The Journal of Maternal-Fetal & Neonatal Medicine
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor & Reli Hershkovitz To cite this article: Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor & Reli Hershkovitz (2015) The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation, The Journal of Maternal-Fetal & Neonatal Medicine, 28:16, 1929-1933, DOI: 10.3109/14767058.2014.972929 To link to this article: http://dx.doi.org/10.3109/14767058.2014.972929
Published online: 30 Dec 2014.
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Date: 03 November 2015, At: 07:36
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(16): 1929–1933 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.972929
ORIGINAL ARTICLE
The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor, and Reli Hershkovitz
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Department of Obstetrics & Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel Abstract
Keywords
Objectives: The aim of this study was to evaluate the role of cervical length measurement in early third trimester (28–32 weeks) as a predictor of preterm delivery (PTD), in women presenting with preterm parturition. Methods: Cervical length was measured prospectively, in singleton pregnancies at 28–32 weeks with preterm contractions (PTC). A multivariate linear regression model was performed to assess the association between cervical length and gestational age at delivery. Logistic regression analysis with PTD before 34 and 37 weeks of gestation as the outcome variable was performed to control for confounders. Results: Fifty-six women were included, mean gestational week at presentation and at delivery were 29.88 ± 1.13 and 37.05 ± 2.86, respectively. There was a direct association between short cervical length at admission and gestational week at delivery (p ¼ 0.027). This association remained significant even after controlling for confounders. Short cervical length was significantly associated with PTD before 34 (p ¼ 0.045) or 37 (p ¼ 0.046) weeks of gestation. Conclusions: Third trimester cervical length measurement in patients with PTC is associated with gestational week at delivery, as well as PTD prior to 34 and 37 weeks of gestation. Therefore, examining cervical length is clinically valuable and probably cost-effective during early third trimester.
Cervical length, preterm delivery, preterm labor, third trimester, transvaginal ultrasound
Introduction Preterm delivery (PTD), occurring prior to 37 completed weeks of gestation, is a leading cause of neonatal morbidity and mortality worldwide, as well as a preceding factor for long-term morbidity of the surviving infants [1–3]. The common pathway of parturition, including uterine contractions, shortening of the uterine cervix and at times decidual activation in the form of prelabor rupture of membranes, is activated during preterm parturition. Shortening of the uterine cervix, best evaluated by transvaginal ultrasound examination (TVUS), is associated with preterm birth, especially among women with a prior history of PTD [4,5]. The changes in cervical length during pregnancy may be viewed as a continuum [6–8]. Serial examinations of cervical length have demonstrated that physiologic changes occur in the uterine cervix prior to spontaneous onset of delivery. These changes may be acute or gradual, taking a course of Address for correspondence: Prof. Reli Hershkovitz, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, Beer-Sheva 84101, Israel. Tel: 972-8-6400423. E-mail: [email protected]
History Received 9 September 2014 Accepted 1 October 2014 Published online 30 December 2014
two or more weeks prior to the onset of labor [9–12]. Among women with a short cervix, the rate of change in cervical length in serial measurements was found to be an independent risk factor for PTD [13]. Measurement of cervical length at mid-trimester is widely accepted as an effective tool for the assessment of the risk for preterm birth [7,14,15]. The utility of cervical length measurements during early third trimester is less established than in mid-trimester. In an unselected low-risk population, cervical length measurement at 28–30 weeks of gestation, was significantly shorter in women who delivered prior to 37 weeks than women who delivered at term (34 ± 6 versus 37 ± 5 mm, respectively) [16]. In symptomatic women presenting to the Labor and Delivery ward with painful regular uterine contractions and intact membranes at 24 to 34 weeks of gestation, cervical length was found to be a significant predicting factor for PTD within 48 h and within 7 d from presentation [17,18], as well as prior to 35 weeks of gestation [17,19]. However, the optimal cutoff for cervical length measurement, mandating treatment for threatened PTD, requires further study [19]. The aim of this study was to evaluate the clinical role of measuring cervical length between 28 and 32 weeks of
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gestation, in symptomatic women presenting with preterm parturition.
