Предвидување на предвремено породување кај асимптоматски пациентки врз основа на инфламаторни медијатори во амнионска течност

Abstract

Summary: Premature delivery defined as < 37 g.w is a serious obstetric problem that affects 11% of pregnancies worldwide. It is associated with significant neonatal morbidity and mortality. Available risk assessment tests for preterm delivery are incredibly important given the enormous personal, economic and health consequences of preterm delivery. The identification of a specific immune mediator and their concentration in the amniotic fluid in the second trimester in asymptomatic patients has attracted much attention as a potential source for the diagnosis and therapy of this problem. Cytokines (IL-1β, IL-6, IL-8, TNF-α) are extremely important in pregnancy and they are produced in the amniotic fluid and are increased if intrauterine inflammation is present. Objective: The study is to demonstrate the ability of inflammatory mediators IL-1β, IL-6, IL-8, TNF-α in amniotic fluid at the onset of early second trimester (16-22 g.w) to predict preterm delivery (<37 g.w.). Material and methods: In this prospective, observational longitudinal study, 150 singleton - pregnancy patients who required medically indicated genetic amniocentesis in the early second trimester (16-22 g.w) were included. This study was performed at the Clinic of Gynecology and Obstetrics, Clinic of Immunology and Human Genetics and Institute of Microbiology with Parasitology, Skopje, Republic of Northern Macedonia. An ultrasound examination was performed at the time of entering the study and signing consent to participate in the study. Amniocentesis was then performed with 5 ml of amniotic fluid, which then determined the concentrations of IL-1β, IL-6, IL-8, TNF-α, leukocyte count, glucose concentration, Gram staining and amnioculture. Transvaginal cervicometry was measured in all patients and microbiological specimens were collected for cervical and vaginal smears. All patients were followed until the date of their delivery, where the gestation week was accurately noted. Results: All 150 patients were in the 16-22 g.w. 20 out of 150 patients had preterm births, while 128 patients gave birth at term. Two patients terminated their pregnancy because of a positive test for genetic amniocentesis. Findings of amniotic fluid leukocytes were present in 57.9% (11) of patients before 37 g.w., and 31.25% (128) of patients after 37g.w. Significantly different glucose values were measured in amniotic fluid depending on the gestational week of delivery (p = 0.038). In premature infants, these values were significantly lower. TNF- α values showed sensitivity of 65% and specificity of 70.5%. IL-6 concentrations in amniotic fluid were significantly different in preterm and term neonates (p <0.0001). Increased concentrations of IL-6 in amniotic fluid increase the risk of preterm birth by approximately 3-fold. Prediction analysis of preterm delivery using the IL-6 marker showed that the area under the ROC curve was 0.789 (95% CI 0.672 - 0.906), with a sensitivity of 75% (15/20), specificity of 82.8% (106 / 128), positive predictive value 40.5% (15/37), and negative predictive value 95% (106/111). IL-8 in amniotic fluid that showed higher values increased the risk of preterm delivery by approximately 3-fold (RR = 3.241, 95% CI 1.121-9.375). Il-8 marker showed sensitivity of 85% (17/20), specificity 82.8% (106/128), positive predictive value 43.6% (17/39), and negative predictive value 97.2% (106/109). All patients, both preterm and term, had normal IL-1β values in amniotic fluid. Conclusion: Premature birth depends on many causes. Inflammatory mediator levels in amniotic fluid taken in medically indicated genetic amniocentesis in the second trimester in asymptomatic patients may serve as a good predictor of preterm birth.