Smoking during pregnancy harms women and infants. Women who continue to smoke during pregnancy generally are poorer and more poorly educated and are more likely to have no partner or have a partner who smokes.
Medications to help stop smoking include nicotine replacement therapy (NRT), bupropion and varenicline. E-cigarettes contain nicotine and are used by some smokers to help avoid smoking. The safety and effectiveness of smoking cessation drugs and e-cigarettes is not known. This updated review sought evidence for the efficacy and safety of any smoking cessation drugs or e-cigarettes when these are used in pregnancy and found nine randomised studies that enrolled a total of 2210 women. Studies tested NRT used with behavioural support (counselling) apart from a small bupropion trial which enrolled only 11 women. Together, these showed borderline evidence to suggest that NRT combined with behavioural support, might help women to stop smoking in later pregnancy. However, when just the higher-quality, placebo-controlled trials were analysed, NRT was found to be no more effective than a placebo.
There was insufficient evidence to conclude whether or not NRT had either positive or negative impacts on rates of miscarriage, stillbirth, preterm birth (less than 37 weeks'), low birthweight (less than 2500 g), admissions of babies to neonatal intensive care or neonatal deaths or whether this affected mean birthweights amongst infants. However, in one trial in which infants were followed to two years of age, those born to women who had been randomised to NRT were more likely to have healthy development.
Side effects observed with NRT included headache, nausea and local reactions (e.g. skin irritation from patches or foul taste from gum).
Studies that reported adherence to medication found that this was generally low and the majority of participants did not use a large proportion of the NRT that was offered or prescribed to them.
More research evidence is needed; in particular, placebo-controlled trials that test higher doses of NRT, encourage high adherence rates and follow infants into childhood are now warranted.
NRT used in pregnancy for smoking cessation increases smoking cessation rates measured in late pregnancy by approximately 40%. There is evidence, suggesting that when potentially-biased, non-placebo RCTs are excluded from analyses, NRT is no more effective than placebo. There is no evidence that NRT used for smoking cessation in pregnancy has either positive or negative impacts on birth outcomes. However, evidence from the only trial to have followed up infants after birth, suggests use of NRT promotes healthy developmental outcomes in infants. Further research evidence on NRT efficacy and safety is needed, ideally from placebo-controlled RCTs which achieve higher adherence rates and which monitor infants' outcomes into childhood. Accruing data suggests that it would be ethical for future RCTs to investigate higher doses of NRT than those tested in the included studies.
Smoking in pregnancy is a public health problem. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion and varenicline) are effective for smoking cessation, however, their efficacy and safety in pregnancy remains unknown. Electronic Nicotine Delivery Systems (ENDS), or e-cigarettes, are becoming widely used but their efficacy and safety when used for smoking cessation in pregnancy are also unknown.
To determine the efficacy and safety of smoking cessation pharmacotherapies (including NRT, varenicline and bupropion), other medications, or ENDS when used for smoking cessation in pregnancy.
We searched the Pregnancy and Childbirth Group's Trials Register (11 July 2015), checked references of retrieved studies, and contacted authors.
Randomised controlled trials (RCTs) conducted in pregnant women with designs that permit the independent effects of any type of pharmacotherapy or ENDS on smoking cessation to be ascertained were eligible for inclusion.
The following RCT designs are included.
Placebo-RCTs: any form of NRT, other pharmacotherapy, or ENDS, with or without behavioural support/cognitive behaviour therapy (CBT), or brief advice, compared with an identical placebo and behavioural support of similar intensity.
RCTs providing a comparison between i) any form of NRT, other pharmacotherapy, or ENDS added to behavioural support/CBT, or brief advice and ii) behavioural support of similar (ideally identical) intensity.
Parallel- or cluster-randomised trials were eligible for inclusion. Quasi-randomised, cross-over and within-participant designs were not, due to the potential biases associated with these designs.
Two review authors independently assessed trials for inclusion and risk of bias and also independently extracted data and cross checked individual outcomes of this process to ensure accuracy. The primary efficacy outcome was smoking cessation in later pregnancy (in all but one trial, at or around delivery); safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being; and we also collated data on adherence with trial treatments.
This review includes a total of nine trials which enrolled 2210 pregnant smokers: eight trials of NRT and one trial of bupropion as adjuncts to behavioural support/CBT. The risk of bias was generally low across trials with virtually all domains of the 'Risk of bias' assessment tool being satisfied for the majority of studies. We found no trials investigating varenicline or ENDS. Compared to placebo and non-placebo controls, there was a difference in smoking rates observed in later pregnancy favouring use of NRT (risk ratio (RR) 1.41, 95% confidence interval (CI) 1.03 to 1.93, eight studies, 2199 women). However, subgroup analysis of placebo-RCTs provided a lower RR in favour of NRT (RR 1.28, 95% CI 0.99 to 1.66, five studies, 1926 women), whereas within the two non-placebo RCTs there was a strong positive effect of NRT, (RR 8.51, 95% CI 2.05 to 35.28, three studies, 273 women; P value for random-effects subgroup interaction test = 0.01). There were no differences between NRT and control groups in rates of miscarriage, stillbirth, premature birth, birthweight, low birthweight, admissions to neonatal intensive care, caesarean section, congenital abnormalities or neonatal death. Compared to placebo group infants, at two years of age, infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' (one trial). Generally, adherence with trial NRT regimens was low. Non-serious side effects observed with NRT included headache, nausea and local reactions (e.g. skin irritation from patches or foul taste from gum), but these data could not be pooled.