Iranian Journal of Medical Sciences

Document Type : Original Article(s)

Authors

1 Department of Normal and Topographic Anatomy with Operative Surgery, West Kazakhstan Marat Ospanov Medical University, Aktobe 030019, Kazakhstan

2 SRI “Sustainability of Ecology and Bioresources”, Al-Farabi Kazakh National University, Al-Farabi 71, Almaty, 050040, Kazakhstan

3 Department of Fundamental Medicine, Faculty of Medicine and Health Care, Al-Farabi Kazakh National University, Tole bi 96, 050012 Almaty, Kazakhstan

4 International Clinic of Reproductive Health “PERSONA” LLP, Almaty 050063, Kazakhstan

5 Khoja Akhmet Yassawi International Kazakh-Turkish University, Turkistan, 161200, Kazakhstan

6 Department of Biotechnology, Auezov South Kazakhstan University, Shymkent, 160012, Kazakhstan

7 Department of Histology, West Kazakhstan Marat Ospanov Medical University, Aktobe 030019, Kazakhstan

10.30476/ijms.2025.102996.3613

Abstract

Background: Premature birth (delivery before 37 weeks of gestation) is a leading cause of neonatal morbidity and mortality worldwide. Specific genetic polymorphisms were associated with immune and inflammatory pathways that might contribute to its pathogenesis. This study investigated the associations between preterm birth and sociodemographic indicators, clinical outcomes, genetic polymorphisms, and microbial factors in Kazakh women.
Methods: This case-control study was conducted from September 2022 to September 2023. It enrolled women with preterm and full-term births in Kyzylorda, Kazakhstan. Data included sociodemographic, clinical variables, genotyping (TLR2 rs4986790 and MBL2 rs11003125), and microbial data. The quantification of Fusobacterium nucleatum (F. nucleatum) in saliva samples was performed using TaqMan real-time PCR. Statistical analysis was conducted using SPSS software (version 26), employing independent sample t tests, Chi square tests, Mann-Whitney U tests, and logistic regression. The level of significance was set at P<0.05.
Results: Sociodemographic analysis showed no significant differences between the studied groups, except for a higher prevalence of previous preterm birth in the case group. Clinical comparisons revealed significantly lower gestational age at delivery, reduced newborn weight and height, decreased placental weight and dimensions, lower hemoglobin levels, and erythrocyte counts in preterm cases. Genetic analysis demonstrated that all women with preterm labor carried the homozygous AA genotype of TLR299 rs4986790, while the GG genotype and the G allele of the MBL2 rs11003125 gene were predominant in this group. Furthermore, the quantitative analysis identified significantly higher F. nucleatum levels associated with premature birth, highlighting a potential microbial role in its pathogenesis. 
Conclusion: These findings suggested that a history of preterm birth, specific genetic polymorphisms, and microbial factors collectively were associated with an increased risk of preterm birth.

Highlights

Gulmira Zhurabekova (Google Scholar)