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Methods A prospective study was conducted between 2011 and 2012 in the Department of Obstetrics and Gynecology at the Soroka University Medical Center, Beer Sheva, Israel, after approval of the Institutional Review Board. The study population was comprised of women with a singleton pregnancy who presented to the Labor and Delivery ward between 28 + 0 to 31 + 6 weeks of gestation with preterm parturition, defined as one of the following: (a) painful or painless uterine contractions documented by external tocodynamometer, showing at least four contractions during 20 min or 10 contractions during 1 h, regardless of the patient’s chief complaint; (b) uterine contractions accompanied by cervical changes on digital exam; or (c) preterm prelabor rupture of membranes (Preterm-PROM) confirmed by sterile examination per speculum by a physician, demonstrating passage of fluid through the cervix, vaginal pooling of amniotic fluid and/ or a positive nitrazine test [20,21]. Exclusion criteria included: women who underwent induced PTD; had unreliable dating for gestational age (unknown last menstrual period (LMP) or irregular menstruation, lack of first or second trimester US confirming gestational age); women with uterine anomalies; women with a cervical cerclage; placenta previa; multiple gestations; known major fetal anomalies or women with prior cervical conization. Measurement of cervical length by TVUS was conducted at presentation to the hospital or within 24 h of admission. All studies were conducted by a selected small group of physicians and trained US technicians using a vaginal probe 9–5 Mhz (VOLUSON E8, GE). Women were requested to empty their urinary bladder prior to examination and all examinations were preformed in lithotomy position, without applying pressure to the probe in order to obtain an optimal measurement. For each woman at least three measurements of cervical length in a sagittal view were undertaken, and the best technical shortest measurement was recorded in the study. Gestational age at presentation and at delivery was determined by LMP, and when possible confirmed by crown rump length (CRL) obtained during first trimester US. When there was a difference in gestational age of more than 7 d between first trimester US and LMP, gestational age was determined by the US exam. Demographic and clinical characteristics as well as obstetrical risk factors, information about prior gestations and obstetrical and perinatal outcomes were retrieved from the obstetrical and medical records. All clinical decisions including administration of antenatal corticosteroids, use of tocolytic agents or conservative management, consisting mainly of hydration and bed rest, were left to the decision of the attending physicians. Statistical analysis was carried out in order to determine the relationships between cervical length and PTD, labor within 48 h or 7 d from presentation, and for any preterm labor prior to 34 and 37 weeks of gestation. Statistical analysis was preformed using SPSS software (SPSS Chicago IL). The univariate analysis was performed
J Matern Fetal Neonatal Med, 2015; 28(16): 1929–1933
using the 2 test or Fisher exact for categorical variables and using t-test or Mann–Whitney for continuous variables. p50.05 was considered statistically significant.
Results Sixty-four women were recruited to the study. Eight women were excluded from the statistical analysis – seven women due to insufficient data regarding gestational age at delivery (giving birth in another hospital) and one woman presenting with Preterm-PROM in which cervical length was not measured during the period of 24-h post admission, as defined in the study protocol. Statistical analysis was preformed for the remaining eligible 56 patients. The clinical characteristics of the patients are shown in Table 1. Median cervical length at the time of admission was 37 mm (range 9–57). Notably, there was a relatively high proportion of nulliparous woman (n ¼ 24, 42.9%) and therefore the median parity was 1 (range 0–5). Six women had a history of PTD (10.7%). A total of 11 women (19.6%) had a cervical length measurement below 25 mm. Distribution of cervical length is presented in Figure 1. Twenty-three patients (41.1%) received antenatal corticosteroids, among them all women with a cervical length below 25 mm (n ¼ 11). Four women (7.1%) received tocolytic agents, no single regime was used. Among women who received tocolytic agents only one had a cervical length below 25 mm, measuring 9 mm. All women receiving tocolytic agents had a latency period of over 4 weeks before delivery. Four women (7.1%) delivered within 48 h from presentation, and a total of five women (8.9%) delivered within 7 d from presentation. Of the five women who delivered within 7 d from presentation, four women had a cervical length measurement below 25 mm at presentation, and only one of them had a history of PTD (cervical length measuring 12 mm). The