A deep dive into risks and outcomes

In a recent study published in Addiction, researchers examined the safety of electronic cigarettes (ECs) and nicotine-containing patches (NRT) as smoking cessation aids during pregnancy using the Pregnancy Trial of Electronic Cigarettes and Patches (PREP) randomized clinical trial (RCT) data.

Smoking is associated with adverse pregnancy outcomes; however, the role of nicotine in producing these effects is unclear. Animal studies show that chronic high doses of nicotine during pregnancy can lead to serious adverse effects, but it is unclear whether this also applies to intermittent self-administered nicotine doses in humans.

NRT is extensively used to assist in quitting smoking, but recent systematic reviews found no significant adverse effects. A few pregnant smokers use ECs; however, data on their safety in pregnancy is limited.

About the study

In the present study, researchers analyzed PREP data to compare safety outcomes among pregnant regular and non-regular users of EC and NRT.

The study involved 1,140 pregnant smokers from 23 hospitals in England and a smoking cessation service in Scotland. The team randomized the participants to the NRT group (5 mg/16-hour nicotine patches) or the EC group (18 mg/ml nicotine). The participants received up to six weekly telephone calls and were contacted again at gestation week 35 (end of pregnancy, EOP). In addition, they obtained safety data three months post-delivery.

The study included pregnant daily smokers requiring smoking cessation assistance, with no preference for EC or NRT, who were not currently using these products. Outcomes included nicotine consumption compared to baseline, birthweight, adverse events (AEs), serious AEs (SAEs), maternal pulmonary symptoms (such as phlegm, breathlessness, wheezing, and cough), and relapse among early abstainers.

The participants provided demographic and smoking history data and saliva samples at baseline. During telephone calls one to four weeks post-target quit date (TQD) and at EOP, participants reported their smoking status and nicotine product usage.

At EOP, the team obtained saliva samples from self-reported smokers, abstainers, and reducers for cotinine analysis. Individuals who did not smoke in the week before EOP were abstainers; those smoking in current times were smokers; and those reporting a ≥50% reduction in their daily cigarette intake at EOP were reducers.

The team performed mixed-effect logistic regression modeling to estimate risk ratios (RR). They excluded individuals who withdrew from the study before delivery, those with a history of elective termination, those giving birth outside study sites, those with missing birth and maternal outcome data, and those having twins.

Results

EC use was more frequent than NRT use (47% [n=539] versus 21% [n=235]) during pregnancy. The difference in use was profound among individuals using electronic cigarettes and nicotine-based patches at EOP (21% [n=232] versus 2.5% [n=28]).

There were non-significant differences among abstainers consuming and not consuming nicotine-based products, with both groups having lower baseline cigarette dependence scores. Birth weight was higher in abstainers consuming nicotine products than in smokers.

Abstainers and smokers using nicotine products did not have worse pregnancy outcomes or more adverse events. EC users reported more improvements in cough and phlegm, and EC or NRT use had no association with relapse.

Among abstainers, there were 131 (67%) regular users of EC and 40 (20%) of NRT, while 25 (13%) abstainers did not use nicotine products regularly. Abstainers using EC at EOP lowered cotinine levels in saliva by 45% (i.e., 49 ng/ml). Salivary cotinine rose by 19% (i.e., 24.0 ng/ml) in dual users, by 10% in female reducers who consumed products containing nicotine, and by 9% among females who did not.

The birth weights of neonates of abstainers using EC or NRT regularly showed no differences (3.3 kg); therefore, the team combined both groups as abstainers consuming nicotine products regularly. There were no significant differences in birth weight between infants born to females who continued smoking and did not use nicotine-containing products and those born to dual users.

Abstainers who did not consume nicotine-containing products (n=25) reported more pre-term deliveries than those using nicotine and a higher percentage of adverse pregnancy outcomes. Among females who could not stop smoking, the team observed non-significant differences between nicotine consumers and non-consumers.

EC users documented more improvements versus non-users of ECs in lowering phlegm (adjusted RR [aRR, 0.5]) and cough (aRR, 0.6). Combining smokers and abstainers, nicotine users and non-users showed no significant differences in AEs (26 vs. 22%; RR, 1.1) or SAEs (12% vs. 15%; RR, 0.8).

Conclusions

Overall, the study findings showed that e-cigarette and nicotine patch users had higher birth weights than smokers but no pregnancy risks. Pregnant smokers using nicotine patches or electronic cigarettes did not seem to have adverse outcomes.

E-cigarette users reduced salivary cotinine levels by 45% at EOP, while dual users increased levels by 19%. Women who reduced cigarette intake by ≥50% increased salivary cotinine by 9-10 percent.