Sistemic Review and Meta-Analysis: PCR For Early Detection Of Infection Intrauterine And Prediction Obstetric Complications In High-Risk Pregnancy
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Intrauterine infection is a major cause obstetric complications, including preterm birth, premature rupture of membranes (PROM), and low birth weight (LBW). Polymerase Chain Reaction (PCR) testing offers rapid and sensitive molecular detection compared to conventional diagnostic methods. This study is a systematic review and meta analysis conducted following the PRISMA 2020 guidelines, aimed at evaluating the effectiveness of PCR in detecting intrauterine infection and predicting performed using PubMed, Scopus, ScienceDirect, Wiley and SpringerLink (2020 - 2025). The pooled analysis demonstrated a sensitivity of 0.90, specificity of 0,93 and an Area Under the Curve (AUC) of 0,95 with a Diagnostic Odds Ratio (DOR) of approximately 120. Postive PCR results were significantly associated with an increased risk of preterm birth (OR 3,4), LBW (OR 2,8) and PROM (OR 2,2). PCR demonstrated high diagnostic accuracy and strong prognostic value, supporting its integration into risk based antenatal screening to reduce perinatal morbidity and mortality.
[1] Yoneda S, Yoneda N, Niimi H, Saito S. Treatment strategies for intra-amniotic infection and/or inflammation in preterm labor cases. Eur J Obstet Gynecol Reprod Biol X [Internet], 27(June):100408. Available from: https://doi.org/10.1016/j.eurox.2025.100408
[2]Chaemsaithong P, Romero R, Pongchaikul P, Warintaksa P, Mongkolsuk P, Bhuwapathanapun M, et al. The rapid diagnosis of intraamniotic infection with nanopore sequencing. Am J Obstet Gynecol [Internet], 233(3):193.e1-193.e18. Available from: https://doi.org/10.1016/j.ajog.2025.02.011
[3] Naseem M, Khan S, Alshaya DS, Shah TA, Noreen S, Rehman FU, et al. ToRCH pathogens-induced histopathological changes in placental tissues and associated post obstetric complications. Acta Trop, 261(January):1–9, 2025.
[4] Huo R, Sun Q, Lv Q, Wang Y, Qi W, Zhang M, et al. Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome. Vol. 359, Life Sciences,1–36 p, 2024
[5] Senousy MA, Shaker OG, Elmaasrawy AHZ, Ashour AM, Alsufyani SE, Arab HH, et al. Serum lncRNAs TUG1, H19, and NEAT1 and their target miR-29b/SLC3A1 axis as possible biomarkers of preeclampsia: Potential clinical insights. Non-coding RNA Res [Internet], 9(4):995–1008, 2024. Available from: https://doi.org/10.1016/j.ncrna.2024.06.007
[6] Márquez Ibarra AA, Barrera Hernández LF, Gregorio EV, Olivas Aguirre FJ, Teresa de Jesús Quintero Vargas J. Microbiota during pregnancy, childbirth, and postpartum, and its relationship with health and disease states. Med Microecol, 25(September):1–36, 2025.
[7] Bateson B, Brown D, Kennedy R. Non-HIV sexually transmitted infections in pregnancy. Obstet Gynaecol Reprod Med, 35(3):57–62, 2025.
[8] Francisca S, Gloria AF, Marco PB, Camila NC, Víctor C, Bredford K. Metformin exposure during pregnancy and lactation affects offspring’s long-term body weight and adipose tissue mass independent of the maternal metabolic state. Biochim Biophys Acta - Mol Basis Dis, 1870(6):1–34, 2024.
[9] Souza RT, Mayrink J, Leite DF, Costa ML, Calderon IM, Filho EAR, et al. Metabolomics applied to maternal and perinatal health: A review of new frontiers with a translation potential. Clinics,74:1–41, 2019.
[10] Palav HC, Bhonde G, Padwal V, Velhal S, Pereira J, Singh AK, et al. Integrated immune monitoring of HCMV infection in pregnant women with complications and its association with adverse pregnancy outcomes. Microb Pathog,179(June):1–7, 2023.
[11] Matulova J, Kacerovsky M, Bolehovska R, Kukla R, Bostik P, Kolarova K, et al. Intra-amniotic inflammation and birth weight in pregnancies with preterm labor with intact membranes: A retrospective cohort study. Front Pediatr,10(November):1–10, 2022.
