Abstract：
OBJECTIVE: With increasingly prevalent folic acid consumption in early pregnancy, concerns about its potentially negative effect on maternal metabolism have been raised. Recent findings regarding folic acid levels in the first trimester and the risk of gestational diabetes mellitus have been inconclusive. The aim of this study was to investigate the association of folic acid status in early pregnancy with gestational diabetes mellitus as well as examine whether glucose levels can be modulated by folic acid status during the same first trimester.
METHODS: This was a retrospective cohort study based on 27 128 Chinese pregnant women who registered during their first prenatal visit from January 2015 to December 2019. Serum folic acid and fasting blood glucose concentrations were measured during the 9th to 13th gestational weeks. Binary logistic regression was applied to estimate the odds ratios of gestational diabetes mellitus by using the serum folic acid levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes mellitus, we established subgroups, in which analyses were stratified by age (<25, 25-29, 30-34, and ≥35 y), parity (nulliparous and parous), prepregnancy body mass index (< 18.5, 18.5-23.9, and ≥ 24 kg/m2), and family history of diabetes (yes and no).
RESULTS: The positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher in those in the middle (Q3) and higher (Q4) quartiles compared with those in Q1 and Q2. A higher risk for gestational diabetes mellitus was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63; 95% CI, 4.56-6.95, and Q4: odds ratio = 5.57; 95% CI, 4.68-6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 and Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots had a positive correlation of serum folic acid level with fasting blood glucose concentration as well as risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level.
CONCLUSIONS: Our findings underscore the importance of maintaining an appropriate folic acid concentration for preserving a lower risk of gestational diabetes mellitus, especially in women with relatively higher blood glucose in early pregnancy. Additionally, folic acid concentration > 32.5 nmol/L may be considered a risk factor for gestational diabetes mellitus. This research suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive folic acid intake.
METHODS: This was a retrospective cohort study based on 27 128 Chinese pregnant women who registered during their first prenatal visit from January 2015 to December 2019. Serum folic acid and fasting blood glucose concentrations were measured during the 9th to 13th gestational weeks. Binary logistic regression was applied to estimate the odds ratios of gestational diabetes mellitus by using the serum folic acid levels quartiles with adjustment for major confounders. To investigate the potential effect of modifying key risk factors for gestational diabetes mellitus, we established subgroups, in which analyses were stratified by age (<25, 25-29, 30-34, and ≥35 y), parity (nulliparous and parous), prepregnancy body mass index (< 18.5, 18.5-23.9, and ≥ 24 kg/m2), and family history of diabetes (yes and no).
RESULTS: The positive association between maternal folate concentrations and fasting blood glucose was observed: the risk for hyperglycemia was higher in those in the middle (Q3) and higher (Q4) quartiles compared with those in Q1 and Q2. A higher risk for gestational diabetes mellitus was found in hyperglycemia of early pregnant women with high folate concentrations (Q3: odds ratio = 5.63; 95% CI, 4.56-6.95, and Q4: odds ratio = 5.57; 95% CI, 4.68-6.64) compared with normal fasting glucose mothers with folate concentrations in Q1 and Q2 after accounting for multiple covariables. Similar patterns were observed for different subgroups. Restricted cubic spline plots had a positive correlation of serum folic acid level with fasting blood glucose concentration as well as risk of gestational diabetes mellitus in a nonlinear pattern, with 32.5 nmol/L as the cutoff point for folic acid level.
CONCLUSIONS: Our findings underscore the importance of maintaining an appropriate folic acid concentration for preserving a lower risk of gestational diabetes mellitus, especially in women with relatively higher blood glucose in early pregnancy. Additionally, folic acid concentration > 32.5 nmol/L may be considered a risk factor for gestational diabetes mellitus. This research suggested that folic acid levels should be monitored during the first trimester from the first prenatal checkup to prevent adverse effects of excessive folic acid intake.
