孕妇稳定补充叶酸后的血清叶酸水平及其影响因素分析

Analysis of serum folic acid level and its influencing factors after stable folic acid supplementation in pregnant women

目的探讨稳定补充叶酸后,孕妇血清叶酸水平及其影响因素。方法选择2019年8月至2020年12月,于复旦大学妇产科医院进行产前检查,并且在正常饮食情况下稳定补充叶酸(400μg/d×60 d)后的718例孕龄为12~24孕周孕妇为研究对象。根据补充叶酸后的血清叶酸水平,将其分为4组:A组(n=23,血清叶酸水平<7 ng/mL),B组(n=170,血清叶酸水平为≥7~14 ng/mL),C组(n=217,血清叶酸水平为≥14~18 ng/mL),D组(n=308,血清叶酸水平为≥18~20 ng/mL)。采用χ^(2)检验及秩和检验,对4组孕妇一般临床资料及血清维生素B12水平、同型半胱氨酸(Hcy)浓度进行统计学比较(单因素分析)。对孕妇稳定补充叶酸后上述4个血清叶酸水平的影响因素,采用无序多分类logistic回归法进行分析。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》。获取所有受试者的知情同意,并与其签署临床研究知情同意书。结果①单因素分析结集显示:4组孕妇血清Hcy浓度、维生素B12水平,孕龄≥12~19孕周与≥19~25孕周构成比比较,差异均有统计学意义(均为P<0.001)。②相对于血清叶酸水平为<7 ng/mL:孕妇血清Hcy浓度每增加1μmol/L,血清叶酸水平为≥7~14 ng/mL、≥14~18 ng/mL、≥18~20 ng/mL的可能性分别降低到原来的0.731倍(OR=0.731)、0.353倍(OR=0.353)、0.471倍(OR=0.471);孕妇血清维生素B12水平每增加1 pg/mL,血清叶酸水平为≥14~18 ng/mL的可能性增加到原来的1.004倍(OR=1.004)。③相对于血清叶酸水平为≥7~14 ng/mL:孕妇血清Hcy浓度每增加1μmol/L,血清叶酸水平为<7 ng/mL、≥14~18 ng/mL、≥18~20 ng/mL的可能性分别为增加到原来的1.369倍(OR=1.369)、降低到原来的0.483倍(OR=0.483)、降低到原来的0.644倍(OR=0.644);孕妇血清维生素B12水平每增加1 pg/mL,血清叶酸水平为≥14~18 ng/mL、≥18~20 ng/mL的可能性分别增加到原来的1.003倍(OR=1.003)、1.003倍(OR=1.003);孕龄≥12~19孕周孕妇血清叶酸水平为≥18~20 ng/mL的可能性是孕龄≥19~25孕周孕妇的2.244倍(OR=2.244)。④相对于血清叶酸水平为≥14~18 ng/mL:孕妇血清Hcy浓度每增加1μmol/L,血清叶酸水平为<7 ng/mL、≥7~14 ng/mL、≥18~20 ng/mL的可能性均分别增加到原来的2.832倍(OR=2.832)、2.069倍(OR=2.069)、孕妇1.333倍(OR=1.333);孕妇血清维生素B12水平每增加1 pg/mL,血清叶酸水平为<7 ng/mL、≥7~14 ng/mL的可能性均降低到原来的0.996倍(OR=0.996)、0.997倍(OR=0.997)。结论血清Hcy浓度及维生素B12水平,以及孕龄,均对孕妇稳定补充叶酸后的血清叶酸水平有影响:血清Hcy浓度主要为负向影响,血清维生素B12水平主要为正向影响,孕龄仅对血清叶酸水平较高级别有影响。

Objective To investigate the serum folic acid level and its influencing factors in pregnant women with periconceptional folic acid supplementation.Methods A total of 718 pregnant women with gestational age of 12 to 24 weeks were enrolled in this study from August 2019 to December 2020 at the Obstetrics and Gynecology Hospital of Fudan University.They underwent prenatal examination and stably intaked folic acid supplementation(400μg/d×60 d)under normal diet.According to serum folic acid level after folic acid supplementation,they were divided into 4 groups:group A(n=23,serum folic acid level<7 ng/mL),group B(n=170,serum folic acid level was≥7-14 ng/mL),group C(n=217,serum folic acid level was≥14-18 ng/mL),and group D(n=308,serum folic acid level was≥18-20 ng/mL).Chi-square test and rank sum test were used to compare general clinical data and serum vitamin B12 level,serum Homocysteine(Hcy)concentration among four groups(monofactor analysis).Multi-classification logistic regression analysis method was used to analyze the influencing factors of 4 levels of serum folic acid of pregnant women after periconceptional folic acid supplementation.The study was conducted in accordance with World Medical Association Declaration of Helsinki revised in 2013.All subjects informed consent and signed the informed consent forms for the clinical study.Results①Monofactor analysis results showed that there were significant differences among four groups in serum Hcy concentration,serum vitamin B12 level and gestational age(≥12-19 gestational weeks,≥19-25 gestational weeks)(P<0.001).②Serum folic acid level of<7 ng/mL was taken as reference:with increased serum Hcy concentration by 1μmol/L in pregnant women,the possibility of serum folic acid levels of≥7-14 ng/mL,≥14-18 ng/mL and≥18-20 ng/mL were decreased to 0.731,0.353 and 0.471 times(OR=0.731,0.353,0.471),respectively.With increased serum vitamin B12 level by 1 pg/mL in pregnant women,the possibility of serum folic acid levels of≥14-18 ng/mL was increased to 1.004 times(OR=1.004).③Serum folic acid level of≥7-14 ng/mL was taken as reference:with increased serum Hcy concentration by 1μmol/L in pregnant women,the possibility of serum folic acid level of<7 ng/mL,≥14-18 ng/mL and≥18-20 ng/mL were increased to 1.369 times(OR=1.369),decreased to 0.483 times(OR=0.483)and decreased to 0.644 times(OR=0.644),respectively.With increased serum vitamin B12 level by 1 pg/mL in pregnant women,the possibility of serum folic acid level of≥14-18 ng/mL and≥18-20 ng/mL increased to 1.003 times(OR=1.003)and 1.003 times(OR=1.003),respectively.The possibility of serum folic acid level of≥18-20 ng/mL in pregnant women with gestation age at≥12-19 weeks was 2.244 times that of pregnant women with gestation age at≥19-25 weeks(OR=2.244).④Serum folic acid level of≥14-18 ng/mL was taken as reference:with increased serum Hcy concentration by 1μmol/L in pregnant women,the possibility of serum folic acid level of<7 ng/mL,≥7-14 ng/mL and≥18-20 ng/mL were increased to 2.832,2.069 and 1.333 times(OR=2.832,2.069,1.333),respectively.With increased serum vitamin B12 level by 1 pg/mL in pregnant women,the possibility of serum folic acid level of<7 ng/mL and≥7-14 ng/mL were decreased to 0.996 and 0.997 times(OR=0.996,0.997).Conclusions Serum Hcy concentration and serum vitamin B12 level,as well as gestational age have significant effects on serum folic acid level of pregnant women with periconceptional folic acid supplementation:serum Hcy concentration is mainly negative and serum vitamin B12 level is mainly positive affected serum folic acid level.Gestational age only affects the higher serum folic acid level in pregnant women.