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北京大学学报（医学版） ›› 2023, Vol. 55 ›› Issue (3): 495-501. doi: 10.19723/j.issn.1671-167X.2023.03.016

• 论著 • 上一篇    下一篇

妇女围受孕期服用叶酸或含叶酸的多种微量营养素补充剂与早产的关联性研究

白银晓1,2,3,刘春毅1,2,3,张杰1,2,3,孟文颖4,金蕾5,靳蕾1,2,3,*()   

  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. 北京市通州区妇幼保健院产科，北京 101100
    5. 北京市通州区妇幼保健院妇女保健科，北京 101100
  • 收稿日期:2022-11-23 出版日期:2023-06-18 发布日期:2023-06-12
  • 通讯作者: 靳蕾 E-mail:jinlei@bjmu.edu.cn
  • 基金资助:
    首都卫生发展科研专项(2020-1-5112);国家社科基金重大项目(21&ZD187)

Association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid and preterm delivery in women

Yin-xiao BAI1,2,3,Chun-yi LIU1,2,3,Jie ZHANG1,2,3,Wen-ying MENG4,Lei JIN5,Lei JIN1,2,3,*()   

  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. Department of Obstetrics, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, China
    5. Department of Maternal Health Care, Tongzhou Maternal and Child Health Hospital of Beijing, Beijing 101100, China
  • Received:2022-11-23 Online:2023-06-18 Published:2023-06-12
  • Contact: Lei JIN E-mail:jinlei@bjmu.edu.cn
  • Supported by:
    the Capital Health Research and Development of Special(2020-1-5112);the National Social Science Fund of China(21&ZD187)

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摘要：

目的: 探索自然受孕、单胎妊娠、阴道自然分娩妇女围受孕期服用叶酸或含叶酸的多种微量营养素补充剂与早产发生风险的关联。方法: 基于北京市通州区妇幼保健院孕期保健系统和医院信息系统开展回顾性队列研究，收集2015年1月至2018年12月自然受孕、单胎妊娠、在北京市通州区妇幼保健院进行产前保健并阴道自然分娩的16 332名孕产妇的信息，将妇女服用营养补充剂的开始时间与频率相结合形成依从性得分。采用Logistic回归模型分析妇女围受孕期是否服用单纯叶酸片(folic acid，FA)或含叶酸的多种微量营养素补充剂(multiple-micronutrients containing folic acid，MMFA)、服用方式、服用依从性得分与早产率的关系。结果: 研究人群的早产率(孕周 < 37周)为3.8%，平均孕龄为(38.98±1.37)周，其中，有6 174(37.8%)名妇女在围受孕期服用了FA，8 646(52.9%)名服用了MMFA，1 512(9.3%)名未服用任何营养补充剂。与未服用营养补充剂的妇女相比，服用FA或MMFA与早产的关联没有统计学意义[调整后的比值比(adjusted odds ratio，aOR)=1.01，95%CI：0.74~1.37]，服用营养补充剂的种类、开始服用时间及频率与早产的关联也未见统计学意义；同样，也未发现围受孕期服用营养补充剂的依从性得分与早产的关联有统计学意义。结论: 尚未发现自然受孕、单胎妊娠、阴道自然分娩的妇女在围受孕期服用FA或MMFA与早产之间的关联，未来需要开展更多的多中心、大规模前瞻性队列研究或随机对照研究来论证妇女围受孕期服用FA或MMFA与早产之间的关联。

关键词: 叶酸, 多种微量营养素, 早产, 围受孕期

Abstract:

Objective: To explore the association between periconceptional supplementation of folic acid or multiple-micronutrients containing folic acid(MMFA) and risk of preterm delivery in women with natural conception, singleton pregnancy and vaginal delivery. Methods: A retrospective cohort study was performed based on the prenatal health care system and hospital information system of Tongzhou Maternal and Child Health Hospital of Beijing and the women who had their prenatal care in the hospital from January 2015 to December 2018 were included. The information of 16 332 women who conceived naturally, had a singleton pregnancy, and delivered vaginally was collected. Compliance scores were constructed based on the time of initiation and the frequency of taking nutritional supplements. The association between maternal periconceptional micronutrient supplementation, including pure folic acid (FA) pills or MMFA and the rate of preterm delivery was evaluated using Logistic regression models. Results: The preterm delivery rate (gestational week < 37 weeks) of the study population was 3.8%, and the mean (standard deviation) of gestational age was (38.98±1.37) weeks. A total of 6 174 (37.8%) women took FA during the periconceptional period, 8 646 (52.9%) women took MMFA, and 1 512 (9.3%) women did not take any nutritional supplements. The association between periconceptional supplementation of FA or MMFA and risk of preterm delivery in women was not statistically significant [adjusted odds ratio (aOR)=1.01, 95%CI: 0.74-1.37]. The associations with preterm birth were not statistically significant in further analysis by the type of nutritional supplements, time of initiation, and the frequency of supplementation. In addition, the association between the compliance score of taking supplements and the rate of preterm delivery was not statistically significant, either. Conclusion: This study did not find an association between the risk of preterm delivery and the use of FA or MMFA during the periconcep-tional period in women with natural conception, singleton pregnancy, and vaginal delivery. In the future, multicenter studies with large-scale prospective cohort or population-based randomized controlled trials are warranted to confirm the association between taking FA or MMFA during the periconceptional period and preterm delivery among women.

