中华流行病学杂志  2018, Vol. 39 Issue (11): 1482-1485   PDF    
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2018.11.012
中华医学会主办。
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文章信息

施佳, 田勇, 雷媛, 康皓.
Shi Jia, Tian Yong, Lei Yuan, Kang Hao.
母体孕期主动或被动吸烟与后代多指(趾)畸形的病例对照研究
Active and passive maternal smoking during pregnancy and risk of having a child with polydactyly: a case-control study
中华流行病学杂志, 2018, 39(11): 1482-1485
Chinese Journal of Epidemiology, 2018, 39(11): 1482-1485
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2018.11.012

文章历史

收稿日期: 2018-03-27
母体孕期主动或被动吸烟与后代多指(趾)畸形的病例对照研究
施佳1 , 田勇1 , 雷媛2 , 康皓1     
1. 430030 武汉, 华中科技大学同济医学院附属同济医院骨科;
2. 430030 武汉, 华中科技大学同济医学院附属同济医院呼吸内科
摘要: 目的 近年来,临床上所见多指(趾)畸形的患儿数量与日俱增。除了遗传因素外,母体怀孕期间自身行为和环境因素的影响也越显重要;然而,关于这些影响的流行病学数据十分匮乏。方法 采用以医院为基础、以患儿年龄配对的1:2病例对照研究,对多指(趾)患儿与正常儿的母亲进行问卷调查。采用交互作用分析、协变量筛选和多元logistic回归分析探究母亲孕期吸烟(主动或被动)和后代多指(趾)畸形的危险因素关系。结果 研究对象共纳入病例组143例,对照组286例。孕妇在怀孕期间吸烟,显著增加后代多指(趾)畸形的发病风险(主动吸烟:OR=4.74,95% CI:1.43~15.65,P=0.011;被动吸烟:OR=2.42,95% CI:1.32~4.44,P=0.004)。调整混杂因素后,母亲孕期吸烟对后代多指(趾)畸形的影响仍显著存在(主动吸烟:aOR=7.27,95% CI:1.72~30.72,P=0.007;被动吸烟:aOR=2.41,95% CI:1.11~5.23,P=0.026)。结论 母亲孕期主动或被动吸烟是后代发生多指(趾)畸形的危险因素,显著增加其发病风险。
关键词: 多指(趾)畸形     主动吸烟     被动吸烟     病例对照研究    
Active and passive maternal smoking during pregnancy and risk of having a child with polydactyly: a case-control study
Shi Jia1 , Tian Yong1 , Lei Yuan2 , Kang Hao1     
1. Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
2. Department of Respiratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
Corresponding author: Kang Hao, Email: kanghao100@vip.sina.com
Fund program: National Nature Science Foundation of China (81472106)
Abstract: Objective The number of children with polydactyly is increasing.In addition to genetic factors, an influence of maternal behavior or environmental effects during pregnancy is becoming increasingly apparent.However, epidemiological data on these effects are lacking. Methods This hospital-based, case-control study enrolled 143 infants with polydactyly and 286 controls without genetic diseases to evaluate the association between active and passive maternal smoking during pregnancy and the likelihood of giving birth to a child with polydactyly. Results Active and passive maternal smoking during pregnancy was associated with an increased risk of giving birth to a child with polydactyly (active smoking:OR=4.74, 95% CI:1.43-15.65, P=0.011; passive smoking:OR=2.42, 95% CI:1.32-4.44, P=0.004).After adjusting for confounders, smoking during pregnancy remained significant influence on polydactyly (active smoking:aOR=7.27, 95% CI:1.72-30.72, P=0.007; passive smoking:aOR=2.41, 95% CI:1.11-5.23, P=0.026). Conclusion Active and passive maternal smoking during pregnancy appears to be a risk factor for polydactyly in newborns.
Key words: Polydactyly     Active smoking     Passive smoking     Case-control study    

