research Excellence Award P20GM103644 from the National Institute of General Medical Sciences, and Institutional Training Grant Award T32DA07242 from NIDA as well as a Canada Research Chair in Pharmacogenomics (Tyndale). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or FDA.
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Declaration of interest
R. F. Tyndale has consulted for Quinn Emanuel and Ethismos. The other authors have no conflicts of interest to declare.
REFERENCES
- Arger CA, Taghavi T, Heil SH, Skelly J, Tyndale RF, Higgins ST, 2019. Pregnancyinduced increases in the nicotine metabolite ratio: examining changes during antepartum and postpartum. Nicotine Tob Res. 21(12), 1706–1710. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berkowitz Z, Price-Green P, Bove FJ, Kaye WE, 2006. Lead exposure and birth outcomes in five communities in Shoshone County, Idaho. Int J Hyg Environ Health 209(2), 123132. [DOI] [PubMed] [Google Scholar]
- Bowker K, Ussher M, Cooper S, Orton S, Coleman T, Campbell KA, 2020. Addressing and overcoming barriers to e-cigarette use for smoking cessation in pregnancy: A qualitative study. Int J Environ Res Public Health. 17(13), 4823. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brandon TH, Goniewicz ML, Hanna NH, Hatsukami DK, Herbst RS, Hobin JA, Ostroff JS, Shields PG, Toll BA, Tyne CA, Viswanath K, Warren GW, 2015. Electronic nicotine delivery systems: a policy statement from the American Association for Cancer Research and the American Society of Clinical Oncology. Clin Cancer Res. 21(3), 514–525. [DOI] [PubMed] [Google Scholar]
- Breland A, McCubbin A, Ashford K, 2019. Electronic nicotine delivery systems and pregnancy: Recent research on perceptions, cessation, and toxicant delivery. Birth Defects Res. 111(17), 1284–1293. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chaffee BW, Couch ET, Gansky SA, 2017. Trends in characteristics and multi-product use among adolescents who use electronic cigarettes, United States 2011–2015. PLoS One. 12(5), e0177073. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chivers LL, Hand DJ, Priest JS, Higgins ST, 2016. E-cigarette use among women of reproductive age: Impulsivity, cigarette smoking status, and other risk factors. Prev Med. 92, 126–134. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cnattingius S, 2004. The epidemiology of smoking during pregnancy: smoking prevalence, maternal characteristics, and pregnancy outcomes. Nicotine Tob Res. 6, 125–40. [DOI] [PubMed] [Google Scholar]
- Clemens MM, Cardenas VM, Fischbach LA, Cen R, Siegel ER, Eswaran H, Ekanem US, Policherla A, Moody HL, Magann EF, Boysen G, 2019. Use of electronic nicotine delivery systems by pregnant women II: Hair biomarkers for exposures to nicotine and tobacco-specific nitrosamines. Tob Induc Dis. 17. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dietz PM, England LJ, Shapiro-Mendoza CK, Tong VT, Farr SL, Callaghan WM, 2010. Infant morbidity and mortality attributable to prenatal smoking in the U.S. American Journal of Prev Med. 39(1), 45–52. [DOI] [PubMed] [Google Scholar]
- Desai N, 2020. Smoking and pregnancy: The era of electronic nicotine delivery systems. Obstet Med. 1753495X19893224. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Evans-Polce RJ, Veliz P, Boyd CJ, McCabe SE, 2020. Initiation patterns and trends of e-cigarette and cigarette use among US adolescents. J Adolesc Health. 66(1), 27–33. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Friedman AS, Horn SJ, 2019. Socioeconomic disparities in electronic cigarette use and transitions from smoking. Nicotine Tob Res. 21(10), 1363–1370. [DOI] [PubMed] [Google Scholar]
- Glover LM, Ma JZ, Kesh A, Tompkins LK, Hart JL, Mattingly DT, Walker K, Robertson RM, Payne T, Sims M, 2018. The social patterning of electronic nicotine delivery system use among US adults. Prev Med. 116, 27–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Guo J, Wu C, Qi X, Jiang S, Liu Q, Zhang J, Cao Y, Chang X, Zhou Z, 2017. Adverse associations between maternal and neonatal cadmium exposure and birth outcomes. Sci Total Environ. 575, 581–587. [DOI] [PubMed] [Google Scholar]
