Abstract
Objective
This systematic review and meta-analysis aimed to evaluate the effects of electronic cigarette (E-cigarette) use and dual-use of E-cigarettes and conventional cigarettes (C-cigarettes) during pregnancy on adverse pregnancy outcomes, compared to C-cigarette use and non-use.
Methods
A two-step search was conducted: first, systematic reviews (SRs) on the effects of E-cigarette use during pregnancy were identified from Medline and Scopus up to November 7, 2023; second, an updated search from the last search of previous SRs to May 30, 2025, was performed to capture additional relevant studies. Eligible studies included observational studies and randomized controlled trials (RCTs) that assessed the impact of E-cigarette or dual-use on adverse pregnancy outcomes, with non-use or C-cigarette use as comparators. A two-stage network meta-analysis was conducted to compare the effects of E-cigarette use, dual-use, and non-use.
Results
Twelve studies (eleven observational and one RCT) were included. E-cigarette use was significantly associated with an increased risk of preterm birth (odds ratio = 1.67; 95% confidence interval [CI]: 1.11 to 2.51) and lower mean birth weight (mean difference = -57 g; 95% CI: -105 to -9) compared to non-use. However, the risks of small for gestational age (SGA), miscarriage, and mean gestational age at delivery in E-cigarette users did not differ from those in non-users. Dual use of E-cigarettes and C-cigarettes was significantly associated with increased risks of SGA, preterm birth, and lower mean birth weight compared to non-use. Compared to C-cigarette use, E-cigarette use was associated with lower risks of SGA and higher mean birth weight, while risks of preterm birth, miscarriage, and mean gestational age at delivery, did not differ between E-cigarette and C-cigarette users.
Conclusion
E-cigarette use during pregnancy was significantly associated with an increased risk of preterm birth and lower mean birth weight compared to non-use. Additionally dual-use was associated with elevated risks of SGA, preterm birth, and lower mean birth weight, compared to non-use. Although E-cigarette use was significantly associated with higher mean birth weight and decreased risk of SGA compared with C-cigarettes, no significant association was observed for other outcomes. These findings may be influenced by residual confounding and further high-quality studies are warranted to clarify the effect of E-cigarette use during pregnancy.
Trial registration
The review protocol has been registered at the PROSPERO website since 19 March 2024 (CRD42024521271).
Supplementary Information
The online version contains supplementary material available at 10.1186/s12889-025-25765-8.
Keywords: Electronic cigarette, Conventional cigarette, Pregnancy, Adverse pregnancy outcomes, Systematic review, Meta-analysis
Background
Electronic cigarettes (E-cigarettes), also known as electronic nicotine delivery systems (ENDS), are a type of handheld inhalation atomizer designed to administer nicotine and volatile organic compounds through a disposable or reusable device. This device may or may not contain nicotine but is free of tar and other by-products of tobacco combustion, which are the primary source of harmful substances found in conventional cigarettes (C-cigarettes).
Decades of research have established that using C-cigarettes during pregnancy is associated with a significant risk of preterm birth and low birth weight, which are common adverse outcomes of pregnancy [1, 2]. However, some pregnant women perceive E-cigarettes as a safer alternative to C-cigarettes and use them as a smoking cessation aid during pregnancy or as a harm reduction strategy during pregnancy [3, 4]. This is based on the belief that E-cigarette vapor typically contains fewer and lower levels of toxic substances than C-cigarette smoke, and that switching to E-cigarettes may potentially reduce health risks.
Although E-cigarette aerosols contain fewer hazardous materials than C-cigarette smoke [5, 6], they still pose potential risks to placental and fetal development. E-cigarette aerosols contain volatile organic compounds, heavy metals, carcinogens, and nicotine, all of which may have adverse effects on the fetus [7]. Results from in-vitro studies indicate that E-cigarette vapor, independent of nicotine, may impede the function of trophoblasts in the placenta, leading to complications in placental structure and the potential for preeclampsia, early miscarriage, premature birth, and even maternal or fetal death [8]. Additionally, findings from animal studies show that nicotine in E-cigarettes could lead to altered DNA methylation, potentially resulting in birth defects, low birth weight, and disruption of organ development in newborns [9].
Although results from animal and in vitro studies suggest a potential negative impact of E-cigarette use on pregnancy outcomes, studies in humans have shown conflicting and inconclusive results [4]. Previous systematic reviews [10, 11] highlighted this uncertainty, reporting mixed evidence regarding the relationship between E-cigarette use and perinatal outcomes. However, these previous systematic reviews usually used data from the same database, such as the Pregnancy Risk Assessment Monitoring System (PRAMS) database, which may contain overlapping pregnancy records, introducing risks of data duplication and potential bias. Additionally, the impact of dual use on adverse pregnancy outcomes has not been comprehensively reviewed, highlighting a critical gap in the existing evidence. Given the rising prevalence of E-cigarette use among pregnant women, including the dual use of E-cigarettes and C-cigarettes [12]—there is an urgent need for conclusive evidence on the effects of E-cigarette use on adverse pregnancy outcomes. To address this concern, we conducted a systematic review and network meta-analysis to estimate the impact of E-cigarette use and dual use of E-cigarettes and C-cigarettes on the risk of adverse pregnancy outcomes. The findings of this review aim to inform clinical counseling for pregnant women regarding the risks and potential benefits of E-cigarette use and to support decision-making in smoking cessation strategies and policy development for this vulnerable population.
