基于病例对照和剂量反应关系的0~6岁儿童先天性心脏病影响因素

闫欢; 曹永文; 叶佳欣; 沈燕飞; 戈小洁; 杨娜; 刘倩倩; 吴杨昊天; 韩雪梅

doi:10.16462/j.cnki.zhjbkz.2021.05.012

基于病例对照和剂量反应关系的0~6岁儿童先天性心脏病影响因素

doi: 10.16462/j.cnki.zhjbkz.2021.05.012

1.
730000 兰州，兰州大学公共卫生学院社会医学与卫生事业管理研究所
2.
730000 兰州，甘肃省妇幼保健院计划财务部
3.
730000 兰州，甘肃省人民医院法律事务办公室

闫欢和曹永文为共同第一作者

基金项目:

甘肃省自然科学基金 18JR3RA054

甘肃省卫生行业科研计划项目 GSWSKY2017-43

详细信息

通讯作者:
韩雪梅，E-mail: xmhan@lzu.edu.cn

中图分类号: R174.6
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- 被引次数: 0
出版历程
- 收稿日期: 2020-07-16
- 修回日期: 2020-10-22
- 网络出版日期: 2021-06-16
- 刊出日期: 2021-05-10

Study on influencing factors of congenital heart disease in children aged 0-6 years based on case-control and dose-esponse relationship

1.
Institute of Social Medicine and Health Management, School of Public Health, Lanzhou University, Lanzhou 730000, China
2.
Department of Planning Finance, Gansu Provincial Maternal and Child Health Care Hospital, Lanzhou 730000, China
3.
Legal Affairs Office of Gansu Provincial People's Hospital, Lanzhou 730000, China

YAN Huan and CAO Yong-wen contributed equally to this article

Funds:

Gansu Natural Science Foundation Project 18JR3RA054

Gansu Health Industry Scientific Research Plan Project GSWSKY2017-43

More Information

Corresponding author: HAN Xue-mei, E-mail: xmhan@lzu.edu.cn

摘要

摘要: 目的分析甘肃省0~6岁儿童先天性心脏病(congenital heart disease, CHD)的非遗传影响因素，为预防儿童CHD提出建议。方法采用分层等距抽样方法，在甘肃全省抽取并筛查5个区县0~6岁儿童29 566例。将从中筛查出的106名CHD患儿作为病例组并随机抽取同年龄、同性别、相同生活环境下的健康儿童318名，作为对照组进行1∶3病例对照匹配；应用Cox比例风险模型拟合Logistic回归分析模型分析儿童CHD的影响因素；应用限制性立方样条模型分析儿童出生体重与CHD患病的剂量反应关系。结果多因素分析结果表明：儿童出生体重、母亲文化程度、食用腌晒食品、药物流产史、孕前服用排卵药物、孕期食用鱼肉、经常体育锻炼与儿童CHD的患病风险均存在相关性(均有P＜0.05)。限制性立方样条反应分析结果显示：儿童出生体重与CHD患病的关联强度呈线性剂量—反应关系(总趋势P＜0.001，非线性P=0.246)。结论建议育龄妇女做好孕前检查，合理使用促排卵药物；孕期妇女要做好孕期保健和筛查，多食用鱼虾等海产品，不食用腌晒食品，适当进行体育锻炼，加强妇幼保健知识的学习降低儿童CHD的患病风险。
- 儿童 /
- 先天性心脏病 /
- 影响因素 /
- 病例对照研究 /
- 剂量反应关系
Abstract: Objective By analyzing the non-genetic factors of congenital heart disease (CHD) in children aged 0 to 6 years in Gansu Province, suggestions were put forward to prevent CHD in children. Methods We chose 29 566 children aged 0 to 6 from 5 districts and counties in Gansu Province from September to December 2016 by stratified isometric sampling method. We selected 106 children with CHD as the case group, and randomly selected 318 children of the same age, gender and living environment from healthy children as the control group for 1∶3 case-control matching. Then, we used logistic regression analysis method fitted by Cox proportional hazard model to analyze the influencing factors of CHD in children. At the same time, the dose-response relationship between birth weight and CHD disease in children was analyzed using a restrictive cubic spline model. Results Low birth weight (P= 0.028), low educational level of the mother (P=0.035), consumption of salted food (P=0.007), medical abortion history (P=0.001), ovulation medication before pregnancy (P < 0.001), consumption of fish during pregnancy (P=0.020) and appropriate physical exercise (P < 0.001) were related to the risk of CHD in children. The results of restrictive cubic spline response analysis showed a linear dose-response relationship between birth weight and congenital heart disease (overall trend P < 0.001, non-linear P=0.246). Conclusions It is suggested that women of childbearing age should take pre-pregnancy examination and rationally use ovulatory drugs. Pregnant women should pay attention to health care and screening during pregnancy, eat more fish, shrimp and other seafood, not eat salted and dried food, take physical exercise appropriately and strengthen the study of maternal and child health care knowledge to reduce the risk of congenital heart disease in children.
- Children /
- Congenital heart disease /
- Influencing factors /
- Case control study /
- Dose-response relationship

