Cited by 2Smoking Behavior and CessationPrenatal Substance Exposure EffectsMaternal and Neonatal Healthcare

The DOI matches its Crossref record; 88 of the 88 references it cites were found in a registry or an index; 1 of the 133 sources its claims cite were checked for support.

Birth outcomes following intrauterine exposure to electronic nicotine delivery systems: a systematic review and meta-analysis

Open access
Johnstone, Samantha, Schenkel, Ashley, Canazzi, Samantha, Eiden, Rina D, Hawk, Jr., Larry W·2026·Nicotine & Tobacco Research

Abstract

Introduction: Despite electronic nicotine delivery systems (ENDS) being used for smoking cessation during pregnancy, the relative consequences are still unclear. Here, we systematically reviewed and meta-analyzed birth outcomes associated with ENDS use. Methods: This review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. OVID (MEDLINE, EMBASE, PsycINFO) and PubMed databases were searched from inception until August 2025, for studies comparing outcomes from in utero exclusive ENDS exposure to non-exposed, exclusive nicotine replacement therapy–exposed, or exclusive combustible cigarette (CC)–exposed neonates. Results: We included k = 22 studies with k = 10 independent samples. In ENDS-exposed vs non-exposed births, there were significantly greater odds of preterm birth (k = 3; moderate confidence) but not small for gestational age (SGA; k = 3; low confidence); these findings were less robust to sensitivity analysis. Additionally, there was no significant difference in SGA (k = 3; moderate confidence) or preterm birth (k = 3; high confidence) between CC-exposed and ENDS-exposed neonates; these findings were robust to sensitivity analysis. Analysis of continuous outcomes found lower birthweight in ENDS- vs non-exposed neonates (k = 4; moderate confidence) and lower birthweight in CC- vs ENDS-exposed neonates (k = 4; low confidence), and no difference in gestational age in either comparison (low confidence). Narrative synthesis suggests quitting ENDS was associated with better birth outcomes, and associations between ENDS and delayed development of infant motor maturity and reflexes. Conclusion: ENDS exposure may confer comparable risk as cigarette smoking to preterm birth. Further research is needed given low to moderate confidence in findings and risk of bias conferred by limited classification of exclusive ENDS use. Implications: With respect to adverse birth outcomes, ENDS may constitute a risk compared to no-nicotine exposure, suggesting the importance of investigating vaping cessation interventions, as well as greater research into alternative smoking cessation interventions for people who are pregnant or want to become pregnant.

Overview

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 22 studies (10 independent samples) found that exclusive intrauterine ENDS exposure was associated with greater odds of preterm birth and lower birthweight versus no nicotine exposure, but odds of preterm birth and SGA were not significantly different from combustible cigarette exposure. Confidence in most estimates was low to moderate, and the authors conclude ENDS may confer comparable risk to smoking for preterm birth while calling for better exposure measurement and vaping-cessation research.

Key findings

  • ENDS-exposed vs non-exposed: significantly greater odds of preterm birth (k = 3; n = 334 vs 56,571; OR = 1.25, 95% CI [1.01, 1.56]; I² = 0%, P = .55), but not SGA (k = 3; n = 988 vs 175,247; OR = 3.48, 95% CI [0.68, 17.76]; I² = 61%, P = .06). The abstract/GRADE narrative reports moderate confidence for preterm birth and low confidence for SGA; Table 1 lists preterm vs non-use as low confidence.
  • CC-exposed vs ENDS-exposed: no significant difference in preterm birth (k = 3; n = 1010 vs 15,061; OR = 0.96, 95% CI [0.82, 1.12]; I² = 0%, P = .87; high confidence) or SGA (k = 3; n = 988 vs 14,932; OR = 1.32, 95% CI [0.37, 4.69]; I² = 67.2%, P = .03; moderate confidence).
  • Continuous outcomes: lower birthweight in ENDS- vs non-exposed neonates (k = 4; n = 726 vs 29,390; SMD = −94.2, 95% CI [−132.2, −4.79], P < .001; moderate confidence), with no gestational-age difference (k = 5; n = 597 vs 54,460; SMD = 0.8, 95% CI [−0.30, 0.47], P = .65; low confidence). CC- vs ENDS-exposed neonates showed lower birthweight in CC-exposed (k = 4; n = 726 vs 2405; SMD = 223.2, 95% CI [29.6, 416.8], P = .20 as reported; low confidence), with no gestational-age difference (k = 3; n = 232 vs 271; SMD = .39, 95% CI [−0.21, 1.00], P = .20; low confidence).
  • Narrative synthesis: quitting ENDS was associated with better birth outcomes in some studies; one study found lower motor maturity and reflexes in ENDS- and CC-exposed infants/toddlers vs non-exposed, with no significant differences between ENDS- and CC-exposed. NRT as a comparator could not be meta-analyzed because only one study assessed it.