[12] Sejer EPF, Pegios P, Lin M, Bashir Z, Wulff CB, Christensen AN, et al. The Combined Use of Cervical Ultrasound and Deep Learning Improves the Detection of Patients at Risk for Spontaneous Preterm Delivery. Am J Obstet Gynecol, (September):1–4, 2025.
[13] Verspyck E, Thill C, Ego A, Machevin E, Brasseur-Daudruy M, Ickowicz V, et al. Screening for small for gestational age infants in early vs late third-trimester ultrasonography: a randomized trial. Am J Obstet Gynecol MFM, 5(11):1–8, 2023.
[14] Rani Agarwal N, Kachhawa G, Oyeyemi BF, Bhavesh NS. Metabolic profiling of serum and urine in preeclampsia and gestational diabetes in early pregnancy. Med Drug Discov, 16(December):1–23, 2022.
[15] Demirdjian SP, Mulhern MS, Kerr MA, Ledwidge M, Alhomaid RM, Thompson PD, et al. Maternal Adiposity and Inflammation: Risk Factors for Iron Deficiency in Pregnancy. Journal of Nutrition, 1–44 p, 2025.
[16] Dall’Asta A, Frusca T, Rizzo G, Ramirez Zegarra R, Lees C, Figueras F, et al. Assessment of the cerebroplacental ratio and uterine arteries in low-risk pregnancies in early labour for the prediction of obstetric and neonatal outcomes. Eur J Obstet Gynecol Reprod Biol, 295(April):18–24, 2024.
[17] Kumar R, Yeni CM, Utami NA, Masand R, Asrani RK, Patel SK, et al. SARS-CoV-2 infection during pregnancy and pregnancy-related conditions: Concerns, challenges, management and mitigation strategies–a narrative review. J Infect Public Health,14(7):863–75, 2021.
[18] Fuentes-Zacarías P, Murrieta-Coxca JM, Gutiérrez-Samudio RN, Schmidt A, Schmidt A, Markert UR, et al. Pregnancy and pandemics: Interaction of viral surface proteins and placenta cells. Vol. 1867, Biochimica et Biophysica Acta - Molecular Basis of Disease,1–44 p, 2021.
[19] Boutin A, Guerby P, Gasse C, Tapp S, Bujold E. Pregnancy outcomes in nulliparous women with positive first-trimester preterm preeclampsia screening test: the Great Obstetrical Syndromes cohort study. Am J Obstet Gynecol, 224(2):204.e1-204.e7, 2021.
[20] Amy L L. Maternal and congenital human cytomegalovirus infection: Laboratory testing for detection and diagnosis. J Clin Microbiol, 62(4):1–20, 2024.
[21] Latifian M, Bagheri Amiri F, Mostafavi E, Esmaeili S. Evidence of Coxiella burnetii infection among pregnant and aborted women: A systematic review and meta-analysis. New Microbes New Infect, 67(October):1–23, 2025.
[22] Zhu M, Zhang X. Effect of IL-18 on intrauterine infection of HBV in mice on cell molecular level. Saudi J Biol Sci, 27(6):1685–90, 2020.
[23] Hcini N, Mchirgui A, Pomar L, Beneteau S, Lambert V, Carles G. Early Prediction of Blood Loss and Postpartum Hemorrhage after Vaginal Delivery by Ultrasound Measurement of Intrauterine Content. Ultrasound Med Biol, 46(11):3145–53, 2020.
[24] De La Fuente Villar BB, Gomes LHF, Portari EA, Ramos CNP, Rocha DN, Pereira JP, et al. Real-time PCR in the diagnosis of congenital toxoplasmosis. Brazilian J Infect Dis, 27(5), 2023.
[25] Zhou YZ, Zhao YH, Chen YL, Luo H, Zhou Y lin, Gu B, et al. Development of a droplet digital PCR method for the detection of Ureaplasma urealyticum. Pract Lab Med, 43, 2025.
[26] Iqbal RA, Nazir S. Potential novel biomarkers for gestational diabetes mellitus in first and early second trimesters: A comprehensive review. Reprod Biol, 25(4):1–7, 2025.
[27] Girón de Velasco-Sada P, Falces-Romero I, Quiles-Melero I, García-Perea A, Mingorance J. Evaluation of two real time PCR assays for the detection of bacterial DNA in amniotic fluid. J Microbiol Methods, 144(January):107–10, 2018.
