中华流行病学杂志  2015, Vol. 36 Issue (9): 949-952   PDF    
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2015.09.009
中华医学会主办。
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文章信息

凌子羽, 王建敏, 李侠, 钟燕, 覃媛媛, 谢胜男, 杨森焙, 张静.
Ling Ziyu, Wang Jianmin, Li Xia, Zhong Yan, Qin Yuanyuan, Xie Shengnan, Yang Senbei, Zhang Jing.
母亲孕前BMI和孕期增重与子代孤独症之间关系的研究
Association between mothers' body mass index before pregnancy or weight gain during pregnancy and autism in children
中华流行病学杂志, 2015, 36(9): 949-952
Chinese Journal of Epidemiology, 2015, 36(9): 949-952
http://dx.doi.org/10.3760/cma.j.issn.0254-6450.2015.09.009

文章历史

投稿日期: 2015-01-28
母亲孕前BMI和孕期增重与子代孤独症之间关系的研究
凌子羽1, 王建敏1, 李侠1, 钟燕2, 覃媛媛1, 谢胜男1, 杨森焙1, 张静1     
1. 430030 武汉, 华中科技大学同济医学院公共卫生学院少儿卫生与妇幼保健学系;
2. 湖南省儿童医院
摘要: 目的 探讨母亲孕前BMI和孕期增重与子代孤独症之间的关系。方法 选取2013-2014年经医疗机构确诊的181例1~5岁孤独症儿童为病例组,采用1 ∶ 1病例对照研究方法选择同地区、同性别、同年龄发育正常的儿童作为对照组。按母亲孕前BMI值分为低、正常和高3组,孕期增重根据美国医学研究所标准分为低、正常和高3组,采用SPSS 18.0软件进行χ2检验和logistic回归分析。结果 两组儿童年龄和性别分布均衡(χ2=0.434,P >0.05)。病例组母亲孕前BMI平均值为(21.28±3.80)kg/m2,高于对照组的(19.87±2.83)kg/m2,差异有统计学意义(χ2=9.580,P<0.05);病例组母亲高BMI人数(10.5%)多于对照组(2.8%);随着孕前BMI增加,子代孤独症患病风险逐渐增大,高BMI组子代孤独症发病风险是正常BMI组的3.7倍(OR=3.71,95%CI:1.34~10.24);病例组正常BMI母亲孕期增重过度(44.1%)高于对照组(33.9%);病例组高BMI母亲孕期增重过度(52.6%)明显高于对照组(20.0%),正常BMI(χ2=8.690,P<0.05)和高BMI(χ2=4.775,P<0.05)母亲孕期增重过度与孤独症发病有关。logistic回归分析显示,母亲孕前高BMI(调整前OR=1.89,95%CI:1.26~2.85;调整后OR=1.52,95%CI:1.19~2.27)和孕期增重过度(调整前OR=1.63,95%CI:1.08~1.25;调整后OR=1.64,95%CI:1.21~2.21)是子代孤独症发生的危险因素。结论 母亲孕前超重/肥胖和孕期增重过度与子代孤独症发生有一定的关系,可能是孤独症的危险因素。
关键词: 妊娠     体重指数     孕期体重     孤独症    
Association between mothers' body mass index before pregnancy or weight gain during pregnancy and autism in children
Ling Ziyu1, Wang Jianmin1, Li Xia1, Zhong Yan2, Qin Yuanyuan1, Xie Shengnan1, Yang Senbei1, Zhang Jing1     
1. Department of Maternal and Child Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;
2. Hunan Children's Hospital
Abstract: Objective To explore the relationship between mothers' body mass index (BMI) before pregnancy or weight gain during pregnancy and autism in children. Methods From 2013 to 2014,the 181 children with autism and 181 healthy children matched by sex and age from same area were included in this study. According to mothers' BMI before pregnancy,the selected cases were divided into 3 groups:low,normal and high group. Then 3 groups were divided into 3 subgroups based on mother's weight gain during pregnancy:low,normal and high group,according to the recommendations of Institute of Medicine. Logistic regression analysis and χ2 test were conducted with SPSS 18.0 software to analysis the relationship between mothers' BMI before pregnancy or weight gain during pregnancy and autism in children. Results The age and sex distributions of case group and control group were consistent(χ2=0.434,P >0.05). The mothers' BMI before pregnancy of case group was higher than that of control group (χ2=9.580,P<0.05),which was (21.28±3.80)kg/m2 for case group and (19.87±2.83)kg/m2 for control group. The proportion of cases in high BMI group (10.5%) was much higher than that in control group(2.8%). The risk of children with autism in high BMI group was 3.7 times higher than that in normal BMI group(OR=3.71,95%CI:1.34-10.24). In normal BMI group,the proportion of mothers who had excessive weight gain during pregnancy was higher in case group(44.1%)than in control group(33.9%). In high BMI group,the proportion of mothers who had excessive weight gain was higher in case group (52.6%) than in control group(20.0%). In normal BMI group(χ2=8.690,P<0.05) and high BMI group(χ2=4.775,P<0.05),the weight gain during pregnancy was associated with autism in children. Logistic regression analysis showed that mothers' BMI before pregnancy(unadjusted OR=1.89,95%CI:1.26-2.85,adjusted OR=1.52,95%CI:1.19-2.27) and weight gain during pregnancy were the risk factors for autism in children(unadjusted OR=1.63,95%CI:1.08-1.25,adjusted OR=1.64,95%CI:1.21-2.21). Conclusion Overweight or obesity before pregnancy and excessive weight gain during pregnancy were associated with autism in children,suggesting that women who plan to be pregnant should pay attention to body weight control.
Key words: Pregnancy     Body mass index     Pregnancy     Autism    

