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Prenatal Cannabis Use and Neonatal Outcomes A Systematic Review and Meta-Analysis

Author/s: 
Jamie O Lo, Chelsea K Ayers, Snehapriya Yeddala, Beth Shaw, Shannon Robalino, Rachel Ward, Devan Kansagara

Importance: Prenatal cannabis use continues to increase, and cannabis remains the most commonly used illegal substance in pregnancy. Accumulating evidence suggests potential adverse effects on fetal and neonatal outcomes following cannabis use in pregnancy.

Objective: To update a living systematic review and meta-analysis to provide a timely understanding regarding cannabis use in pregnancy and fetal and neonatal outcomes.

Data sources: The previous review was updated by searching bibliographic databases MEDLINE, CINAHL, PsycInfo, Global Health, and Evidence-Based Medicine Reviews Cochrane Database of Systematic Reviews from November 1, 2021, through April 4, 2024.

Study selection: Cohort or case-control studies comparing pregnancies with and without prenatal cannabis use on prespecified fetal or neonatal outcomes with adjustment for confounders, such as co-use of tobacco products, were included. Two independent reviewers screened studies, with disagreements resolved through discussion.

Data extraction and synthesis: Included studies were extracted by 1 reviewer and confirmed by a second. Risk of bias was assessed with the Newcastle-Ottawa Scale. Random-effects meta-analyses of unadjusted and adjusted odds ratios (ORs) were performed for all primary outcomes. Results were synthesized using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Main outcomes and measures: Primary outcomes were preterm birth (PTB; <37 weeks of gestation), small for gestational age (SGA), low birth weight (LBW; <2500 g), and perinatal mortality.

Results: For this update, 8 new studies with 1 709 998 participants were added, for a total of 51 studies synthesized (N = 21 146 938). From meta-analyses of adjusted effect sizes, moderate-certainty evidence indicated that cannabis use in pregnancy was associated with increased odds of LBW (20 studies; OR, 1.75; 95% CI, 1.41-2.18), PTB (20 studies; OR, 1.52; 95% CI, 1.26-1.83), and SGA (12 studies; OR, 1.57; 95% CI, 1.36-1.81), and low-certainty evidence indicated that it was associated with greater odds of perinatal mortality (6 studies; OR, 1.29; 95% CI, 1.07-1.55). Previously, the evidence was rated as very low or low certainty.

Conclusions and relevance: Cannabis use in pregnancy was associated with greater odds of PTB, SGA, and LBW even after adjusting for co-use of tobacco products, and confidence in these findings increased from low in the prior review to moderate in the current meta-analysis. The findings of this study may help inform patient counseling and future public health policies.

Keywords 
Pregnancy prenatal cannabis cannabis cannabis use infants

Electronic Cigarettes vs Varenicline for Smoking Cessation in Adults: A Randomized Clinical Trial

Author/s: 
Anna Tuisku, Mikko Rahkola, Pentti Nieminen, Tuula Toljamo

Importance: Little is known about the relative effectiveness of nicotine-containing electronic cigarettes (ECs) compared with varenicline as smoking cessation aids.

Objective: To determine the relative effectiveness of ECs in smoking cessation.

Design, setting, and participants: This randomized placebo-controlled single-center trial was conducted in northern Finland. Participants aged 25 to 75 years who smoked daily and had volunteered to quit smoking were recruited from August 1, 2018, to February 20, 2020, via local media. The trial included 52 weeks of follow-up. All data analyses were conducted from September 1, 2022, to January 15, 2024. The participants, study nurses, and researchers were masked to group assignment.

Intervention: The participants were assigned by block randomization to receive 18 mg/mL of nicotine-containing ECs together with placebo tablets, varenicline with standard dosing together with nicotine-free ECs, or placebo tablets together with nicotine-free ECs, all combined with a motivational interview, with the intervention phase lasting for 12 weeks.

Main outcome and measure: The primary outcome was self-reported 7-day conventional cigarette smoking abstinence as confirmed by the exhaled carbon monoxide level on week 26. The analysis followed the intent-to-treat principle.

Results: Of the 561 recruited participants, 458 (81.6%) eligible participants (257 women [56%]; 201 men [44%]; mean [SD] age, 51 [11.6] years) were randomized. The primary outcome occurred in 61 of 152 participants (40.4%) in the EC group, 67 of 153 (43.8%) in the varenicline group, and 30 of 153 (19.7%) in the placebo group (P < .001). In the pairwise comparison, placebo differed statistically significantly from ECs (risk difference [RD], 20.7%; 95% CI, 10.4-30.4; P < .001) and varenicline (RD, 24.1%; 95% CI, 13.7-33.7; P < .001), but the difference was statistically insignificant between ECs and varenicline (RD, 3.4%; 95% CI, -7.6 to 14.3; P = .56). No serious adverse events were reported.

Conclusions: This randomized clinical trial found that varenicline and nicotine-containing ECs were both effective in helping individuals in quitting smoking conventional cigarettes for up to 6 months.

Keywords 
e-cigarettes cigarettes Varenicline smoking smoking cessation

Association Between E-Cigarette Use and Chronic Obstructive Pulmonary Disease by Smoking Status: Behavioral Risk Factor Surveillance System 2016 and 2017

Author/s: 
Osei , A.D., Mirbolouk, M., Orimoloye, O.A., Dzaye, O.

