Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Population
2.2. Measurement of Folic Acid Supplementation, Blood Glucose, and Diagnosis of GDM
2.3. Covariates
2.4. Statistical Analysis
3. Results
3.1. Demographic Characteristics of the Participants
3.2. Folic Acid Supplementation and the Risk of GDM
3.3. Dose and Duration of Folic Acid Supplementation and the Risk of GDM
3.4. Sensitivity Analyses
4. Discussion
Strengths and Limitations
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Appendix A
Subgroups | OR (95% CI) | p Value | ||
---|---|---|---|---|
Total GDM | Age (years) | <35 | 0.89 (0.73~1.09) | 0.268 |
≥35 | 0.82 (0.64~1.04) | 0.103 | ||
BMI (kg/m2) | <25 | 0.78 (0.66~0.93) | 0.006 | |
≥25 | 1.07 (0.75~1.52) | 0.713 | ||
Pregnancy | Singleton | 0.87 (0.74~1.02) | 0.084 | |
Multiple | 0.75 (0.38~1.51) | 0.422 | ||
FBG diagnosed GDM | Age (years) | <35 | 1.03 (0.75~1.41) | 0.856 |
≥35 | 1.31 (0.87~1.98) | 0.195 | ||
BMI (kg/m2) | <25 | 1.00 (0.75~1.33) | 0.980 | |
≥25 | 1.37 (0.85~2.23) | 0.196 | ||
Pregnancy | Singleton | 1.13 (0.87~1.46) | 0.351 | |
Multiple | 1.20 (0.36~4.00) | 0.765 | ||
1-h PBG diagnosed GDM | Age (years) | <35 | 0.90 (0.70~1.14) | 0.390 |
≥35 | 0.80 (0.61~1.06) | 0.118 | ||
BMI (kg/m2) | <25 | 0.78 (0.63~0.95) | 0.016 | |
≥25 | 1.04 (0.70~1.54) | 0.847 | ||
Pregnancy | Singleton | 0.86 (0.71~1.04) | 0.117 | |
Multiple | 0.82 (0.35~1.91) | 0.647 | ||
2-h PBG diagnosed GDM | Age (years) | <35 | 0.84 (0.66~1.12) | 0.168 |
≥35 | 0.65 (0.50~0.85) | 0.001 | ||
BMI (kg/m2) | <25 | 0.73 (0.60~0.90) | 0.002 | |
≥25 | 0.72 (0.49~1.05) | 0.089 | ||
Pregnancy | Singleton | 0.75 (0.62~0.89) | 0.001 | |
Multiple | 0.93 (0.40~2.15) | 0.866 |
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Characteristics | Total | GDM | Non-GDM | χ2/t | p | |
---|---|---|---|---|---|---|
N (%) | N (%) | |||||
Age (years) | Mean ± SD | 32.35 ± 4.69 | 33.27 ± 4.73 | 32.02 ± 4.63 | 18.45 | <0.001 |
<25 | 592 (2.42) | 81 (1.27) | 511 (2.83) | 333.94 | <0.001 | |
25~30 | 5964 (24.41) | 1152 (18.01) | 4812 (26.68) | |||
30~35 | 10,367 (42.44) | 2747 (42.95) | 7620 (42.26) | |||
≥35 | 7506 (30.73) | 2416 (37.77) | 5090 (28.23) | |||
Pre-pregnancy BMI (kg/m2) | Mean ± SD | 21.44 ± 3.50 | 22.50 ± 3.33 | 21.06 ± 3.49 | 28.72 | <0.001 |
<18.5 | 5648 (23.12) | 605 (9.46) | 5043 (27.97) | 1024.49 | <0.001 | |
18.5~23.9 | 13,689 (56.04) | 3934 (61.51) | 9755 (54.10) | |||
24.0~27.9 | 4147 (16.98) | 1512 (23.64) | 2635 (14.61) | |||
≥28 | 945 (3.87) | 345 (5.39) | 600 (3.33) | |||
Gravidity | 1 | 8072 (33.05) | 2135 (33.39) | 5937 (32.93) | 0.92 | 0.631 |
2 | 6668 (27.30) | 1718 (26.86) | 4950 (27.46) | |||
≥3 | 9684 (39.65) | 2542 (39.75) | 7142 (39.61) | |||
Parity | 0 | 15,332 (62.77) | 4056 (63.42) | 11,276 (62.54) | 1.58 | 0.209 |
≥1 | 9093 (37.32) | 2339 (36.58) | 6754 (37.46) | |||
Smoking | Yes | 696 (2.90) | 199 (3.19) | 497 (2.80) | 2.45 | 0.117 |
