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Journal of Peking University (Health Sciences) ›› 2023, Vol. 55 ›› Issue (3): 495-501. doi: 10.19723/j.issn.1671-167X.2023.03.016

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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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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

CLC Number: 

  • R172

Figure 1

Flowchart of participants selection"

Table 1

General characteristics of the participants in the study"

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)

Table 2

Relationship between the formula, time of initiation, frequency of taking nutritional supplements in the periconceptional period and gestational age"

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

Table 3

Association of nutritional supplement formula, time of initiation and frequency with preterm delivery"

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)

Table 4

Association between compliance score of taking nutritional supplements in the peri-conceptional period and preterm delivery"

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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