[28] Elongi Moyene JP, Beya DT, Nyota PK, Masidi JM, Kilembo EL, Natuhoyila AN, et al. Evaluation of the Performance of fullPIERS (Preeclampsia Integrated Estimate of Risk Scoring) in Predicting Maternal-Fetal Complications in Congolese Women with Preeclampsia. J Obstet Gynaecol Canada, 47(7):1–7, 2025.
[29] van Leeuwen LM, Fourie E, van den Brink G, Bekker V, van Houten MA. Diagnostic value of maternal, cord blood and neonatal biomarkers for early-onset sepsis: a systematic review and meta-analysis. Clin Microbiol Infect, 30(7):850–7, 2024.
[30] Guetat C, Roussel L, De Antonio M, Accoceberry M, Houlle C, Petillon F, et al. Does delocalised PCR for Streptococcus B in the labour ward allow adequate administration of antibiotics to prevent early neonatal infection? Brazilian J Infect Dis, 29(4):1–14, 2025.
[31] Liu Y, Ma J, Li X, Zhao H, Ai Q, Zhang L, et al. No microorganism was detected in amniotic fluid of healthy pregnancies from the second trimester to the delivery. Microbiome [Internet], 13(1), 2025. Available from: https://doi.org/10.1186/s40168-024-02024-3
[32] Zhang L, Li M, Sun Q, Yu H. Analysis of factors affecting the prognosis of patients with pancreatic cancer patients with obstructive jaundice. Chinese J Intern Med, 63(5):474–9, 2024.
[33] Katsura D, Tsuji S, Hayashi K, Tokoro S, Hoshiyama T, Kita N, et al. Amniotic fluid interleukin-6 and neutrophil gelatinase-associated lipocalin for predicting fetal inflammatory response syndrome based on histological chorioamnionitis and funisitis. Taiwan J Obstet Gynecol, 62(4):516–20, 2023.
[34] Mappa I, D’Antonio F, Khalil A, De Vito M, Alameddine S, Capannolo G, et al. Prognostic Value of Amniotic Fluid Viral Load to Predict Adverse Outcome in Pregnancies Complicated by Congenital Cytomegalovirus Infection: A Multicenter Study. Fetal Diagn Ther, 50(1):1–7, 2023.
[35] Abedian R, Esboei BR, Kordi S, Roshan HS, Hezarjaribi HZ, Rahmani Z, et al. Efficacy of amniotic fluid, blood and urine samples for the diagnosis of toxoplasmosis in pregnant women candidates for amniocentesis using serological and molecular techniques. BMC Pregnancy Childbirth, 24(1), 2024.
[36] Pizula J, Torosyan N, Solimon S, Thangathurai J, Mehra A, Chatfield A, et al. Outcome of Pregnancy in Women With Congenitally Corrected Transposition of the Great Arteries: A Systematic Review. Am J Cardiol, 250(September):9–16, 2025.
[37] Chin TH, Hsu YC, Soong YK, Lee CL, Wang HS, Huang HY, et al. Obstetric and perinatal outcomes of pregnancy in patients with repeated implantation failure. Taiwan J Obstet Gynecol, 58(4):487–91, 2019.
[38] Naha R, Anees A, Chakrabarty S, Naik PS, Pandove M, Pandey D, et al. Placental mitochondrial DNA mutations and copy numbers in intrauterine growth restricted (IUGR) pregnancy. Mitochondrion, 55(November):85–94, 2020.
[39] Zaidi H, Lahlou L, Chraybi M, Barkat A, Elamrani S, Lamalmi N. Correlation between placental bacterial PCR results and histological chorioamnionitis: a prospective study on 41 placentas. J Biol Res, 97(1), 2024.
[40] Sánchez-Luquez K, Schadock IC, Gonçalves CV, Tornatore M, Finger-Jardim F, Avila EC, et al. Impact of TLR7 and TLR9 polymorphisms on susceptibility to placental infections and pregnancy complications. J Reprod Immunol, 146(August):1–7, 2021.
[41] Côté ML, Giguère Y, Forest JC, Audibert F, Johnson JA, Okun N, et al. First-Trimester PlGF and PAPP-A and the Risk of Placenta-Mediated Complications: PREDICTION Prospective Study. J Obstet Gynaecol Canada, 47(2):1–17, 2024.
[42] Abgral M, Albersammer L, Carrara J, Guillet-Caruba C, Benachi A, De Luca D, et al. Impact of combined vaginal group B Streptococcus screening (culture and rapid PCR) in pregnant women on neonatal morbidity and mortality. J Infect Public Health, 18(10):1–17, 2025.