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图 1 儿童出生体重与CHD患病关联的限制性立方样条图

Figure 1. Restrictive cubic spline diagram of the association between birth weight and CHD disease in children

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图 2 男性儿童出生体重与CHD患病关联的限制性立方样条图

Figure 2. Restrictive cubic spline diagram of the association between birth weight and CHD disease in male children

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图 3 女性儿童出生体重与CHD患病关联的限制性立方样条图

Figure 3. Restrictive cubic spline diagram of the association between birth weight and CHD disease in female children

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表 1 病例组和对照组儿童和母亲基本情况[n(%)]

Table 1. Basic information of children and mothers in case group and control group [n(%)]

基本特征	病例组(n=106)	对照组(n=318)	t/χ²值	P值
儿童
性别			0.000	1.000
男	51(48.1)	153(48.1)
女	55(51.9)	165(51.9)
年龄(岁)			0.000	1.000
0~＜1	21(19.8)	63(19.8)
1~＜2	21(19.8)	63(19.8)
2~＜3	15(14.2)	45(14.2)
3~＜4	25(23.6)	75(23.6)
4~＜5	12(11.3)	36(11.3)
5~6	12(11.3)	36(11.3)
出生体重(kg)			6.180	0.045
＜2.50	16(15.1)	23(7.2)
2.50~4.00	88(83.0)	285(89.6)
＞4.00	2(1.9)	10(3.1)
母亲
文化程度			7.408	0.025
初中及以下	85(80.2)	248(78.0)
高中或中专或技校	20(18.9)	45(14.2)
大专及以上	1(0.9)	25(7.9)
职业			0.138	0.933
农民	94(88.7)	279(87.7)
家庭主妇	5(4.7)	18(5.7)
其他	7(6.6)	21(6.6)
月收入(元)			7.928	0.019
＜2 000	67(63.2)	151(47.5)
2 000~＜4 000	32(30.2)	140(44.0)
≥4 000	7(6.6)	27(8.5)
本次生育年龄(x±s), 岁)	26.35±5.57	26.94±4.73	-1.071	0.285
分娩孕周(x±s), 周)	39.30±1.63	39.24±1.14	0.416	0.677

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表 2 儿童CHD影响因素的单因素Logistic回归分析模型分析

Table 2. Single factor Logistic regression analysis of CHD influencing factors in children

