High-Dose Folic Acid Supplement Use From Prepregnancy Through Midpregnancy Is Associated With Increased Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study

Li, Qian; Zhang, Yu; Huang, Li; Zhong, Chunrong; Chen, Renjuan; Zhou, Xian; Chen, Xi; Li, Xiating; Cui, Weigang; Xiong, Ting; Gao, Qin; Xu, Shangzhi; Wu, Yuanjue; Wang, Xiaoyi; Zhang, Guofu; Zhang, Xu; Lin, Lixia; Gao, Duan; Xiao, Mei; Xiong, Guoping; Yang, Huixia; Yang, Ningning; Yang, Xuefeng; Hao, Liping; Zhang, Jin; Yang, Nianhong

doi:10.2337/dc18-2572

Cited by 38 publications

(39 citation statements)

References 5 publications

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“…16 In this case, RBC folate is an ideal index of effectiveness of folate supplementation because food fortification with FA has not been implemented in China, and FA supplements were the only source of synthetic FA used by the study population. Furthermore, a Chinese study confirmed that high-dose (≥800 μg/d) FA supplementation from prepregnancy to midpregnancy is significantly associated with a higher GDM risk, 15 supporting our findings.…”

Section: Discussionsupporting

confidence: 88%

“…However, our findings correspond to those of a Chinese study in which high-dosage (≥800 μg/d) FA supplementation from prepregnancy to midpregnancy was significantly associated with higher GDM risk. 15 Second, we measured RBC folate concentration only once during early pregnancy. However, increased folate levels in the second or the third trimester of pregnancy are also associated with high GDM risk.…”

Section: Resultsmentioning

confidence: 99%

“…13,14 Furthermore, higher dosages (≥800 μg/d) of FA supplements and longer supplementation durations are associated with higher GDM risks. 15 Therefore, evaluating the folate levels of pregnant women is necessary. The determinants of folate status may be multifactorial, including genetic, biological, and socioeconomic components.…”

Section: Introductionmentioning

confidence: 99%

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Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and MTHFR C677T Polymorphisms in Chinese Women

Liu¹,

Liu²,

Ma³

et al. 2020

DMSO

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Red blood cell (RBC) folate indicates long-term folate intake, and methylenetetrahydrofolate reductase (MTHFR) gene is the main gene affecting folate status. Increasing evidence suggests an association between gestational diabetes mellitus (GDM) and increased folate levels. Whether RBC folate concentrations in the first trimester of pregnancy or polymorphisms of MTHFR C677T (rs1801133) affect GDM risk in Chinese pregnant women remains unknown. Therefore, we analyzed the associations of RBC folate concentrations and rs1801133 polymorphisms with GDM risk among pregnant women in China. Methods: A total of 366 women with a singleton pregnancy were followed prospectively from their first prenatal visit to delivery. RBC folate concentrations and rs1801133 polymorphisms were assessed during the first trimester of pregnancy. Binary logistic regression analyses were performed to determine the odds ratios (ORs) of GDM and 95% confidence intervals (CIs) by using the RBC folate concentration quartiles and rs1801133 polymorphisms. Results: Participants with the TT genotype had the highest RBC folate concentrations. Those with heterozygous or homozygous variants did not have a significantly higher risk of GDM than did women with C alleles. After adjustments for covariates, women in the highest quartile for RBC folate concentration had a higher risk of GDM (adjusted OR = 2.473, 95% CI = 1.013-6.037, P = 0.047) than did those in the lowest quartile, but this association was nonsignificant after adjustment for rs1801133 polymorphisms. Conclusion: Higher RBC folate, partly caused by MTHFR 677C→T, may be associated with increased GDM risk, even in early pregnancy. Assessing RBC folate status and appropriately supplementing folate during early pregnancy, particularly for patients with MTHFR 677C→T, may prevent GDM. Further studies with larger populations are warranted.