Key words: Folic acid, Multiple-micronutrient, Premature birth, Periconceptional period

中图分类号: 

  • R172

图1

研究对象的筛选流程"

表1

研究对象的基本特征"

Characteristics Total, n (%)
(n=16 332)		 FA, n (%)
(n=6 174)		 MMFA, n (%)
(n=8 646)		 No use, n (%)
(n=1 512)		 χ2 P
Ethnic 1.983 0.371
   Han 15 403 (94.3) 5 820 (94.3) 8 145 (94.2) 1 438 (95.1)
   Others 929 (5.7) 354 (5.7) 501 (5.8) 74 (4.9)
Maternal age/years 58.013 < 0.001
   16- 2 245 (13.7) 844 (13.7) 1 106 (12.8) 295 (19.5)
   25- 8 262 (50.6) 3 157 (51.1) 4 438 (51.3) 667 (44.1)
   30- 4 665 (28.6) 1 742 (28.2) 2 492 (28.8) 431 (28.5)
   35-48 1 160 (7.1) 431 (7.0) 610 (7.1) 119 (7.9)
Education level 381.451 < 0.001
   Missing 132 (0.8) 42 (0.7) 49 (0.6) 41 (2.7)
   Middle school or lower 1 618 (10.0) 678 (11.1) 651 (7.6) 289 (19.6)
   High school or secondary technical school 3 152 (19.5) 1 212 (19.8) 1 526 (17.8) 414 (28.1)
   College 5 095 (31.5) 1 929 (31.5) 2 760 (32.1) 406 (27.6)
   University or above 6 335 (39.1) 2 313 (37.7) 3 660 (42.6) 362 (24.6)
Occupation 221.993 < 0.001
   Missing 368 (2.3) 125 (2.0) 140 (1.6) 103 (6.8)
   Government agency 1 513 (9.5) 536 (8.9) 799 (9.4) 178 (12.6)
   Professional technicians 3 405 (21.3) 1 327 (21.9) 1 903 (22.4) 175 (12.4)
   Office clerk or related personnel 2 519 (15.8) 857 (14.2) 1 500 (17.6) 162 (11.5)
   Business/services 3 077 (19.3) 1 194 (19.7) 1 653 (19.4) 230 (16.3)
   Unemployment 2 581 (16.2) 1 018 (16.8) 1 258 (14.8) 305 (21.6)
   Others 2 869 (18.0) 1 117 (18.5) 1 393 (16.4) 359 (25.5)
Parents household registration types 30.894 < 0.001
   Both of parents were none local 6 802 (41.6) 2 584 (41.9) 3 576 (41.4) 642 (42.5)
   The mother registered locally 6 383 (39.1) 2 287 (37.0) 3 515 (40.7) 581 (38.4)
   Only the father registered locally 3 147 (19.3) 1 303 (21.1) 1 555 (18.0) 289 (19.1)
Pre-pregnancy BMI 8.330 0.215
   Missing 21 (0.1) 6 (0.1) 11 (0.1) 4 (0.3)
   Underweight 2 251 (13.8) 826 (13.4) 1 227 (14.2) 198 (13.1)
   Normal 10 737 (65.8) 4 078 (66.1) 5 689 (65.9) 970 (64.3)
   Overweight 2 627 (16.1) 988 (16.0) 1 368 (15.8) 271 (18.0)
   Obesity 696 (4.3) 276 (4.5) 351 (4.1) 69 (4.6)
Parity 133.442 < 0.001
   Missing 460 (2.8) 205 (3.3) 245 (2.8) 10 (0.7)
   Nulliparity 9 026 (56.9) 3 536 (59.2) 4 844 (57.7) 646 (43.0)
   Multiparity 6 846 (43.1) 2 433 (40.8) 3 557 (42.3) 856 (57.0)
Pre-pregnant diabetes 2.242 0.326
   No 16 219 (99.3) 6 128 (99.3) 8 593 (99.4) 1 498 (99.1)
   Yes 113 (0.7) 46 (0.7) 53 (0.6) 14 (0.9)
Gestational diabetes 15.378 0.001
   No 12 706 (77.8) 4 793 (77.6) 6 677 (77.2) 1 236 (81.7)
   Yes 3 626 (22.2) 1 381 (22.4) 1 969 (22.8) 276 (18.3)
Gestational hypertension 1.911 0.385
   No 15 648 (95.8) 5 899 (95.5) 8 295 (95.9) 1 454 (96.2)
   Yes 684 (4.2) 275 (4.5) 351 (4.1) 58 (3.8)
Liver disease 0.872 0.647
   No 16 045 (98.2) 6 069 (98.3) 8 495 (98.3) 1 481 (97.9)
   Yes 287 (1.8) 105 (1.7) 151 (1.7) 31 (2.1)
Thyroid disease 0.968 0.617
   No 15 593 (95.5) 5 882 (95.3) 8 265 (95.6) 1 446 (95.6)
   Yes 739 (4.5) 292 (4.7) 381 (4.4) 66 (4.4)
Delivery year 231.248 < 0.001
   2015 3 016 (18.5) 1 149 (18.6) 1 436 (16.6) 431 (28.5)
   2016 5 054 (30.9) 2 166 (35.1) 2 554 (29.5) 334 (22.1)
   2017 4 506 (27.6) 1 640 (26.6) 2 470 (28.6) 396 (26.2)
   2018 3 756 (23.0) 1 219 (19.7) 2 186 (25.3) 351 (23.2)