No | 23,273 (97.10) | 6039 (96.81) | 17,234 (97.20) | |||
Drinking | Yes | 3458 (14.37) | 873 (13.84) | 2585 (14.55) | 1.91 | 0.1467 |
No | 20,612 (85.63) | 5434 (86.16) | 15,178 (85.45) | |||
Folic acid supplementation | Yes | 23,606 (96.63) | 6148 (96.12) | 17,458 (96.81) | 6.88 | 0.009 |
No | 823 (3.37) | 248 (3.88) | 575 (3.19) | |||
Number of pregnancies | Singleton | 22,897 (93.73) | 6044 (94.50) | 16,853 (93.46) | 8.69 | 0.003 |
Multiple | 1532 (6.27) | 352 (5.50) | 1180 (6.54) | |||
Macrosomia history | Yes | 28 (0.11) | 2 (0.03) | 26 (0.14) | 5.26 | 0.022 |
No | 24,401 (99.89) | 6394 (99.97) | 18,007 (99.86) | |||
FBG | Mean ± SD | 4.48 ± 0.43 | 4.83 ± 0.54 | 4.35 ± 0.0.30 | 85.88 | <0.001 |
1-h PBG | Mean ± SD | 8.04 ± 1.89 | 10.12 ± 1.55 | 7.30 ± 1.38 | 136.05 | <0.001 |
2-h PBG | Mean ± SD | 6.90 ± 1.57 | 8.63 ± 1.52 | 6.29 ± 1.03 | 136.98 | <0.001 |
Model | OR (95% CI) | p Value | |
---|---|---|---|
Total GDM (n = 6396) | 1 | 0.82 (0.70~0.95) | 0.009 |
2 | 0.82 (0.71~0.96) | 0.012 | |
3 | 0.86 (0.74~1.01) | 0.063 | |
FBG diagnosed GDM (n = 2154) | 1 | 1.00 (0.79~1.25) | 0.965 |
2 | 1.05 (0.82~1.34) | 0.706 | |
3 | 1.13 (0.88~1.46) | 0.327 | |
1-h PBG diagnosed GDM (n = 3920) | 1 | 0.80 (0.67~0.95) | 0.012 |
2 | 0.81 (0.68~0.96) | 0.017 | |
3 | 0.86 (0.72~1.03) | 0.101 | |
2-h PBG diagnosed GDM (n = 3857) | 1 | 0.71 (0.60~0.85) | <0.001 |
2 | 0.72 (0.60~0.85) | <0.001 | |
3 | 0.75 (0.63~0.90) | 0.002 |
Folic Acid Supplementation | N (%) | OR | 95% CI | p |
---|---|---|---|---|
Average intake, μg/day | ||||
<400 | 62 (4.75) | 1.29 | 0.72~2.33 | 0.389 |
400–800 | 283 (21.69) | 1.32 | 0.97~1.82 | 0.081 |
≥800 | 960 (73.56) | reference | ||
Duration, months | ||||
<3 | 1111 (85.66) | 0.93 | 0.61~1.42 | 0.742 |
≥3 | 186 (14.34) | reference | ||
Average intake and duration | ||||
<400 | 62 (4.76) | 1.24 | 0.60~2.57 | 0.557 |
400–800, <3 | 235 (18.04) | 1.30 | 0.74~2.28 | 0.361 |
400–800, ≥3 | 48 (3.68) | 1.15 | 0.51~2.61 | 0.735 |
≥800, <3 | 834 (64.01) | 0.95 | 0.58~1.56 | 0.847 |
≥800, ≥3 | 124 (9.52) | reference |
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Chen, H.; Hu, Y.; Li, Y.; Zhou, W.; Zhou, N.; Yang, H.; Chen, Q.; Li, Y.; Huang, Q.; Chen, Z. Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study. Nutrients 2022, 14, 4061. https://doi.org/10.3390/nu14194061
Chen H, Hu Y, Li Y, Zhou W, Zhou N, Yang H, Chen Q, Li Y, Huang Q, Chen Z. Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study. Nutrients. 2022; 14(19):4061. https://doi.org/10.3390/nu14194061
Chicago/Turabian StyleChen, Hongyan, Yaqiong Hu, Yannan Li, Wenzheng Zhou, Niya Zhou, Huan Yang, Qing Chen, Yawen Li, Qiao Huang, and Zhen Chen. 2022. "Association of Folic Acid Supplementation in Early Pregnancy with Risk of Gestational Diabetes Mellitus: A Longitudinal Study" Nutrients 14, no. 19: 4061. https://doi.org/10.3390/nu14194061