Skip to main content

Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis

Abstract

Purpose

This study aimed at clarifying the association of maternal and neonatal methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms with preterm birth (PTB) and low birth weight (LBW) susceptibility, respectively.

Materials and methods

A systematic search of Embase, Medline, China Biological Medicine Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Wanfang Database was performed before June, 2016. The frequencies of maternal and neonatal MTHFR C677T genotypes in the cases and controls and other information were extracted by two independent investigators. Odds ratios (ORs) with 95% confidence intervals (CIs) were adopted to estimate the relationships between MTHFR C677T polymorphisms and PTB as well as LBW by random or fixed effect models.

Results

Twenty-five studies from 20 articles concerning maternal and neonatal MTHFR C677T gene polymorphism with PTB and LBW were included in this study. Maternal MTHFR C677T polymorphism was associated with PTB risk under allele contrast (T vs. C, OR = 1.36, 95% CI 1.02–1.81), homozygote (TT vs. CC, OR = 1.70, 95% CI 1.07–2.68), and recessive (TT vs. CT + CC, OR = 1.49, 95% CI 1.00–2.22) model, but not dominant or heterozygote model. Maternal MTHFR C677T polymorphism was also associated with LBW risk under allele contrast (OR = 1.69, 95% CI 1.25–2.28), homozygote (OR = 2.26, 95% CI 1.44–3.54), dominant (OR = 1.71, 95% CI 1.19–2.47), recessive (OR = 1.79, 95% CI 1.42–2.26) model, but not heterozygote model. No associations between neonatal MTHFR C677T polymorphism and PTB or LBW were found under all genetic models.

Conclusions

Identification of maternal MTHFR C677T mutation may play a key role for primary prevention of PTB as well as LBW and screening pregnant women of high risk in developing countries.

This is a preview of subscription content, access via your institution.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

References

  1. Sapkota A, Chelikowsky AP, Nachman KE, Cohen AJ, Ritz B (2010) Exposure to particulate matter and adverse birth outcomes: a comprehensive review and meta-analysis. Air Qual Atmos Health (London) 5(4):1–13

    Google Scholar 

  2. Martínez-Martínez RE, Moreno-Castillo DF, Loyola-Rodríguez JP, Sánchez-Medrano AG, Miguel-Hernández JHS, Olvera-Delgado JH, Domínguez-Pérez RA (2016) Association between periodontitis, periodontopathogens and preterm birth: is it real? Arch Gynecol Obstet 294(1):47–54. doi:10.1007/s00404-015-3945-1

    Article  PubMed  Google Scholar 

  3. Beck S, Wojdyla D, Say L, Betran AP, Merialdi M, Requejo JH, Rubens C, Menon R, Van Look PF (2010) The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ 88(1):31–38. doi:10.2471/blt.08.062554

    Article  PubMed  Google Scholar 

  4. Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE (2015) Global, regional, and national causes of child mortality in 2000–13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet 385(9966):430–440. doi:10.1016/s0140-6736(14)61698-6

    Article  PubMed  Google Scholar 

  5. Lawn JE, Kinney M (2014) Preterm birth: now the leading cause of child death worldwide. Sci Transl Med 6(263):263ed221. doi:10.1126/scitranslmed.aaa2563

    Article  Google Scholar 

  6. United Nations Children’s Fund and World Health Organization (2004) Low birthweight: country, regional and global estimates. UNICEF, New York

  7. Adetola AO, Tongo OO, Orimadegun AE, Osinusi K (2011) Neonatal mortality in an urban population in Ibadan, Nigeria. Pediatr Neonatol 52(5):243–250. doi:10.1016/j.pedneo.2011.06.001

    Article  PubMed  Google Scholar 

  8. Jiang M, Qiu J, Zhou M, He X, Cui H, Lerro C, Lv L, Lin X, Zhang C, Zhang H, Xu R, Zhu D, Dang Y, Han X, Zhang H, Bai H, Chen Y, Tang Z, Lin R, Yao T, Su J, Xu X, Liu X, Wang W, Wang Y, Ma B, Qiu W, Zhu C, Wang S, Huang H, Zhao N, Li X, Liu Q, Zhang Y (2015) Exposure to cooking fuels and birth weight in Lanzhou, China: a birth cohort study. BMC Public Health 15:712. doi:10.1186/s12889-015-2038-1