- Hajek P, Phillips-Waller A, Przulj D, Pesola F, Myers Smith K, Bisal N, Li J, Parrott S, Sasieni P, Dawkins L, Ross L, Goniewicz ML, Wu Q, McRobbie HJ, 2019. A Randomized Trial of E-Cigarettes versus Nicotine-Replacement Therapy. N Engl J Med, 380(7), 629–637. [DOI] [PubMed] [Google Scholar]
- Hammond D, Reid JL, Rynard VL, Fong GT, Cummings KM, McNeill A, Hitchman S, Thrasher JF, Goniewicz ML, Bansal-Travers M, O’Connor R, Levy D, Borland R, White CM, 2019. Prevalence of vaping and smoking among adolescents in Canada, England, and the United States: repeat national cross-sectional surveys. BMJ. 365, l2219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harlow AF, Stokes A, Brooks DR, 2019. Socioeconomic and racial/ethnic differences in e-cigarette uptake among cigarette smokers: longitudinal analysis of the population assessment of tobacco and health (PATH) study. Nicotine Tob Res. 21(10), 1385–1393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haverkos HW, Soon G, Steckley SL, Pickworth W, 2003. Cigarette smoking and cervical cancer: Part I: a meta-analysis. Biomed Pharmacother. 57(2), 67–77. [DOI] [PubMed] [Google Scholar]
- Hayatbakhsh MR, Clavarino A, Williams GM, Sina M, Najman JM, 2012. Cigarette smoking and age of menopause: a large prospective study. Maturitas. 72(4), 346–352. [DOI] [PubMed] [Google Scholar]
- Higgins ST, Slade EP, Shepard DS, 2020. Decreasing smoking during pregnancy: Potential economic benefit of reducing sudden unexpected infant death. Prev Med. 106238. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hyland A, Ambrose BK, Conway KP, Borek N, Lambert E et al. , 2017. Design and methods of the Population Assessment of Tobacco and Health (PATH) Study. Tob Control. 26(4), 371–378. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jackson SE, Farrow E, Brown J, Shahab L, 2020. Is dual use of nicotine products and cigarettes associated with smoking reduction and cessation behaviours? A prospective study in England. BMJ Open. 10(3), e036055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, Neff LJ, 2018. Current cigarette smoking among adults—United States, 2016. Morb Mortal Wkly Rep. 67(2), 53. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Judkins DR, 1990. Fay’s method for variance estimation. J Off Stat. 6, 223–229. [Google Scholar]
- Kim S, 2020. Changes in Multiple and Different Tobacco Product Use Behaviors in Women Before and During Pregnancy: An Analysis of Longitudinal Population Assessment of Tobacco and Health Data. Am J Prev Med. 59(4), 588–592. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurti AN, Bunn JY, Tang K, Nighbor T, Gaalema DE, Coleman-Cowger V, Coleman SRM, Higgins ST, 2020. Impact of electronic nicotine delivery systems and other respondent characteristics on tobacco use transitions among a US national sample of women of reproductive age. Drug Alcohol Depend. 207, 107801. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurti AN, Redner R, Bunn JY, Tang K, Nighbor T et al. , 2018. Examining the relationship between pregnancy and quitting use of tobacco products in a US national sample of women of reproductive age. Prev Med. 117, 52–60. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lanza HI, Leventhal AM, Cho J, Braymiller JL, Krueger EA, McConnell R, Barrington-Trimis JL, 2020. Young adult e-cigarette use: A latent class analysis of device and flavor use, 2018–2019. Drug Alcohol Depend. 108258. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Liu B, Xu G, Rong S, Santillan DA, Santillan MK, Snetselaar LG, Bao W, 2019. National estimates of e-cigarette use among pregnant and nonpregnant women of reproductive age in the United States, 2014–2017. JAMA Pediatr. 