title: Do serial measurements of cervical length improve the prediction of preterm birth in asymptomatic women with twin gestations?
abstract: BACKGROUND
  Cervical length at midtrimester is a powerful predictor of preterm birth in twin gestations. However, given the fact that, in some cases, cervical shortening may become evident only later during the second trimester, it seems reasonable that serial monitoring of cervical length may improve the detection of preterm birth in women with twins. However, data in support of such a practice are limited and conflicting. The contradictory results may be related to the fact that in most of these studies, the analysis of the predictive value of serial measurements of cervical length was limited to data derived from only two sequential measurements of cervical length, while data on the predictive value of multiple (>2) measurements are scarce.
  
  
  OBJECTIVE
  We sought to determine whether serial measurements of cervical length can improve the prediction of preterm birth in asymptomatic women with twin gestations compared with a single measurement of cervical length at midgestation.
  
  
  METHODS
  This was a retrospective cohort study of women with twin pregnancies followed up in a tertiary medical center from 2012 through 2014. All participants underwent routine measurement of cervical length at midgestation and every 2-3 weeks thereafter until 28-32 weeks. For each patient, cervical length was determined at the following time periods: 18+0 to 21+6 weeks (period 1, routine exam), 22+0 to 24+6 weeks (period 2), 25+0 to 27+6 weeks (period 3), and 28+0 to 32+0 weeks (period 4). Measurements of cervical length at periods 2-4 were analyzed in the form of either absolute length (in millimeters) or percent shortening relative to cervical length at period 1. The performance of a stepwise algorithm that incorporated serial measurements of cervical length for the prediction of preterm birth was compared to that achieved with a single measurement of cervical length at period 1.
  
  
  RESULTS
  Overall, 441 women with twin pregnancies who were eligible for the study underwent a total of 2374 cervical length measurements. The association of a short cervix (<10th percentile) with preterm birth at <32 weeks persisted in each of the 4 periods of gestation [odds ratio (95% confidence interval): 7.2 (3.1-16.5), 15.3 (6.4-36.7), 10.3 (4.4-24.3), and 23.1(8.3-64.1), respectively]. Compared with a single measurement of cervical length at midgestation (period 1), a stepwise algorithm integrating serial cervical length measurements from all 4 successive gestational age periods resulted in a significant increase in the area under the receiver operating characteristic curve (0.917 vs 0.613, P < .001). Similarly, when a target false-positive rate of 5% was used, the same stepwise algorithm was associated with a higher detection rate (69% vs 28%, P < .001), higher positive likelihood ratio (14.54 vs 5.12), and lower negative likelihood ratio (0.32 vs 0.76) for preterm birth at <32 weeks compared with a single measurement of cervical length at period 1.
  
  
  CONCLUSIONS
  Integration of serial measurements of cervical length using a stepwise algorithm in asymptomatic women with twin gestations can improve the detection of women at risk of preterm birth. Prospective studies are needed to validate these findings, and to investigate whether improved risk assessment performance is sufficient to offset the additional costs associated with serial cervical length measurements.
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada. Electronic address: nir.melamed@sunnybrook.ca.
authors.forename: Nir
authors.initials: N
authors.lastname: Melamed
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Pittini
authors.affiliation: Department of Obstetrics and Gynecology, Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Liran
authors.initials: L
authors.lastname: Hiersch
authors.affiliation: Department of Obstetrics and Gynecology, Lis Hospital for Women, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
authors.forename: Yariv
authors.initials: Y
authors.lastname: Yogev
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI; Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Korzeniewski
authors.affiliation: Perinatology Research Branch, Program for Perinatal Research and Obstetrics, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, and Detroit, MI; Center for Molecular Medicine and Genetics, Wayne State University, Detroit, MI; Department of Epidemiology and Biostatistics, Michigan State University, East Lansing, MI; Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, MI.
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.affiliation: Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Sunnybrook Health Sciences Center, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jon
authors.initials: J
authors.lastname: Barrett
mesh_terms: D000328:Adult; D000465:Algorithms; D058070:Asymptomatic Diseases; D054791:Cervical Length Measurement / Q000379:methods*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011247:Pregnancy; D011262:Pregnancy Trimester, Second; D011263:Pregnancy Trimester, Third; D059285:Pregnancy, Twin; D047928:Premature Birth / Q000175:diagnosis* / Q000209:etiology; D011295:Prenatal Care / Q000379:methods*; D012189:Retrospective Studies; D018570:Risk Assessment
keywords: biomarker; cervical ripening; cervical shortening; cervix; labor; longitudinal study; prediction; pregnancy; prematurity; preterm labor; screening; ultrasound