Abstract
Preterm birth (PTB), defined as delivery before 37 weeks of gestation, is the leading cause of neonatal death worldwide. Latvia, with a PTB rate of 5.45%, offers a useful model for understanding outcomes. This paper discusses a phenotype-based approach to PTB prevention, focusing on underlying mechanisms such as cervical insufficiency, infection, inflammation, and hormonal or genetic factors. The use of second-trimester transvaginal ultrasound enables early detection of a short cervix and the implementation of interventions such as vaginal progesterone and cerclage. Genomic studies indicate that up to 67% of women with cervical insufficiency carry rare variants in genes involved in collagen structure or progesterone pathways, supporting a multifactorial etiology. Vaginal microbiota alterations and intra-amniotic inflammation also contribute to PTB risk, highlighting the need for integrated molecular and microbial screening. Management includes targeted antibiotic therapy, which can resolve inflammation in up to 75% of cases and prolong pregnancy. When PTB is imminent, corticosteroids, magnesium sulfate, early referral, and adherence to golden hour protocols are essential. Delivery at experienced centers can reduce neonatal mortality by 50% in births before 32 weeks. Cesarean delivery may lower perinatal risk, particularly in cases of breech presentation. Europe should adopt unified standards for prevention and care, strengthen referral systems, and develop monitoring networks. Every preterm birth is an opportunity for personalized care; every baby counts.
References
Kinney M V, Lawn JE, Howson CP, Belizan J. 15 million preterm births annually: what has changed this year? Reprod Health. 2012;9:28.
Beck S, Wojdyla D, Say L, et al. The worldwide incidence of preterm birth: a systematic review of mater nal mortality and morbidity. Bull World Health Organ. 2010;88(1):31-38.
Menon R. Preterm birth: a global burden on maternal and child health. Pathog Glob Health. 2012;106(3):139-140.
Walani SR. Global burden of preterm birth. Int J Gynaecol Obstet. 2020;150(1):31-33.
Zeitlin J, Alexander S, Barros H, et al.; Euro-Peristat Scientific Committee. Perinatal health monitoring through a European lens: eight lessons from the Euro-Peristat report on 2015 births. BJOG. 2019;126(13):1518-1522.
Andzane D, Volozonoka L, Zolovs M, Kornete A, Rezeberga D, Miskova A. Preterm birth in Latvia: Two‐decade national trends, structure, and risk factors. Acta Obstet Gynecol Scand. 2025;104(10):1929-1938.
Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science. 2014;345(6198):760-765.
Coutinho CM, Sotiriadis A, Odibo A, et al. ISUOG Practice Guidelines: role of ultrasound in the prediction of spontaneous preterm birth. Ultrasound Obstet Gynecol. 2022;60(3):435-456.
Khalil A, Rodgers M, Baschat A, et al. ISUOG Practice Guidelines: role of ultrasound in twin pregnancy. Ultrasound Obstet Gynecol. 2016;47(2):247-263.
Kūkoja K, Villeruša A, Zīle-Velika I. Relationship between Maternal Socioeconomic Factors and Preterm Birth in Latvia. Medicina (Kaunas). 2024;60(5):826.
Pereira E, Tessema G, Gissler M, Regan AK, Pereira G. Re-evaluation of gestational age as a predictor for subsequent preterm birth. PLoS One. 2021;16(1):e0245935.
Guzman ER, Rosenberg JC, Houlihan C, Ivan J, Waldron R, Knuppel R. A new method using vaginal ultrasound and transfundal pressure to evaluate the asymptomatic incompetent cervix. Obstet Gynecol. 1994;83(2):248-252.
Ji X, Wu C, Chen M, et al. Analysis of risk factors related to extremely and very preterm birth: a retrospective study. BMC Pregnancy Childbirth. 2022;22(1):818.
Romero R, Conde-Agudelo A, Rehal A, et al. Vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations with a short cervix: an updated individual patient data meta-analysis. Ultrasound Obstet Gynecol. 2022;59(2):263-266.
Owen J, Hankins G, Iams JD, et al. Multicenter randomized trial of cerclage for preterm birth prevention in high-risk women with shortened midtrimester cervical length. Am J Obstet Gynecol. 2009;201(4):375.e1-8.
Melchor JC, Khalil A, Wing D, Schleussner E, Surbek D. Prediction of preterm delivery in symptomatic women using PAMG-1, fetal fibronectin and phiGFBP-1 tests: Systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;52(4):442-451.
Karampitsakos T, Mavrogianni D, Machairiotis N, et al. The Impact of Amniotic Fluid Interleukin-6, Interleukin-8, and Metalloproteinase-9 on Preterm Labor: A Narrative Review. Biomedicines. 2025;13(1):118.
Aung MT, Yu Y, Ferguson KK, et al. Prediction and associations of preterm birth and its subtypes with eicosanoid enzymatic pathways and inflammatory markers. Sci Rep. 2019;9(1):17049.