    Article  PubMed  PubMed Central  Google Scholar 

  9. Oftedal AM, Busterud K, Irgens LM, Haug K, Rasmussen S (2016) Socio-economic risk factors for preterm birth in Norway 1999–2009. Scand J Public Health 44(6):587–592. doi:10.1177/1403494816653288

    Article  PubMed  Google Scholar 

  10. Tellapragada C, Eshwara VK (2016) Risk factors for preterm birth and low birth weight among pregnant indian women: a hospital-based prospective study. J Prev Med Public Health 49(3):165–175. doi:10.3961/jpmph.16.022

    Article  PubMed  PubMed Central  Google Scholar 

  11. Handelzalts JE, Krissi H, Levy S, Freund Y, Carmiel N, Ashwal E, Peled Y (2016) Personality, preterm labor contractions, and psychological consequences. Arch Gynecol Obstet 293(3):575–582. doi:10.1007/s00404-015-3898-4

    Article  PubMed  Google Scholar 

  12. Chen H, Yang X, Lu M (2016) Methylenetetrahydrofolate reductase gene polymorphisms and recurrent pregnancy loss in China: a systematic review and meta-analysis. Arch Gynecol Obstet 293(2):283–290. doi:10.1007/s00404-015-3894-8

    CAS  Article  PubMed  Google Scholar 

  13. Gong M, Dong W, He T, Shi Z, Huang G, Ren R, Huang S, Qiu S, Yuan R (2015) MTHFR 677C > T polymorphism increases the male infertility risk: a meta-analysis involving 26 studies. PLoS One 10(3):e0121147. doi:10.1371/journal.pone.0121147

    Article  PubMed  PubMed Central  Google Scholar 

  14. Goyette P, Pai A, Milos R, Frosst P, Tran P, Chen Z, Chan M, Rozen R (1998) Gene structure of human and mouse methylenetetrahydrofolate reductase (MTHFR). Mamm Genome 9(8):652–656. doi:10.1007/s003359900838

    CAS  Article  PubMed  Google Scholar 

  15. Pan Y, Zhang W, Ma J, Du Y, Li D, Cai Q, Jiang H, Wang M, Zhang Z, Wang L (2012) Infants’ MTHFR polymorphisms and nonsyndromic orofacial clefts susceptibility: a meta-analysis based on 17 case–control studies. Am J Med Genet A 158a(9):2162–2169. doi:10.1002/ajmg.a.35503

    Article  PubMed  Google Scholar 

  16. Facco F, You W, Grobman W (2009) Genetic thrombophilias and intrauterine growth restriction: a meta-analysis. Obstet Gynecol 113(6):1206–1216

    Article  PubMed  Google Scholar 

  17. Chen J, Chen L, Zhu LH, Zhang ST, Wu YL (2016) Association of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with preterm delivery and placental abruption: a systematic review and meta-analysis. Acta Obstet Gynecol Scand 95(2):157–165

    CAS  Article  PubMed  Google Scholar 

  18. Wang H, Hu Y-F, Hao J-H, Chen Y-H, Su P-Y, Wang Y, Yu Z, Fu L, Xu Y-Y, Zhang C, Tao F-B, Xu D-X (2015) Maternal zinc deficiency during pregnancy elevates the risks of fetal growth restriction: a population-based birth cohort study. Sci Rep 5:11262. doi:10.1038/srep11262

    Article  PubMed  PubMed Central  Google Scholar 

  19. Infante-Rivard C, Rivard GE, Guiguet M, Gauthier R (2005) Thrombophilic polymorphisms and intrauterine growth restriction. Epidemiology 16(3):281–287

    Article  PubMed  Google Scholar 

  20. Stroup DF, Berlin JA, Morton SC, Olkin I, Williamson GD, Rennie D, Moher D, Becker BJ, Sipe TA, Thacker SB (2000) Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 283(15):2008–2012

    CAS  Article  PubMed  Google Scholar 

  21. Song Y-q, Gao Y-l, Pan Z-c, Zhang Y, Li J-h, Wang K-j, Li J-s, Tan H, Fu Q (2016) Preparation and characterization of controlled heparin release waterborne polyurethane coating systems. Chin J Polym Sci 34(6):679–687. doi:10.1007/s10118-016-1787-3

