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Journal of Peking University (Health Sciences) ›› 2025, Vol. 57 ›› Issue (3): 473-480. doi: 10.19723/j.issn.1671-167X.2025.03.010

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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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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

CLC Number: 

  • R17

Table 1

Maternal and perinatal characteristics among the comparison groups of FA or MMFA"

Table 2

Association between maternal periconceptional supplementation of FA or MMFA and risk for PMR"

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)

Table 3

Relationship between maternal periconceptional supplementation of FA or MMFA and plasma Hcy concentration in the first trimester of pregnant period"

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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