fifth woman, who had a cervical length of 46 mm, was discharged and returned the next day with Preterm-PROM and was delivered by a cesarean section due to breech presentation. Seven women (12.5%) delivered before 34 weeks of gestation, four of them presenting with a cervical length of less than 25 mm. Sixteen women (28.6%) delivered before 37 weeks of gestation, six of them presenting with a cervical length of less than 25 mm. In a multivariate logistic regression analysis controlling for parity, gestational week at presentation and history of prior PTD, cervical length was not found to be significantly associated with delivery within 48 h or 7 d. A multivariate linear regression analysis showed a significant direct association between cervical length and gestational age at delivery, when controlling for parity, gestational week Table 1. Clinical and obstetrical characteristics of women presenting with preterm parturition at 28–32 weeks’ gestation (56 women). Parameter Parity Gestational week at presentation (weeks) Cervical length (mm) Gestational week at delivery (weeks)
Mean ± SD 1.13 ± 1.25 29.88 ± 1.13 35.04 ± 10.87 37.05 ± 2.86
Cervical length nd PTD at 28–32 weeks
DOI: 10.3109/14767058.2014.972929
at presentation and history of prior PTD (p ¼ 0.027, r ¼ 0.502). There was also a correlation between cervical length and the latency interval from gestational week at presentation to gestational week at delivery (p ¼ 0.006, r ¼ 0.392; Figure 2). A univariate logistic regression analysis demonstrated that cervical length was associated with PTD before 34 weeks of gestation (p ¼ 0.045) and before 37 weeks of gestation (p ¼ 0.046). However, in a multivariate logistic regression model, controlling for cervical length, parity, gestational week at presentation and history of PTD, the association between cervical length and PTD before 34 and 37 weeks of gestation was not significant.
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Discussion In this study, we have demonstrated a direct association between cervical length measurement and gestational week at delivery and between cervical length and the latency period to delivery, in women between 28 and 32 weeks of gestation presenting with PTC. However, in our study, PTD before 34 and before 37 weeks of gestation was not found to be independently associated with cervical length. Measurement of cervical length at mid-trimester has been proposed as an effective tool for the assessment of the risk for preterm birth. This was established by large-scale populationbased prospective studies which showed that the risk of PTD is inversely related to cervical length [7,14,15]. It was also demonstrated that a combination of maternal risk factors for PTD with cervical length measurement, had a higher detection rate for subsequent preterm birth than cervical length alone [14,15,22,23]. A short cervix, measuring less than 25 mm, was found to have the best predictive accuracy for preterm birth in asymptomatic women with prior PTD [5,22,24,25]. Measurements of cervical length below 15 mm in a low-risk population were found in approximately 2% of women [26]. When detected before 20 weeks of gestation, this was found to be associated with a 50% risk of spontaneous early PTD [27], and a shorter diagnosis-to-delivery interval, as well as a lower median gestational age at delivery [28].
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Recent studies have suggested that screening for cervical length at mid-trimester should be used as an important, costeffective tool for the detection of PTD [4,29,30]. Other studies have examined an earlier cervical length screening strategies during the first trimester, especially when there is a history of prior PTD, but their utility is still debatable [31,32]. To date such screening strategies have not been routinely implemented [33,34]. As previously mentioned, the utility of cervical length measurements during early third trimester is less established than in mid-trimester. The findings of the current study are consistent with the previous studies showing an association between cervical length and PTD in symptomatic women in the early third trimester [17–19]. The population in our study was comprised of a relatively high proportion of nulliparous women, especially when considering the multiparous population in our district. Of the remaining multiparous women (n ¼ 32), six had a history of PTD. Only one woman with a history of PTD delivered preterm at 36 weeks of gestation. The present study is underpowered for deducing conclusions about the relationship between a history of PTD and the risk for current PTD. Multivariate logistic regression using this variable also failed to show statistical significance. The high proportion of nulliparous women found in this study might be the result
Figure 2. Latency interval to delivery according to cervical length at admission (Pearson’s r linear ¼ 0.392).
Figure 1. Distribution of cervical length, mean length 35.04 ± 10.87 mm.