    CAS  Article  Google Scholar 

  22. O’Connell D (2002) The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses. Appl Eng Agric 18(6):727–734

    Google Scholar 

  23. Gu WJ, Wang F, Tang L, Liu JC (2015) Single-dose etomidate does not increase mortality in patients with sepsis: a systematic review and meta-analysis of randomized controlled trials and observational studies. Chest 147(2):335–346. doi:10.1378/chest.14-1012

    Article  PubMed  Google Scholar 

  24. Higgins JP, Thompson SG, Deeks JJ, Altman DG (2003) Measuring inconsistency in meta-analyses. BMJ 327(7414):557–560. doi:10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  25. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188

    CAS  Article  PubMed  Google Scholar 

  26. Mantel N, Haenszel W (1959) Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 22(4):719–748

    CAS  PubMed  Google Scholar 

  27. Wu YL, Hu CY, Lu SS, Gong FF, Feng F, Qian ZZ, Ding XX, Yang HY, Sun YH (2014) Association between methylenetetrahydrofolate reductase (MTHFR) C677T/A1298C polymorphisms and essential hypertension: a systematic review and meta-analysis. Metabolism 63(12):1503–1511. doi:10.1016/j.metabol.2014.10.001

    CAS  Article  PubMed  Google Scholar 

  28. Sterne JAC, Sutton AJ, Ioannidis JPA, Terrin N, Jones DR, Lau J, Carpenter J, Rücker G, Harbord RM, Schmid CH, Tetzlaff J, Deeks JJ, Peters J, Macaskill P, Schwarzer G, Duval S, Altman DG, Moher D, Higgins JPT (2011) Recommendations for examining and interpreting funnel plot asymmetry in meta-analyses of randomised controlled trials. BMJ 342:d4002. doi: 10.1136/bmj.d4002

  29. Jin ZC, Zhou XH, He J (2015) Statistical methods for dealing with publication bias in meta-analysis. Stat Med 34(2):343–360. doi:10.1002/sim.6342

    Article  PubMed  Google Scholar 

  30. Willi C, Bodenmann P, Ghali WA, Faris PD, Cornuz J (2007) Active smoking and the risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 298(22):2654–2664. doi:10.1001/jama.298.22.2654

    CAS  Article  PubMed  Google Scholar 

  31. Chen DF, Hu YH, Yang F, Wu BY, Chen L, Fang ZA, Wang LH (2004) Mother’s and child’s methylenetetrahydrofolate reductase C677T polymorphism is associated with preterm delivery and low birth weight. Beijing Da Xue Xue Bao 36(3):248–253 (Chinese)

    CAS  PubMed  Google Scholar 

  32. Resch B, Gallistl S, Kutschera J, Mannhalter C, Muntean W, Mueller WD (2004) Thrombophilic polymorphisms—Factor V Leiden, prothrombin G20210A, and methylenetetrahydrofolate reductase C677T mutations—and preterm birth. Wien Klin Wochenschr 116(17–18):622–626

    CAS  Article  PubMed  Google Scholar 

  33. Valdez LL, Quintero A, Garcia E, Olivares N, Celis A, Rivas F Jr, Rivas F (2004) Thrombophilic polymorphisms in preterm delivery. Blood Cells Mol Dis 33(1):51–56. doi:10.1016/j.bcmd.2004.04.011

    CAS  Article  PubMed  Google Scholar 

  34. Engel SM, Olshan AF, Siega-Riz AM, Savitz DA, Chanock SJ (2006) Polymorphisms in folate metabolizing genes and risk for spontaneous preterm and small-for-gestational age birth. Am J Obstet Gynecol 195(5):1231.e1–1231.e11. doi:10.1016/j.ajog.2006.07.024

    Article  Google Scholar 

  35. Tiwari D, Bose PD, Das S, Das CR, Datta R, Bose S (2015) MTHFR (C677T) polymorphism and PR (PROGINS) mutation as genetic factors for preterm delivery, fetal death and low birth weight: a Northeast Indian population based study. Meta Gene 3:31–42