Keywords

  1. Khandre V, Potdar J, Keerti A. Preterm Birth: An Overview. Cureus. 2022;14:e33006. doi: 10.7759/cureus.33006. PubMed PMID: 36712773; PubMed Central PMCID: PMCPMC9879350.
  2. Mead EC, Wang CA, Phung J, Fu JY, Williams SM, Merialdi M, et al. The Role of Genetics in Preterm Birth. Reprod Sci. 2023;30:3410-27. doi: 10.1007/s43032-023-01287-9. PubMed PMID: 37450251; PubMed Central PMCID: PMCPMC10692032.
  3. Agarwal R, Agrawal R. Exploring Risk Factors and Perinatal Outcomes of Preterm Birth in a Tertiary Care Hospital: A Comprehensive Analysis. Cureus. 2024;16:e53673. doi: 10.7759/cureus.53673. PubMed PMID: 38455809; PubMed Central PMCID: PMCPMC10918306.
  4. Vander Haar EL, So J, Gyamfi-Bannerman C, Han YW. Fusobacterium nucleatum and adverse pregnancy outcomes: Epidemiological and mechanistic evidence. Anaerobe. 2018;50:55-9. doi: 10.1016/j.anaerobe.2018.01.008. PubMed PMID: 29409815; PubMed Central PMCID: PMCPMC6750227.
  5. Medley N, Vogel JP, Care A, Alfirevic Z. Interventions during pregnancy to prevent preterm birth: an overview of Cochrane systematic reviews. Cochrane Database Syst Rev. 2018;11:CD012505. doi: 10.1002/14651858.CD012505.pub2. PubMed PMID: 30480756; PubMed Central PMCID: PMCPMC6516886.
  6. Anchita, Zhupankhan A, Khaibullina Z, Kabiyev Y, Persson KM, Tussupova K. Health impact of drying Aral Sea: One health and socio-economical approach. Water. 2021;13:3196. doi: 10.3390/w13223196.
  7. Fetene G, Tesfaye T, Negesse Y, Dulla D. Factors associated with preterm birth among mothers who gave birth at public Hospitals in Sidama regional state, Southeast Ethiopia: Unmatched case-control study. PLoS One. 2022;17:e0265594. doi: 10.1371/journal.pone.0265594. PubMed PMID: 35442955; PubMed Central PMCID: PMCPMC9020679.
  8. King S, Matvienko-Sikar K, Laplante DP. Natural disasters and pregnancy: population-level stressors and interventions. Prenatal stress and child development. 2021:523-64. doi: 10.1007/978-3-030-60159-1_18.
  9. Etil T, Opio B, Odur B, Lwanga C, Atuhaire L. Risk factors associated with preterm birth among mothers delivered at Lira Regional Referral Hospital. BMC Pregnancy Childbirth. 2023;23:814. doi: 10.1186/s12884-023-06120-4. PubMed PMID: 37996791; PubMed Central PMCID: PMCPMC10666300.
  10. Wadon M, Modi N, Wong HS, Thapar A, O’Donovan MC. Recent advances in the genetics of preterm birth. Ann Hum Genet. 2020;84:205-13. doi: 10.1111/ahg.12373. PubMed PMID: 31853956; PubMed Central PMCID: PMCPMC7187167.
  11. Auriti C, Prencipe G, Moriondo M, Bersani I, Bertaina C, Mondi V, et al. Mannose-Binding Lectin: Biologic Characteristics and Role in the Susceptibility to Infections and Ischemia-Reperfusion Related Injury in Critically Ill Neonates. J Immunol Res. 2017;2017:7045630. doi: 10.1155/2017/7045630. PubMed PMID: 28246614; PubMed Central PMCID: PMCPMC5299167.
  12. Robertson SA, Hutchinson MR, Rice KC, Chin PY, Moldenhauer LM, Stark MJ, et al. Targeting Toll-like receptor-4 to tackle preterm birth and fetal inflammatory injury. Clin Transl Immunology. 2020;9:e1121. doi: 10.1002/cti2.1121. PubMed PMID: 32313651; PubMed Central PMCID: PMCPMC7156293.
  13. Strauss JF, 3rd, Romero R, Gomez-Lopez N, Haymond-Thornburg H, Modi BP, Teves ME, et al. Spontaneous preterm birth: advances toward the discovery of genetic predisposition. Am J Obstet Gynecol. 2018;218:294-314. doi: 10.1016/j.ajog.2017.12.009. PubMed PMID: 29248470; PubMed Central PMCID: PMCPMC5834399.
  14. Campbell EE, Gilliland J, Dworatzek PDN, De Vrijer B, Penava D, Seabrook JA. Socioeconomic Status and Adverse Birth Outcomes: A Population-Based Canadian Sample. J Biosoc Sci. 2018;50:102-13. doi: 10.1017/S0021932017000062. PubMed PMID: 28270256.
  15. Maher GM, Ward LJ, Hernandez L, Kublickas M, Duvekot JJ, McCarthy FP, et al. Association between socioeconomic status with pregnancy and neonatal outcomes: An international multicenter cohort. Acta Obstet Gynecol Scand. 2023;102:1459-68. doi: 10.1111/aogs.14659. PubMed PMID: 37602747; PubMed Central PMCID: PMCPMC10577636.
  16. Suff N, Xu VX, Dalla Valle G, Carter J, Brennecke S, Shennan A. Prior term delivery increases risk of subsequent recurrent preterm birth: An unexpected finding. Aust N Z J Obstet Gynaecol. 2022;62:500-5. doi: 10.1111/ajo.13504. PubMed PMID: 35220589; PubMed Central PMCID: PMCPMC9543374.