[43] Uddipto K, Quinlivan JA, Mendz GL. The Existence of an Intra-Amniotic Microbiome: Assessing a Controversy. Biology (Basel), 13(11):1–28, 2024.
[44] Oepkes D, van Scheltema PA. Intrauterine fetal transfusions in the management of fetal anemia and fetal thrombocytopenia. Semin Fetal Neonatal Med,12(6):432–8, 2007.
[45] Wang F, Yi L, Ming F, Dong R, Wang F, Chen R, et al. Evaluation of the Xpert Xpress GBS test for rapid detection of group B Streptococcus in pregnant women . Microbiol Spectr, 12(1):1–24, 2024.
[46] Dellu MFD, Mexitalia M, Rosidi A. Maternal perception of sickness as a risk factor of stunting in children aged 2-5 years. UNIVERSA Med, 35(3):156–64, 2016.
[47] Suff N, Karda R, Diaz JA, Ng J, Baruteau J, Perocheau D, et al. Ascending Vaginal Infection Using Bioluminescent Bacteria Evokes Intrauterine Inflammation, Preterm Birth, and Neonatal Brain Injury in Pregnant Mice. Am J Pathol, 188(10):2164–76, 2018.
[48] Liu T, Gu J, Wan L, Hu Q, Teng J, Liu H, et al. Anti-β2GPI domain 1 antibodies stratify high risk of thrombosis and late pregnancy morbidity in a large cohort of Chinese patients with antiphospholipid syndrome. Thromb Res, 185(January):142–9, 2020.
[49] Zaidi H, Lahlou L, Chraybi M, Barkat A, Elamrani S, Lamalmi N. Correlation between placental bacterial PCR results and histological chorioamnionitis: a prospective study on 41 placentas. J Biol Res, 97(1):1–6, 2024.
[50] Soucek O, Kacerovsky M, Musilova I, Kukla R, Bolehovska R, Bostik P, et al. Amniotic and cervical fluids progranulin levels in pregnancies complicated by spontaneous preterm delivery with respect to intra-amniotic complications—a retrospective cohort study. Sci Rep, 15(1):1–9, 2025.
[51] Hernandez P V., Chen L, Zhang R, Jackups R, Nelson DM, He M. The effects of preconception and early gestation SARS-CoV-2 infection on pregnancy outcomes and placental pathology. Ann Diagn Pathol [Internet], 62:152076, 2023. Available from: https://doi.org/10.1016/j.anndiagpath.2022.152076
[52] Al Baloushi M, Ahmed B, Konje JC. Infections as a Cause of Preterm Birth: Amniotic Fluid Sludge—An Ultrasound Marker for Intra-Amniotic Infections and a Risk Factor for Preterm Birth. Diagnostics,15(16):1–17, 2025.
[53] Dunn JKE, Chakraborty P, Reuvers E, Gallagher L, Kernohan KD, Lacaria M, et al. Outcomes of a Population-Based Congenital Cytomegalovirus Screening Program. JAMA Pediatr, 179(3):332–9, 2025.
[54] Huang Q, Xu Q, Chen M, Fan W, Huang H. Application of non-invasive prenatal testing for fetal chromosomal disorders in low-risk pregnancies: a follow-up study in central China. Front Genet,16:1–14, 2025.
[55] Sorrenti S, Elbarbary N, D’Antonio F, Mascio D Di, Khalil A. Diagnosis and management of congenital Cytomegalovirus: Critical Appraisal of Clinical Practice Guidelines. Eur J Obstet Gynecol Reprod Biol, 306:172–80, 2025.
[56] Wang G, Chen W, Chen X, Hou H, Zhang J, Han Z. Detection of Ureaplasma parvum in amniotic fluids via reanalysis of prenatal copy number variation sequencing data: an exploratory study. Front Cell Infect Microbiol, 15(August):1–12, 2025.
[57] Rudkjøbing VB, Thomsen TR, Xu Y, Melton-Kreft R, Ahmed A, Eickhardt S, et al. Comparing culture and molecular methods for the identification of microorganisms involved in necrotizing soft tissue infections. BMC Infect Dis [Internet],16(1):1–13, 2016. Available from: http://dx.doi.org/10.1186/s12879-016-1976-2
[58] Markensan G, Martin R, Foley K, Yancey M. The use of the polymerase chain reaction to detect bacteria in amniotic fluid in pregnancies complicated bypreterm labor. Acta Diabetol Lat,176(1 PART II):1–6, 1997.