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of a selection bias, namely since nulliparous women tend to pay more attention to uterine discomfort and seek more medical attention. Notably, the use of tocolytic agents was not common in our study population, and such agents were used only in four (7.1%) of women, among them only one women with a cervical length of less than 25 mm. The scarce use of tocolytic agents, left to the decision of the attending physician, leads to lack of power in the statistical analysis of their influence. The current study is a prospective study, with pre-defined inclusion and exclusion criteria, designed to shed light on the role of cervical length measurement in a specific everyday clinical situation in the third trimester. However, the relatively small sample size does not allow conducting significant subgroup analysis, as in the case of patients with a history of prior PTD, or evaluating the significance of delivery within 48 h or 7 d from cervical length measurement. Another drawback of this study is that the cervical length measurement was conducted by several examiners. Although a selected group of examiners was chosen for this study, inter-observer variability is still a possible bias in this set-up [35]. In summary, early third trimester cervical length measurements in symptomatic women is associated with gestational age at delivery, as well as with the latency period to delivery. This knowledge might help physicians in their management of these patients, deciding on administration of antenatal corticosteroids, bed rest or administration of tocolytic agents. We encourage physicians to use this simple, available sonographic tool, alongside with physical examination. Further studies using larger populations are needed in order to assess the utility of cervical length measurements in early third trimester, as well as the optimal cervical length cut-off requiring medical intervention. Moreover, measurement of cervical length in third trimester is probably cost-effective; however, this remains to be evaluated.
Declaration of interest None of the authors have a conflict of interest.
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9. Guzman ER, Mellon R, Vintzileos AM, et al. Relationship between endocervical canal length between 15–24 weeks gestation and obstetric history. J Matern Fetal Med 1998;7:269–72. 10. Bergelin I, Valentin L. Patterns of normal change in cervical length and width during pregnancy in nulliparous women: a prospective, longitudinal ultrasound study. Ultrasound Obstet Gynecol 2001;18: 217–22. 11. Bergelin I, Valentin L. Normal cervical changes in parous women during the second half of pregnancy-a prospective, longitudinal ultrasound study. Acta Obstet Gynecol Scand 2002;81:31–8. 12. Meijer-Hoogeveen M, Van Holsbeke C, Van Der Tweel I, et al. Sonographic longitudinal cervical length measurements in nulliparous women at term: prediction of spontaneous onset of labor. Ultrasound Obstet Gynecol 2008;32:652–6. 13. Moroz LA, Simhan HN. Rate of sonographic cervical shortening and the risk of spontaneous preterm birth. Am J Obstet Gynecol 2012;206:234.e1–5. 14. To MS, Skentou CA, Royston P, et al. Prediction of patient-specific risk of early preterm delivery using maternal history and sonographic measurement of cervical length: a population-based prospective study. Ultrasound Obstet Gynecol 2006;27:362–7. 15. Celik E, To M, Gajewska K, et al; Fetal Medicine Foundation Second Trimester Screening Group. Cervical length and obstetric history predict spontaneous preterm birth: development and validation of a model to provide individualized risk assessment. Ultrasound Obstet Gynecol 2008;31:549–54. 16. Tongsong T, Kamprapanth P, Srisomboon J, et al. Single transvaginal sonographic measurement of cervical length early in the third trimester as a predictor of preterm delivery. Obstet Gynecol 1995;86:184–7. 17. Tsoi E, Fuchs IB, Rane S, et al. Sonographic measurement of cervical length in threatened preterm labor in singleton pregnancies with intact membranes. Ultrasound Obstet Gynecol 2005;25:353–6. ¨ nal A, Demirci E, et al. Sonographic measurement of 18. Demirci O, U cervical length and risk of preterm delivery. J Obstet Gynaecol Res 2011;37:809–14. 