变量	β值	s_x	Wald	OR(95% CI)值	P值
母亲文化程度
初中级以下				1.000
高中或中专	0.267	0.306	0.760	1.306(0.717~2.378)	0.383
大专及以上	-2.217	1.033	4.604	0.109(0.014~0.825)	0.032
母亲月收入(元)
＜2 000				1.000
2 000~＜4 000	-0.654	0.245	7.126	0.520(0.322~0.840)	0.008
≥4 000	-0.538	0.457	1.391	0.584(0.239~1.428)	0.238
新鲜蔬菜(斤/周)
从不吃				1.000
＜5	-0.576	0.498	1.336	0.562(0.212~1.493)	0.248
≥5	-1.192	0.545	4.790	0.304(0.104~0.883)	0.029
新鲜水果(斤/周)
从不吃				1.000
＜2.5	-0.555	0.591	0.880	0.574(0.108~1.829)	0.348
≥2.5	-1.241	0.626	3.927	0.289(0.085~0.987)	0.048
食用粗粮(500 g/周)
从不吃				1.000
＜1	-0.645	0.451	2.052	0.524(0.217~1.268)	0.152
≥1	-1.171	0.535	4.798	0.310(0.109~0.884)	0.028
食用鱼肉(50 g/周)
从不吃				1.000
≤7	-0.327	0.322	1.032	0.721(0.384~1.355)	0.310
＞7	-1.825	0.662	7.596	0.161(0.044~0.590)	0.006
腌晒食品
从不				1.000
有时	0.392	0.316	1.537	1.480(0.796~2.749)	0.215
经常	1.631	0.526	9.619	5.111(1.823~14.332)	0.002
饮水方式
纯净水				1.000
自来水	0.194	0.471	0.171	1.215(0.483~3.057)	0.680
井水	-0.159	0.570	0.077	0.853(0.279~2.607)	0.781
溪、河水	0.274	0.684	0.161	1.315(0.344~5.025)	0.689
沟塘湖水	1.934	0.985	3.856	6.920(1.004~47.726)	0.050
取暖方式
集中暖气				1.000
用电	0.197	0.792	0.073	1.218(1.098~4.329)	0.787
太阳能	-11.751	511.497	0.001	0.000(0.000~0.000)	0.982
烧煤	0.779	0.350	4.958	2.180(1.098~4.329)	0.026
燃料类型
天燃气				1.000
煤	0.935	0.630	2.201	2.547(0.741~8.761)	0.138
电磁炉	1.566	0.642	5.954	4.787(1.361~16.839)	0.015
柴	1.045	0.653	2.565	2.844(0.791~10.222)	0.109
其他	1.383	0.846	2.674	3.986(0.760~20.903)	0.102
被动吸烟
否				1.000
偶尔	0.247	0.267	0.857	1.281(0.759~2.162)	0.354
经常	1.292	0.408	10.050	3.641(1.638~8.096)	0.002
儿童出生体重(kg)	-1.016	0.235	18.761	0.362(0.229~0.573)	＜0.001
2.50~4.00				1.000
＜2.50	0.553	0.272	4.144	1.739(1.021~2.962)	0.042
＞4.00	-0.348	0.715	0.236	0.706(0.174~2.869)	0.627
月经初潮年龄(岁)	0.135	0.074	3.361	1.145(0.991~1.324)	0.067
人工流产史(是=0, 否=1)	0.970	0.507	3.653	2.637(0.976~7.130)	0.056
药物流产史(是=0, 否=1)	-1.946	0.690	7.952	0.143(0.037~0.552)	0.005
哺乳史(是=0, 否=1)	1.281	0.606	4.475	3.600(1.099~11.796)	0.034
经常体育锻炼(是=0, 否=1)	1.214	0.293	17.148	3.366(1.895~5.980)	＜0.001
婚前体检(是=0, 否=1)	0.426	0.237	3.230	1.531(0.962~2.438)	0.072
孕前服用排卵药物(是=0, 否=1)	-2.485	1.118	4.940	0.083(0.009~0.746)	0.026
孕期服用叶酸(是=0, 否=1)	0.584	0.228	6.590	1.794(1.148~2.802)	0.010
孕期先兆流产(是=0, 否=1)	-1.792	0.866	4.281	0.167(0.031~0.910)	0.039
严重早孕反应(是=0, 否=1)	-0.584	0.304	3.704	0.558(0.308~1.011)	0.054
妊娠合并症(是=0, 否=1)	-2.351	0.802	8.601	0.095(0.020~0.458)	0.003
母亲慢性呼吸系统疾病(是=0, 否=1)	-2.015	0.837	5.800	0.133(0.026~0.687)	0.016

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表 3 儿童CHD影响因素的多因素Logistic回归分析模型分析

Table 3. Multivariate Logistic regression analysis of CHD influencing factors in children

