刘倩, 毛宝宏, 代志蓉, 王文第, 虎亚光, 刘青, 王燕侠. 母血和新生儿脐血锌水平与新生儿先天性心脏病发病风险的巢式病例对照研究[J]. 环境与职业医学, 2022, 39(6): 665-671. DOI: 10.11836/JEOM21376
引用本文: 刘倩, 毛宝宏, 代志蓉, 王文第, 虎亚光, 刘青, 王燕侠. 母血和新生儿脐血锌水平与新生儿先天性心脏病发病风险的巢式病例对照研究[J]. 环境与职业医学, 2022, 39(6): 665-671. DOI: 10.11836/JEOM21376
LIU Qian, MAO Baohong, DAI Zhirong, WANG Wendi, HU Yaguang, LIU Qing, WANG Yanxia. A nested case-control study on zinc levels in maternal whole blood and fetal cord blood and risk of congenital heart disease in offspring[J]. Journal of Environmental and Occupational Medicine, 2022, 39(6): 665-671. DOI: 10.11836/JEOM21376
Citation: LIU Qian, MAO Baohong, DAI Zhirong, WANG Wendi, HU Yaguang, LIU Qing, WANG Yanxia. A nested case-control study on zinc levels in maternal whole blood and fetal cord blood and risk of congenital heart disease in offspring[J]. Journal of Environmental and Occupational Medicine, 2022, 39(6): 665-671. DOI: 10.11836/JEOM21376

母血和新生儿脐血锌水平与新生儿先天性心脏病发病风险的巢式病例对照研究

A nested case-control study on zinc levels in maternal whole blood and fetal cord blood and risk of congenital heart disease in offspring

  • 摘要: 背景 锌是胎儿心脏正常发育所必需的微量元素,过量的锌会产生毒性。孕母和新生儿锌水平与新生儿发生先天性心脏病(CHD)的关系尚不明确。

    目的 研究孕母和新生儿锌暴露水平对新生儿CHD发病风险的影响。

    方法 研究对象资料及生物样本均来源于2010—2012年在甘肃省妇幼保健院建立的兰州地区出生队列。该队列采用问卷调查的方法在孕早期对研究对象进行基线调查并在孕中期、孕晚期及产后42 d分别进行随访。分别采集孕晚期孕母静脉血和分娩时新生儿脐静脉血,并从医疗记录中提取其出生结局信息。本研究选择出生后经超声心动检查诊断并在42 d后随访时仍明确诊断的97例CHD患儿作为病例组,从数据库中按照母亲年龄、地域进行1∶2配对选择出生后健康的194例足月儿作为对照组。采用电感耦合等离子体质谱法分别检测孕母全血样本和新生儿脐血样本锌质量浓度(后称浓度)。根据对照组孕母全血和新生儿脐血锌浓度的第25、75百分位数(P25P75)将锌暴露分为低、中、高三组,调整孕母孕早期阴道流血、孕前补充叶酸和维生素、新生儿出生体重和脐绕颈4项混杂因素后,应用多因素条件logistic 回归分析孕母和新生儿锌暴露水平与新生儿发生CHD的关系,并进一步根据疾病分类进行亚组分析。

    结果 CHD组和对照组孕母全血锌浓度的中位数M和(P25P75)分别为5.034(3.456,6.644)mg·L−1和4.693(3.411,5.646)mg·L−1,差异具有统计学意义(P=0.029)。CHD组新生儿脐血锌浓度的MP25P75)为2.153(1.479,2.405)mg·L−1,对照组为1.636(1.304,1.979)mg·L−1,两组差异具有统计学意义(P<0.001)。单纯型CHD组孕母全血和新生儿脐血锌浓度高于对照组,差异具有统计学意义(均P<0.05)。多因素条件logistic回归模型分析显示,调整混杂因素后,与孕母中等锌暴露水平组(3.41~5.65 mg·L−1)相比,高锌暴露水平组(>5.65 mg·L−1)子代CHD发病风险为2.225倍(OR=2.225,95%CI:1.017~4.868)。与新生儿中等锌暴露组(1.30~1.98 mg·L−1)相比,高锌暴露组(>1.98 mg·L−1)的CHD发病风险也增高(OR=4.132,95%CI:1.801~9.480)。亚组分析显示,与中等锌暴露水平组相比,高锌暴露水平孕母的子代单纯型CHD发病风险增高(OR=4.081,95%CI:1.427~11.669),高锌暴露水平的新生儿发生单纯型CHD(OR=7.122,95%CI:2.126~23.854)和复杂型CHD(OR=5.165,95%CI:1.859~14.346)的风险均增高。

