Claire Ravinder, Chamberlain Catherine, Davey Mary-Ann, Cooper Sue E, Berlin Ivan, Leonardi-Bee Jo, Coleman Tim
University of Nottingham, Division of Primary Care, Room 1502, Tower Building, University Park, Nottingham, Nottinghamshire, UK, NG7 2RD.
La Trobe University, Judith Lumley Centre, 251 Faraday Street, Melbourne, Vic, Australia, 3000.
Cochrane Database Syst Rev. 2020 Mar 4;3(3):CD010078. doi: 10.1002/14651858.CD010078.pub3.
Tobacco smoking in pregnancy causes serious health problems for the developing fetus and mother. When used by non-pregnant smokers, pharmacotherapies (nicotine replacement therapy (NRT), bupropion, and varenicline) are effective for increasing smoking cessation, however their efficacy and safety in pregnancy remains unknown. Electronic cigarettes (ECs) 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 and ECs used during pregnancy for smoking cessation in later pregnancy and after childbirth, and to determine adherence to smoking cessation pharmacotherapies and ECs for smoking cessation during pregnancy.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (20 May 2019), trial registers, and grey literature, and checked references of retrieved studies.
Randomised controlled trials (RCTs) conducted in pregnant women, comparing smoking cessation pharmacotherapy or EC use with either placebo or no pharmacotherapy/EC control. We excluded quasi-randomised, cross-over, and within-participant designs, and RCTs with additional intervention components not matched between trial arms.
We followed standard Cochrane methods. The primary efficacy outcome was smoking cessation in later pregnancy; safety was assessed by 11 outcomes (principally birth outcomes) that indicated neonatal and infant well-being. We also collated data on adherence to trial treatments. We calculated the risk ratio (RR) or mean difference (MD) and the 95% confidence intervals (CI) for each outcome for each study, where possible. We grouped eligible studies according to the type of comparison. We carried out meta-analyses where appropriate.
We included 11 trials that enrolled a total of 2412 pregnant women who smoked at enrolment, nine trials of NRT and two trials of bupropion as adjuncts to behavioural support, with comparable behavioural support provided in the control arms. No trials investigated varenicline or ECs. We assessed four trials as at low risk of bias overall. The overall certainty of the evidence was low across outcomes and comparisons as assessed using GRADE, with reductions in confidence due to risk of bias, imprecision, and inconsistency. Compared to placebo and non-placebo (behavioural support only) controls, there was low-certainty evidence that NRT increased the likelihood of smoking abstinence in later pregnancy (RR 1.37, 95% CI 1.08 to 1.74; I² = 34%, 9 studies, 2336 women). However, in subgroup analysis by comparator type, there was a subgroup difference between placebo-controlled and non-placebo controlled RCTs (test for subgroup differences P = 0.008). There was unclear evidence of an effect in placebo-controlled RCTs (RR 1.21, 95% CI 0.95 to 1.55; I² = 0%, 6 studies, 2063 women), whereas non-placebo-controlled trials showed clearer evidence of a benefit (RR 8.55, 95% CI 2.05 to 35.71; I² = 0%, 3 studies, 273 women). An additional subgroup analysis in which studies were grouped by the type of NRT used found no difference in the effectiveness of NRT in those using patches or fast-acting NRT (test for subgroup differences P = 0.08). There was no evidence of a difference 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. In one study infants born to women who had been randomised to NRT had higher rates of 'survival without developmental impairment' at two years of age compared to the placebo group. Non-serious adverse effects observed with NRT included headache, nausea, and local reactions (e.g. skin irritation from patches or foul taste from gum), but data could not be pooled. Adherence to NRT treatment regimens was generally low. We identified low-certainty evidence that there was no difference in smoking abstinence rates observed in later pregnancy in women using bupropion when compared to placebo control (RR 0.74, 95% CI 0.21 to 2.64; I² = 0%, 2 studies, 76 women). Evidence investigating the safety outcomes of bupropion use was sparse, but the existing evidence showed no difference between the bupropion and control group.
AUTHORS' CONCLUSIONS: NRT used for smoking cessation in pregnancy may increase smoking cessation rates in late pregnancy. However, this evidence is of low certainty, as the effect was not evident when potentially biased, non-placebo-controlled RCTs were excluded from the analysis. Future studies may therefore change this conclusion. We found no evidence that NRT has either positive or negative impacts on birth outcomes; however, the evidence for some of these outcomes was also judged to be of low certainty due to imprecision and inconsistency. We found no evidence that bupropion may be an effective aid for smoking cessation during pregnancy, and there was little evidence evaluating its safety in this population. Further research evidence on the efficacy and safety of pharmacotherapy and EC use for smoking cessation in pregnancy is needed, ideally from placebo-controlled RCTs that achieve higher adherence rates and that monitor infants' outcomes into childhood. Future RCTs of NRT should investigate higher doses than those tested in the studies included in this review.