Introduction: The association between e-cigarette use and chronic bronchitis, emphysema, and
chronic obstructive pulmonary disease has not been studied thoroughly, particularly in populations
defined by concomitant combustible smoking status.

Methods: Using pooled 2016 and 2017 data from the Behavioral Risk Factor Surveillance System,
investigators studied 705,159 participants with complete self-reported information on e-cigarette use,
combustible cigarette use, key covariates, and chronic bronchitis, emphysema, or chronic obstructive
pulmonary disease. Current e-cigarette use was the main exposure, with current use further classified
as daily or occasional use. The main outcome was defined as reported ever having a diagnosis of

chronic bronchitis, emphysema, or chronic obstructive pulmonary disease. For all the analyses, multi-
variable adjusted logistic regression was used, with the study population stratified by combustible ciga-
rette use status (never, former, or current). All the analyses were conducted in 2019.

Results: Of 705,159 participants, 25,175 (3.6%) were current e-cigarette users, 64,792 (9.2%) current
combustible cigarette smokers, 207,905 (29.5%) former combustible cigarette smokers, 432,462

(61.3%) never combustible cigarette smokers, and 14,036 (2.0%) dual users of e-cigarettes and combus-
tible cigarettes. A total of 53,702 (7.6%) participants self-reported chronic bronchitis, emphysema, or

chronic obstructive pulmonary disease. Among never combustible cigarette smokers, current e-ciga-
rette use was associated with 75% higher odds of chronic bronchitis, emphysema, or chronic obstruc-
tive pulmonary disease compared with never e-cigarette users (OR=1.75, 95% CI=1.25, 2.45), with

daily users of e-cigarettes having the highest odds (OR=2.64, 95% CI=1.43, 4.89). Similar associations
between e-cigarette use and chronic bronchitis, emphysema, or chronic obstructive pulmonary disease
were noted among both former and current combustible cigarette smokers.
Conclusions: The results suggest possible e-cigarette−related pulmonary toxicity across all thecategories of combustible cigarette smoking status, including those who had never smoked combus-
tible cigarettes.

Keywords 
vaping e-cigarette

Pulmonary Illness Related to E-Cigarette Use in Illinois and Wisconsin - Preliminary Report

Author/s: 
Layden, J.E., Ghinai, I, Pray, I, Kimball, A, Layer, M, Tenforde, M, Navon, L, Hoots, B, Salvatore, PP, Elderbrook, M, Haupt, T, Kanne, J, Patel, MT, Saathoff-Huber, L, King, BA, Schier, JG, Mikosz, CA, Meiman, J

BACKGROUND:

E-cigarettes are battery-operated devices that heat a liquid and deliver an aerosolized product to the user. Pulmonary illnesses related to e-cigarette use have been reported, but no large series has been described. In July 2019, the Wisconsin Department of Health Services and the Illinois Department of Public Health received reports of pulmonary disease associated with the use of e-cigarettes (also called vaping) and launched a coordinated public health investigation.

METHODS:

We defined case patients as persons who reported use of e-cigarette devices and related products in the 90 days before symptom onset and had pulmonary infiltrates on imaging and whose illnesses were not attributed to other causes. Medical record abstraction and case patient interviews were conducted with the use of standardized tools.

RESULTS:

There were 53 case patients, 83% of whom were male; the median age of the patients was 19 years. The majority of patients presented with respiratory symptoms (98%), gastrointestinal symptoms (81%), and constitutional symptoms (100%). All case patients had bilateral infiltrates on chest imaging (which was part of the case definition). A total of 94% of the patients were hospitalized, 32% underwent intubation and mechanical ventilation, and one death was reported. A total of 84% of the patients reported having used tetrahydrocannabinol products in e-cigarette devices, although a wide variety of products and devices was reported. Syndromic surveillance data from Illinois showed that the mean monthly rate of visits related to severe respiratory illness in June through August of 2019 was twice the rate that was observed in the same months in 2018.

CONCLUSIONS:

Case patients presented with similar clinical characteristics. Although the features of e-cigarette use that were responsible for injury have not been identified, this cluster of illnesses represents an emerging clinical syndrome or syndromes. Additional work is needed to characterize the pathophysiology and to identify the definitive causes.

Keywords 
vaping caution

Electronic Nicotine Delivery Systems (ENDS)

Electronic nicotine delivery systems (ENDS), also called electronic cigarettes, e-cigarettes, vaping devices, or vape pens, are battery-powered devices used to smoke or “vape” a flavored solution which usually contains nicotine. The American Academy of Family Physicians (AAFP) recognizes the alarmingly increased use of ENDS, especially among youth and young adults, as well as its use by those attempting to quit smoking tobacco.

The AAFP calls for further research to assess ENDS’ safety, quality, and efficacy as a potential cessation device. The AAFP also recommends that the marketing and advertising of ENDS to children and youth cease immediately. The AAFP encourages members to screen for ENDS use starting with school-age children, to discuss the potential harms of ENDS, and to recommend cessation interventions with e-cigarette users. The AAFP encourages members to inform patients who use ENDS, especially children, that the majority of these products contain nicotine and are addictive.  (2014 COD) (April 2019 BOD)

Keywords 
adolescent adult child nicotine tobacco vaping family electronic protocol U.S.
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