    结论 在本人群的暴露水平下,孕母和新生儿高锌暴露水平可能与CHD的发病有关。

     

    Abstract: Background Zinc is a trace element essential for normal fetal heart development, and excess zinc can be toxic. The relationship between maternal and fetal zinc levels and the development of congenital heart disease (CHD) in the offspring is unclear.

    Objective To study the effects of maternal and neonatal zinc exposure levels on the risk of developing CHD in the offspring.

    Methods The data and biological samples of the study subjects were derived from the birth cohort established by Gansu Provincial Maternity and Child Care Hospital in Lanzhou from 2010 to 2012. Questionnaire surveys were conducted at baseline in the first trimester and at follow-up visits in the second trimester, the third trimester, and 42 d after delivery. Maternal venous blood during the third trimester and neonatal umbilical venous blood at delivery were collected, and information on their birth outcomes was extracted from medical records. Ninety-seven children with CHD diagnosed by echocardiography at birth and confirmed at the follow-up after 42 d were selected as the case group, and 194 healthy full-term infants were selected as the control group, 1∶2 matched for maternal age and geographical location from the database. The zinc concentrations in whole blood of pregnant mothers and umbilical cord blood of fetuses in both groups were measured by inductively coupled plasma mass spectrometry. According to the quartiles P25 and P75 of zinc levels in the whole blood of pregnant mothers and neonatal cord blood in the control group, zinc exposure was divided into three groups: low, medium, and high. After adjusting for maternal vaginal bleeding in early pregnancy, pre-pregnancy folic acid and vitamin supplementation, birth weight, and umbilical cerclage confounders, a multiple conditional logistic regression model was applied to analyze the associations between maternal whole blood and fetal umbilical cord blood zinc levels and the risk of CHD in the offspring, and a further subgroup analysis was performed by disease classification.

    Results The medians (P25, P75) of maternal whole blood zinc levels in the case group and the control group were 5.034 (3.456, 6.644) and 4.693 (3.411, 5.646) mg·L−1, respectively, with significant differences between the two groups (P=0.029). The medians (P25, P75) of neonatal cord blood zinc level was 2.153 (1.479, 2.405) mg·L−1 in the case group and 1.636 (1.304, 1.979) mg·L−1 in the control group, with significant differences between the two groups (P<0.001). The zinc levels of maternal whole blood and neonatal cord blood in the simple CHD group were significantly higher than those in the control group (P<0.05). The multiple conditional logistic regression model showed that compared with the maternal medium zinc exposure level group (3.41-5.65 mg·L−1), the risk of offspring CHD was 2.225 times of the high exposure level group (>5.65 mg·L−1) (OR=2.225, 95%CI: 1.017-4.868). Compared with the neonatal medium zinc exposure level group (1.30-1.98 mg·L−1), the neonatal high exposure level group (>1.98 mg·L−1) also had an increased risk of CHD (OR=4.132, 95%CI: 1.801-9.480). The subgroup analysis results showed that compared with corresponding medium exposure level groups, the risk of simple CHD in the offspring of the maternal high zinc exposure level group was increased (OR=4.081, 95%CI: 1.427-11.669), and the risks of simple CHD (OR=7.122, 95%CI: 2.126-23.854) and complex CHD (OR=5.165, 95%CI: 1.859-14.346) of neonates of the neonatal high zinc exposure level group were increased.

    Conclusion Under the exposure levels of the study population, high concentrations of zinc exposure in pregnant mothers and neonates may be associated with the incidence of CHD.

     

/

返回文章
返回