个体化补充叶酸对新生儿出生缺陷的影响
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摘要
目的分析不同叶酸代谢关键酶基因型及个体化补充叶酸对孕妇血清同型半胱氨酸(Hcy)水平和出生缺陷发生的影响。方法将丽水市妇幼保健院妇产科2017年11月至2018年5月657例进行孕检的孕妇作为研究对象,在首次孕检时对研究对象血清Hcy含量与MTRR A66G和MTHFR A1298C、C677T位点情况进行测定。按照基因测定结果,分为A组(中高度风险,301例)与B组(低度风险+未发现风险,356例)。其中,A组给予叶酸800μg/d,B组给予叶酸400μg/d,均至孕3个月。记录两组Hcy水平和新生儿出生缺陷情况。结果 657例进行孕检的孕妇MTRR A66G基因型GG、MTHFR A1298C基因型CC、C677T基因型TT三种纯合突变频率分别为6.39%(42/657)、5.78%(38/657)、26.94%(177/657)。个体化补充叶酸前,A组孕妇血清中Hcy的表达水平显著高于B组(t=18.09,P<0.01);个体化补充叶酸后,两组孕妇血清中Hcy的表达水平无显著差异(t=0.99,P>0.05)。个体化补充叶酸前,当血清中Hcy的表达水平超过8.55μmol/L时,提示叶酸利用能力中重度风险的特异性及敏感度分别78.09%、81.06%。两组新生儿总出生缺陷率比较无显著差异(χ~2=0.05,P>0.05)。结论不同叶酸代谢关键酶基因型及孕妇血清Hcy检测有利于为不同孕妇提供个体化补充叶酸治疗,减少出生缺陷的发生率。
Objective To analyze the effects of genotypes of different folic acid metabolism key enzymes and individualized folic acid supplementation on the level of serum homocysteine(Hcy) in pregnant women and birth defects. Methods A total of 657 pregnant women taking pregnancy test during November 2017 to May 2018 in Department of Obstetrics and Gynecology in Zhejiang Lishui Maternal and Child Health Hospital were selected as subjects. The serum Hcy content and the MTRR A66 G, MTHFR A1298 C and C677 T loci were measured at the first pregnancy test. According to the results of gene test, they were divided into group A(moderate and high risk, 301 cases) and group B(low risk or no risk, 356 cases). In group A, folic acid was given 800μg/d and group B was given folic acid 400μg/d till 3 months. Hcy levels and neonatal birth defects in two groups were recorded. Results The homozygous mutation frequencies of MTRR A66 G genotype GG, MTHFR A1298 C genotype CC and C677 T genotype TT in 657 cases were 6.39%(42/657), 5.78%(38/657) and 26.94%(177/657), respectively. Before individualized folic acid supplementation, the expression level of Hcy in group A was significantly higher than that in group B(t=18.09,P<0.01). After individualized folic acid supplementation, there was no significant difference in the expression of Hcy between two groups(t=0.99,P>0.05). Before individualized folic acid supplementation, when the expression level of Hcy in serum was more than 8.55μmol/L, the specificity and sensitivity of the moderate and high risk of folic acid utilization were 78.09% and 81.06%, respectively.Conclusion The genotypes of the key enzymes of folic acid metabolism and the detection of serum Hcy in pregnant women are beneficial to providing individualized supplemental folic acid treatment for different pregnant women and reduce the incidence of birth defects.
Objective To analyze the effects of genotypes of different folic acid metabolism key enzymes and individualized folic acid supplementation on the level of serum homocysteine(Hcy) in pregnant women and birth defects. Methods A total of 657 pregnant women taking pregnancy test during November 2017 to May 2018 in Department of Obstetrics and Gynecology in Zhejiang Lishui Maternal and Child Health Hospital were selected as subjects. The serum Hcy content and the MTRR A66 G, MTHFR A1298 C and C677 T loci were measured at the first pregnancy test. According to the results of gene test, they were divided into group A(moderate and high risk, 301 cases) and group B(low risk or no risk, 356 cases). In group A, folic acid was given 800μg/d and group B was given folic acid 400μg/d till 3 months. Hcy levels and neonatal birth defects in two groups were recorded. Results The homozygous mutation frequencies of MTRR A66 G genotype GG, MTHFR A1298 C genotype CC and C677 T genotype TT in 657 cases were 6.39%(42/657), 5.78%(38/657) and 26.94%(177/657), respectively. Before individualized folic acid supplementation, the expression level of Hcy in group A was significantly higher than that in group B(t=18.09,P<0.01). After individualized folic acid supplementation, there was no significant difference in the expression of Hcy between two groups(t=0.99,P>0.05). Before individualized folic acid supplementation, when the expression level of Hcy in serum was more than 8.55μmol/L, the specificity and sensitivity of the moderate and high risk of folic acid utilization were 78.09% and 81.06%, respectively.Conclusion The genotypes of the key enzymes of folic acid metabolism and the detection of serum Hcy in pregnant women are beneficial to providing individualized supplemental folic acid treatment for different pregnant women and reduce the incidence of birth defects.