变量	β值	s _x	Wald	OR(95% CI)值	P值
母亲文化程度
大专及以上				1.000
初中级以下	1.892	1.010	3.508	6.635(0.667~3.753)	0.061
高中或中专	2.176	1.033	4.440	8.812(0.003~0.445)	0.035
儿童出生体重(kg)
2.50~4.00				1.000
＜2.50	0.616	0.279	4.859	1.851(1.071~3.201)	0.028
＞4.00	-0.378	0.720	0.275	0.685(0.176~2.810)	0.600
食用鱼肉(50 g/周)
从不吃				1.000
≤7	-0.098	0.269	0.132	0.907(00.536~1.536)	0.716
＞7	-1.461	0.629	5.386	0.232(0.068~0.797)	0.020
食用腌晒食品
从不				1.000
有时	0.337	0.294	1.316	1.401(0.787~2.493)	0.251
经常	1.081	0.403	7.195	2.949(1.338~6.498)	0.007
药物流产史(是=0, 否=1)	-1.350	0.407	10.986	0.259(0.117~0.576)	0.001
孕前服用排卵药物(是=0, 否=1)	-1.934	0.525	13.586	0.145(0.052~0.404)	＜0.001
经常体育锻炼(是=0, 否=1)	0.982	0.224	19.203	2.671(1.721~4.144)	＜0.001
注：模型采用逐步向前分析法，调整了母亲文化程度、儿童出生体重、食用鱼肉、食用腌晒食品、药物流产史、孕前服用排卵药物、经常体育锻炼。

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参考文献(26)