    Article  PubMed  PubMed Central  Google Scholar 

  36. Wang BJ, Liu MJ, Wang Y, Dai JR, Tao JY, Wang SN, Zhong N, Chen Y (2015) Association between SNPs in genes involved in folate metabolism and preterm birth risk. Genet Mol Res 14(1):850–859

    CAS  Article  PubMed  Google Scholar 

  37. Du JY, Yang XY, Gong B, Guan YY, Mei LY, Li YM (2013) Relationship of plasma homocysteine levels, folate levels and MTHFR gene polymorphisms with premature delivery. J Sun Yat-sen Univ (Med Sci) 34(6):894–899 (Chinese)

    CAS  Google Scholar 

  38. Nan Y, Li H (2015) MTHFR genetic polymorphism increases the risk of preterm delivery. Int J Clin Exp Pathol 8(6):7397–7402

    PubMed  PubMed Central  Google Scholar 

  39. Kupferminc MJ, Eldor A, Steinman N, Many A, Bar-Am A, Jaffa A, Fait G, Lessing JB (1999) Increased frequency of genetic thrombophilia in women with complications of pregnancy. N Engl J Med 340(1):9–13

    CAS  Article  PubMed  Google Scholar 

  40. Gebhardt GS, Scholtz CL, Hillermann R, Odendaal HJ (2001) Combined heterozygosity for methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C is associated with abruptio placentae but not with intrauterine growth restriction. Eur J Obstet Gynecol Reprod Biol 97(2):174–177

    CAS  Article  PubMed  Google Scholar 

  41. Infante-Rivard C, Rivard GE, Yotov WV, Genin E, Guiguet M, Weinberg C, Gauthier R, Feoli-Fonseca JC (2002) Absence of association of thrombophilia polymorphisms with intrauterine growth restriction. N Engl J Med 347(1):19–25. doi:10.1056/nejm200207043470105

    CAS  Article  PubMed  Google Scholar 

  42. Kupferminc MJ, Many A, Bar-Am A, Lessing JB, Ascher-Landsberg J (2002) Mid-trimester severe intrauterine growth restriction is associated with a high prevalence of thrombophilia. BJOG 109(12):1373–1376

    Article  PubMed  Google Scholar 

  43. Ulukuş M, Eroǧlu Z, Yeniel AÖ, Toprak E, Kosova B, Turan ÖD, Ulukuş M (2006) Frequency of factor V Leiden (G1691A), prothrombin (G20210A) and methylenetetrahydrofolate reductase (C677T) genes mutations in woman with adverse pregnancy outcome. J Turk Ger Gynecol Assoc 7(3):195–201

    Google Scholar 

  44. Ozbek N, Atac FB, Verdi H, Cetintas S, Gurakan B, Haberal A (2008) Relationship between small-for-gestational age births and maternal thrombophilic mutations. Thromb Res 122(2):175–178. doi:10.1016/j.thromres.2007.10.004

    CAS  Article  PubMed  Google Scholar 

  45. He P, Meng H, Zhang JP (2007) Relationship of MTHFR C677T polymorphisms and fetal growth restriction. Maternal Child Health Care China 22 (35):5032–5034. doi:10.3969/j.issn.1001-4411.2007.35.047 (in Chinese)

    Google Scholar 

  46. Leng JJ (2009) The relationship of MTHFR C677T polymorphism and plasma homocysteine level with fetal growth restriction. Guangzhou Medical College, China

    Google Scholar 

  47. Zhong QA, Qiu XQ, Zeng XY, Deng YY, Wu TY (2009) Association of low birth weight with genetic polymorphism of MTHFR and CBS in mother. Chin J Birth Health Hered 17 (3):22–24. doi:10.13404/j.cnki.cjbhh.2009.03.055 (in Chinese)

    Google Scholar 

  48. Yang Y, Jin L, Yuan JJ, Wu D, Shang Q, Wu L, Han X, Liang B, Xu L, Tang JL (2010) Association of genetic polymorphisms in methylenetetrahydrofolate reductase gene, plasminogen activator inhibitor-1 gene with preterm birth and spastic cerebral palsy. J Appl Clin Pediatr 25(20):1580–1582 (Chinese)