引文
[1]Williams J,Mai C T,Mulinare J,et al. Updated estimates of neural tube defects prevented by mandatory folic Acid fortification-United States, 1995-2011[J]. MMWR Morb Mortal Wkly Rep,2015,64(1):1-5.
[2]杨冬梅,李敏清,庞丽红,等.孕前及孕早期补充小剂量叶酸对孕妇及胎儿的意义[J].广西医科大学学报,2016,33(1):96-97.
[3]李引弟,岳红云,李华,等.孕期叶酸摄入与MTHFR基因多态性对产后抑郁的影响[J].中国妇幼健康研究,2017,28(6):632-635.
[4]Wilson R D,Audibert F,Brock J A,et al. Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies[J]. J Obstet Gynaecol Can,2015,37(6):534-549.
[5]魏海青,郭燕,胡殿珍,等.基因检测叶酸利用能力的个体差异性临床观察[J].河北医药,2015,37(14):2133-2135.
[6]Atta C A M,Fiest K M,Frolkis A D,et al. Global birth prevalence of spina bifida by folic acid fortification status: a systematic review and meta-analysis[J]. Am J Public Health, 2016, 106(1):e24-e34.
[7]Czeizel A E,Vereczkey A,Szabó I. Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case–control study[J]. Eur J Obstet Gynecol Reprod Biol,2015,193:34-39.
[8]杜景云,杨新颖,龚波,等.血浆同型半胱氨酸和叶酸及MTHFR基因多态性与早产的相关性[J].中山大学学报(医学科学版),2013,34(6):894-899.
[9]Bestwick J P,Huttly W J,Morris J K,et al. Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women[J]. PloS One,2014, 9(2):e89354.
[10]王战,张乐,闫会娜,等.北京市高知地区孕妇增补叶酸的知信行现况调查[J].中国妇幼健康研究,2017,28(10):1272-1275.
[11]Plumptre L,Masih S P,Ly A,et al. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood, 2[J]. Am J Clin Nutrit,2015,102(4): 848-857.
[12]Ailes E C,Gilboa S M,Gill S K,et al. Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011[J]. Birth Defects Res Part A Clin Mol Teratol,2016,106(11):940- 949.
[13]杨文方,王加丽,张彤,等.陕西西安地区汉族孕龄女性MTHFR基因多态性的分布研究[J].中国生育健康杂志, 2017,28(3): 243-247.
[14]Chitayat D,Matsui D,Amitai Y,et al. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update[J]. J Clin Pharmacol, 2016, 56(2): 170-175.
[2]杨冬梅,李敏清,庞丽红,等.孕前及孕早期补充小剂量叶酸对孕妇及胎儿的意义[J].广西医科大学学报,2016,33(1):96-97.
[3]李引弟,岳红云,李华,等.孕期叶酸摄入与MTHFR基因多态性对产后抑郁的影响[J].中国妇幼健康研究,2017,28(6):632-635.
[4]Wilson R D,Audibert F,Brock J A,et al. Pre-conception folic acid and multivitamin supplementation for the primary and secondary prevention of neural tube defects and other folic acid-sensitive congenital anomalies[J]. J Obstet Gynaecol Can,2015,37(6):534-549.
[5]魏海青,郭燕,胡殿珍,等.基因检测叶酸利用能力的个体差异性临床观察[J].河北医药,2015,37(14):2133-2135.
[6]Atta C A M,Fiest K M,Frolkis A D,et al. Global birth prevalence of spina bifida by folic acid fortification status: a systematic review and meta-analysis[J]. Am J Public Health, 2016, 106(1):e24-e34.
[7]Czeizel A E,Vereczkey A,Szabó I. Folic acid in pregnant women associated with reduced prevalence of severe congenital heart defects in their children: a national population-based case–control study[J]. Eur J Obstet Gynecol Reprod Biol,2015,193:34-39.
[8]杜景云,杨新颖,龚波,等.血浆同型半胱氨酸和叶酸及MTHFR基因多态性与早产的相关性[J].中山大学学报(医学科学版),2013,34(6):894-899.
[9]Bestwick J P,Huttly W J,Morris J K,et al. Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women[J]. PloS One,2014, 9(2):e89354.
[10]王战,张乐,闫会娜,等.北京市高知地区孕妇增补叶酸的知信行现况调查[J].中国妇幼健康研究,2017,28(10):1272-1275.
[11]Plumptre L,Masih S P,Ly A,et al. High concentrations of folate and unmetabolized folic acid in a cohort of pregnant Canadian women and umbilical cord blood, 2[J]. Am J Clin Nutrit,2015,102(4): 848-857.
[12]Ailes E C,Gilboa S M,Gill S K,et al. Association between antibiotic use among pregnant women with urinary tract infections in the first trimester and birth defects, National Birth Defects Prevention Study 1997 to 2011[J]. Birth Defects Res Part A Clin Mol Teratol,2016,106(11):940- 949.
[13]杨文方,王加丽,张彤,等.陕西西安地区汉族孕龄女性MTHFR基因多态性的分布研究[J].中国生育健康杂志, 2017,28(3): 243-247.
[14]Chitayat D,Matsui D,Amitai Y,et al. Folic acid supplementation for pregnant women and those planning pregnancy: 2015 update[J]. J Clin Pharmacol, 2016, 56(2): 170-175.