Methods
This study is a sub-study of the systematic review and meta-analysis of the effect of E-cigarettes on health outcomes. The protocol of this systematic review has been registered on the PROSPERO website (CRD42024521271). Ethical approval of the review protocol is not required because this systematic review and meta-analysis used secondary data from published articles.
Study selection
A two-step search strategy was performed to identify relevant studies. First, systematic reviews, with or without meta-analysis, were searched in the Medline and Scopus databases from their inception until November 7, 2023. Systematic reviews were included if they assessed the effects of using E-cigarettes during pregnancy on adverse pregnancy and neonatal outcomes. Primary studies identified from the systematic reviews were then screened to select relevant studies. Second, an updated search was conducted to identify additional primary studies published after the most recent search dates of the previous systematic reviews (January 2021) up to May 30, 2025.
Search terms and search strategies for each database for both steps are presented in the Additional Appendix 1 and 2. Individual studies identified from previous systematic reviews and from the updated search were combined, and then selected by two independent reviewers (KS and TA). Full texts were reviewed if decisions could not be made based on titles and abstracts. Disagreements between the two reviewers were resolved by consensus with a third party.
Observational studies (i.e., cross-sectional, case–control, or cohort studies) and randomized controlled trials (RCTs) were eligible for this review if they met the following criteria: (1) were conducted in pregnant women, (2) compared the effects of using E-cigarettes or dual using of E-cigarettes and C-cigarettes during pregnancy to using C-cigarettes or non-smoking, and (3) reported adverse pregnancy or neonatal outcomes.
Exposures of interest and comparators
The exposures of interest were E-cigarettes use or dual use of E-cigarettes and C-cigarettes. E-cigarette use was defined as the use of battery-powered devices that deliver nicotine, flavorings, and other substances for inhalation without combustion [13]. These devices include ENDS that vary in design, size, and nicotine content, such as vape pens, tanks, mods, and pod-mods. The comparator was the use of C-cigarettes or non-use of both E-cigarettes and C-cigarettes. Smokeless tobacco products, such as chewing tobacco, snuff, snus, and dissolvable tobacco products, were not included in this review.
Outcomes of interest
The outcomes of interest were adverse pregnancy outcomes, referred to as health problems occurring in the mother and/or newborn during pregnancy, labor, and delivery, or the postpartum period [14]. These included pregnancy complications (e.g., miscarriage, hypertensive disorders of pregnancy, antepartum and postpartum hemorrhage), small for gestational age (SGA), preterm birth, stillbirth/intrauterine fetal death, neonatal death, and congenital anomalies. The mean difference of birth weight and gestational age at delivery between interested exposures and comparators was also included.
Data extraction
Data were independently extracted by two reviewers (KS and TA). The extracted data included study characteristics (author’s name, year of publication, study design, and setting), participant details (mean age, gestational age, percentages of employment, and living with partners), and definitions of exposures and comparators. For continuous outcomes (e.g., birth weight, gestational age at delivery), the number of participants, mean, and standard deviation by exposure and comparator groups were extracted. For dichotomous outcomes, the frequency of occurrence and non-occurrence of outcomes in the exposure and comparator groups were extracted.
Risk of bias assessment
The methodological quality of the included studies was evaluated using the Newcastle–Ottawa Scale (NOS) for observational studies [15] and the Cochrane risk-of-bias tool for randomized trials (RoB 2) for RCTs [16]. The NOS assesses the quality of cohort, cross-sectional, and case–control studies in three main categories, including selection of samples, comparability, and assessment of outcome. Each item in the NOS was rated as one star if it was of high quality, with a maximum of one star per item, except for the comparability item, which could receive up to two stars.
For RoB 2, five domains were assessed (bias arising from the randomization process, bias due to deviations from intended interventions, bias due to missing outcome data, bias in measurement of the outcome, and bias in selection of reported results). Each domain was graded as low, some concern, or high risk. If all domains for a study were assessed as low risk, the overall risk of bias was judged as low risk. If multiple domains were assessed as having some concern, or high risk, the overall risk of bias was judged as high risk.
