Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study

Zhu, Beibei; Ge, Xing; Huang, Kun; Mao, Leijing; Yan, Shuangqin; Xu, Yu; Huang, Sanhuan; Hao, Jiahu; Zhu, Peng; Niu, Ying; Tong, Shilu; Tao, Fangbiao

doi:10.2337/dc15-2389

Cited by 62 publications

(86 citation statements)

References 5 publications

(3 reference statements)

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“…A Chinese cohort study reported that daily folic acid supplement intake in early pregnancy was associated with a high risk of GDM. 18 In the present study, we showed that higher serum folate concentrations were significantly associated with higher blood glucose concentrations, especially 1and 2-hour plasma glucose. However, the association with GDM risk was weak, albeit statistically significant, and could be observed only after adjusting for vitamin B 12 concentration.…”

Section: Discussionsupporting

confidence: 55%

“…10 Meanwhile, a cohort study in China indicated that folic acid consumption in early pregnancy may increase the risk of GDM. 18 It has been reported that higher maternal folate coupled with lower vitamin B 12 was associated with a higher GDM risk in Singapore. 12 However, the most recent study in Canada showed that maternal blood 1-carbon nutrients may not affect the risk of GDM.…”

Section: Introductionmentioning

confidence: 99%

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Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Hou

Yan

et al. 2019

Journal of Diabetes

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Highlights• Higher folate and lower vitamin B 12 levels were associated with higher glucose and a higher risk of gestational diabetes mellitus (GDM). • The association between folate and vitamin B 12 imbalance and GDM risk can be further modified by maternal risk factors. Abstract Background: This study examined whether folate and vitamin B 12 imbalance is associated with gestational diabetes mellitus (GDM) and explored interactions between B vitamin imbalance and maternal risk factors for GDM. Methods: A cross-sectional study was performed in 406 Chinese pregnant women. Serum folate, vitamin B 12 , and blood glucose concentrations were measured at 24 to 28 weeks gestation during GDM screening. A diagnosis of GDM was made based on International Association of Diabetes and Pregnancy Study Groups criteria (fasting plasma glucose [FPG] ≥5.1 mM, 1-hour plasma glucose ≥10.0 mM, or 2-hour plasma glucose ≥8.5 mM). Binary logistic regression was used to obtain odds ratios (ORs) after controlling for different confounders. Results: Higher folate levels were associated with higher glucose concentrations and a higher risk of GDM (OR 1.98; 95% confidence interval [CI] 1.00-3.90), whereas higher vitamin B 12 levels were associated with lower FPG and a lower risk of GDM (OR 0.30; 95% CI 0.15-0.60). A higher folate: vitamin B 12 ratio was associated with higher glucose and a higher risk of GDM (OR 3.08; 95% CI 1.63-5.83). The presence of both a higher folate: vitamin B 12 ratio and advanced age further increased the OR to 2.13 (95% CI 1.09-4.15) with a significant additive interaction. Furthermore, a higher folate: vitamin B 12 ratio and a higher prepregnancy body mass index (pp-BMI) were synergistically associated with an increased risk of GDM (OR 3.03; 95% CI 1.40-6.57). Conclusions: An imbalance between folate and vitamin B 12 , represented by a higher folate: vitamin B 12 ratio, was highly associated with GDM risk, and this association could be further modified by maternal age and pp-BMI. K E Y W O R D S folate, gestational diabetes mellitus, pregnancy, synergistic effect, vitamin B 12

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Hou

Yan

et al. 2019

Journal of Diabetes

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“…However, all pregnant women in the public-sector health service are given a folic acid supplement of 5 mg a day, which far exceeds the increased requirements of 600 micrograms during pregnancy. While supplementation of folate in pregnancy is given to reduce the chances of neural tube defects, a recent study by Zhu [ 71 ] illustrated that this daily supplementation may increase the risk of. This is therefore a possible cause for concern and the policy in South Africa and elsewhere may need reviewing.…”