[1]	王惠珊, 袁雪, 奚一生, 等. 19 432名婴幼儿先天性心脏病患病率的调查研究[J]. 中国儿童保健杂志, 2001, 9(4): 236-238. https://www.cnki.com.cn/Article/CJFDTOTAL-ERTO200104010.htm Wang HS, Yuan X, Xi YS, et al. Prevalence of congenital heart disease in 19432 infants and young children[J]. Chin J Child Health Care, 2001, 9(4): 236-238. https://www.cnki.com.cn/Article/CJFDTOTAL-ERTO200104010.htm
[2]	黄奎奎, 陈丕亮, 马琼, 等. 甘肃省2010-2016年围生儿出生缺陷的现况分析[J]. 中国妇幼保健, 2018, 33(20): 4737-4741. DOI: 10.7620/zgfybj.j.issn.1001-4411.2018.20.57. Huang KK, Chen PL, Ma Q, et al. Birth defects in Gansu Province in 2010-2016 perinatals status analysis[J]. Maternal and Child Health Care of China, 2018, 33(20): 4737-4741. DOI: 10.7620/zgfybj.j.issn.1001-4411.2018.20.57.
[3]	桂逢春. 2008~2012年什邡市出生缺陷分析[J]. 中国妇幼保健, 2015, 30(3): 440-442. DOI: 10.7620/zgfybj.j.issn.1001-4411.2015.03.39. Gui FC. Shifang City from 2008 to 2012 in birth defects analysis[J]. Maternal and Child Health Care of China, 2015, 30(3): 440-442. DOI: 10.7620/zgfybj.j.issn.1001-4411.2015.03.39.
[4]	王卫平. 儿科学[M]. 第8版. 北京: 人民卫生出版社, 2013: 292. Wang WP. Pediatrics[M]. 8th edition. Beijing: People's Medical Publishing House, 2013: 292.
[5]	Yang J, Carmichael SL, Canfield M, et al. Socioeconomic status in relation to selected birth defects in a large multicentered US case-control study[J]. Am J Epidemiol, 2007, 167(2): 145-154. DOI: 10.1093/aje/kwm283.
[6]	Chen Y, Li G, Ruan Y, et al. An epidemiological survey on low birth weight infants in China and analysis of outcomes of full-term low birth weight infants[J]. BMC Pregnancy Childbirth, 2013, 13: 242. DOI: 10.1186/1471-2393-13-242.
[7]	胡美娜, 赵银珠, 邹晓璇, 等. 低出生体重发生率及影响因素[J]. 中国生育健康杂志, 2019, 30(2): 127-130. DOI: 10.3969/j.issn.1671-878X.2019.02.006 Hu MN, Zhao YZ, Zou XX, et al. Incidence and influencing factors of low birth weight[J]. Chin J Reproductive Health, 2019, 30(2): 127-130. DOI: 10.3969/j.issn.1671-878X.2019.02.006
[8]	张钰. 天津市新生儿低出生体重发生率及其影响因素研究[D]. 天津: 天津医科大学, 2018. Zhang Y. Incidence of low birth weight and its influencing factors in Tianjin[D]. Tianjin: Tianjin Medical University, 2018.
[9]	Kecskes Z, Cartwright DW. Poor outcome of very low birthweight babies with serious congenital heart disease[J]. Arch Dis Child Fetal Neonatal Ed, 2002, 87(1): F31-F33. DOI: 10.1136/fn.87.1.F31.
[10]	Obermann-Borst SA, Vujkovic M, de Vries JH, et al. A maternal dietary pattern characterised by fish and seafood in association with the risk of congenital heart defects in the offspring[J]. BJOG, 2011, 118(10): 1205-1215. DOI: 10.1111/j.1471-0528.2011.02984.x.
[11]	邱伟涛. 兰州市2628例妊娠期妇女膳食营养状况调查[D]. 兰州: 兰州大学, 2010. Qiu WT. Investigation on dietary nutrition status of 2628 pregnant women in Lanzhou city[D]. Lanzhou: Lanzhou University, 2010.
[12]	杨生秀, 刘晓玲. 银川市某院产前检查孕妇膳食营养状况调查[J]. 宁夏医科大学学报, 2014, 36(1): 52-55. DOI: 10.16050/j.cnki.issn1674-6309.2014.01.006. Yang SX, Liu XL. Investigation on dietary nutrition status of pregnant women during prenatal examination in a hospital in Yinchuan City[J]. Journal of Ningxia Medical University, 2014, 36(1): 52-55. DOI: 10.16050/j.cnki.issn1674-6309.2014.01.006.
[13]	崔璀, 张振华, 孙忠清, 等. 242名青岛孕妇妊娠期膳食营养摄入状况和孕期增重的调查[C]. 妇幼与青少年营养进展学术研讨会及《中国孕妇、乳母和0-6岁儿童膳食指南》宣传推广会, 2009: 12. Cui ZL, Zhang ZH, Sun ZQ, et al. Investigation of dietary nutrition intake and weight gain during pregnancy in 242 pregnant women in Qingdao[C]. Progress seminar on Maternal, Child and Adolescent Nutrition and promotion of Dietary Guidelines for Pregnant Women, Nursing Mothers and Children aged 0-6 years in China, 2009: 12.
