Use of Cervical Elastography at 18 to 22 Weeks Gestation in the Prediction of Spontaneous Preterm Birth
OBJECTIVES/OBJECTIVE:To develop standard cervical elastography nomograms for singleton pregnancies at 18-22 weeks gestation using the E-cervix ultrasound application; assess intra-observer reliability of the E-cervix elastography parameters; and determine if these cervical elastography measurements can be used in the prediction of spontaneous preterm birth. METHODS:This was a prospective cohort study of pregnant women undergoing cervical length screening assessment via transvaginal ultrasound examination at 18 - 22 weeks gestation. A semi-automatic, cervical elastography application (E-cervix) was utilized during the transvaginal examination to calculate five quantitative parameters (Internal Os Stiffness, External Os Stiffness, Internal to External Os Stiffness Ratio, Hardness Ratio, Elasticity Contrast Index) and create a standard nomogram for each one of them. The intra-observer reliability was calculated using Shrout-Fliess reliability. Cervical elastography parameters were compared between those who delivered preterm (<37 weeks) spontaneously versus full term. A multivariable logistic regression model was performed to determine the ability of the cervical elastography parameters to predict spontaneous preterm birth. RESULTS:742 women were included of which 49 (6.6%) had a spontaneous preterm delivery. A standard nomogram was created for each of the cervical elastography parameters from those who had a full term birth in the index pregnancy (n=693). Intra-observer reliability was good or excellent (intraclass correlation (ICC) = 0.757 - 0.887) for each of the cervical elastography parameters except External Os Stiffness which was poor (ICC = 0.441). In univariate analysis, none of the cervical elastography parameters were associated with a statistically significant increased risk of spontaneous preterm birth. In a multivariable model adjusting for history of preterm birth, gravidity, ethnicity, cervical cerclage and vaginal progesterone use, increasing Elasticity Contrast Index was significantly associated with an increased risk of spontaneous preterm birth (OR 1.15, 95%CI [1.02, 1.30]; P=0.02). CONCLUSIONS:Cervical elastography parameters are reliably measured and are stable across 18-22 weeks gestation. Based on our findings, the Elasticity Contrast Index was associated with an increased risk for spontaneous preterm birth and may be the parameter useful for future research.
Progesterone effects on vaginal cytokines in women with a history of preterm birth
OBJECTIVE:To determine the effect of intramuscular progesterone on the vaginal immune response of pregnant women with a history of prior preterm birth. METHODS:A prospective, cohort study of women at 11-16 weeks gestation, â‰¥18 years of age, and carrying a singleton pregnancy was conducted from June 2016 to August 2017 after IRB approval. Women in the progesterone arm had a history of preterm birth and received weekly intramuscular 17-hydroxyprogesterone caproate. Controls comprised of women with healthy, uncomplicated pregnancies. Excluded were women with vaginitis, diabetes mellitus, hypertension, or other chronic diseases affecting the immune response. A vaginal wash was performed at enrollment, at 26-28 weeks, and at 35-36 weeks gestation. Samples underwent semi-quantitative detection of human inflammatory markers. Immunofluorescence pixel density data was analyzed and a P value <0.05 was considered significant. RESULTS:There were 39 women included, 10 with a prior preterm birth and 29 controls. The baseline demographics and pregnancy outcomes for both groups were similar in age, parity, race, BMI, gestational age at delivery, mode of delivery, and birth weight. Enrollment cytokines in women with a prior preterm birth, including IL-1 alpha (39.2Â±25.1% versus 26.1Â±13.2%; P = 0.04), IL-1 beta (47.9Â±26.4% versus 24.9Â±17%; P<0.01), IL-2 (16.7Â±9.3% versus 11.3Â±6.3%; P = 0.03), and IL-13 (16.9Â±12.4% versus 8.2Â±7.4%; P = 0.01) were significantly elevated compared to controls. In the third trimester the cytokine densities for IL-1 alpha (26.0Â±18.2% versus 22.3Â±12.0%; P = 0.49), IL-1 beta (31.8Â±15.9% versus 33.1Â±16.8%; P = 0.84), IL-2 (10.0Â±8.4% versus 10.9Â±5.9%; P = 0.71), and IL-13 (9.1Â±5.9% versus 10.0Â±6.5%; P = 0.71) were all statistically similar between the progesterone arm and controls, respectively. CONCLUSION/CONCLUSIONS:There is an increased cytokine presence in vaginal washings of women at risk for preterm birth which appears to be modified following the administration of 17- hydroxyprogesterone caproate to levels similar to healthy controls.