Skip to main content Skip to main navigation menu Skip to site footer

High maternal homocysteine (Hcy) levels as a risk factor of preterm labor: a case-control study

  • Anak Agung Gede Putra Wiradnyana ,
  • Anak Agung Ngurah Jaya Kusuma ,
  • Tjokorda Gde Agung Suwardewa ,
  • Anom Suardika ,
  • Made Bagus Dwi Aryana ,
  • Nyoman Gede Budiana ,
  • Putu Doster Mahayasa ,
  • IP Popy Kusuardiyanto ,


Background: Preterm labor is a serious perinatology problem with the consequences of increasing morbidity and mortality in neonates. Increased levels of homocysteine (Hcy) in serum have been reported to play a role in the pathogenesis of various pregnancy complications, including preterm labor. This study aimed to determine whether serum. Hcy levels are a risk factor for preterm labor.

Methods: This case-control study was conducted from January to June 2021. The case and control group included a consecutive woman with preterm and term labor. Homocysteine level was measured from maternal blood samples during labor. Maternal age, parity, and body mass index (BMI) data were also collected and compared between those two groups.

Results: A total of 30 preterm deliveries and 30 term deliveries were included in the study. The mean Hcy level in the preterm group was 17.26±6.814 mmol/L and in the term group was 9.788±4.532 mmol/L. Serum Hcy levels were classified as high (≥12.85 mmol/L) and low (<12.85 mmol/L) level. High serum Hcy level increased the risk of preterm labor by 9.118 times compared to low Hcy (p=0.001; 95% CI=2.581 – 32.211). There was no significant association between age, parity, and BMI with preterm labor (p>0.05).

Conclusion: High maternal serum Hcy level is a risk factor for preterm labor. Prospective studies with larger samples are required to confirm these results.