[59] Oh KJ, Kim SM, Hong JS, Maymon E, Erez O, Panaitescu B, et al. Twenty-four percent of patients with clinical chorioamnionitis in preterm gestations have no evidence of either culture-proven intraamniotic infection or intraamniotic inflammation. Am J Obstet Gynecol, 216(6):604.e1-604.e11, 2017.
[60] Romero R, Miranda J, Chaemsaithong P, Chaiworapongsa T, Kusanovic JP, Dong Z, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Neonatal Med, 28(12):1394–409, 2015.
[61] DiGiulio DB, Romero R, Kusanovic JP, Gómez R, Kim CJ, Seok KS, et al. Prevalence and Diversity of Microbes in the Amniotic Fluid, the Fetal Inflammatory Response, and Pregnancy Outcome in Women with Preterm Pre-Labor Rupture of Membranes. Am J Reprod Immunol, 64(1):38–57, 2010.
[62] Cobo T, Palacio M, Navarro-Sastre A, Ribes A, Bosch J, Filella X, et al. Predictive value of combined amniotic fluid proteomic biomarkers and interleukin-6 in preterm labor with intact membranes. Am J Obstet Gynecol, 200(5):499, 2009.e1-499.e6.
[63] Areia AL, Areia M, Mota-Pinto A. Procalcitonin in preterm rupture of membranes: a systematic review and meta-analysis. Arch Gynecol Obstet, 303(4):917–24, 2021.
[64] Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. Rev Panam Salud Publica/Pan Am J Public Heal, 46:1–10, 2022.
[65] Shamseer L, Moher D CM. Preferred reporting items for systematic review and metaanalysis protocols (PRISMA-P) 2015: Elaboration and explanation. BMJ, 349(g7647), 2015.
[66] Whiting PF, Rutjes AWS, Westwood ME, Mallett S, Deeks JJ, Reitsma JB, et al. Quadas-2: A revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med, 155(8):529–36, 2011.
[67] Farooqui R, Siddiqui QUA. Diagnostic accuracy of procalcitonin in maternal plasma to detect early intra-amniotic infection in preterm premature rupture of the membranes with respect of highvaginal swab as gold standard. Pakistan J Med Sci, 38(1):310–4, 2022.
[68] Tork M, Sadeghi M, Asgarian-Omran H, Basirpour B, Ahmadi S, Ghasemzadeh F, et al. Assessment of simultaneous IgM, IgG avidity, and IgA testing in diagnosis of acute toxoplasmosis in pregnant women: a systematic review and meta-analysis study. BMC Pregnancy Childbirth, 25(1), 2025.
[69] Parsaei M, Dashtkoohi M, Salmani TA, Najafi MS, Haddadi M, Ghaemi M, et al. Potential ]efficacy of digital polymerase chain reaction for non-invasive prenatal screening of autosomal aneuploidies: a systematic review and meta-analysis. BMC Pregnancy Childbirth [Internet], 24(1):1–12, 2024. Available from: https://doi.org/10.1186/s12884-024-06655-0
[70] Oh KJ, Lee J, Romero R, Park HS, Hong J, Yoon BH. A new rapid bedside test to diagnose and monitor intra-amniotic inflammation in preterm PROM using transcervically collected fluid, 223(3):1–30, 2022.
[71] Cobo T, Ferrero S, Haavisto A, Luokola P, Sanchez-garcia AB, Bosch J, et al. A multivariable prediction model for intra- amniotic infection in patients with preterm labor and intact membranes including a point of care system that measures amniotic fl uid MMP-8. J Perinat Med [Internet], 52(2):136–42, 2024. Available from: https://doi.org/10.1515/jpm-2023-0405
[72] Simsek HU, Kasap M, Tamer GS, Caliskan S, Corakci A, Caliskan E. Using 16S rRNA-Specific PCR On Preoperative Amniotic Fluid Samples to Predict Success Of Emergency Cerclage Placement. Eskisehir Med J, 6(1):28–35, 2025.
[73] Tanimura K, Tairaku S, Ebina Y, Morioka I, Nagamata S, Deguchi K, et al. Prediction of Congenital Cytomegalovirus Infection in High-Risk Pregnant Women, 64:159–65, 2017.
[74] Park H, Park KH, Kim YM, Kook SY, Jeon SJ, Yoo H. Plasma inflammatory and immune proteins as predictors of intra-amniotic infection and spontaneous preterm delivery in women with preterm labor : a retrospective study,1–9, 2018.
