Association between maternal iron nutrition during pregnancy and congenital heart disease in offspring based on a case-control study
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摘要:
目的 探讨母亲孕期铁营养与子代先天性心脏病(congenital heart disease，CHD)的关系。 方法 数据来源于陕西省2014年1月―2016年12月开展的CHD病例对照研究，对纳入孕妇进行膳食营养问卷调查。采用条件logistic回归分析模型分析母亲孕期铁营养与子代CHD及其各亚型的关系，并进行亚组分析探索其稳定性。 结果 在调整了混杂因素后，母亲孕期增补铁剂降低了子代CHD的发生风险(< 30 d：OR=0.54, 95% CI: 0.37~0.79；≥30 d：OR=0.25, 95% CI: 0.16~0.38)，孕期膳食铁摄入量较高(≥29 mg/d)降低了子代CHD的发生风险(OR=0.69, 95% CI: 0.54~0.88)，亚组分析结果显示，母亲孕期铁营养和子代CHD的关系稳定。此外，母亲孕期增补铁剂≥30 d子代在室间隔缺损(ventricular septal defect, VSD)、房间隔缺损(atrial septal defect, ASD)、动脉导管未闭(patent ductus arteriosus, PDA)、法洛四联症(tetralogy of fallot, TOF)上发生风险均降低，增补铁剂 < 30 d子代在ASD发生风险降低，孕期膳食铁摄入量较高(≥29 mg/d)子代在VSD、PDA发生风险均降低。 结论 母亲孕期铁营养水平升高降低了子代CHD的发生风险，孕妇孕期应注意机体铁营养的摄入和补充，促进母婴健康。 Abstract:Objective The study aims to explore the relationship between maternal iron nutrition during pregnancy and congenital heart disease (CHD) in offspring. Methods A matched case-control study was conducted in Shaanxi Province from January 2014 to December 2016, and a food frequency questionnaire was used to collect dietary nutrition during pregnancy among women. The conditional logistic regression model was adopted to examine the association between maternal iron nutrition during pregnancy and CHD and its subtypes in offsprings, and subgroup analysis was further performed to test results stability. Results After adjusting for confounding factors, maternal iron supplementation during pregnancy reduced the risk for CHD in offsprings (< 30 days: OR=0.54, 95% CI: 0.37-0.79; ≥ 30 days: OR=0.25, 95% CI: 0.16-0.38). Higher dietary iron intake during pregnancy (≥29mg/d) reduced the risk for CHD in offsprings (OR=0.69, 95% CI: 0.54-0.88). The subgroup analysis showed that the relationship between maternal iron nutrition during pregnancy and CHD was stable. In addition, the risk of ventricular septal defect (VSD), atrial septal defect (ASD), patent ductus arteriosus (PDA), and tetralogy of fallot (TOF) in the offspring was lower among mothers with iron supplementation ≥30 days during pregnancy. If the mothers supplemented iron less than 30 days, the risk for ASD in the offspring would reduce. The risk of VSD and PDA in the offspring was lower among mothers with a higher dietary iron intake during pregnancy (≥29mg/d). Conclusions The higher iron nutrition level of mothers during pregnancy is associated with the reduced risk for CHD in offspring. Pregnant women should ensure adequate iron intake during pregnancy to promote the health of mothers and babies. -
Key words:
- Iron nutrition /
- Congenital heart disease /
- Pregnancy /
- Case-control study
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图 1 母亲孕期膳食铁摄入量与子代CHD关系的亚组分析
注：调整了除亚组变量外的其他协变量，以孕期膳食铁摄入量 < 29 mg/d为参考。