Statistical analysis
Analysis was stratified according to the type of study (RCT vs. observational study). A pairwise meta-analysis was performed if there were at least 3 studies comparing similar exposure, comparator, and outcome. Unstandardized mean differences (USMD) of continuous outcomes (i.e., birth weight and gestational age at delivery), and odds ratios (OR) of dichotomous outcomes (i.e., SGA, preterm birth, and miscarriage) were pooled using the inverse variance method if there was no heterogeneity between studies, or the random effects model (DerSimonion and Laird method) if heterogeneity was present. Q test and I2 statistic were used to assess heterogeneity between studies. Heterogeneity was judged present if I2 was ≥ 25% or P-value from Q test < 0.10). Given the limited number of included studies that reported adjusted effect sizes, we pooled only the crude mean differences and ORs to estimate the effects of E-cigarette use and dual-use, while the adjusted mean differences and ORs were summarized qualitatively. Sensitivity analyses were conducted by excluding the studies rated as having poor or fair methodological quality, if at least three studies remained for the assessment of the corresponding outcome.
A two-stage frequentist network meta-analysis was applied to compare the effects of E-cigarette, C-cigarette, dual E-cigarette and C-cigarette use, and non-use. Relative treatment effect (USMDs and ORs) along with variance–covariance for each study was estimated. A random-effect multivariate meta-analysis with a consistency model was applied to pool relative treatment effects estimated from each study [17]. Publication bias was assessed using a comparison-adjusted funnel plot, with an asymmetric funnel plot suggesting the possible presence of publication bias.
All statistical analyses were performed using STATA version 18. A p-value less than 0.05 was considered as the threshold for significance for all tests except for Q-tests, where a p-value threshold less than 0.10 was used.
Patient and public involvement
Patients or the public were not involved in the design, conduct, reporting, or dissemination plans of our research.
Results
In the first step of study selection, 100 primary studies were identified from five previous systematic reviews and screened for eligibility. Of these, four primary studies met the inclusion criteria (see Additional Fig. 1 A).
Fig. 1.
Pooled odds ratio of small for gestational age between electronic cigarettes, conventional cigarettes, and non-use
In the second step, 384 primary studies were identified through an updated search. Of these, 24 studies were selected for full-text review. To avoid duplication of the same database sources used across studies, only the most recent and comprehensive publication representative of each database was included. Sixteen studies were subsequently excluded, including eight that used overlapping databases, which were removed due to potential duplication of pregnancy records (see Additional Table 1). As a result, twelve studies (8 studies from updated searching and 4 studies from previous systematic reviews) [18–29] were finally included in this review (see Additional Fig. 1B).
Characteristics of the included studies are described in Additional Table 2. All of the studies were published between 2019 and 2024, with five cross-sectional studies, five cohort studies, one case–control study, and one RCT. This single RCT [28] aimed to assess the adverse pregnancy outcomes in pregnant women currently smoking C-cigarettes, who switched from C-cigarettes to E-cigarettes or nicotine replacement therapy (NRT), and women who quit C-cigarette use without using E-cigarettes or NRT, compared to women who continued using C-cigarettes. Therefore, the meta-analysis included only observational studies, and the results from the RCT were only qualitatively described.
All studies were conducted in Western countries, with seven from the U.S., three from the U.K., and two from other European countries. Approximately half of the studies collected data on E-cigarette exposure during the third trimester. Among the observational studies, five studies defined exposure as the use of E-cigarettes or C-cigarettes at the time of data collection or within the past 30 days. Three studies defined exposure as the use of E-cigarettes or C-cigarettes during the third trimester, whereas four studies assessed exposure across all trimesters of pregnancy (see Additional Table 3). Regarding the definition of non-use, most studies (10 out of 12) defined non-use as the absence of current E-cigarette or C-cigarette use, or no use during pregnancy. In contrast, two studies defined non-use as never use of E-cigarettes or C-cigarettes [25, 26]. In all studies, exposure status was determined based on self-reported questionnaires. However, two studies [21, 28] incorporated biological indicators alongside questionnaire data, which helped validate the self-reported findings. The mean age of participants ranged from 26.9 to 30.8 years, and the employment rate among participants ranged from 12.2% to 95.9%.
Risk of bias assessment
The overall risk of bias for cohort studies was rated as low, i.e., good quality for all studies. However, all included cohort studies had poor quality in the domain of ascertainment of exposure (Additional Table 4). For case–control and cross-sectional studies, the Nanninga [26] and Froggatt studies [21] had fair overall quality because of issues related to comparability between subjects in different exposure and outcome groups (see Additional Tables 5 and 6). For the single RCT, the overall risk of bias was high due to concerns about the randomization process, deviation from the intended intervention, and missing outcome data (Additional Table 7).
Birth weight
Of 5 observational studies reporting the outcome of birth weight, two studies compared E-cigarettes with C-cigarettes, dual-use, and non-use [23, 25], while one study compared E-cigarettes with C-cigarettes and non-use [21], and two studies compared E-cigarette use with non-use [27, 29].