  17. Koullali B, van Zijl MD, Kazemier BM, Oudijk MA, Mol BWJ, Pajkrt E, et al. The association between parity and spontaneous preterm birth: a population based study. BMC Pregnancy Childbirth. 2020;20:233. doi: 10.1186/s12884-020-02940-w. PubMed PMID: 32316915; PubMed Central PMCID: PMCPMC7175552.
  18. Girsen AI, Mayo JA, Carmichael SL, Phibbs CS, Shachar BZ, Stevenson DK, et al. Women’s prepregnancy underweight as a risk factor for preterm birth: a retrospective study. BJOG. 2016;123:2001-7. doi: 10.1111/1471-0528.14027. PubMed PMID: 27172996; PubMed Central PMCID: PMCPMC5069076.
  19. Vieira ACF, Alves CMC, Rodrigues VP, Ribeiro CCC, Gomes-Filho IS, Lopes FF. Oral, systemic and socioeconomic factors associated with preterm birth. Women Birth. 2019;32:e12-e6. doi: 10.1016/j.wombi.2018.02.007. PubMed PMID: 29551483.
  20. Khong TY, Mooney EE, Ariel I, Balmus NC, Boyd TK, Brundler MA, et al. Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement. Arch Pathol Lab Med. 2016;140:698-713. doi: 10.5858/arpa.2015-0225-CC. PubMed PMID: 27223167.
  21. Yamamura K, Baba Y, Miyake K, Nakamura K, Shigaki H, Mima K, et al. Fusobacterium nucleatum in gastroenterological cancer: Evaluation of measurement methods using quantitative polymerase chain reaction and a literature review. Oncol Lett. 2017;14:6373-8. doi: 10.3892/ol.2017.7001. PubMed PMID: 29151903; PubMed Central PMCID: PMCPMC5678348.
  22. Soltani M, Tabatabaee HR, Saeidinejat S, Eslahi M, Yaghoobi H, Mazloumi E, et al. Assessing the risk factors before pregnancy of preterm births in Iran: a population-based case-control study. BMC Pregnancy Childbirth. 2019;19:57. doi: 10.1186/s12884-019-2183-0. PubMed PMID: 30727983; PubMed Central PMCID: PMCPMC6364407.
  23. Najafi Z, Mirghafourvand M, Ghanbari-Homaie S. Are women with preterm labour at risk for negative birth experience? a comparative cross-sectional study from Iran. BMC Pregnancy Childbirth. 2023;23:252. doi: 10.1186/s12884-023-05575-9. PubMed PMID: 37055771; PubMed Central PMCID: PMCPMC10099674.
  24. Mao Y, Wei H, Gong Y, Peng L, Chen Y. Association of MBL2 gene polymorphisms and MBL levels with dilated cardiomyopathy in a Chinese Han population. BMC Med Genomics. 2024;17:11. doi: 10.1186/s12920-023-01787-2. PubMed PMID: 38167099; PubMed Central PMCID: PMCPMC10763076.
  25. Mukherjee S, Huda S, Sinha Babu SP. Toll-like receptor polymorphism in host immune response to infectious diseases: A review. Scand J Immunol. 2019;90:e12771. doi: 10.1111/sji.12771. PubMed PMID: 31054156.
  26. Hu L, Tao H, Tao X, Tang X, Xu C. TLR2 Arg753Gln Gene Polymorphism Associated with Tuberculosis Susceptibility: An Updated Meta-Analysis. Biomed Res Int. 2019;2019:2628101. doi: 10.1155/2019/2628101. PubMed PMID: 30733958; PubMed Central PMCID: PMCPMC6348792.
  27. Choteau L, Vancraeyneste H, Le Roy D, Dubuquoy L, Romani L, Jouault T, et al. Role of TLR1, TLR2 and TLR6 in the modulation of intestinal inflammation and Candida albicans elimination. Gut Pathog. 2017;9:9. doi: 10.1186/s13099-017-0158-0. PubMed PMID: 28289440; PubMed Central PMCID: PMCPMC5310049.
  28. El-Nabi SH, Sayed S, Abd-Elhafez MA, Elfiky M, Abdel Moneim AE, El-Garawani I. Arg753Gln Polymorphisms in the Toll-Like Receptor 2 Gene are Associated with Cytomegalovirus Infection in Egyptian Bone Marrow Recipients. Endocr Metab Immune Disord Drug Targets. 2020;20:619-24. doi: 10.2174/1871530319666191018124710. PubMed PMID: 31656159.
  29. Skevaki C, Pararas M, Kostelidou K, Tsakris A, Routsias JG. Single nucleotide polymorphisms of Toll-like receptors and susceptibility to infectious diseases. Clin Exp Immunol. 2015;180:165-77. doi: 10.1111/cei.12578. PubMed PMID: 25560985; PubMed Central PMCID: PMCPMC4408151.
  30. Kania KD, Hareza D, Wilczynski JR, Wilczynski M, Jarych D, Malinowski A, et al. The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer. Cells. 2022;11. doi: 10.3390/cells11193137. PubMed PMID: 36231099; PubMed Central PMCID: PMCPMC9563956.
  31. Wang AC, Wu FX, Gao YS, Sheng XG. Toll-like receptor 4 single-nucleotide polymorphisms Asp299Gly and Thr399Ile in ovarian cancers. Oncol Lett. 2014;8:438-40. doi: 10.3892/ol.2014.2113. PubMed PMID: 24959291; PubMed Central PMCID: PMCPMC4063650.
  32. Sun M, Jiang H, Meng T, Liu P, Chen H. Association Between TLR4 Gene Polymorphisms and Risk of Preeclampsia: Systematic Review and Meta-Analysis. Med Sci Monit. 2021;27:e930438. doi: 10.12659/MSM.930438. PubMed PMID: 34334784; PubMed Central PMCID: PMCPMC8343538.