孕期吸烟会给发育中的胎儿和母亲带来严重的健康问题。对于非孕期吸烟者，药物疗法（尼古丁替代疗法（NRT）、安非他酮和伐尼克兰）在促进戒烟方面是有效的，然而其在孕期的疗效和安全性尚不清楚。电子烟（ECs）的使用越来越广泛，但其用于孕期戒烟的疗效和安全性同样未知。
确定孕期使用的戒烟药物疗法和电子烟在孕晚期及产后戒烟的疗效和安全性，并确定孕期对戒烟药物疗法和电子烟的依从性。
我们检索了Cochrane妊娠与分娩组试验注册库（2019年5月20日）、试验注册库和灰色文献，并检查了检索到的研究的参考文献。
在孕妇中进行的随机对照试验（RCT），比较戒烟药物疗法或电子烟的使用与安慰剂或无药物疗法/电子烟对照。我们排除了半随机、交叉和参与者内设计，以及试验组之间未匹配额外干预成分的RCT。
我们遵循Cochrane的标准方法。主要疗效结局是孕晚期戒烟；通过11项结局（主要是出生结局）评估安全性，这些结局表明新生儿和婴儿的健康状况。我们还整理了关于试验治疗依从性的数据。在可能的情况下，我们计算了每项研究各结局的风险比（RR）或平均差（MD）以及95%置信区间（CI）。我们根据比较类型对符合条件的研究进行分组。在适当的情况下进行荟萃分析。
我们纳入了11项试验，共招募了2412名入组时吸烟的孕妇，9项NRT试验和2项安非他酮作为行为支持辅助手段的试验，对照组提供了类似的行为支持。没有试验研究伐尼克兰或电子烟。我们评估4项试验总体偏倚风险较低。使用GRADE评估，证据的总体确定性在各结局和比较中均较低，由于偏倚风险、不精确性和不一致性，可信度降低。与安慰剂和非安慰剂（仅行为支持）对照相比，低确定性证据表明NRT增加了孕晚期戒烟的可能性（RR 1.37，95%CI 1.08至1.74；I² = 34%，9项研究，2336名女性）。然而，在按对照类型进行的亚组分析中，安慰剂对照和非安慰剂对照的RCT之间存在亚组差异（亚组差异检验P = 0.008）。在安慰剂对照的RCT中，效果证据不明确（RR 1.21，95%CI 0.95至1.55；I² = 0%，6项研究，2063名女性），而非安慰剂对照试验显示出更明显的获益证据（RR 8.55，95%CI 2.05至35.71；I² = 0%，3项研究，273名女性）。另一项按使用的NRT类型对研究进行分组的亚组分析发现，使用贴片或速效NRT的人群中NRT的有效性没有差异（亚组差异检验P = 0.08）。NRT组和对照组在流产率、死产率、早产率、出生体重、低出生体重、新生儿重症监护病房入院率、剖宫产率、先天性异常或新生儿死亡率方面没有差异。在一项研究中，与安慰剂组相比，随机分配到NRT的女性所生婴儿两岁时“无发育障碍存活”的比例更高。NRT观察到的非严重不良反应包括头痛、恶心和局部反应（如贴片引起的皮肤刺激或口香糖的难闻味道），但数据无法合并。对NRT治疗方案的依从性普遍较低。我们发现低确定性证据表明，与安慰剂对照相比，孕期使用安非他酮的女性在孕晚期观察到的戒烟率没有差异（RR 0.74，95%CI 0.21至2.64；I² = 0%，2项研究，76名女性）。调查安非他酮使用安全性结局的证据很少，但现有证据表明安非他酮组和对照组之间没有差异。
孕期用于戒烟的NRT可能会提高孕晚期的戒烟率。然而，这一证据的确定性较低，因为当分析中排除可能存在偏倚的非安慰剂对照RCT时，效果并不明显。因此，未来的研究可能会改变这一结论。我们没有发现证据表明NRT对出生结局有正面或负面影响；然而，由于不精确性和不一致性，其中一些结局的证据也被判定为确定性较低。我们没有发现证据表明安非他酮可能是孕期戒烟的有效辅助手段，而且几乎没有证据评估其在该人群中的安全性。需要进一步的研究证据来证明孕期药物疗法和电子烟用于戒烟的疗效和安全性，理想情况下来自安慰剂对照的RCT，这些试验能实现更高的依从率，并监测婴儿至儿童期的结局。未来NRT的RCT应研究比本综述中纳入的研究更高的剂量。