From a pairwise meta-analysis, the mean birthweight of infants in the E-cigarette group was significantly lower than the non-use group (USMD = −57 g; 95% CI: −105 to −10; I2 = 6.19%), see Additional Fig. 2A. When comparing birth weight in the E-cigarette group with the C-cigarette group, mean birth weight of infants was significantly higher in E-cigarette group than that in C-cigarette group, with USMD of 247 g (95% CI: 122 to 372; I2 = 56.47%), Additional Fig. 2B. The results of the sensitivity analysis, conducted by excluding the study with fair methodological quality [21], were consistent with the main analysis. The mean birth weight in the E-cigarette group remained significantly lower than that in the non-use group (USMD = −59 g; 95% CI: −107 to −10), but significantly higher than the C-cigarette group (USMD = 225 g; 95% CI: 87 to 363).
Fig. 2.
Pooled odds ratio of preterm birth between electronic cigarettes, conventional cigarettes, and non-use
Four observational studies were included in the network meta-analysis of birth weight (Additional Fig. 3 A and Additional Table 8). The global test suggested consistent results (χ2 = 1.10, p-value = 0.777). The network meta-analysis indicated that the mean birth weight of infants in the C-cigarette and dual use groups was significantly lower than that in the non-use group with USMDs of −277 g (95% CI: −368 to −186) and −269 g (95% CI: −373 to −166), respectively (Additional Fig. 4). Additionally, the mean birth weight of infants in the E-cigarette group was significantly higher than that in the C-cigarette and dual use groups with USMDs of 239 g (95% CI: 143 to 336), and 232 g (95% CI: 125 to 338), respectively. Mean birth weight of E-cigarette use was not different from that of non-use (see Table 1 and Additional Fig. 4). The adjusted mean differences reported in the studies by Opondo [27] and Hawkins [23] were consistent with the crude effect results: mean birth weight did not differ significantly between the E-cigarette and non-use groups. Conversely, the birth weight of infants in the C-cigarette and dual-use groups was significantly lower than that in the non-use group (Additional Table 8).
Table 1.
Mean difference of birth weight (above diagonal line) and gestational age at delivery (below diagonal line) estimated from network meta-analysis
| Non-use |
−269.37 (−373.15, −165.59) |
−276.99 (−367.75, −186.23) |
−37.74 (−111.65, 36.17) |
|
−0.21 (−0.49, 0.07) |
Dual use |
−7.62 (−118.21, 102.97) |
231.63 (125.42, 337.84) |
|
−0.32 (−0.40, −0.24) |
−0.11 (−0.40, 0.18) |
Conventional cigarettes |
239.25 (142.99, 335.51) |
|
−0.17 (−0.36, 0.02) |
0.04 (−0.30, 0.38) |
0.15 (−0.05 0.35) |
Electronic cigarettes |
Results are mean difference (95% confidence intervals) of birth weight (above diagonal line) and gestational age (below diagonal line) between each pair of exposure from network meta-analysis. Comparisons are read from right to left. For example, the mean difference of birth weight between E-cigarette compared to conventional cigarette is 239.25 (95% CI: 142.99 to 335.51)
The comparison-adjusted funnel plot was symmetrical, suggesting no publication bias (Additional Fig. 5 A).
Gestational age at delivery
Of the four observational studies that provided data on mean gestational age at delivery, two investigated the comparisons of E-cigarettes vs C-cigarettes vs dual-use vs non-use [23, 25], while one study focused on the comparisons of E-cigarettes vs C-cigarettes vs non-use [21], and one study compared E-cigarettes with non-use [27].
Results from the pairwise meta-analysis indicated that mean gestational age at delivery in the E-cigarette group was not different from the non-use group with USMD of −0.08 week (95%CI:−0.39 to 0.23; I2 = 41.77%), see Additional Fig. 6A. Additionally, the mean gestational age at delivery did not differ between E-cigarette and C-cigarette groups (USMD = 0.20 week; 95%CI:−0.19 to 0.59; I2 = 38.91 Additional Fig. 6B. When the study with fair methodological quality was excluded [21], the mean gestational age at delivery in the E-cigarette group was significantly lower than that in the non-use group, with a USMD of − 0.21 weeks (95% CI: − 0.41 to − 0.01). However, the comparison between the E-cigarette and C-cigarette groups remained unchanged, with a USMD of 0.08 weeks (95% CI: − 0.16 to 0.31).
A network meta-analysis was performed based on four observational studies (see Additional Table 9 and Additional Fig. 3B) with a consistency model (Global χ2 = 1.54, P-value = 0.673). Relative exposure effects indicated that mean gestational age at delivery in E-cigarette and dual use groups did not clearly differ from the non-use group. However, mean gestational age at delivery in the C-cigarette group was significantly lower than that in the non-use group with the USMD of −0.32 week (95% CI: −0.40 to −0.24). The mean gestational age at delivery in the E-cigarette group was not different from that in the C-cigarette and dual-use groups (see Table 1 and Additional Fig. 7). The adjusted mean differences in gestational age at delivery reported by Opondo [27] and Hawkins [23] were consistent with the crude estimates. These findings indicated that a lower mean gestational age at delivery was observed only in the C-cigarette use group compared with the non-use group (Additional Table 9).