173(6), 600–602. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez AA, Redner R, Kurti AN, Keith DR, Villanti AC, Stanton CA, Gaalema DE, Bunn JY, Doogan NJ, Cepeda-Benito A, Roberts ME, Higgins ST, 2018. Tobacco and nicotine delivery product use in a US national sample of women of reproductive age. Prev Med. 117, 61–68. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopes van Balen VA, van Gansewinkel TAG, de Haas S, Spaan JJ, Ghossein-Doha C, van Kuijk SMJ, van Drongelen J, Cornelis T, Spaanderman MEA, 2019. Maternal kidney function during pregnancy: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 54(3), 297–307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Majeed B, Linder D, Eissenberg T, Tarasenko YN, Smith D, Ashley DL, 2020. Cluster analysis of urinary tobacco biomarkers among US adults: Population Assessment of Tobacco and Health (PATH) biomarker study (2013–2014). Prev Med. 106218. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCarthy PJ, 1969. Pseudo-replication: Half samples. Int Stat Rev. 37, 239–264. [Google Scholar]
- McMillen RC, Gottlieb MA, Shaefer RMW, Winickoff JP, Klein JD, 2014. Trends in electronic cigarette use among US adults: use is increasing in both smokers and nonsmokers. Nicotine Tob Res. 17(10), 1195–1202. [DOI] [PubMed] [Google Scholar]
- Nayak P, Pechacek TF, Weaver SR, Eriksen MP, 2016. Electronic nicotine delivery system dual use and intention to quit smoking: Will the socioeconomic gap in smoking get greater?. Addict Behav. 61, 112–116. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neisler J, Reitzel LR, Garey L, Kenzdor DE, Hebert ET, Vijayaraghavan M, Businelle MS, 2018. Concurrent nicotine and tobacco product use among homeless smokers and associations with cigarette dependence and other factors related to quitting. Drug Alcohol Depend. 185, 133–140. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Obisesan OH, Osei AD, Uddin SI, Dzaye O, Cainzos-Achirica M et al. , 2020. E-Cigarette Use Patterns and High-Risk Behaviors in Pregnancy: Behavioral Risk Factor Surveillance System, 2016–2018. Am J Prev Med. 59(2), 187–195. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pauly JR, Slotkin TA, 2008. Maternal tobacco smoking, nicotine replacement and neurobehavioural development. Acta Paediatr. 97(10), 1331–1337. [DOI] [PubMed] [Google Scholar]
- Perkins M, Wright RO, Amarasiriwardena CJ, Jayawardene I, Rifas-Shiman SL, Oken E, 2014. Very low maternal lead level in pregnancy and birth outcomes in an eastern Massachusetts population. Ann Epidemiol. 24(12), 915–919. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rezk-Hanna M, Toyama J, Ikharo E, Brecht ML, Benowitz NL, 2019. E-Hookah Versus E-Cigarettes: findings from Wave 2 of the PATH Study (2014–2015). Am J Prev Med. 57(5), e163–e173. [DOI] [PubMed] [Google Scholar]
- SAS Institute Inc. (2013). Base SAS® 9.4 Procedures Guide: Statistical Procedures, Second Edition. Cary, NC; SAS Institute. [Google Scholar]
- Soneji SS, Knutzen KE, Villanti AC, 2019. Use of flavored e-cigarettes among adolescents, young adults, and older adults: findings from the population assessment for tobacco and health study. Public Health Rep. 134(3), 282–292. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sun H, Chen W, Wang D, Jin Y, Chen X, Xu Y, 2014. The effects of prenatal exposure to low-level cadmium, lead and selenium on birth outcomes. Chemosphere. 108, 33–39. [DOI] [PubMed] [Google Scholar]
- Taghavi T, Arger CA, Heil SH, Higgins ST, Tyndale RF, 2018. Cigarette consumption and biomarkers of nicotine exposure during pregnancy and postpartum. Addict. 113(11), 2087–2096. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Xie X, Ding G, Cui C, Chen L, Gao Y, Zhou Y, Shi R, Tian Y, 2013. The effects of low-level prenatal lead exposure on birth outcomes. Environ Pollut. 175, 30–34. [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