[75] Zhong L, Yan Y, Chen L, Sun N, Li H, Wang Y, et al. Nanopore-based metagenomics analysis reveals microbial presence in amniotic fluid : A prospective study. Heliyon [Internet], 10(6):e28163, 2024. Available from: https://doi.org/10.1016/j.heliyon.2024.e28163
[76] Digiulio DB, Romero R, Amogan HP, Kusanovic JP, Elisabeth M, Gotsch F, et al. Microbial Prevalence , Diversity and Abundance in Amniotic Fluid During Preterm Labor : A Molecular and Culture-Based Investigation, 3(8):1–10, 2008.
[77] Vajrychova M, Stranik J, Kupcik R, Sadibolova M, Kukla R, Bolehovska R, et al. Quantification of intra-amniotic inflammation in late preterm prelabour rupture of membranes, 1–11, 2025.
[78] Chaemsaithong P, Romero R, Docheva N, Chaiyasit N, Bhatti G, Pacora P, et al. Comparison of rapid MMP-8 and interleukin-6 point -of - care tests to identify intra-amniotic inflammation/infection and impending preterm delivery in patients with preterm labor and intact membranes. HHS Public Access, 31(2):228–44, 2019.
[79] You Y, Son DG, Kwon DEJ, Park MH, Lee K, Kim YJ. New insight into the analysis of amniotic fluid microflora using 16S rRNA gene sequencing. JMM Case Reports,1–4, 2016.
[80] Andresen IJ, Zucknick M, Degnes ML, Angst MS, Aghaeepour N, Romero R, et al. Prediction of late-onset preeclampsia using plasma proteomics : a longitudinal multi- cohort study. Sci Rep,14:1–19, 2024.
[81] Lappin MR. Microbiology and Infectious Disease. In: Small Animal Clinical Diagnosis by Laboratory Methods, p. 315–36, 2020.
[82] Badar J, Rehman Y. Advancements in Methods Used to Detect and Culture Medically Important Anaerobic Bacteria. Biosci Rev, 3(2):43–53, 2021.
[83] Morimoto S, Usui H, Kobayashi T, Katou E, Goto S, Tanaka H, et al. Bacterial-Culture-Negative Subclinical Intra-Amniotic Infection Can Be Detected by Bacterial 16S Ribosomal-DNA – Amplifying Polymerase Chain Reaction. Jpn J Infect Dis, 71:274–80, 2018.
[84] Abayasekara LM, Perera J, Chandrasekharan V, Gnanam VS, Udunuwara NA, Liyanage DS, et al. Detection of bacterial pathogens from clinical specimens using conventional microbial culture and 16S metagenomics : a comparative study. BMC Infect Dis, 1–11, 2017.
[85] Samuel L. Direct-from-Blood Detection of Pathogens : a Review of. J Clin Microbiol, 61(7):1–15, 2023.
[86] Schoonbroodt S, Ichanté J, Boffé S, Devos N, Devaster J, Taddei L, et al. Real-time PCR has advantages over culture-based methods in identifying major airway bacterial pathogens in chronic obstructive pulmonary disease : Results from three clinical studies in Europe and North America, (February):1–13, 2023.
[87] Spangler FL, Williams C, Aberger ME, Wilson BA, Ajib K, Gholami SS, et al. Diagnostic Microbiology & Infectious Disease Clinical utility of PCR compared to conventional culture and sensitivity testing for management of complicated urinary tract infections in adults : Part II . Evaluation of diagnostic concordance , discordant results , and antimicrobial selection efficacy. Diagnostic Microbiol Infect Dis [Internet], 111(3):116646, 2025. Available from: https://doi.org/10.1016/j.diagmicrobio.2024.116646
[88] Parwati I, Chaidir L, Yunus M. Evaluation of a real-time PCR assay performance to detect Mycobacterium tuberculosis , rifampicin , and isoniazid resistance in sputum specimens : a multicenter study in two major cities of Indonesia, (May):1–8, 2024.
[89] Scaturro M, Girolamo A, Bella A, Rota MC, Marella AM, Amari R, et al. Interlaboratory comparison of culture-and PCR-based methods for Legionella pneumophila detection in drinking water samples. Appl Enviromental Microbiol, 91(6):1–15, 2025.
[90] Valledor S, Valledor I, Concepción M, Seral C, Castillo J. Comparison of several Real- Time PCR Kits versus a Culture- dependent Algorithm to Identify Enteropathogens in Stool Samples. Nat Res Sci Reports, 10(4301):1–8, 2020.