多指(趾)畸形是最常见的先天性手部畸形之一[1-2],在新生儿中的发病率为0.03%~0.19%[3-5]。男孩的发病率高于女孩,近年来总体发病率呈增加趋势[1, 3]。虽然多指(趾)畸形可以在出生后进行手术矫正[6],但部分患儿可能需要进行多次矫正手术以达到预期的外观,对孩子的身心甚至整个家庭都有一定程度的负面影响。研究证明遗传因素与多指(趾)之间存在风险关系[7],如GLI家族锌指3 (GLI3)和基因IQCE均可致病[8-10]。然而,大多数多指(趾)畸形患者并没有家族病史,这促使我们研究环境中可能存在的危险因素。怀孕期间的不利因素会增加胎儿肢体异常的风险[11-17]。母亲孕期饮酒、接触可卡因、妊娠期糖尿病、从事具有暴露风险的职业均可能导致先天性出生缺陷[11, 17-20]。然而母亲孕期吸烟是否会增加后代肢体畸形尤其是多指(趾)畸形仍然存在争议。部分研究表明孕期主动吸烟会增加胎儿出生缺陷的发病率[18],但是母亲孕期的被动吸烟问题仍被忽视。本研究基于病例对照研究,探讨经多因素分层和控制混杂因素后母亲孕期主动或被动吸烟与后代多指(趾)畸形发病的关系,为预防胎儿先天性多指(趾)畸形提供科学依据。

对象与方法

1.研究对象:选取2015年9月至2017年10月华中科技大学同济医学院附属同济医院骨科或小儿外科确诊为先天性多指(趾)畸形的住院患儿的母亲为病例组。诊断标准为临床确诊为先天性多指(趾)畸形,由≥2名具有≥5年临床工作经验的医师独立确诊患儿为多指(趾)畸形,并由影像学资料共同证实。对照组为连续性选取相同时间段因外伤就诊的患儿的母亲,以年龄相差不超过1岁进行1 : 2配对。剔除有任何慢性病史或家族病史和因记忆障碍或精神症状不能准确回答问题者。本研究通过华中科技大学伦理委员会批准,所有研究对象均签署了知情同意书。

2.研究方法:由经统一培训的2位调查员对患儿母亲进行一对一面对面调查,另1位调查员在问卷开始前对调查对象进行编号并记录其患儿是否为多指(趾)畸形,以降低询问过程中的主观偏倚。问卷调查员之间互相独立完成询问并对对方的结果不知情,最终调查结果由两份问卷对比后得出并剔除问卷填写不合格者。

问卷内容包括一般情况(孕龄、产前体重、身高、文化程度、户籍类型、职业、家庭人均月收入、患儿性别与出生体重)、母亲孕期情况(主动吸烟、被动吸烟、饮酒、孕期情绪、有效睡眠时间、阴道出血、发热、感冒、先兆流产、妊娠剧吐、贫血、化学物质、射线或噪音接触以及孕期合并症)和家族病史(母亲是否有慢性病史以及患儿父母双方是否有家族多指(趾)病史或近亲婚配史)。主动吸烟定义为吸烟行为天数≥3 d/周[21],被动吸烟定义为≥30 min/周[22];饮酒定义为≥1次/周[23]

3.统计学分析:采用EpiData 3.1软件建立数据库并进行数据双录入,R语言和易侕软件进行统计学分析。病例组和对照组的均值和比例均为正态分布的数值变量。t检验用于分析人口特征的差异,χ2检验和OR值检验风险因素与多指(趾)畸形的关系。在对混杂变量进行调整后,通过多元logistic回归分析评价母体孕期吸烟与后代多指(趾)畸形的关系。以P<0.05为两组间差异有统计学意义。

结果

1.一般情况:本次研究共调查2015年9月至2017年10月于同济医院骨科或小儿外科住院拟行多指(趾)截指(趾)矫形术的160例患儿的母亲。经过剔除标准筛选,共纳入143名患儿母亲。经过患儿年龄匹配,对照组共纳入286名其他疾病患儿的母亲。两组在家庭人均月收入、家庭户籍类型、家族多指(趾)病史(父系或母系)、近亲婚配史、母亲孕期情绪状态、孕期是否吸烟(主动或被动)、阴道出血、产前体重和孕期是否接触噪音等变量间差异有统计学意义(P<0.05)(表 1)。