19. Wulff CB, Ekelund CK, Hedegaard M, Tabor A. Can a 15-mm cervical length cutoff discriminate between low and high risk of preterm delivery in women with threatened preterm labor? Fetal Diagn Ther 2011;29:216–23. 20. Mercer BM. Preterm premature rupture of the membranes. Obstet Gynecol 2003;101:178–93. 21. ACOG Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 80: premature rupture of membranes. Clinical management guidelines for obstetrician-gynecologists. Obstet Gynecol 2007;109:1007–19. 22. Iams JD, Goldenberg RL, Mercer BM, et al. The Preterm Prediction Study: recurrence risk of spontaneous preterm birth. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 1998;178:1035–40. 23. Iams JD, Goldenberg RL, Mercer BM, et al. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. The preterm prediction study: can low-risk women destined for spontaneous preterm birth be identified? Am J Obstet Gynecol 2001;184:652–5. 24. Owen J, Yost N, Berghella V, et al; Maternal-Fetal Medicine Units Network. Can shortened midtrimester cervical length predict very early spontaneous preterm birth? Am J Obstet Gynecol 2004;191: 298–303. 25. Berghella V, Roman A, Daskalakis C, et al. Gestational age at cervical length measurement and incidence of preterm birth. Obstet Gynecol 2007;110:311–17. 26. Heath VC, Southall TR, Souka AP, et al. Cervical length at 23 weeks of gestation: prediction of spontaneous preterm delivery. Ultrasound Obstet Gynecol 1998;12:312–17. 27. Hassan SS, Romero R, Berry SM, et al. Patients with an ultrasonographic cervical length 5 or ¼15 mm have nearly a 50% risk of early spontaneous preterm delivery. Am J Obstet Gynecol 2000;182:1458–67. 28. Vaisbuch E, Romero R, Erez O, et al. Clinical significance of early (520 weeks) vs. late (20–24 weeks) detection of sonographic short cervix in asymptomatic women in the mid-trimester. Ultrasound Obstet Gynecol 2010;36:471–81. 29. Campbell S. Universal cervical-length screening and vaginal progesterone prevents early preterm births, reduces neonatal
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morbidity and is cost saving: doing nothing is no longer an option. Ultrasound Obstet Gynecol 2011;38:1–9. 30. Werner EF, Han CS, Pettker CM, et al. Universal cervical-length screening to prevent preterm birth: a cost-effectiveness analysis. Ultrasound Obstet Gynecol 2011;38:32–7. 31. Berghella V, Talucci M, Desai A. Does transvaginal sonographic measurement of cervical length before 14 weeks predict preterm delivery in high-risk pregnancies? Ultrasound Obstet Gynecol 2003;21:140–4. 32. Greco E, Gupta R, Syngelaki A, et al. First-trimester screening for spontaneous preterm delivery with maternal characteristics and cervical length. Fetal Diagn Ther 2012;31:154–61.
Cervical length nd PTD at 28–32 weeks
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33. ACOG Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 130: prediction and prevention of preterm birth. Obstet Gynecol 2012;120:964–73. 34. Parry S, Simhan H, Elovitz M, Iams J. Universal maternal cervical length screening during the second trimester: pros and cons of a strategy to identify women at risk of spontaneous preterm delivery. Am J Obstet Gynecol 2012; 207:101–6. 35. Valentin L, Bergelin I. Intra- and interobserver reproducibility of ultrasound measurements of cervical length and width in the second and third trimesters of pregnancy. Ultrasound Obstet Gynecol 2002; 20:256–62.
ISSN: 1476-7058 (Print) 1476-4954 (Online) Journal homepage: http://www.tandfonline.com/loi/ijmf20
The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor & Reli Hershkovitz To cite this article: Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor & Reli Hershkovitz (2015) The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation, The Journal of Maternal-Fetal & Neonatal Medicine, 28:16, 1929-1933, DOI: 10.3109/14767058.2014.972929 To link to this article: http://dx.doi.org/10.3109/14767058.2014.972929
Published online: 30 Dec 2014.
