Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial
Effect of nicotine patches in pregnancy on infant and maternal outcomes at 2 years: follow-up from the randomised, double-blind, placebo-controlled SNAP trial
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DOI：
10.1016/s2213-2600(14)70157-2
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发表时间：
2014-09-01
影响因子：
76.2
通讯作者：
Coleman, Tim
中科院分区：
文献类型：
--
作者：
Cooper, Sue;Taggar, Jaspal;Coleman, Tim
背景 SNAP（妊娠期吸烟与尼古丁）试验对妊娠吸烟者的尼古丁替代疗法 (NRT) 贴片与安慰剂进行了比较；尽管 NRT 在前 4 周内使戒烟率增加了一倍，但到分娩时，未发现孕产妇吸烟或分娩结果存在差异。因此，怀孕期间使用标准剂量的 NRT 被认为对戒烟无效。 NRT 对接受治疗的母亲的孩子的后续影响尚不清楚，因为没有试验调查妊娠期 NRT 使用对出生后的影响。为了评估怀孕期间使用 NRT 是否会对婴儿造成伤害，我们旨在比较 NRT 和安慰剂对产后 2 年婴儿发育的影响。方法 2007 年 5 月 1 日至 2010 年 2 月 26 日期间，从英格兰的 7 家医院招募了 1050 名年龄在 16-45 岁、妊娠 12-24 周、每天至少吸 5 支烟的怀孕吸烟者，并进行随访，直到他们的婴儿出生后2岁。通过计算机生成的伪随机代码（具有随机变化大小的排列块）将参与者随机分配（1:1），接受为期 8 周的 NRT 贴片疗程（15 毫克/16 小时）（n=521）或匹配的安慰剂（n=529）；两组都接受了行为戒烟支持。随机分组按地点分层，参与者、医疗保健专业人员和研究人员不了解治疗分配情况。参与者和分娩婴儿的主要结果于 2012 年发表；我们展示出生后两年试验队列的结果。分娩后，向参与者发布了调查问卷，如果没有回复，则向家庭医生发布了调查问卷。 2岁时的主要结局是婴儿在没有发育障碍的情况下存活（即没有残疾或行为或发育问题）。治疗组在意向治疗的基础上进行比较。该试验在 Controlled-Trials.com 上注册，编号 ISRCTN07249128。 2 年时返回调查问卷，调查对象为 1010 名活产单胎婴儿中的 891 名（88%）（503 名中的 445 名（88%）接受 NRT 治疗，507 名中的 446 名（88%）接受安慰剂）。由于数据缺失，1010 名单胎婴儿中的 888 名 (88%) 记录了发育结果，包括 4 名婴儿死亡； NRT 组 503 名婴儿中有 445 名（88%），安慰剂组 507 名婴儿中有 443 名（87%）。在 NRT 组中，445 名婴儿中有 323 名（73%）没有损伤，而安慰剂组 443 名婴儿中有 290 名（65%）没有损伤（比值比 [OR] 1.40，95% CI 1 05-1 86，p=0 023）。 2 年时，NRT 组 521 名母亲中的 15 名 (3%) 和安慰剂组 529 名母亲中 9 名 (2%) 自我报告自怀孕期间设定的戒烟日期以来长期戒烟（OR 1. 71，95% CI 0. 74-3. 94，p = 0.20）。未收集产后不良事件，但之前报告的不良妊娠和出生结局在两组中相似。 解释 妊娠期间使用 NRT 戒烟的妇女所生的婴儿更有可能发育未受损。 NRT 对长期戒烟没有影响，但在怀孕期间随机分组后不久确实导致暂时戒烟量加倍，这可以解释研究结果。如果后续研究证实这一结果，这对妊娠期吸烟管理具有潜在影响。
Background The SNAP (Smoking and Nicotine in Pregnancy) trial compared nicotine replacement therapy (NRT) patches with placebo in pregnant smokers; although NRT doubled cessation rates in the first 4 weeks, by delivery no differences in maternal smoking or birth outcomes were noted. As a result, NRT used in standard doses during pregnancy is considered ineffective for smoking cessation. Subsequent effects of NRT on the children of treated mothers are unknown because no trials have investigated the effect of gestational NRT use beyond birth. To assess whether NRT use in pregnancy might cause harm to infants, we aimed to compare effects of NRT and placebo on infant development 2 years after delivery.Methods 1050 pregnant smokers aged 16-45 years, at 12-24 weeks' gestation, and smoking at least five cigarettes per day were recruited from seven hospitals in England between May 1, 2007, and Feb 26, 2010, and followed up until their infants were 2 years old. Participants were randomly assigned (1:1) via a computer-generated pseudorandom code with permuted blocks of randomly varying size to receive 8-week courses of NRT patches (15 mg/16 h) (n=521) or matched placebo (n=529); both groups received behavioural smoking cessation support. Randomisation was stratified by site with participants, health-care professionals, and research staff masked to treatment allocation. The primary results for participants and infants at delivery were published in 2012; we present results from the trial cohort 2 years after birth. After delivery, questionnaires were posted to participants and, if there was no response, to family physicians. The primary outcome at 2 years was infants' survival without developmental impairment (ie, no disability or problems with behaviour or development). Treatment groups were compared on an intention-to-treat basis. The trial is registered with Controlled-Trials.com, number ISRCTN07249128.Findings Questionnaires were returned at 2 years for 891 (88%) of 1010 live singleton births (445 of (88%) 503 given NRT and 446 (88%) of 507 given placebo). Because of missing data, developmental outcomes, including four infant deaths, were documented for 888 of (88%) 1010 singleton infants; 445 (88%) of 503 infants in NRT group and 443 (87%) of 507 infants in placebo. In the NRT group, 323 (73%) of 445 infants had no impairment compared with 290 (65%) of 443 infants in the placebo group (odds ratio [OR] 1.40, 95% CI 1 05-1 86, p=0 023). At 2 years, 15 (3%) of 521 mothers in the NRT group and nine (2%) of 529 mothers in the placebo groups self-reported prolonged smoking abstinence since a quit date set in pregnancy (OR 1. 71, 95% CI 0. 74-3. 94, p=0.20). Adverse events were not collected after delivery, but previously reported adverse pregnancy and birth outcomes were similar in the two groups.Interpretation Infants born to women who used NRT for smoking cessation in pregnancy were more likely to have unimpaired development. NRT had no effect on prolonged abstinence from smoking but did cause a temporary doubling of smoking cessation shortly after randomisation during pregnancy, which could explain findings. If findings are confirmed by subsequent research, this has potential implications for the management of smoking in pregnancy.