Main results:
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. However, subgroup analysis of placebo-RCTs provided a lower RR in favour of NRT, whereas within the two non-placebo RCTs there was a strong positive effect of NRT. 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.

Authors' conclusions:
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.