The comparison-adjusted funnel plot was asymmetric, suggesting publication bias for this outcome (see Additional Fig. 5B).
Small for gestational age
Four observational studies reported the outcomes of SGA and compared the use of E-cigarette vs. C-cigarette, dual-use, and non-use [18, 19, 25, 26]. All studies defined SGA as a birth weight below the 10th percentile for GA at delivery. A pairwise meta-analysis indicated that using E-cigarettes during pregnancy did not significantly increase the odds of SGA compared to non-use, with a pooled OR of 1.68 (95% CI: 0.87 to 3.26; I2 = 60.87%), see Fig. 1A.
The dual-use during pregnancy significantly increased the odds of SGA in infants compared to non-use, with a pooled OR of 2.39 (95%CI: 2.12 to 2.68; I2 = 0%), see Fig. 1B. However, when comparing E-cigarette to C-cigarette and dual use, the odds of SGA were not different between E-cigarette and C-cigarette or dual-use (see Fig. 1C and D). When the study with fair methodological quality was excluded [26], the results remained consistent with the main findings. The use of E-cigarettes was not associated with higher odds of SGA infants compared with non-use, with a pooled OR of 1.34 (95% CI: 0.81 to 2.23). In contrast, dual-use of E-cigarettes and C-cigarettes was significantly associated with higher odds of SGA compared with non-use, with a pooled OR of 2.39 (95% CI: 2.12 to 2.69).
A network meta-analysis of 4 observational studies showed inconsistency (global χ2 = 28.98; p-value = < 0.001). Thus, a network meta-analysis with an inconsistency model was performed. Odds of SGA were not different between E-cigarette use and non-use, see Additional Table 10 and Additional Fig. 3C. In contrast, C-cigarette use and dual-use were significantly associated with increased odds of SGA, compared to non-use, with ORs of 2.21 (95%CI:1.63 to 3.00) and 2.55 (95%CI:1.81 to 3.59), respectively (Table 2 and Additional Fig. 8).
Table 2.
Odds ratio of small for gestational age (above diagonal line) and preterm birth (below diagonal line) estimated from network meta-analysis
| Non-use |
2.55 (1.81,3.59) |
2.21 (1.63, 3.00) |
1.36 (0.96,1.93) |
|
1.63 (1.20,2.21) |
Dual-use |
0.87 (0.62,1.21) |
0.53 (0.37,0.77) |
|
1.47 (0.97,2.23) |
0.90 (0.66,1.24) |
Conventional cigarettes |
0.61 (0.43,0.87) |
|
1.67 (1.11,2.51) |
1.02 (0.74,1.42) |
1.13 (0.87,1.48) |
Electronic-cigarettes |
Results are pooled odds ratios (95% confidence intervals) of small for gestational age (above diagonal line) and preterm birth (below diagonal line) between each pair of exposure from network meta-analysis. Comparisons are read from right to left. For example, the pooled odds ratio of small for gestational age of E-cigarette compared to conventional cigarette is 0.61 (95% CI: 0.43 to 0.87)
The odds of SGA were significantly lower with E-cigarette use compared to C-cigarette and dual use, with ORs of 0.61 (95%CI:0.43 to 0.87) and 0.53 (95%CI:0.37 to 0.77), respectively. The adjusted ORs reported in Cardenas's study [19] indicated no significant association between e-cigarette use, C-cigarette use, or dual-use and the odds of SGA when compared with non-use (Additional Table 10).
The comparison-adjusted funnel plot was asymmetrical, indicating the presence of publication bias (Additional Fig. 5 C).
Preterm birth
Three observational studies reported the outcome of preterm birth. Of these, two studies compared E-cigarette use, C-cigarette use, dual-use, and non-use [18, 26]; and one study compared E-cigarette use and non-use [27]. A pairwise meta-analysis showed significant effects of E-cigarettes on increased odds of preterm birth when compared to non-use (Fig. 2A) with the pooled ORs of 1.74 (95%CI:1.50 to 2.01; I2 = 0%). Risk of preterm birth did not differ between E-cigarette users and C-cigarette users (pooled OR = 1.15; 95% CI: 0.99 to 1.33; I2 = 0%), see Fig. 2B.