[91] Khodaparast M, Sharley D, Marshall S, Beddoe T. Advances in point-of-care and molecular techniques to detect waterborne pathogens. npj Clean Water [Internet]. 2024; Available from: http://dx.doi.org/10.1038/s41545-024-00368-9
[92] Chen M, Lan X, Zhu L, Ru P, Xu W, Liu H. PCR Mediated Nucleic Acid Molecular Recognition Technology for Detection of Viable and Dead Foodborne Pathogens. Foods, 11(2675):1–9, 2022.
[93] Shehata HR, Hassane B, Newsmaster SG. Real-time polymerase chain reaction methods for strain specific identification and enumeration of strain Lacticaseibacillus paracasei. Front Microbiol, (January):1–13, 2023.
[94] Bogaerts P, Castro RR De, Mendonça R De, Huang T, Denis O, Glupczynski Y. Validation of carbapenemase and extended- spectrum β -lactamase multiplex endpoint PCR assays according to ISO 15189, 3–4, 2025.
[95] Beer RR, Wielders J, Boursier G, Vodnik T, Vanstapel F, Huisman W, et al. Validation and verification of examination procedures in medical laboratories : opinion of the EFLM Working Group Accreditation and ISO / CEN standards ( WG-A / ISO ) on dealing with ISO 15189 : 2012 demands for method verification and validation, 31714885, 2020.
[96] Verweij JJ. Validation and maintaining laboratory developed molecular tests compliant with ISO15189 for diagnosis of intestinal parasitic infections. Expert Rev Mol Diagn, 22(6):595–601, 2022.
[97] Harle A, Dubois C, Rouyer M, Merlin J-L. [ Method validation according to ISO 15189 and SH GTA 04 : application for the detection of KRAS mutations using PCR TaqMan assay ]. Ann Biol Clin, 71(5):603–7, 2013.
[98] Romero R, Sci DM, Miranda J, Chaiworapongsa T, Korzeniewski SJ, Chaemsaithong P, et al. Prevalence and Clinical Significance of Sterile Intra-amniotic Inflammation in Patients with Preterm Labor and Intact Membranes. Am J Reprod Immunol, 72(5):458–74, 2014.
[99] Stinson LF, Berman Y, Li S, Keelan JA, Dickinson JE, Doherty DA, et al. Characterisation of Mid-Gestation Amniotic Fluid Cytokine and Bacterial DNA Profiles in Relation to Pregnancy Outcome in a Small Australian Cohort. Microorganisms, 11:2–12, 2023.
[100] Kacerovsky M, Stranik J, Kukla R, Bolehovska R, Bostik P, Matulova J, et al. Intra-amniotic infection and sterile intra-amniotic inflammation in women with preterm labor with intact membranes are associated with a higher rate of Ureaplasma species DNA presence in the cervical fluid. J Matern Fetal Neonatal Med, 35(25):7344–52, 2022.
[101] Kreitmann L, Miglietta L, Xu K, Malpartida-cardenas K, Souza GD, Kaforou M, et al. Next-generation molecular diagnostics : Leveraging digital technologies to enhance multiplexing in real-time PCR. Trends Anal Chem, 160(March):1–25, 2023.
[102] Wu L, Qi K, Yang W, Xi G, Ma J, Tu J. Advances of nanopore sensors toward virus detection and diagnostic application. R Soc Chem, 1–34, 2025.
[103] King J, Harder T, Beer M, Pohlmann A. Rapid multiplex MinION nanopore sequencing workflow for Influenza A viruses, 1–8, 2020.
[104] Gu W, Deng X, Lee M, Sucu Y, Arevalo S, Federman S, et al. Rapid Pathogen Detection by Metagenomic Next-Generation Sequencing of Infected Body Fluids. Nat Med, 27(1):115–24., 2021
[105] Fu Y, Chen Q, Xiong M, Zhao J, Shen S, Chen L, et al. Clinical Performance of Nanopore Targeted Sequencing for. Microbiol Spectr, 10(2):1–13, 2022.
[106] Basavaraj A, Crystal B, Sverre C, Jawad B, Robert A, Johansen TEB, et al. Culture and amplification ‑ free nanopore sequencing for rapid detection of pathogens and antimicrobial resistance genes from urine. Eur J Clin Microbiol Infect Dis [Internet], 43(11):2177–90, 2024. Available from: https://doi.org/10.1007/s10096-024-04929-1
[107] Yoneda N, Yoneda S, Niimi H, Ueno T, Hayashi S, Ito M, et al. Polymicrobial Amniotic Fluid Infection with Mycoplasma / Ureaplasma and Other Bacteria Induces Severe Intra-Amniotic Inflammation Associated with Poor Perinatal Prognosis in Preterm Labor. Am J Reprod Immunol, 75(2):112–25, 2016.