表 1 调查对象基本特征

2.影响因素分析:

(1) 单因素分析:家庭人均月收入、家族多指(趾)病史、近亲婚配史、主动或被动吸烟、孕期阴道出血和噪音接触均与后代是否发生多指(趾)畸形显著相关(表 2)。

表 2 多指(趾)单因素分析结果

(2) 多元logistic回归分析:通过交互作用分析和协变量筛选进一步检测母亲孕期吸烟与后代多指(趾)畸形的关系。单因素分析时,母亲孕期吸烟(主动吸烟:OR=4.74,95%CI:1.43~15.65,P=0.011;被动吸烟:OR=2.42,95%CI:1.32~4.44,P=0.004)与后代多指(趾)畸形的关系是独立存在的(表 2);调整混杂变量[母亲孕期情绪、户籍类型、家庭人均月收入、家族多指(趾)病史、近亲婚配史、母亲孕期情绪、阴道出血]后,这种关联依旧存在(主动吸烟:aOR=7.27,95%CI:1.72~30.72,P=0.007;被动吸烟:aOR=2.41,95%CI:1.11~5.23,P=0.026)。

(3) 分层分析:按新生儿性别、孕龄、家族多指(趾)病史、文化程度、家庭人均月收入情况进行分层,调整户籍类型、近亲婚配史、母亲孕期情绪、阴道出血后,母亲孕期吸烟与后代多指(趾)畸形的关系稳定存在(表 3)。

表 3 孕期吸烟与后代多指(趾)畸形的分层分析
讨论

本研究结果表明母亲孕期主动或被动吸烟与新生儿多指(趾)畸形的风险增加显著相关。调整混杂因素后,其相关性仍然显著存在(主动吸烟:aOR=7.27,95%CI:1.72~30.72,P=0.007;被动吸烟:aOR=2.41,95%CI:1.11~5.23,P=0.026)。怀孕期间主动或被动吸烟会造成胎儿DNA的细胞遗传损害,导致染色体不稳定,这种损害与其他可能导致畸形的环境或化学诱变物质具有协同作用[24-25]

过往研究发现母亲孕期主动吸烟会增加多种出生缺陷的发病风险[18, 26],还会显著降低胎儿出生体重并增加早产、死产风险[27-28];被动吸烟也可能会造成胎儿出现严重的出生缺陷[29]。母亲孕期吸烟不仅影响妊娠结局,在后代长期的认知能力(低学业成就和一般认知能力等)和外化行为(刑事定罪和药物滥用等)上也有显著的不良影响[30-31]。然而,这些研究未将多指(趾)畸形单独列出,而是将其纳入先天性肢端畸形中进行笼统研究,这势必增加了母亲孕期吸烟与后代多指(趾)畸形关系中的不确定性。而本研究将多指(趾)畸形作为独立结局进行研究,单独研究分析了母亲孕期主动或被动吸烟与后代多指(趾)畸形的相关性。

本研究存在局限性。首先,本研究采用问卷调查形式的病例研究,容易出现回忆偏倚;另外,本研究样本量较小,仍需要大样本量的队列研究对结果加以验证。此外,本研究采用回顾性病例对照分析方法,调查对象无法准确的回忆孕期吸烟或被动吸烟的具体数量,但我们在问卷设计中对主动吸烟和被动吸烟等变量进行了严格定义,在一定程度上可减少偏倚。

综上所述,孕妇在孕期主动或被动吸烟是胎儿多指(趾)畸形的危险因素,提示二手烟暴露也可能影响到新生儿健康。相关部门应努力提高对孕妇吸烟,尤其是更容易被忽略的二手烟危害的认识,加大关于烟草使用带来的不良后果的宣传,鼓励孕妇及其家人减少吸烟或戒烟,以减少孕期烟草暴露。

利益冲突

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