A network meta-analysis with consistency model was performed based on three observational studies (global χ2 = 1.20, P-value = 0.274), see Additional Fig. 3D and Additional Table 11. The ORs for E-cigarette use and dual-use compared to non-use were 1.67 (95% CI: 1.11 to 2.51) and 1.63 (95% CI: 1.20 to 2.21), respectively (Table 2 and Additional Fig. 9). These results suggest that using E-cigarettes and dual-use of E- and C-cigarettes during pregnancy were associated with the increased odds of preterm birth, compared to non-use. However, the results from Opondo's study [27] indicated that after adjusting for smoking pattern and sociodemographic characteristics, E-cigarette use was not associated with increased odds of preterm birth when compared to non-use (see Additional Table 11). The odds of preterm birth with E-cigarette use were not different when compared to C-cigarette use and dual use, with ORs of 1.13 (95% CI: 0.87 to 1.48) and 1.02 (95% CI: 0.74 to 1.42), respectively. The comparison-adjusted funnel plot was symmetrical, suggesting a lack of evidence for publication bias (Additional Fig. 5D).
Miscarriage
Three observational studies reported the outcome of miscarriage. Two studies compared E-cigarette use, with C-cigarette use, dual-use, and non-use [24, 26], while one study compared E-cigarette use with C-cigarette use and non-use [20]. A pairwise meta-analysis found that E-cigarette use did not increase the odds of miscarriage, compared to non-use, with pooled ORs of 1.70 (95% CI: 0.29 to 9.97; I2 = 79.25%), see Additional Fig. 10).
A network meta-analysis of 3 observational studies had a consistency model (global χ2 = 0.17, p-value = 0.920), see Additional Fig. 3E and Additional Table 12. E-cigarette use, and dual-use during pregnancy did not significantly increase the odds of miscarriage, compared to non-use, with ORs of 1.97 (95% CI: 0.51 to 7.69), and 3.35 (95% CI: 0.49 to 23.10), respectively (Additional Table 13 and Additional Fig. 11). Moreover, the risks of miscarriage were not significantly different among E-cigarette use, C-cigarette use, and dual-use. The adjusted OR reported by Cohn’s study [20] showed results consistent with the crude estimates, indicating that the odds of miscarriage did not differ between the E-cigarette use and non-use groups (Additional Table 12).
The comparison-adjusted funnel plot was asymmetric, suggesting the presence of publication bias, see Additional Fig. 5E.
Results from RCT
Results from the RCT [28] indicated that the mean birth weight and gestational age at delivery, as well as odds of having SGA and miscarriage in pregnant women who switched from C-cigarettes to E-cigarettes or NRT, were not clearly different from those in pregnant women who quit C-cigarettes. However, the mean birth weight of infants born to mothers who switched from C-cigarettes to E-cigarettes was higher than the mean birth weight of infants born to mothers who continued to use C-Cigarettes (mean difference = 200 g; 95%CI: 71 to 329). The risks of preterm birth and low birth weight were higher among women who switched from C-cigarettes to E-cigarettes compared with those who switched from C-cigarettes to NRT; however, these differences were not significant, with RRs of 3.13 (95% CI: 0.41 to 25.00) and 1.35 (95% CI: 0.41 to 4.55), respectively. Furthermore, the mean gestational age at delivery and mean birth weight were comparable between the E-cigarette and NRT groups, with mean differences of 0.28 weeks (95% CI: −0.81 to 1.36) and 0.01 g (95% CI: − 0.21 to 0.22), respectively.
Other outcomes
Other outcomes, including adverse maternal outcomes, hypertension in pregnancy, NICU admission, and head circumference, were summarized qualitatively due to a small number of studies for each of these outcomes. The effect of E-cigarette use relative to non-use during pregnancy on these outcomes is summarized in Additional Table 14.
One study [22] found that E-cigarette use during pregnancy significantly increased the risk of hypertension compared to non-use, but was not significantly associated with increased risks of adverse maternal outcomes and congenital anomalies. Additionally, two studies reported inconsistent results regarding NICU admission: one found a higher risk associated with E-cigarette use, while the other found a lower risk; however, neither result reached statistical significance. Furthermore, the mean head circumference of infants born to mothers who used E-cigarettes during pregnancy was not significantly different from that of infants born to non-users.
Discussion
Our findings demonstrated that E-cigarette use during pregnancy was significantly associated with an increased risk of preterm birth and lower mean birth weight compared to non-use. However, it was not significantly associated with increased odds of SGA, miscarriage, or reduced mean gestational age at delivery. In addition, dual-use of E-cigarettes and C-cigarettes during pregnancy was significantly associated with increased risk of SGA and preterm birth, and lower mean birth weight compared to non-use. When compared to C-cigarette use and dual-use, the E-cigarette use was significantly associated with a lower risk of SGA and a higher mean birth weight. However, the risks of preterm birth, miscarriage, and mean gestational age at delivery did not significantly differ among the E-cigarette, C-cigarette, and dual-use groups. Our findings emphasize that E-cigarette use during pregnancy may not be safe and may not serve as a harm reduction alternative compared to C-cigarettes.
