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北京大学学报（医学版） ›› 2025, Vol. 57 ›› Issue (3): 473-480. doi: 10.19723/j.issn.1671-167X.2025.03.010

• 论著 • 上一篇    下一篇

母亲围受孕期服用叶酸营养素补充剂与围产儿死亡率的关系

刘畅1,2,3,4, 李炤1,2,3,4, 金蕾5, 刘春毅1,2,3,4, 王春静5,6, 张杰1,2,3,4, 靳蕾1,2,3,4,*()   

  1. 1. 北京大学公共卫生学院流行病与卫生统计学系, 北京 100191
    2. 北京大学生育健康研究所, 北京 100191
    3. 国家卫生健康委员会生育健康重点实验室, 北京 100191
    4. 北京大学女性生育力促进全国重点实验室, 北京 100191
    5. 北京市通州区妇幼保健院妇女保健科, 北京 101100
    6. 北京市通州区妇幼保健院产科, 北京 101100
  • 收稿日期:2025-02-06 出版日期:2025-06-18 发布日期:2025-06-13
  • 通讯作者: 靳蕾
  • 基金资助:
    国家重点研发计划(2021YFC2700700); 国家重点研发计划(2021YFC2700704)

Association between maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid and perinatal mortality rate

Chang LIU1,2,3,4, Zhao LI1,2,3,4, Lei JIN5, Chunyi LIU1,2,3,4, Chunjing WANG5,6, Jie ZHANG1,2,3,4, Lei JIN1,2,3,4,*()   

  1. 1. Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing 100191, China
    2. Institute of Reproductive and Child Health, Peking University, Beijing 100191, China
    3. National Health Commission Key Laboratory of Reproductive Health, Beijing 100191, China
    4. State Key Laboratory of Female Fertility Promotion, Peking University, Beijing 100191, China
    5. Department of Maternal Health Care, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, China
    6. Department of Obstetrics, Tongzhou Maternal and Child Health Care Hospital of Beijing, Beijing 101100, China
  • Received:2025-02-06 Online:2025-06-18 Published:2025-06-13
  • Contact: Lei JIN
  • Supported by:
    the National Key Research and Development Program of China(2021YFC2700700); the National Key Research and Development Program of China(2021YFC2700704)

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摘要：

目的: 了解北京市通州地区围产儿死亡率情况，探索母亲围受孕期服用叶酸营养素补充剂与围产儿死亡率的关系。方法: 基于北京市通州区妇幼保健系统开展回顾性队列研究，收集2013年1月至2018年12月94 490例围产儿结局及其母亲围受孕期服用叶酸营养素补充剂的信息，应用泊松(Poisson)对数线性模型分析母亲围受孕期服用叶酸营养素补充剂情况与围产儿死亡率的关系。结果: 通州区围产儿死亡率为2.71‰。母亲围受孕期服用叶酸营养素补充剂组与未服用营养素补充剂组围产儿死亡率分别为2.63‰和3.43‰，差异无统计学意义[粗风险比(crude risk ratio，cRR)=0.77，95%CI：0.54~1.14]。调整母亲民族、年龄、文化程度、职业、户籍地、产次、胎数、孕周、是否应用辅助生殖技术、分娩年份和孕前体重指数潜在混杂因素后，母亲围受孕期服用叶酸营养素补充剂与围产儿死亡率的关联也未见统计学意义[调整风险比(adjusted risk ratio，aRR)=0.93，95% CI：0.77~1.13]。服用单纯叶酸组与服用含有叶酸的复合营养素组的围产儿死亡率分别为2.23‰和2.99‰，差异有统计学意义(cRR= 1.34，95%CI: 1.02~1.76)，调整潜在混杂因素后，差异仍具有统计学意义(aRR=1.31, 95%CI: 1.06~1.62)。进一步分析叶酸营养补充剂开始服用时间和服用频率与围产儿死亡的关系，服用组开始服用的时间及服用频率(孕前或孕后及低频或高频)与未服用叶酸营养素补充剂组比较，无论是否调整混杂因素，围产儿死亡率差异均无统计学意义。结论: 北京市通州区围产儿死亡率低于全国平均水平，尚未发现母亲围受孕期服用叶酸营养素补充剂与围产儿死亡率间存在关联，围受孕期服用含叶酸的复合营养素与围产儿死亡的关系需要进一步研究。

关键词: 围受孕期, 营养补充剂, 叶酸, 围产儿, 死亡率

Abstract:

Objective: To describe the prevalence of perinatal death in Tongzhou District of Beijing, and to estimate the association between maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid and perinatal mortality rate. Methods: A retrospective cohort study was conducted based on the maternal and child care system in Tongzhou District of Beijing. The subjects were 94 490 perinatal who were born during January 2013 to December 2018. The information on perinatal outcomes and maternal periconceptional supplementation of folic acid or multiple micronutrients containing folic acid were collected. The Poisson log-linear model was used to estimate the association between maternal periconceptional folic acid or multiple micronutrients supplementation and perinatal mortality rate. Results: The overall perinatal mortality rate was 2.71‰. The perinatal mortality rates for maternal nutrients supplementation containing folic acid and no supplementation during periconceptional period were 2.63‰ and 3.43‰, respectively, and the difference in rates was not statistically significant [crude risk ratio (cRR) = 0.77, 95%CI: 0.54-1.14]. After adjusting for potential confounding factors including ethnicity, age, education level, occupation, household registration, parity, numbers of fetuses, gestational age, pregnant with assisted reproductive technology, delivery year and pre-pregnancy body mass index, the rates remained not statistically significant [adjusted risk ratio (aRR) = 0.93, 95%CI: 0.77-1.13]. The perinatal mortality rates were 2.23‰ and 2.99‰ for pure folic acid and multi-nutrients supplements containing folic acid, respectively, and the difference in rates was statistically significant (cRR = 1.34, 95% CI: 1.02-1.76). The rates difference remained statistically significant after adjusting for potential confounders (aRR = 1.31, 95% CI: 1.06-1.62). Additionally, the perinatal mortality rates differences among the non-supplementation group and the supplementation group with variate timing of initiation (pre-conception or post-conception) or frequency of supplementation (low-frequency or high-frequency) were not statistically significant, regardless of adjusting for confounders. Conclusion: The overall perinatal mortality rate was lower than the national average level in Tongzhou District of Beijing. Maternal periconceptional supplementation of pure folic acid or micronutrients containing folic acid had no impact on perinatal mortality. The association between maternal periconceptional supplementation of multiple micronutrients containing folic acid and perinatal mortality rate need further research.

Key words: Periconceptional period, Micronutrients supplementation, Folic acid, Perinatal infant, Mortality rate

中图分类号: 

  • R17

表1

叶酸营养素补充剂不同比对组研究对象基本特征"

表2

母亲围受孕期服用营养补充剂与围产儿死亡率关系"

n PM, n(‰) cRR (95%CI) aRR (95%CI)a aRR (95%CI)b
FA/MMFA supplementation
  No use 9 043 31 (3.43) 1 1 1
  Use 85 447 225 (2.63) 0.77 (0.54-1.14) 0.89 (0.75-1.05) 0.93 (0.77-1.13)
Formula of the supplements
  FA 37 587 84 (2.23) 1 1 1
  MMFA 47 166 141 (2.99) 1.34 (1.02-1.76) 1.29 (1.07-1.56) 1.31 (1.06-1.62)
Initiation time of supplementation
  No use 9 043 31 (3.43) 1 1 1
  Post-conception 39 294 112 (2.85) 0.83 (0.57-1.26) 0.94 (0.74-1.18) 0.95 (0.73-1.22)
  Pre-conception 45 472 113 (2.49) 0.72 (0.49-1.10) 0.87 (0.69-1.09) 0.89 (0.68-1.15)
Frequency of supplementation
  No use 9 043 31 (3.43) 1 1 1
  1-7 d/10 d 44 724 126 (2.82) 0.82 (0.56-1.24) 0.94 (0.75-1.17) 0.98 (0.77-1.25)
  ≥8 d/10 d 40 052 99 (2.47) 0.72 (0.49-1.10) 0.84 (0.66-1.07) 0.84 (0.63-1.11)

表3

围受孕期服用叶酸营养素补充剂与孕早期血浆Hcy浓度的关系"

Status of supplementation n Hcy/(μmol/L), M (P25, P75) P
FA/MMFA supplementation ＜0.001
  No use 1 427 6.5 (5.6, 7.7)
  Use 15 627 6.1 (5.3, 7.0)
Formula of the supplements ＜0.001
  FA 5 853 6.2 (5.4, 7.2)
  MMFA 9 757 6.0 (5.3, 6.9)
Initiation time of supplementation ＜0.001
  Pre-conception 7 500 6.0 (5.3, 6.9)
  Post-conception 8 124 6.2 (5.4, 7.2)
Frequency of supplementation ＜0.001
  1-7 d/10 d 8 889 6.2 (5.4, 7.2)
  ≥8 d/10 d 6 733 6.0 (5.3, 6.9)
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ISSN 1671-167X
CN 11-4691/R
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