Submit your article to this journal
Article views: 42
View related articles
View Crossmark data
Citing articles: 1 View citing articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=ijmf20 Download by: [Universite Laval]
Date: 03 November 2015, At: 07:36
http://informahealthcare.com/jmf ISSN: 1476-7058 (print), 1476-4954 (electronic) J Matern Fetal Neonatal Med, 2015; 28(16): 1929–1933 ! 2014 Informa UK Ltd. DOI: 10.3109/14767058.2014.972929
ORIGINAL ARTICLE
The clinical utility of sonographic cervical length in the management of preterm parturition at 28–32 weeks of gestation Neta Benshalom-Tirosh, Dan Tirosh, Barak Aricha-Tamir, Adi Y. Weintraub, Offer Erez, Moshe Mazor, and Reli Hershkovitz
Downloaded by [Universite Laval] at 07:36 03 November 2015
Department of Obstetrics & Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer Sheva, Israel Abstract
Keywords
Objectives: The aim of this study was to evaluate the role of cervical length measurement in early third trimester (28–32 weeks) as a predictor of preterm delivery (PTD), in women presenting with preterm parturition. Methods: Cervical length was measured prospectively, in singleton pregnancies at 28–32 weeks with preterm contractions (PTC). A multivariate linear regression model was performed to assess the association between cervical length and gestational age at delivery. Logistic regression analysis with PTD before 34 and 37 weeks of gestation as the outcome variable was performed to control for confounders. Results: Fifty-six women were included, mean gestational week at presentation and at delivery were 29.88 ± 1.13 and 37.05 ± 2.86, respectively. There was a direct association between short cervical length at admission and gestational week at delivery (p ¼ 0.027). This association remained significant even after controlling for confounders. Short cervical length was significantly associated with PTD before 34 (p ¼ 0.045) or 37 (p ¼ 0.046) weeks of gestation. Conclusions: Third trimester cervical length measurement in patients with PTC is associated with gestational week at delivery, as well as PTD prior to 34 and 37 weeks of gestation. Therefore, examining cervical length is clinically valuable and probably cost-effective during early third trimester.
Cervical length, preterm delivery, preterm labor, third trimester, transvaginal ultrasound
Introduction Preterm delivery (PTD), occurring prior to 37 completed weeks of gestation, is a leading cause of neonatal morbidity and mortality worldwide, as well as a preceding factor for long-term morbidity of the surviving infants [1–3]. The common pathway of parturition, including uterine contractions, shortening of the uterine cervix and at times decidual activation in the form of prelabor rupture of membranes, is activated during preterm parturition. Shortening of the uterine cervix, best evaluated by transvaginal ultrasound examination (TVUS), is associated with preterm birth, especially among women with a prior history of PTD [4,5]. The changes in cervical length during pregnancy may be viewed as a continuum [6–8]. Serial examinations of cervical length have demonstrated that physiologic changes occur in the uterine cervix prior to spontaneous onset of delivery. These changes may be acute or gradual, taking a course of Address for correspondence: Prof. Reli Hershkovitz, Department of Obstetrics and Gynecology, Faculty of Health Sciences, Soroka University Medical Center, Ben-Gurion University of the Negev, POB 151, Beer-Sheva 84101, Israel. Tel: 972-8-6400423. E-mail: [email protected]
History Received 9 September 2014 Accepted 1 October 2014 Published online 30 December 2014
two or more weeks prior to the onset of labor [9–12]. Among women with a short cervix, the rate of change in cervical length in serial measurements was found to be an independent risk factor for PTD [13]. Measurement of cervical length at mid-trimester is widely accepted as an effective tool for the assessment of the risk for preterm birth [7,14,15]. The utility of cervical length measurements during early third trimester is less established than in mid-trimester. In an unselected low-risk population, cervical length measurement at 28–30 weeks of gestation, was significantly shorter in women who delivered prior to 37 weeks than women who delivered at term (34 ± 6 versus 37 ± 5 mm, respectively) [16]. In symptomatic women presenting to the Labor and Delivery ward with painful regular uterine contractions and intact membranes at 24 to 34 weeks of gestation, cervical length was found to be a significant predicting factor for PTD within 48 h and within 7 d from presentation [17,18], as well as prior to 35 weeks of gestation [17,19]. However, the optimal cutoff for cervical length measurement, mandating treatment for threatened PTD, requires further study [19]. The aim of this study was to evaluate the clinical role of measuring cervical length between 28 and 32 weeks of
1930
N. Benshalom-Tirosh et al.
gestation, in symptomatic women presenting with preterm parturition.