Goldenberg RL, Goepfert AR, Ramsey PS. Biochemical markers for the prediction of preterm birth. Am J Obstet Gynecol. 2005;192(5 Suppl):S36-46.
Li M, Liu M, Chen P, et al. Amniotic fluid proteomic analysis identifies IL1RL1, APOE, and NECTIN4 as new biomarkers for preterm birth. BMC Pregnancy Childbirth. 2024;24(1):530.
Volozonoka L, Rots D, Kempa I, et al. Genetic landscape of preterm birth due to cervical insufficiency: Comprehensive gene analysis and patient next-generation sequencing data interpretation. PLoS One. 2020;15(3):e0230771.
Voložonoka L, Bārdiņa L, Kornete A, et al. Unravelling the genetic landscape of cervical insufficiency: Insights into connective tissue dysfunction and hormonal pathways. PLoS One. 2024;19(9):e0310718.
Jia B, Tang L, Liu H, et al. Potential roles of the interactions between gut microbiota and metabolites in LPS-induced intrauterine inflammation (IUI) and associated preterm birth (PTB). J Transl Med. 2024;22(1):7.
Ansari AZ, You YA, Lee G, et al. Dysbiotic Vaginal Microbiota Induces Preterm Birth Cascade via Pathogenic Molecules in the Vagina. Metabolites. 2024;14(1):45.
Ferrante M, Oliveri Conti G, Pulvirenti E, Favara C, Fiore M, Cristaldi A. The vaginal microbiota and preterm birth: A systematic review. Eur J Obstet Gynecol Reprod Biol. 2025;311:114007.
Conde-Agudelo A, Romero R. Vaginal progesterone does not prevent recurrent preterm birth in women with a singleton gestation, a history of spontaneous preterm birth, and a midtrimester cervical length >25 mm. Am J Obstet Gynecol. 2022;227(6):923-926.
Alfirevic Z ST, Medley N. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2017;6(6):CD008991.
Oh KJ, Romero R, Park JY, et al. Evidence that antibiotic administration is effective in the treatment of a subset of patients with intra-amniotic infection/inflammation presenting with cervical insufficiency. Am J Obstet Gynecol. 2019;221(2):140.e1-140.e18.
Yoon BH, Romero R, Park JY, et al. Antibiotic administration can eradicate intra-amniotic infection or intra-amniotic inflammation in a subset of patients with preterm labor and intact membranes. Am J Obstet Gynecol. 2019;221(2):142.e1-142.e22.
Kornete A, Volozonoka L, Zolovs M, et al. Management of Pregnancy with Cervical Shortening: Real-Life Clinical Challenges. Medicina (Kaunas). 2023;59(4):653.
Dagklis T, Akolekar R, Villalain C, et al. Management of preterm labor clinical practice guideline and recommendation by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation. Eur J Obstet Gynecol Reprod Biol. 2023;291:196-205.
Dagklis T, Şen C, Tsakiridis I, et al. The use of antenatal corticosteroids for fetal maturation: clinical practice guideline by the WAPM-World Association of Perinatal Medicine and the PMF-Perinatal Medicine Foundation. J Perinat Med. 2022;50(4):375-385.
Sasaki Y, Ishikawa K, Yokoi A, et al. Short- and Long-Term Outcomes of Extremely Preterm Infants in Japan According to Outborn/Inborn Birth Status. Pediatr Crit Care Med. 2019;20(10):963-969.
Chien LY, Whyte R, Aziz K, Thiessen P, Matthew D, Lee SK; Canadian Neonatal Network. Improved outcome of preterm infants when delivered in tertiary care centers. Obstet Gynecol. 2001;98(2):247-252.
Helenius K, Gissler M, Lehtonen L. Trends in centralization of very preterm deliveries and neonatal survival in Finland in 1987–2017. Transl Pediatr. 2019;8(3):227-232.
Phibbs CS, Passarella M, Schmitt SK, Martin A, Lorch SA. The Impact of Hospital Delivery Volumes of Newborns Born Very Preterm on Mortality and Morbidity. J Pediatr. 2025;276:114323.
Demertzidou E, Chatzakis C, Cavoretto P, et al. Effect of mode of delivery on perinatal outcome in severe preterm birth: systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2023;62(4):471-485.
Kowalczyk-Buss J, Demertzidou E, El-Toukhy S, Ramadan G, Akolekar R. Extreme Preterm Delivery Between 24+0 and 27+6 Weeks: Factors Affecting Perinatal Outcome. J Clin Med. 2025;14(4):1064.
Seidler AL, Aberoumand M, Hunter KE, et al.; iCOMP Collaborators. Deferred cord clamping, cord milking, and immediate cord clamping at preterm birth: a systematic review and individual participant data meta-analysis. Lancet. 2023;402(10418):2209-2222.
Katheria AC, Ines F, Lee HC, et al. Deferred Cord Clamping With High Oxygen in Extremely Preterm Infants. JAMA Pediatr. 2025;179(9):971-978.
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