We have found a significant association between E-cigarette use and an increased risk of preterm birth and lower mean birth weight, compared to non-use. This highlights potential health risks to pregnant women from hazards associated with E-cigarettes, including nicotine and various secondary compounds formed during high-temperature atomization of liquids [30]. These findings are consistent with concerns raised by previous in-vitro and animal studies, which suggest that E-cigarette use may impair fetal development and trophoblast function, potentially contributing to adverse pregnancy outcomes [8].
However, our study found no significant association between E-cigarette use and increased odds of SGA, or mean gestational age at delivery when compared to non-use. These findings may suggest a relative reduction in harm rather than a complete absence of risk. The lack of statistical significance could be attributed to limited statistical power. Therefore, additional large-scale and long-term studies are needed to confirm these findings. Additionally, exposure misclassification may have occurred due to the frequent reliance on self-reported data for C-cigarette and E-cigarette use, which are susceptible to recall and social desirability bias—particularly among pregnant women who may underreport smoking due to stigma. Most included studies used self-report measures, with some relying on retrospective recall during the postpartum period. Only a few studies [21, 28] included biological markers to validate self-reports and reduce the risk of misclassification. Such biases may have diluted true associations, leading to an underestimation of potential risks of E-cigarette use.
The confounding bias might be especially important to consider. Previous research has indicated that social determinants such as educational level, income, and social support play a significant role in birth weight and SGA [31], while the primary biological pathway for preterm birth is linked to placental function and uterine overdistension [32]. Our study found that infants born to pregnant women using E-cigarettes had significantly higher birth weights and lower odds of being SGA compared to those born to women using C-cigarette or dual-users. However, the disparities in socioeconomic and demographic characteristics between these groups may have influenced the observed associations, potentially affecting the validity of the pooled estimates for SGA and birth weight outcomes. The evidence from previous research has also shown that C-cigarette smokers and dual-users often face greater social disadvantage, as reflected in key social determinants of health, compared to exclusive E-cigarette users [33]. This pattern was consistent in our included studies, where imbalances in socioeconomic and demographic characteristics among user groups may have influenced the observed associations. It is also important to note that our meta-analysis relied primarily on unadjusted effect estimates, as few studies reported adjusted odds ratios. This limits the opportunity to control for confounding variables such as maternal health behaviors and background characteristics. Consequently, the associations between E-cigarette use and lower odds of SGA or higher mean birth weight, compared with C-cigarette smoking or dual-use, may partly reflect differences in baseline risk rather than true exposure-related effects.
E-cigarette use among pregnant women is increasing. One major concern is that some pregnant women see E-cigarettes as a safer option than C-cigarettes. Previous studies have suggested that pregnant women often view E-cigarettes as a better alternative to C-cigarettes [34, 35]. Most pregnant women who use E-cigarettes do so with the intention of quitting or reducing C-cigarette smoking [4]. This behavior has led to increasing interest in E-cigarettes as potential harm reduction tools during pregnancy. Our study adds important new evidence by directly addressing this issue. Specifically, our network meta-analysis evaluated the effects of dual-use and found that it offers no protective benefit. On the contrary, dual-use was consistently associated with adverse perinatal outcomes, with statistically significant effects across multiple indicators. Notably, the effect sizes for dual-use were comparable to—or even greater than—those for C-cigarette use alone. These findings highlight that combining both nicotine sources may not provide any benefit and could, in fact, increase risk, underscoring the need for targeted cessation strategies that discourage dual-use during pregnancy.
Another potential source of nicotine for pregnant women attempting to quit smoking is NRT. NRT is generally regarded as safer than E-cigarettes, as it provides nicotine without exposing users to the metals and other harmful chemical constituents present in E-cigarette aerosols. However, our study did not specifically aim to compare the risks of adverse pregnancy outcomes between E-cigarette and NRT use. Evidence from a single RCT included in this review showed no significantly higher risks of preterm birth and low birth weight among women who used E-cigarettes compared with those who used NRT, while the mean gestational age at delivery and birth weight were comparable between the two groups. Therefore, further studies are warranted to clarify whether E-cigarette use poses a greater risk of adverse pregnancy outcomes than NRT use.
Our study has several strengths. Firstly, we applied network meta-analysis to compare the relative exposure effects on adverse outcomes between E-cigarette and C-cigarette to investigate the hypothesis of harm reduction associated with E-cigarette use. Additionally, the effects of dual E-cigarette and C-cigarette use on adverse pregnancy outcomes were also explored in our review. These findings provided comprehensive evidence that extends beyond traditional pairwise comparisons, enabling a broader understanding of the relative risks across different patterns of cigarette use during pregnancy. Secondly, our work is distinguished from previous systematic reviews and meta-analyses that primarily relied on data from similar sources, such as the PRAMS dataset. These earlier reviews may have included overlapping pregnancy records (e.g., from 2016), introducing risks of data duplication and potential bias. In contrast, our review included only non-overlapping studies representing distinct populations. When multiple studies were derived from similar datasets, we prioritized the most comprehensive and recent publication. Lastly, with the growing number of primary studies investigating the effects of E-cigarette use in pregnancy over the past few years, our meta-analysis integrates more recent and diverse data sources. This approach enhances both the robustness and the generalizability of our findings.