  1. World Health Organization. WHO report on global preterm birth [Online]. 2015. Accessed 5 June 2020.
  2. Purisch SE, Gyamfi-Bannerman C. Epidemiology of preterm birth. Seminars in perinatology. 2017;41(7): 387–391
  3. Sentana O, Kardana M. The associated factor of preterm birth incidence in Sanglah Hospital Denpasar. Medicina. 2017;48(2):83-87.
  4. Fortunato SJ, Menon R. Distinct molecular events suggest different pathways for preterm labor and premature rupture of membranes. Am J Obstet Gynecol. 2001; 184(7):1399-405
  5. Gaiday AN, Tussupkaliyev AB, Bermagambetova SK, et al. effect of homocysteine of pregnancy: a systematic review. Chemico-Biological Interaction. 2018;293:70-76
  6. Maayan-metzger A, Lubetsky A, Kuint J, et al. The Impact of genetic and environmental factors on homocysteine levels in preterm neonates. Pediatric Blood & Cancer. 2013; 60(4). DOI:10.1002/pbc.24352
  7. Dhobale M, Chavan P, Kulkarni A, et al. Reduced folate, increased vitamin B(12) and homocysteine concentrations in women delivering preterm. Annals of nutrition & metabolism. 2012;61(1):7–14
  8. Qiu X, Gao F, Qiu Y, et al. Association of maternal serum homocysteine concentration levels in late stage of pregnancy with preterm births: a nested case-control study. The journal of maternal-fetal & neonatal. 2018;31(20):2673–2677
  9. Murphy MM, Fernandez-Ballart JD. Homocysteine in pregnancy. Advances in clinical chemistry. 2011;53:105–137
  10. Cha HH, Kim JM, Kim HM, et al. Association between gestational age at labor and lymphocyte-monocyte ratio in the routine second trimester complete blood cell count. Yeungnam Univ J Med. 2021;38(1):34-38
  11. Khatoon F, Gupta H, Sinha P, et al. Prediction of preterm birth on the basis of complete blood count parameters. J South Asian Feder Obst Gynae. 2020;12(5):288–290.
  12. Daglar HK, Kirbas A, Kaya B, et al. The value of complete blood count parameters in predicting preterm labor. European Review for Medical and Pharmacological Sciences. 2016;20:801-805
  13. Funchs F, Monet B, Ducruet T, et al. effect of maternal age on the risk of preterm birth: a large cohort study. PLoS One. 2018; 13(1):e0191002
  14. Londero AP, Rosseti E, Pittini C, et al. Maternal age and the risk of adverse pregnancy outcomes: a retrospective cohort study. BMC Pregnancy and Childbirth. 2019; 19: 261
  15. Chen KH, Chen IC, Yang YC, et al. The trends and associated factors of preterm deliveries from 2001 to 2011 in Taiwan. Medicine. 2019;98:13(e15060)
  16. Sungkar A, Fattah AN, Surya R, et al. High preterm birth at Cipto Mangunkusumo Hospital as a national referral hospital in Indonesia. Medical Journal of Indonesia. 2017;26(3):198-203
  17. Li L, Chen Y, Lin Z, et al. Association of pre-pregnancy body mass index with adverse pregnancy outcome among first-time mothers. PeerJ. 2020;8:e10123
  18. Dudenhausen JW, Kunze M, Wittwer-Backofen U, et al. The relationship between maternal age, body mass index, and the rate of preterm birth. J Turk Ger Gynecol Assoc. 2018;19:182-6
  19. Silva FP, Souza RT, Cecatti JG, et al. role of body mass index and gestational weight gain on preterm birth and adverse perinatal outcomes. Scientific Reports. 2019;9:13093
  20. Vinturache A, McKeating A, Daly N, et al. Maternal body mass index and the prevalence of spontaneous and elective preterm deliveries in an Irish obstetric population: a retrospective cohort study. BMJ Open. 2017;7:e015258.
  21. Denlord M, Zeitlin J. Epidemiology of late preterm and early term births-an international perspective. Semin Fetal Neonatal Med. 2019;24(1):3-10
  22. Koullali B, van Zijl MD, Kazemier BM, et al. The association between parity and spontaneous preterm birth: a population-based study. BMC Pregnancy and Childbirth. 2020;20:233
  23. Dai C, Fei Y, Li J, et al. A Novel review of homocysteine and pregnancy complications. BioMed Research International. 2021. Article ID 6652231
  24. Hoffman M. Hypothesis: hyperhomocysteinemia is an indicator of oxidant stress. Medical hypotheses. 2011;77(6):1088–1093
  25. Liu C, Luo D, Wang Q, et al. Serum homocysteine and folate concentrations in early pregnancy and subsequent events of adverse pregnancy outcome: the Sichuan Homocysteine study. BMC pregnancy and childbirth. 2020;20(1):176
  26. Ronnenberg AG, Goldman MB, Chen D, et al. Preconception homocysteine and B vitamin status and birth outcomes in Chinese women. The American journal of clinical nutrition. 2002;76(6):1385–1391
  27. Raka-Widiana I, Suwitra K, Elyshanti R, Sutarka N. Serum homocysteine concentrations inversely correlates to intima-media thickness of carotid arteries: an impact to enverse epidemiology in predialytic chronic kidney disease. Bali Medical Journal. 2013;2(2):83–93.
  28. Menon R. Oxidative stress damage as a detrimental factor in preterm birth pathology. Frontiers in immunology. 2014;5:567
  29. Prabawa IPY, Lestari AAW, Muliarta IM, Mardhika PE, Pertiwi GAR, Bhargah A, Rampengan SH. The Stromal Cell-derived Factor-1/CXCL12 3’A-gene Polymorphism is Related to the Increased Risk of Coronary Artery Disease: A Systematic Review and Meta-analysis. Open Access Maced J Med Sci. 2020;8(F): 197-202.

How to Cite

Wiradnyana, A. A. G. P., Kusuma, A. A. N. J., Suwardewa, T. G. A., Suardika, A., Aryana, M. B. D., Budiana, N. G., Mahayasa, P. D., & Kusuardiyanto, I. P. (2022). High maternal homocysteine (Hcy) levels as a risk factor of preterm labor: a case-control study. Bali Medical Journal, 11(3), 2057–2061.




Search Panel

Anak Agung Gede Putra Wiradnyana
Google Scholar
BMJ Journal

Anak Agung Ngurah Jaya Kusuma
Google Scholar
BMJ Journal

Tjokorda Gde Agung Suwardewa
Google Scholar
BMJ Journal

Anom Suardika
Google Scholar
BMJ Journal

Made Bagus Dwi Aryana
Google Scholar
BMJ Journal

Nyoman Gede Budiana
Google Scholar
BMJ Journal

Putu Doster Mahayasa
Google Scholar
BMJ Journal

IP Popy Kusuardiyanto
Google Scholar
BMJ Journal