Section: Discussionmentioning

confidence: 99%

Dietary Intake and Beliefs of Pregnant Women with Gestational Diabetes in Cape Town, South Africa

et al. 2018

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This study investigated the dietary intake of pregnant women with gestational diabetes mellitus (GDM) and their beliefs relating to the consumption of fruits and vegetables (F&V) and sugary foods and drinks. A cross-sectional study was conducted on 239 pregnant women with GDM in Cape Town. Dietary intake was assessed using a quantified Food Frequency Questionnaire and beliefs relating to food choices were assessed using the Theory of Planned Behaviour (TPB). The mean energy intake was 7268 KJ, carbohydrate was 220 (±104.5) g, protein 60.3 (±27.5) g and fat 67.7 (±44.2) g. The macronutrient distribution was 55% carbohydrates, 14.5% protein and 30.5% fat of total energy. The majority of the sample had inadequate intakes of vitamin D (87.4%), folate (96.5%) and iron (91.3%). The median (IQR) amount of added table sugar and sugar sweetened beverages (SSBs) was 4.0 (0.00–12.5) g and 17.9 (0.0–132.8) mL per day, respectively. Only 31.4% met the recommendation (400 g per day) for F&V. Beliefs that it was not easy to exclude sugary foods/drinks and that knowing how to control cravings for sugary foods/drinks are areas to target messages on the sugar content of SSBs. In conclusion, the dietary intake of these women was not optimal and fell short of several nutritional guidelines for pregnant women with hyperglycaemia. The strongly held beliefs regarding sugary foods/drinks may contribute to poor adherence to nutritional guidelines among pregnant women with GDM in South Africa.

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“…Meanwhile, the concern has been raised as to whether the increased folate status has potential effects on GDM. Zhu et al () reported that daily FA supplement consumption in early pregnancy was related to the increased risk of GDM. However, the association of serum folate in the third trimester of pregnancy with GDM risk was not observed in a UK population (Sukumar et al, ).…”

Section: Introductionmentioning

confidence: 99%

Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus

Xie

et al. 2019

Food Science & Nutrition

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Interest in the high folate status of pregnant women has increased due to its role in the prevention of neural tube defects (NTDs). The effect of increased red blood cell (RBC) folate status during the second trimester of pregnancy on gestational diabetes mellitus (GDM) remains unclear. We measured RBC folate concentrations by competitive protein‐binding assay and obtained clinical information from electronic medical records. Logistic regression analysis was used to explore the associations of RBC folate concentrations with risks of gestational diabetes mellitus (GDM). We further assessed the potential nonlinear relations between continuous log‐transformed RBC folate concentrations and GDM risk by using the restricted cubic splines. We observed high RBC folate concentrations in GDM patients compared to control group [median (interquartile range, IQR), GDM vs. controls: 1,554.03 (1,240.54–1,949.99) vs. 1,478.83 (1,124.60–1,865.71) nmol/L, p = .001]. Notably, high folate concentrations were significantly associated with an increased risk of GDM [RR per 1‐SD increase: 1.16 (1.03, 1.30), p = .012] after adjustment for maternal age, parity, and body mass index (BMI) at enrollment. In the restricted cubic spline model, a test of the null hypothesis of the linear relationship was rejected (p = .001). Our study firstly showed that maternal RBC folate concentrations during the second trimester of pregnancy increase the risk of GDM in a Chinese population. Further randomized clinical trials (RCTs) are warranted to confirm the adverse effect.

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Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study

Cited by 62 publications

References 5 publications

Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Dietary Intake and Beliefs of Pregnant Women with Gestational Diabetes in Cape Town, South Africa

Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus

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Folic Acid Supplement Intake in Early Pregnancy Increases Risk of Gestational Diabetes Mellitus: Evidence From a Prospective Cohort Study

Cited by 62 publications

References 5 publications

Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus

Joint effects of folate and vitamin B12 imbalance with maternal characteristics on gestational diabetes mellitus

Dietary Intake and Beliefs of Pregnant Women with Gestational Diabetes in Cape Town, South Africa

Association of maternal folate status in the second trimester of pregnancy with the risk of gestational diabetes mellitus

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Product

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Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus

Joint effects of folate and vitamin B₁₂ imbalance with maternal characteristics on gestational diabetes mellitus