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Section: Discussionsupporting

confidence: 88%

Section: Resultsmentioning

confidence: 99%

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Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and MTHFR C677T Polymorphisms in Chinese Women

Liu¹,

Liu²,

Ma³

et al. 2020

DMSO

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“…The potential confounding variables were identified from previous studies [5,6,7,12]. Sociodemographic factors included maternal age at pregnancy (<25, 25–29, 30–34, ≥35 years old) [14], maternal education (≤junior high school, senior high school, ≥college degree) [6,12], and monthly household income (≤2000, 2001–5000, > 5000 CNY) [18].…”

Section: Methodsmentioning

confidence: 99%

“…Moreover, a prospective study in China ( n = 326) showed that women who did not take FA and took FA for > 90 days had a higher incidence of GDM compared with those who took FA for ≤60 days [6]. Another Chinese cohort study ( n = 4353) showed that FA supplement use ≥800 µg/day from pre-conceptional ≥4 weeks until ≥16 weeks during pregnancy was associated with higher GDM risk compared with non-users [7]. Due to the limited number of studies, the association between daily FA supplementation and GDM has been controversial at present.…”

Section: Introductionmentioning

confidence: 99%

The Associations between the Duration of Folic Acid Supplementation, Gestational Diabetes Mellitus, and Adverse Birth Outcomes based on a Birth Cohort

Cheng

Sha

Gao

et al. 2019

IJERPH

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This study aimed to examine the associations between the duration of folic acid (FA) supplementation, gestational diabetes mellitus (GDM), and adverse birth outcomes. A total of 950 mother-offspring pairs participated in the cohort study during 2015 in Changsha, China. The data were collected through home visits and perfected by maternal and child healthcare handbooks. Generalized linear models and stratified analyses were used for statistical analyses. The incidence of GDM in our cohort was 10.2%. FA supplementation for ≥3 months before pregnancy was associated with an increased risk of GDM (adjusted relative risk (aRR): 1.72; 95% CI: 1.17–2.53) and decreased risk of small-for-gestational-age (SGA) birth (aRR: 0.40; 95% CI: 0.18–0.88). In the group of FA supplementation for ≥3 months during pregnancy, GDM was associated with an increased risk of cesarean delivery (aRR: 1.36; 95% CI: 1.06–1.75) and macrosomia (aRR: 2.11; 95% CI: 1.06, 4.20), but the aRRs were lower than the RRMH 1.53 (95% CI: 1.01–2.34) and 2.43 (95% CI: 1.27–4.66). Our study suggested that the longer duration of FA supplementation before pregnancy might increase the risk of GDM, but decrease the risk of SGA birth. Longer duration of FA supplementation during pregnancy had beneficial effects on birth outcomes in women with GDM. Further studies should consider a larger sample size to confirm these findings.

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Association between maternal folate status and gestational diabetes mellitus

Yang

Cai

Zhang

2021

Food Science & Nutrition

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Studies on the association between maternal folate status and gestational diabetes mellitus (GDM) have yielded inconsistent results. This meta‐analysis was performed to determine whether there may exist some association between maternal folate status and GDM. Unrestricted searches of PubMed, Web of Science, Cochrane, and Embase were conducted. All relevant studies on the association between maternal folat status and GDM risk were screened. The standardized mean difference (SMD) with 95% CIs was used to determine the association between maternal folate and GDM. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random‐effects models to assess the impact of maternal folate status on GDM risk. 12 studies were included. The overall data revealed that compared with the non‐GDM group, women with GDM had higher level of folate (SMD 0.41, 95% CI 0.07 to 0.21, I2 = 17.2%) in second or third trimester. We also found that maternal high folate status may be associated with increased risk of GDM (OR 2.16, 95% CI 1.70 to 2.74, I2 = 0.0%). Compared with non‐GDM group, women with GDM are prone to higher folate level. Moreover, high maternal folate status may predict a higher risk of GDM. As the number of included studies was limited, further large population studies are needed in the future.

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High-Dose Folic Acid Supplement Use From Prepregnancy Through Midpregnancy Is Associated With Increased Risk of Gestational Diabetes Mellitus: A Prospective Cohort Study

Cited by 38 publications

References 5 publications

<p>Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and <em>MTHFR</em> C677T Polymorphisms in Chinese Women</p>

<p>Associations Between Gestational Diabetes Mellitus Risk and Folate Status in Early Pregnancy and <em>MTHFR</em> C677T Polymorphisms in Chinese Women</p>

The Associations between the Duration of Folic Acid Supplementation, Gestational Diabetes Mellitus, and Adverse Birth Outcomes based on a Birth Cohort

Association between maternal folate status and gestational diabetes mellitus

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