    CAS  Google Scholar 

  49. Mei M, Xi HL, Ren HY, Guo HY, Wang YT, Li J (2015) The relationship between MTHFR Gene, PAI gene polymorphism and preterm birth. Prog Modern Biomed 15(33):6435–6438. doi:10.13241/j.cnki.pmb.2015.33.009 (in Chinese)

    Google Scholar 

  50. Glanville T, Yates Z, Ovadia L, Walker JJ, Lucock M, Simpson NA (2006) Fetal folate C677T methylenetetrahydrofolate reductase gene polymorphism and low birth weight. J Obstet Gynaecol 26(1):11–14. doi:10.1080/01443610500363865

    CAS  Article  PubMed  Google Scholar 

  51. Uvuz F, Kilic S, Yilmaz N, Tuncay G, Cakar E, Yuksel B, Bilge U (2009) Relationship between preterm labor and thrombophilic gene polymorphism: a prospective sequential cohort study. Gynecol Obstet Invest 68(4):234–238

    Article  PubMed  Google Scholar 

  52. Colson NJ, Naug HL, Nikbakht E, Zhang P, McCormack J (2015) The impact of MTHFR 677 C/T genotypes on folate status markers: a meta-analysis of folic acid intervention studies. Eur J Nutr. doi:10.1007/s00394-015-1076-x

    PubMed  Google Scholar 

  53. Clarke R, Bennett DA, Parish S, Verhoef P, Dotsch-Klerk M, Lathrop M, Xu P, Nordestgaard BG, Holm H, Hopewell JC, Saleheen D, Tanaka T, Anand SS, Chambers JC, Kleber ME, Ouwehand WH, Yamada Y, Elbers C, Peters B, Stewart AF, Reilly MM, Thorand B, Yusuf S, Engert JC, Assimes TL, Kooner J, Danesh J, Watkins H, Samani NJ, Collins R, Peto R (2012) Homocysteine and coronary heart disease: meta-analysis of MTHFR case–control studies, avoiding publication bias. PLoS Med 9(2):e1001177. doi:10.1371/journal.pmed.1001177

    Article  PubMed  PubMed Central  Google Scholar 

  54. Alizadeh S, Djafarian K, Moradi S, Shab-Bidar S (2016) C667T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene and susceptibility to myocardial infarction: a systematic review and meta-analysis. Int J Cardiol 217:99–108. doi:10.1016/j.ijcard.2016.04.181

    Article  PubMed  Google Scholar 

  55. Fitzmaurice C, Dicker D, Pain A, Hamavid H, Moradi-Lakeh M, MacIntyre MF, Allen C, Hansen G, Woodbrook R, Wolfe C, Hamadeh RR, Moore A, Werdecker A, Gessner BD, Te Ao B, McMahon B, Karimkhani C, Yu C, Cooke GS, Schwebel DC, Carpenter DO, Pereira DM, Nash D, Kazi DS, De Leo D, Plass D, Ukwaja KN, Thurston GD, Yun Jin K, Simard EP, Mills E, Park EK, Catala-Lopez F, deVeber G, Gotay C, Khan G, Hosgood HD 3rd, Santos IS, Leasher JL, Singh J, Leigh J, Jonas JB, Sanabria J, Beardsley J, Jacobsen KH, Takahashi K, Franklin RC, Ronfani L, Montico M, Naldi L, Tonelli M, Geleijnse J, Petzold M, Shrime MG, Younis M, Yonemoto N, Breitborde N, Yip P, Pourmalek F, Lotufo PA, Esteghamati A, Hankey GJ, Ali R, Lunevicius R, Malekzadeh R, Dellavalle R, Weintraub R, Lucas R, Hay R, Rojas-Rueda D, Westerman R, Sepanlou SG, Nolte S, Patten S, Weichenthal S, Abera SF, Fereshtehnejad SM, Shiue I, Driscoll T, Vasankari T, Alsharif U, Rahimi-Movaghar V, Vlassov VV, Marcenes WS, Mekonnen W, Melaku YA, Yano Y, Artaman A, Campos I, MacLachlan J, Mueller U, Kim D, Trillini M, Eshrati B, Williams HC, Shibuya K, Dandona R, Murthy K, Cowie B, Amare AT, Antonio CA, Castaneda-Orjuela C, van Gool CH, Violante F, Oh IH, Deribe K, Soreide K, Knibbs L, Kereselidze M, Green M, Cardenas R, Roy N, Tillmann T, Li Y, Krueger H, Monasta L, Dey S, Sheikhbahaei S, Hafezi-Nejad N, Kumar GA, Sreeramareddy CT, Dandona L, Wang H, Vollset SE, Mokdad A, Salomon JA, Lozano R, Vos T, Forouzanfar M, Lopez A, Murray C, Naghavi M (2015) The global burden of cancer 2013. JAMA Oncol 1(4):505–527. doi:10.1001/jamaoncol.2015.0735