摘要：
目标：随着妊娠早期叶酸消费的日益普遍，人们对其对母体代谢的潜在负面影响表示担忧。关于孕早期叶酸水平和妊娠糖尿病风险的最新发现尚无定论。这项研究的目的是调查妊娠早期叶酸状态与妊娠糖尿病的关系，并检查在相同的妊娠早期是否可以通过叶酸状态调节葡萄糖水平。
方法：这是一项回顾性队列研究，基于2015年1月至2019年12月首次产前检查期间登记的27128名中国孕妇。在第9至13孕周测量血清叶酸和空腹血糖浓度。通过使用血清叶酸水平四分位数并调整主要混杂因素，应用二元逻辑回归来估计妊娠期糖尿病的优势比。探讨改变妊娠期糖尿病关键危险因素的潜在作用。我们建立了分组，其中分析按年龄分层(<25、25-29、30-34和≥35岁)，奇偶校验(无产和无产)，孕前体重指数（<18.5、18.5-23.9和≥24kg/m2），和糖尿病家族史（是和不是）。
结果：观察到母体叶酸浓度与空腹血糖之间的正相关：与Q1和Q2相比，中四分位数（Q3）和高四分位数（Q4）的患者发生高血糖的风险更高。在考虑多个协变量后，与Q1和Q2中叶酸浓度正常的空腹血糖母亲相比，高叶酸浓度的早期孕妇的高血糖风险更高（Q3：比值比=5.63；95％CI，4.56-6.95和Q4：比值比=5.57；95％CI，4.68-6.64）。对于不同的亚组观察到类似的模式。限制性三次样条图血清叶酸水平与空腹血糖浓度以及妊娠期糖尿病风险呈非线性正相关，以32.5nmol/L作为叶酸水平的截止点。
结论：我们的研究结果强调了维持适当的叶酸浓度对于降低妊娠期糖尿病风险的重要性。尤其是妊娠早期血糖相对较高的女性。此外,叶酸浓度>32.5nmol/L可能是妊娠期糖尿病的危险因素。这项研究表明，从第一次产前检查开始，应在孕早期监测叶酸水平，以防止过量摄入叶酸的不利影响。
方法：这是一项回顾性队列研究，基于2015年1月至2019年12月首次产前检查期间登记的27128名中国孕妇。在第9至13孕周测量血清叶酸和空腹血糖浓度。通过使用血清叶酸水平四分位数并调整主要混杂因素，应用二元逻辑回归来估计妊娠期糖尿病的优势比。探讨改变妊娠期糖尿病关键危险因素的潜在作用。我们建立了分组，其中分析按年龄分层(<25、25-29、30-34和≥35岁)，奇偶校验(无产和无产)，孕前体重指数（<18.5、18.5-23.9和≥24kg/m2），和糖尿病家族史（是和不是）。
结果：观察到母体叶酸浓度与空腹血糖之间的正相关：与Q1和Q2相比，中四分位数（Q3）和高四分位数（Q4）的患者发生高血糖的风险更高。在考虑多个协变量后，与Q1和Q2中叶酸浓度正常的空腹血糖母亲相比，高叶酸浓度的早期孕妇的高血糖风险更高（Q3：比值比=5.63；95％CI，4.56-6.95和Q4：比值比=5.57；95％CI，4.68-6.64）。对于不同的亚组观察到类似的模式。限制性三次样条图血清叶酸水平与空腹血糖浓度以及妊娠期糖尿病风险呈非线性正相关，以32.5nmol/L作为叶酸水平的截止点。
结论：我们的研究结果强调了维持适当的叶酸浓度对于降低妊娠期糖尿病风险的重要性。尤其是妊娠早期血糖相对较高的女性。此外,叶酸浓度>32.5nmol/L可能是妊娠期糖尿病的危险因素。这项研究表明，从第一次产前检查开始，应在孕早期监测叶酸水平，以防止过量摄入叶酸的不利影响。
