The Independent Association of a Short Cervix, Positive Fetal Fibronectin, Amniotic Fluid Sludge, and Cervical Funneling with Spontaneous Preterm Birth in Twin Pregnancies

Abstract

Objective To estimate the independent association of a short cervical length (CL), positive fetal fibronectin (fFN), amniotic fluid (AF) sludge, and cervical funneling with spontaneous preterm birth in twin pregnancies. Methods Retrospective cohort study of twin pregnancies managed by a single maternal-fetal medicine practice from June 2005 to February 2014. All patients underwent transvaginal sonographic CL and fFN testing. We reviewed all images from the first CL at 22(0/7) to 25(6/7) weeks for the presence of (1) a short CL, which is defined as ≤25 mm, (2) AF sludge, and (3) cervical funneling, and also recorded (4) the fFN result from that time. Image reviewers were blinded to pregnancy outcomes. Patients with cerclage were excluded. Using logistic regression, we calculated the independent association between these four biomarkers and spontaneous preterm birth. Results A total of 635 patients with twin pregnancies were included. The markers independently associated with spontaneous preterm birth <35 weeks were short CL (adjusted odds ratio [aOR]: 10.73; 95% confidence interval [CI]: 3.21-35.81), positive fFN (aOR: 3.25; 95% CI: 1.13-9.33), and AF sludge (aOR: 2.11; 95% CI: 1.04-4.27). Similarly, these three markers were independently associated with earlier gestational ages at delivery. Cervical funneling was not independently associated with spontaneous preterm birth <35 weeks nor gestational age at delivery. The risk of spontaneous preterm birth increased significantly with the number of positive biomarkers (short CL, positive fFN, and AF sludge). Conclusion In twin pregnancies, a short CL, positive fFN, and AF sludge are independently associated with spontaneous preterm birth. Cervical funneling is not independently associated with spontaneous preterm birth in twins.

Amniotic immune biomarkers as risk factors in women with different symptoms of threatened late miscarriage

“…Our limited model found TNFα to be associated with pregnancy loss, but a larger study is needed to verify if IL8 is an independent risk factor for these patients. We also failed to find a significant effect of “sludge” on late miscarriage in this group, although other researchers have identified it as an independent risk factor 13,14 for preterm birth and one study reported a much higher prevalence of “sludge” in women who delivered preterm 30 . Considering we had only 6 patients with “sludge” in the contractions group, larger prospective studies are needed.…”

“…To our knowledge, there are no studies examining the joint effect of all common cytokines for their independent contribution to risk. The presence of sludge in amniotic fluid has also been shown to be associated with the risk of preterm delivery, 13,14 but these studies did not adjust for the potential contribution of amniotic cytokines.…”

The Association between Fetal Fibronectin, Cervical Length, and Amniotic Fluid Sludge with Histological Indicators of Placental Inflammation in Twin Gestations

“…We have previously published the association of these screening tests with preterm delivery in twins. 3 Over the course of the study period, all twin placentas were routinely sent for pathologic evaluation after delivery to be reviewed by board certified pathologists who were unaware of the patients' test results. Acute inflammatory lesions were characterized by the presence of neutrophils, while chronic inflammatory lesions are usually characterized by the presence of chronic inflammatory infiltrates such as plasma cells, histiocytes, and lymphocytes.…”

“…predict preterm birth, various tests, specifically fetal fibronectin (FFN), transvaginal cervical length (CL), and amniotic fluid (AF) sludge, have been useful in modern obstetrics to estimate the risk of preterm delivery in singletons, and recently, we noted the independent association of these three screening tests with preterm birth in twins. 3 The American College of Obstetricians and Gynecologists offers no formal guidelines recommending placental examination based on specific clinical conditions except for stillbirth. 4 Yet, histologic evaluation of the placenta has been recommended in all twin gestations.…”

The prediction of preterm delivery: What is new?

“…Spiegelman et al assessed the independent association of cervical length, fetal fibronectin amniotic fluid sludge, and cervical funnelling with spontaneous preterm birth in twin pregnancies [66]. They retrospectively assessed ultrasound images from 22 to 26 weeks gestation for the presence of a short cervix (defined as < 25 mm), cervical funnelling, and fibronectin from 635 twin pregnancies, finding the presence of sludge, a positive fetal fibronectin, and short cervix correlated with birth < 35 weeks gestation.…”