    Article  PubMed  Google Scholar 

  56. Liu X, Lv L, Zhang H, Zhao N, Qiu J, He X, Zhou M, Xu X, Cui H, Liu S, Lerro C, Lin X, Zhang C, Zhang H, Xu R, Zhu D, Dang Y, Han X, Bai H, Chen Y, Tang Z, Lin R, Yao T, Su J, Wang W, Wang Y, Ma B, Huang H, Liang J, Qiu W, Liu Q, Zhang Y (2016) Folic acid supplementation, dietary folate intake and risk of preterm birth in China. Eur J Nutr 55(4):1411–1422. doi:10.1007/s00394-015-0959-1

    CAS  Article  PubMed  Google Scholar 

  57. Zeng Z, Zhu J (2010) Low folic acid supplement intake rate among women in northern China with a high-prevalence of neural tube defects, 2008. Prev Med 51(3–4):338–339. doi:10.1016/j.ypmed.2010.07.015

    Article  PubMed  Google Scholar 

  58. Blancquaert D, Storozhenko S, Loizeau K, De Steur H, De Brouwer V, Viaene J, Ravanel S, Rébeillé F, Lambert W, Van Der Straeten D (2010) Folates and folic acid: from fundamental research toward sustainable health. Crit Rev Plant Sci 29(1):14–35. doi:10.1080/07352680903436283

    CAS  Article  Google Scholar 

  59. Shelnutt KP, Kauwell GP, Gregory JF 3rd, Maneval DR, Quinlivan EP, Theriaque DW, Henderson GN, Bailey LB (2004) Methylenetetrahydrofolate reductase 677 C→T polymorphism affects DNA methylation in response to controlled folate intake in young women. J Nutr Biochem 15(9):554–560. doi:10.1016/j.jnutbio.2004.04.003

    CAS  Article  PubMed  Google Scholar 

  60. Guinotte CL, Burns MG, Axume JA, Hata H, Urrutia TF, Alamilla A, McCabe D, Singgih A, Cogger EA, Caudill MA (2003) Methylenetetrahydrofolate reductase 677 C→T variant modulates folate status response to controlled folate intakes in young women. J Nutr 133(5):1272–1280

    CAS  PubMed  Google Scholar 

Download references

Author contributions

H. Wu: Project development, Manuscript writing; P. Zhu: Results interpretation; X. Geng: Data collection; Z. Gao: Data collection; Z. Liu: Data analysis; L. Cui: Data analysis; B. Jiang: Project development, Manuscript revision; L. Yang: Project supervision, Manuscript revision.

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Baofa Jiang or Liping Yang.

Ethics declarations

Funding

This study was funded by Shandong Provincial Natural Science Foundation, China (Grant Number ZR2015HM076).

Conflict of interest

Author H. Wu declares that he has no conflict of interest. Author P. Zhu declares that she has no conflict of interest. Author X. Geng declares that he has no conflict of interest. Author Z. Liu declares that he has no conflict of interest. Author L. Cui declares that she has no conflict of interest. Author Z. Gao declares that he has no conflict of interest. Author B. Jiang declares that he has no conflict of interest. Author L. Yang declares that she has no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Wu, H., Zhu, P., Geng, X. et al. Genetic polymorphism of MTHFR C677T with preterm birth and low birth weight susceptibility: a meta-analysis. Arch Gynecol Obstet 295, 1105–1118 (2017). https://doi.org/10.1007/s00404-017-4322-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-017-4322-z

Keywords

  • Methylenetetrahydrofolate reductase
  • Preterm birth
  • Low birth weight
  • Polymorphism
  • Meta-analysis