[14]	曹晓辉, 孙丽洲. 939例孕妇妊娠期膳食营养摄入状况调查[J]. 江苏医药, 2012, 38(20): 2408-2410. DOI: 10.19460/j.cnki.0253-3685.2012.20.016. Cao XH, Sun LZ. Investigation of dietary nutrition intake of 939 pregnant women during pregnancy[J]. Jiangsu Pharmaceutical, 2012, 38(20): 2408-2410. DOI: 10.19460/j.cnki.0253-3685.2012.20.016.
[15]	孙曦. 长沙市东湖社区孕妇营养、BMI与妇幼健康关系的初步研究[D]. 长沙: 湖南农业大学, 2017. Sun X. A preliminary study on the relationship between nutrition and BMI of pregnant women and maternal and child health in Donghu Community, Changsha City[D]. Changsha: Hunan Agricultural University, 2017.
[16]	赵灵琴. 铅、汞等重金属元素和微量元素对胎儿先天畸形及早期自然流产影响的流行病学研究[D]. 上海: 复旦大学, 2008. Zhao LQ. An epidemiological study on the effects of heavy metals such as lead, mercury and trace elements on fetal congenital malformation and early spontaneous abortion[D]. Shanghai: Fudan University, 2008.
[17]	刘法佳, 吴燕燕, 李来好, 等. 降低腌制食品中亚硝酸盐含量的研究进展[J]. 广东农业科学, 2011, 38(1): 165-167. DOI: 10.19460/j.cnki.0253-3685.2012.20.016. Liu FJ, Wu YY, Li LH, et al. Research progress on reducing the content of nitrite in preserved food[J]. Guangdong Agricultural Science, 2011, 38(1): 165-167. DOI: 10.19460/j.cnki.0253-3685.2012.20.016.
[18]	邢秀雅. 孕妇饮食模式及其与妊娠结局关联的队列研究[D]. 合肥: 安徽医科大学, 2010. Xing XY. A cohort study on dietary patterns of pregnant women and their association with pregnancy outcomes[D]. Hefei: Anhui Medical University, 2010.
[19]	张艳华. 初孕药物流产对再孕影响分析[J]. 慢性病学杂志, 2010, 12(7): 597-598. https://www.cnki.com.cn/Article/CJFDTOTAL-YYSO201007017.htm Zhang YH. Analysis of the influence of medical abortion in first pregnancy on repregnancy[J]. Chron Pathematol J, 2010, 12(7): 597-598. https://www.cnki.com.cn/Article/CJFDTOTAL-YYSO201007017.htm
[20]	陆新妹, 王志坚. 前置胎盘发病因素及其妊娠结局的临床分析[J]. 中国妇幼保健, 2014, 29(24): 3892-3894. DOI: 10.3969/j.issn.1671-878x.2019.02.006 Lu XM, Wang ZJ. Clinical analysis of the risk factors of placenta previa and its pregnancy outcomes[J]. Chinese Journal of Maternal and Child Health, 2014, 29(24): 3892-3894. doi: 10.3969/j.issn.1671-878x.2019.02.006
[21]	姜子燕, 孙丽洲, 周欣, 等. 前置胎盘产前出血与妊娠结局关系研究[J]. 中国实用妇科与产科杂志, 2019, 35(2): 214-220. DOI:10.19538/j.fk2019020120. Jiang ZY, Sun LZ, Zhou X, et al. A study on the relationship between prenatal bleeding of placenta previa and pregnancy Outcome[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2019, 35(2): 214-220. DOI: 10.19538/J.FK2019020120.
[22]	郑曼利, 何少茹, 刘玉梅, 等. hsPDA对极低出生体重儿的血流动力学影响[C]. 中华医学会第十七次全国儿科学术大会论文汇编, 2012: 2. Zheng ML, He SR, Liu YM, et al. Hemodynamic effects of hsPDA on very low birth weight infants[C]. The 17th National Pediatric Academic Congress of the Chinese Medical Association, 2012: 2.
[23]	Liu F, Yang YN, Xie X, et al. Prevalence of Congenital Heart Disease in Xinjiang Multi-Ethnic Region of China[J]. PLos One, 2015, 10(8): e0133961. DOI: 10.1371/journal.pone.0133961.
[24]	曾珣, 李尚为. 促排卵药物的机制及治疗选择[J]. 实用妇产科杂志, 2013, 29(6): 401-403. https://www.cnki.com.cn/Article/CJFDTOTAL-SFCZ201306004.htm Zeng X, Li SW. Mechanism and treatment choice of drugs for ovulation induction[J]. Journal of Practical Obstetrics and Gynecology, 2013, 29(6): 401-403. https://www.cnki.com.cn/Article/CJFDTOTAL-SFCZ201306004.htm
[25]	王健, 赵君利. 促排卵药物的合理应用[J]. 中国医院药学杂志, 2008, 28(14): 1205-1208. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYZ200814025.htm Wang J, Zhao JL. Rational application of ovulatory drugs[J]. Chin Hosp Pharm J, 2008, 28(14): 1205-1208. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGYZ200814025.htm
[26]	胡琳莉, 朱桂金. 超促排卵的并发症及相关问题[J]. 中国实用妇科与产科杂志, 2006, (5): 391-394. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF200605037.htm Hu LL, Zhu GJ. Complications of superovulation induction and related problems[J]. Chinese Journal of Practical Gynecology and Obstetrics, 2006, (5): 391-394. https://www.cnki.com.cn/Article/CJFDTOTAL-ZGSF200605037.htm