[108] Id GK, Doloy A, Schmitz T, Chitrit Y, Bouhanna P, Carbonne B, et al. Antibiotics for amniotic-fluid colonization by Ureaplasma and / or Mycoplasma spp . to prevent preterm birth : A randomized trial. PLoS One, 7:1–13, 2018.
[109] Id MK, Pliskova L, Bolehovska R, Lesko D, Gerychova R, Janku P, et al. Cervical Gardnerella vaginalis in women with preterm prelabor rupture of membranes. PLoS One [Internet], 22:1–19, 2021. Available from: http://dx.doi.org/10.1371/journal.pone.0245937
[110] Witt RG, Blair L, Frascoli M, Rosen MJ, Nguyen QH, Bercovici S, et al. Detection of microbial cell-free DNA in maternal and umbilical cord p ... Detection of microbial cell-free DNA in maternal and umbilical cord p ... PLoS One, 15:1–10, 2020.
[111] Tong X, Yu X, Du Y, Su F, Liu Y, Li H, et al. Peripheral Blood Microbiome Analysis via Noninvasive Prenatal Testing Reveals the Complexity of Circulating Microbial Cell-Free DNA. Microbiol Spectr,10(3):1–13, 2022.
[112] Aversa ED, Breveglieri G, Boutou E, Balassopoulou A, Voskaridou E, Pellegatti P, et al. Droplet Digital PCR for Non-Invasive Prenatal Detection of Fetal Single-Gene Point Mutations in Maternal Plasma. Int J Mol Sci, 23(2819):1–15, 2022.
[113] Lynn MK, Stanley M, Aquino R, Michelle P, Rivas C, Miranda X, et al. Employing digital PCR for enhanced detection of perinatal Toxoplasma gondii infection : A cross-sectional surveillance and maternal- infant outcomes study in El Salvador. PLoS Negl Trop Dis [Internet], 1–14, 2024. Available from: http://dx.doi.org/10.1371/journal.pntd.0012153
[114] Chaemsaithong P, Romero R, Pongchaikul P, Vivithanaporn P, Lertrut W, Jaovisidha A, et al. Rapid diagnosis of intra-amniotic infection using nanopore-based sequencing. J Perinat Med [Internet], 51(6):769–74, 2023. Available from: https://doi.org/10.1515/jpm-2022-0504
[115] Liu Y, Li X, Zhu B, Ms HZ, Ms QA, Ms YT, et al. Midtrimester amniotic fluid from healthy pregnancies has no microorganisms using multiple methods of microbiologic inquiry. Am J Obstet Gynecol [Internet], 223(2):248.e1-248.e21, 2020. Available from: https://doi.org/10.1016/j.ajog.2020.01.056
[116] Lim ES, Rodriguez C, Holtz LR. Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community. Microbiome, 6(87):1–8, 2018.
[117] Guo Y, Charoenkwan P, Traisrisilp K, Piyamongkol W. Application of Digital Polymerase Chain Reaction ( dPCR ) in Non-Invasive Prenatal Testing ( NIPT ). Biomolecules, 15(360):1–33, 2025.
[118] Adil M, Kolarova TR, Doebley A, Chen LA, Tobey CL, Galipeau P, et al. Preeclampsia risk prediction from prenatal cell-free DNA screening. Nat Med [Internet], 31(April), 2025. Available from: http://dx.doi.org/10.1038/s41591-025-03509-w
[119] Helali N El, Habibi F, Azria E, Giovangrandi Y, Autret F, Durand-zaleski I, et al. Point-of-Care Intrapartum Group B Streptococcus Molecular Screening : Effectiveness and Costs. Obs Gynecol, 133(2):276–81, 2019.
[120] Helmig RB, Gertsen JB. Intrapartum PCR-assay for detection of Group B Streptococci ( GBS ). Eur J Obstet Gynecol Reprod Biol X [Internet], 4:1–4, 2019. Available from: https://doi.org/10.1016/j.eurox.2019.100081
[121] Kopanitsa G, Metsker O, Kovalchuk S. Machine Learning Methods for Pregnancy and Childbirth Risk Management. J Pers Med, 13(975):1–12, 2023.
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