目前,孤独症病因尚未完全明确[1]。国外研究显示,人群肥胖率与孤独症患病率有关[2],随着社会经济发展和生活水平提高,肥胖妇女孕期增重过多的比例也逐年升高[3]。本研究通过对孤独症和非孤独症儿童母亲孕前及孕期情况回顾性调查,探讨母亲孕前体重和孕期增重与子代孤独症发生的关系。

对象与方法

1.调查对象:选取2013-2014年在长沙、武汉、厦门和柳州市的医疗保健机构确诊的181例1~5岁孤独症儿童作为病例组,病例组均符合美国精神病学会《精神障碍诊断和统计手册》第4版(Diagnostic and Statistical Manual of MentalDisorder 4th,DSM-Ⅳ)诊断标准;采用病例对照研究1:1配对设计在上述医疗保健机构的儿童保健门诊选取同地区、同性别、年龄相差不超过3个月且无智力、发育障碍及其他神经精神系统疾病的儿童为对照组。

2.调查方法:采用自拟的《儿童行为及相关因素调查表》对病例组和对照组儿童的监护人进行问卷调查,内容包括儿童一般情况(性别、年龄、出生情况等)和母亲孕前及孕产期情况等;通过查询孕产妇监测管理系统或查阅孕期保健手册等方式核实母亲的孕前及分娩前体重,数据不详者予以剔除。在调查儿童家长知情同意下,由调查员说明调查事项并完成问卷的填写及核对,对有疑问和漏项的问卷及时询问并加以修正。

3.孕前BMI及孕期增重划分标准:

(1)孕前BMI划分标准:根据中国成人超重和肥胖症预防控制指南[4],将母亲孕前BMI (kg/m2)分为低(<18.5)、正常(18.5~24.9)和高(≥25.0)3组。

(2)孕期增重划分标准:根据美国医学研究所(IOM)制定的母亲孕期增重范围[5]将孕期增重分为低、中、高3组。

4.统计学分析:采用EpiData 3.1软件建立数据库并双份录入数据,经数据唯一性检验和逻辑核查无误后,采用SPSS 18.0软件进行统计学分析,包括χ2检验和logistic回归分析。

结果

1.两组儿童性别和年龄分布:共调查181对儿童,其中男童158对(87.3%),女童23对(12.7%),性别比为6.87:1。年龄分布在1~5岁之间,以3~4岁居多,占37.29%,年龄M为3.5岁。

2.母亲孕前BMI比较:病例组母亲孕前BMI平均值为(21.28±3.80) kg/m2,高于对照组的(19.87±2.83) kg/m2,差异有统计学意义(χ2=9.580,P<0.05)。病例组母亲高BMI (BMI≥25.0 kg/m2)人数占10.5%,高于对照组(2.8%),低BMI (BMI<18.5 kg/m2)人数占19.3%,低于对照组(28.7%),高BMI组子代患孤独症的风险是正常BMI组的3.7倍(OR=3.71,95% CI:1.34~10.24)。见表 1