However, our study has limitations. First, heterogeneity was observed across studies for certain outcomes, but potential sources could not be explored due to the limited number of studies within each pooled estimate. The observed heterogeneity may have arisen from differences in the definitions of exposures, and the timing of cigarette use during pregnancy across studies. These variations underscore the need for standardized approaches in future research to improve the comparability of findings. Longitudinal studies with repeated measurements of cigarette use throughout pregnancy are also warranted to capture dynamic patterns such as quitting, switching products, and transitions between exclusive use, dual use, and cessation. Incorporating these dimensions will be essential to strengthen prenatal counseling on the risks of E-cigarette use during pregnancy and to inform public health recommendations.
Most studies defined non-use as the absence of E-cigarette or C-cigarette use at the time of data collection or during pregnancy. Consequently, the non-use group might include both former smokers and never-users. Furthermore, all studies assessed exposure status using self-reported questionnaires, which may have introduced misclassification bias and affected the robustness of the findings. Moreover, none of the included studies examined the dose–response relationship between smoking intensity, nicotine strength and adverse pregnancy outcomes. This gap limits the ability to assess the magnitude of the risk of adverse pregnancy outcomes associated with E-cigarette use in the existing evidence. Therefore, future research should adopt more comprehensive exposure assessments that account for the frequency, duration, and intensity of use, as well as nicotine dose and product type, and link these parameters to adverse pregnancy outcomes.
Due to the limited number of studies, we were unable to pool data on several adverse outcomes, including hypertension in pregnancy, NICU admission, and congenital anomalies. Small sample sizes and insufficient power may also account for the non-significant findings regarding E-cigarette related harms. To clarify the effects of E-cigarette use in pregnancy, more prospective longitudinal studies are needed. Moreover, studies examining postnatal outcomes—such as neurodevelopment and long-term child health—are essential to fully assess the impact of prenatal E-cigarette exposure. Robust methodological approaches will strengthen the evidence base to guide clinical and public health recommendations about the safety of E-cigarette use during pregnancy.
Lastly, the literature search was conducted in two databases—MEDLINE and Scopus. Unpublished studies and grey literature were not included, which may have introduced publication bias. Egger’s test was not performed because of the small number of included studies. Although the funnel plot analysis showed no apparent evidence of publication bias for birth weight and preterm birth outcomes, the possibility of such bias cannot be entirely excluded given the limited number of studies available.
Conclusion
Our findings suggest that E-cigarette use during pregnancy may not be safe, as it is significantly associated with an increased risk of preterm birth and reduced mean birth weight compared to non-use. While our study found the association between E-cigarette use and the lower risk of SGA and mean birth weight compared to C-cigarette use, the risks of other adverse pregnancy outcomes did not differ significantly between E-cigarette and C-cigarette use. Thus, our evidence regarding E-cigarettes as a harm reduction alternative to C-cigarettes is inconclusive. These findings may be influenced by residual confounding, and further large-scale prospective cohort studies or RCTs are warranted to confirm the impact of of E-cigarette use on pregnancy outcomes.
Supplementary Information
Acknowledgements
Not applicable.
Abbreviations
- BW
Birth weight
- C-cigarette
Conventional cigarette
- CI
Confidence interval
- E-cigarette
Electronic cigarette
- ENDS
Electronic nicotine delivery systems
- GA
Gestational age at delivery
- NICU
Neonatal intensive care unit
- NOS
Newcastle and Ottawa scale
- OR
Odds ratio
- PRAMS
Pregnancy Risk Assessment Monitoring System
- RCT
Randomized controlled trial
- ROB-2
Cochrane risk of bias assessment tool
- RR
Relative risk
- SGA
Small for gestational age
- USMD
Unstandardized mean difference
Authors’ contributions
K.S. and T.A. are involved in the study conception, study design, study selection, data extraction, risk of bias assessment, data analysis, data interpretation. N.C., S.B., A.TA., and P.P. are involved in study design, and study selection. G.J.M, and J.A. are involved in study design, and result interpretation. P.I. is involved in data extraction, and risk of bias assessment. A.TH. is involved in study conception, study design, data analysis, and result interpretation. K.S. and T.A. wrote the first draft of the manuscript, and all authors edited, reviewed, and approved the final version of the manuscript. K.S. and T.A. are the guarantor of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Funding
Open access funding provided by Mahidol University. This study was supported by the Tobacco Control Research and Knowledge Management Center (grant no. 67-P1-0154). T.A. was in receipt of grant.
Data availability
The datasets generated during and/or analyzed in the current study are available from the supplementary materials.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Footnotes
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Data Availability Statement
The datasets generated during and/or analyzed in the current study are available from the supplementary materials.