Figure 1. Subgroup analysis of the relationship between maternal dietary iron intake during pregnancy and CHD in offspring
图 2 母亲孕期铁剂增补与子代CHD关系的亚组分析
注：调整了除亚组变量外的其他协变量，以孕期无铁剂增补为参考。
Figure 2. Subgroup analysis of the relationship between maternal iron supplementation during pregnancy and CHD in offspring
表 1 研究对象一般资料[n(%)]
Table 1. General information of subjects [n(%)]
指标 病例组(n=600) 对照组(n=1 200) χ2值 P值 指标 病例组(n=600) 对照组(n=1 200) χ2值 P值 母亲年龄(岁) 3.085 0.079 孕早期感冒 22.227 < 0.001 < 30岁 378(63.00) 806(67.17) 是 185(30.83) 249(20.75) ≥30岁 222(37.00) 394(32.83) 否 415(69.17) 951(79.25) 母亲民族 10.658 0.001 孕早期发烧 3.161 0.075 汉族 585(97.50) 1 192(99.33) 是 54(9.00) 80(6.67) 少数民族 15(2.50) 8(0.67) 否 546(91.00) 1 120(93.33) 母亲受教育程度 88.615 < 0.001 孕期饮酒 15.298 < 0.001 高中及以下 264(44.00) 270(22.50) 是 18(3.00) 8(0.67) 大专及以上 336(56.00) 930(77.50) 否 582(97.00) 1 192(99.33) 母亲户籍类型 178.249 < 0.001 孕期被动吸烟 36.090 < 0.001 城镇居民 201(33.50) 800(66.67) 是 345(57.50) 510(42.50) 农村居民 399(66.50) 400(33.33) 否 255(42.50) 690(57.50) 家庭财富指数 116.335 < 0.001 孕期染烫头发 13.292 < 0.001 贫穷 313(52.17) 331(27.58) 是 37(6.17) 32(2.67) 中等 167(27.83) 398(33.17) 否 563(93.83) 1 168(97.33) 富裕 120(20.00) 471(39.25) 孕期服用叶酸 21.160 < 0.001 孕次 24.396 < 0.001 是 476(79.33) 1 051(87.58) 1次 236(39.33) 620(51.67) 否 124(20.67) 149(12.42) ≥2次 364(60.67) 580(48.33) 
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表 2 母亲孕期铁营养与子代CHD关系的logistic回归分析
Table 2. Logistic regression analysis of the relationship between maternal iron nutrition during pregnancy and CHD in offspring
指标 病例[n(%)] 对照[n(%)] 模型1 模型2 模型3 OR (95% CI)值, P值 调整OR (95% CI)值a, P值 调整OR (95% CI)值b, P值 孕期铁剂增补 否 520(86.67) 774(64.50) 1.00 1.00 1.00 增补 < 30 d 48(8.00) 176(14.67) 0.41(0.29~0.58), < 0.001 0.53(0.36~0.76), 0.001 0.54(0.37~0.79), 0.001 增补≥30 d 32(5.33) 250(20.83) 0.20(0.13~0.29), < 0.001 0.23(0.15~0.34), < 0.001 0.25(0.16~0.38), < 0.001 孕期膳食铁摄入 < 29 mg/d 434(72.33) 721(60.08) 1.00 1.00 1.00 ≥29 mg/d 166(27.67) 479(39.92) 0.57(0.45~0.70), < 0.001 0.65(0.51~0.82), < 0.001 0.69(0.54~0.88), 0.003 注：a调整了母亲民族、母亲受教育程度、母亲户籍类型、家庭财富指数、孕次；b调整所有基线协变量(母亲民族、母亲受教育程度、母亲户籍类型、家庭财富指数、孕次、孕早期感冒、孕期饮酒、孕期被动吸烟、孕期染烫头发、孕期服用叶酸)。
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表 3 母亲孕期铁营养与子代CHD关系的疾病异质性分析
Table 3. Disease heterogeneity analysis of the relationship between maternal iron nutrition during pregnancy and CHD in offspring
指标 VSD(n=187) 调整OR (95% CI)值 ASD(n=75) 调整OR (95% CI)值 PDA(n=75) 调整OR (95% CI)值 AVSD(n=51) 调整OR (95% CI)值 TOF(n=45) 调整OR (95% CI)值 孕期铁剂增补 否 1.00 1.00 1.00 1.00 1.00 增补 < 30 d 0.59(0.30~1.16) 0.26(0.07~0.91) 0.57(0.23~1.40) 0.61(0.18~2.06) 0.11(0.01~1.78) 增补≥30 d 0.20(0.09~0.44) 0.25(0.08~0.74) 0.22(0.06~0.82) 0.82(0.20~3.31) 0.14(0.02~0.79) 孕期膳食铁摄入 < 29 mg/d 1.00 1.00 1.00 1.00 1.00 ≥29 mg/d 0.63(0.40~0.99) 0.77(0.36~1.65) 0.47(0.23~0.95) 0.70(0.30~1.67) 0.66(0.20~2.18) 注: 调整了母亲民族、母亲受教育程度、母亲户籍类型、家庭财富指数、孕次。
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