Methods

  • PRISMA-reported systematic review and meta-analysis pre-registered with PROSPERO (CRD42024584628); searched PubMed, OVID MEDLINE, EMBASE, and PsycINFO in September 2024, March 2025, and August 2025.
  • Included original peer-reviewed studies of newborns, infants, or toddlers (0 days to 3 years) with exclusive in utero ENDS exposure compared with no nicotine exposure, exclusive combustible cigarette exposure, or exclusive NRT exposure, on validated birth or neurodevelopmental outcomes; excluded animal models, meta-analyses, and systematic reviews. Included k = 22 studies with k = 10 independent samples.
  • Random-effects meta-analysis for binary outcomes using most-adjusted ORs and for continuous outcomes using standardized mean differences, requiring at least three studies per outcome; assessed risk of bias with ROBINS-E/ROBINS-I, GRADE certainty, I² heterogeneity, trim-and-fill, influential-case analyses, and sensitivity analyses substituting PRAMS samples; analyses in R with metafor.

Limitations

  • The paper states that ENDS-exposed samples were substantially smaller than non-exposed or cigarette-exposed groups; ENDS exposure was typically poorly quantified (frequency, quantity, and nicotine concentration often unreported), mostly self-report with only five studies using bioverification; exposure classification often relied on last-3-months use and may miss product switching; some ORs were derived from unadjusted cell counts; no included studies investigated co-exposure to alcohol or cannabis; only one study assessed neurodevelopmental outcomes; and most studies had some or high risk of bias.
  • The paper states that handling of overlapping PRAMS samples was not pre-registered, and sensitivity analyses substituting PRAMS studies produced inconsistent significance for preterm birth and SGA versus non-exposed.
  • Evident in the text: confidence ratings for preterm birth versus non-exposed differ between the abstract/GRADE narrative (moderate) and Table 1 (low), and the CC- vs ENDS-exposed birthweight result reports a confidence interval excluding zero alongside P = .20.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1093/ntr/ntag118

Cites

88 of 88 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Verification

Claims the paper makes

43 Not checked yet · 39 Own method · 23 Own result · 20 Check pending · 15 Own interpretation · 5 No full text of the sources · 2 Sources not found · 1 Partly supported · accuracy not yet measured

Verify all 101 references — free account

Show all 67 claims

  • It may state two separate claims as one. 54
  • Probably not a substantial claim. 39
81 of 81
  • The paper relies on this without support.

    The included studies' study-defined classifications of exclusive ENDS use adequately distinguish exclusive ENDS exposure from other nicotine exposures for the meta-analytic estimates to be valid.

    “Note that groups were classified based on study-defined exclusivity, which is detailed in Supplemental Table S1.”
    “There was a high degree of variability among studies with respect to classification of exposure, with k = 8 PRAMS studies defining exclusive use in the last 3 months of gestation and the remaining PRAMS studies defining exclusive use in the 3 months prior to and last 3 months during gestation, and k = 2 assessing use in the past 30 days at survey completion.”
  • The paper relies on this without support.

    The included studies' exposure classifications (e.g., product used in the last 3 months of pregnancy) adequately represent intrauterine ENDS/CC exposure for the meta-analyses.

    “ENDS and CC exposure were grouped based on classifications from included studies, most typically the product used in the last 3 months of pregnancy, either with or without consideration of use in the last 3 months before pregnancy.”
  • The paper relies on this without support.

    The no-nicotine exposure group is unexposed to nicotine.

    “compared to no nicotine exposure”
3 of 3

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

6 of 6

Citations

Cites

Show all 88 references

Research works printed but not linked: 4

  1. Health UDo, Services H, 2014, The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General
  2. U.S. Department of Health and Human Services, 2001, Women and Smoking: A Report of the Surgeon General: Department of Health and Human Services
  3. Eaton, 2018, Toxicology of E-Cigarette Constituents
  4. Schoon, 2010, Childhood cognitive ability and adult academic attainment: evidence from three British cohort studies, 241

Cited by

Sorted by citations

Metadata

Authors
Johnstone, S., Schenkel, A., Canazzi, S., Eiden, R. D., & Hawk, Jr.
Affiliations
  • University at Buffalo, State University of New York (US)
  • Pennsylvania State University (US)
  • Department of Psychology, State University of New York at Buffalo , Buffalo, NY 14260 ,
Venue
Nicotine & Tobacco Research
Published
2026-05-23
Volume
28
Issue
10
Pages
1635-1649
ISSN
  • 1462-2203 (ISSN-L)
  • 1469-994X
OpenAlex
W7162197577
Cited by
2
References
88
Citations by year
2026: 2
FWCI
2.14
Type
journal article
Language
en
Open access
Locations
  • Nicotine & Tobacco Research (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Center for Advancing Translational Sciences (UG3 TR004797-02)
  • National Cancer Institute (R01 CA266170-01A1)
  • National Institutes of Drug Abuse (R01 DA054276-01A1, 3R01DA054276-03S1)
  • Canadian Institutes of Health Research Doctoral Foreign Study (202310DFD-513256-DRA-86383)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Smoking Behavior and Cessation
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Maternal and Neonatal Healthcare
Keywords
electronic cigarettes, birth outcomes, preterm birth, small for gestational age, birth weight, combustible cigarettes, nicotine replacement therapy, smoking cessation, infant motor development, prenatal nicotine exposure
MeSH terms
Female, Humans, Infant, Newborn, Infant, Small for Gestational Age, Pregnancy, Pregnancy Outcome, Prenatal Exposure Delayed Effects, Smoking Cessation, Premature Birth, Electronic Nicotine Delivery Systems

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

A language model drew the claims from the paper on 2026-11-11, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).

A second model labelled each claim on 2026-11-11 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).

Cited sources are checked with a language model’s help (gpt-6-sol).

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review