表2

围受孕期服用营养补充剂的配方、开始时间和频率与孕龄的关系"

Use of nutritional supplements n (%)Gestational age/weeks
${\bar x}$±s P10 P25 P50 P75 P90 P value
Total 16 332 (100.0) 38.98±1.37 37 38 39 40 40
Nutritional supplements 0.743a
   No 1 512 (9.3) 38.99±1.40 38 38 39 40 40
   Yes 14 820 (90.7) 38.97±1.37 37 38 39 40 40
Supplements formula 0.348a
   FA 6 174 (41.7) 38.96±1.39 37 38 39 40 40
   MMFA 8 646 (58.3) 38.98±1.35 37 38 39 40 40
FA
   Timing of supplementation initiation 0.755a
      Before the conception 3 614 (58.5) 38.96±1.36 37 38 39 40 40
      After the conception 2 560 (41.5) 38.97±1.44 38 38 39 40 40
   Frequercy (in 10 d) 0.981a
      Irregular (< 8 d) 2 921 (47.3) 38.96±1.44 38 38 39 40 40
      Regular (≥8 d) 3 253 (52.7) 38.96±1.35 37 38 39 40 40
MMFA
   Timing of supplementation initiation 0.012a
      Before the conception 3 395 (39.3) 38.94±1.37 37 38 39 40 40
      After the conception 5 251 (60.7) 39.01±1.33 38 38 39 40 40
   Frequercy (in 10 d) 0.072a
      Irregular (< 8 d) 5 597 (64.8) 39.00±1.36 38 38 39 40 40
      Regular (≥8 d) 3 047 (35.2) 38.95±1.33 37 38 39 40 40

表3

围受孕期服用营养补充剂的配方、开始时间和频率与早产的关系"

Use of nutritional supplementsPreterm delivery
% (n/N) cOR (95%CI) aOR (95%CI)*
Nutritional supplements
   No 5.58% (55/986) 1 1
   Yes 5.75% (563/9 785) 1.03 (0.78-1.37) 1.01 (0.74-1.37)
Supplements formula
   FA 6.34% (258/4 070) 1 1
   MMFA 5.34% (305/5 715) 0.83 (0.70-0.99) 0.85 (0.71-1.02)
FA
   Timing of supplementation initiation
      Before the conception 6.15% (145/2 359) 0.93 (0.72-1.19) 0.90 (0.68-1.18)
      After the conception 6.60% (113/1 711) 1 1
   Frequency (in 10 d)
      Irregular (< 8 d) 6.54% (127/1 942) 1 1
      Regular (≥8 d) 6.16% (131/2 128) 0.94 (0.73-1.21) 0.93 (0.71-1.22)
MMFA
   Timing of supplementation initiation
      Before the conception 5.50% (123/2 237) 1.05 (0.83-1.33) 0.95 (0.74-1.22)
      After the conception 5.23% (182/3 478) 1 1
   Frequency (in 10 d)
      Irregular (< 8 d) 5.38% (199/3 697) 1 1
      Regular (≥8 d) 5.25% (106/2 018) 0.97 (0.76-1.24) 0.87 (0.67-1.12)

表4

围受孕期服用营养补充剂的依从性得分与早产的关系"

Compliance scorePreterm delivery
% (n/N) cOR (95%CI) aOR (95%CI)*
FA
   0 5.58% (55/986) 1 1
   1 6.62% (112/1 691) 1.20 (0.86-1.67) 1.19 (0.84-1.70)
   2 5.98% (15/251) 1.08 (0.60-1.94) 0.99 (0.53-1.85)
   3 6.17% (130/2 108) 1.11 (0.80-1.54) 1.08 (0.76-1.54)
MMFA
   0 5.58% (55/986) 1 1
   1 5.23% (179/3 424) 0.93 (0.68-1.27) 0.96 (0.69-1.34)
   2 7.33% (20/273) 1.34 (0.79-2.27) 1.36 (0.78-2.36)
   3 5.24% (103/1 964) 0.94 (0.67-1.31) 0.86 (0.59-1.24)
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ISSN 1671-167X
CN 11-4691/R
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