表 1 孤独症儿童和对照组儿童母亲孕前 BMI(kg/m2x±s)

3.母亲孕期增重情况:低BMI母亲孕期过度增重与子代孤独症发病无关(χ2=0.411,P>0.05);病例组正常BMI母亲孕期增重均值为(16.00±4.72) kg,高于对照组的(14.75±5.23) kg,病例组母亲孕期高增重占44.1%,高于对照组(33.9%)。病例组高BMI母亲孕期增重均值为(7.60±4.09) kg,高于对照组的(5.17 ± 4.10) kg,病例组母亲孕期高增重占52.6%,高于对照组(20.0%)。正常BMI组和高BMI组中,母亲孕期增重程度与孤独症发病有关(正常BMI组χ2=8.690,P=0.003,高BMI组χ2=4.775,P=0.04)。见表 2

表 2 孤独症儿童和对照组儿童母亲孕期增重情况

4.母亲孕前BMI和孕期增重与孤独症关系的logistic回归分析:先以是否患孤独症为因变量,分别以母亲孕前BMI和孕期增重为自变量进行单因素logistic回归分析,结果显示,母亲孕前高BMI (OR=1.89,95% CI:1.26~2.85)和孕期增重过度(OR=1.63,95% CI:1.08~1.25)是子代孤独症患病的危险因素;再以是否患孤独症为因变量,母亲文化程度、年龄、胎次、先兆流产、孕期营养、疾病史、药物史等可能影响分析结果的变量作为调整因素等进行多因素logistic回归分析,结果显示,孕前高BMI (OR=1.52,95% CI:1.19~2.27)和孕期增重过度(OR=1.64,95% CI:1.21~2.21)是子代孤独症患病的危险因素。见表 3。对孕前BMI和孕期增重过度进行交互作用的分析,显示二者存在较低交互作用(OR=1.004,95% CI:1.001~1.006)。

表 3 母亲孕前 BMI和孕期增重情况与孤独症关系的 logistic回归分析
讨论

孤独症是一种病因未明的发育障碍性疾病。本研究显示,母亲孕前超重/肥胖和孕期增重过度可能增加子代患孤独症发病风险,高BMI组其子代患孤独症的风险是正常BMI组的3.7倍,高于国外研究结果[6, 7],且随着母亲孕前BMI增加,子代孤独症患病风险逐渐增大。正常BMI和高BMI中,母亲孕期增重程度与孤独症发病有关,病例组母亲孕期高增重比例大于对照组。logistic回归分析也显示,母亲孕前高BMI和孕期增重过度是子代孤独症发生的危险因素。

母亲孕前及孕期体重变化对孤独症的影响可能与遗传和胎儿神经系统发育有一定关系[8]。研究显示,孕前肥胖的母亲可能携带有16p11.2异常基因组并传给子代,16p11.2基因组的缺失与重复不仅会导致神经系统发育异常[8, 9, 10, 11],还能造成肥胖[12]。研究显示携带有该异常基因的人群所表现出的症状可能会完全不同,在某些外部因素的作用下,使子代呈现出孤独症相关症状[8]。流行病学研究显示,孕期过度增重对子代神经精神发育产生潜在的长期不良影响[13, 14],孕期增重过度与摄入高脂膳食密切相关,高脂饮食能导致后代海马氧化应激和炎性反应增强[14],造成多巴胺能神经元和5-羟色胺合成失调[15],增加胎儿神经系统发育异常的风险[16]。动物实验表明,母亲肥胖对子代神经系统的损害可能来自于肥胖引起的瘦素抵抗机制[17]。瘦素对维持正常生殖功能和胎儿生长发育有重要作用[18]。动物实验表明,先天或后天肥胖的啮齿类动物血液中瘦素呈现较高水平[19],人体内瘦素水平与BMI和脂肪含量呈正相关,约95%的超重/肥胖者存在高瘦素血症[20],较高的瘦素水平会导致大脑发育受损,引起语言、社交和运动技能等多方面障碍[18]

目前,国内有关母亲孕前及孕期体重与子代孤独症发生关系的研究较少,本次研究样本量偏小,存在一定局限性,有待进一步扩大样本量深入研究。

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