Downloaded by [Universite Laval] at 07:36 03 November 2015
Methods A prospective study was conducted between 2011 and 2012 in the Department of Obstetrics and Gynecology at the Soroka University Medical Center, Beer Sheva, Israel, after approval of the Institutional Review Board. The study population was comprised of women with a singleton pregnancy who presented to the Labor and Delivery ward between 28 + 0 to 31 + 6 weeks of gestation with preterm parturition, defined as one of the following: (a) painful or painless uterine contractions documented by external tocodynamometer, showing at least four contractions during 20 min or 10 contractions during 1 h, regardless of the patient’s chief complaint; (b) uterine contractions accompanied by cervical changes on digital exam; or (c) preterm prelabor rupture of membranes (Preterm-PROM) confirmed by sterile examination per speculum by a physician, demonstrating passage of fluid through the cervix, vaginal pooling of amniotic fluid and/ or a positive nitrazine test [20,21]. Exclusion criteria included: women who underwent induced PTD; had unreliable dating for gestational age (unknown last menstrual period (LMP) or irregular menstruation, lack of first or second trimester US confirming gestational age); women with uterine anomalies; women with a cervical cerclage; placenta previa; multiple gestations; known major fetal anomalies or women with prior cervical conization. Measurement of cervical length by TVUS was conducted at presentation to the hospital or within 24 h of admission. All studies were conducted by a selected small group of physicians and trained US technicians using a vaginal probe 9–5 Mhz (VOLUSON E8, GE). Women were requested to empty their urinary bladder prior to examination and all examinations were preformed in lithotomy position, without applying pressure to the probe in order to obtain an optimal measurement. For each woman at least three measurements of cervical length in a sagittal view were undertaken, and the best technical shortest measurement was recorded in the study. Gestational age at presentation and at delivery was determined by LMP, and when possible confirmed by crown rump length (CRL) obtained during first trimester US. When there was a difference in gestational age of more than 7 d between first trimester US and LMP, gestational age was determined by the US exam. Demographic and clinical characteristics as well as obstetrical risk factors, information about prior gestations and obstetrical and perinatal outcomes were retrieved from the obstetrical and medical records. All clinical decisions including administration of antenatal corticosteroids, use of tocolytic agents or conservative management, consisting mainly of hydration and bed rest, were left to the decision of the attending physicians. Statistical analysis was carried out in order to determine the relationships between cervical length and PTD, labor within 48 h or 7 d from presentation, and for any preterm labor prior to 34 and 37 weeks of gestation. Statistical analysis was preformed using SPSS software (SPSS Chicago IL). The univariate analysis was performed
J Matern Fetal Neonatal Med, 2015; 28(16): 1929–1933
using the 2 test or Fisher exact for categorical variables and using t-test or Mann–Whitney for continuous variables. p50.05 was considered statistically significant.
Results Sixty-four women were recruited to the study. Eight women were excluded from the statistical analysis – seven women due to insufficient data regarding gestational age at delivery (giving birth in another hospital) and one woman presenting with Preterm-PROM in which cervical length was not measured during the period of 24-h post admission, as defined in the study protocol. Statistical analysis was preformed for the remaining eligible 56 patients. The clinical characteristics of the patients are shown in Table 1. Median cervical length at the time of admission was 37 mm (range 9–57). Notably, there was a relatively high proportion of nulliparous woman (n ¼ 24, 42.9%) and therefore the median parity was 1 (range 0–5). Six women had a history of PTD (10.7%). A total of 11 women (19.6%) had a cervical length measurement below 25 mm. Distribution of cervical length is presented in Figure 1. Twenty-three patients (41.1%) received antenatal corticosteroids, among them all women with a cervical length below 25 mm (n ¼ 11). Four women (7.1%) received tocolytic agents, no single regime was used. Among women who received tocolytic agents only one had a cervical length below 25 mm, measuring 9 mm. All women receiving tocolytic agents had a latency period of over 4 weeks before delivery. Four women (7.1%) delivered within 48 h from presentation, and a total of five women (8.9%) delivered within 7 d from presentation. Of the five women who delivered within 7 d from presentation, four women had a cervical length measurement below 25 mm at presentation, and only one of them had a history of PTD (cervical length measuring 12 mm). The fifth woman, who had a cervical length of 46 mm, was discharged and returned the next day with Preterm-PROM and was delivered by a cesarean section due to breech presentation. Seven women (12.5%) delivered before 34 weeks of gestation, four of them presenting with a cervical length of less than 25 mm. Sixteen women (28.6%) delivered before 37 weeks of gestation, six of them presenting with a cervical length of less than 25 mm. In a multivariate logistic regression analysis controlling for parity, gestational week at presentation and history of prior PTD, cervical length was not found to be significantly associated with delivery within 48 h or 7 d. A multivariate linear regression analysis showed a significant direct association between cervical length and gestational age at delivery, when controlling for parity, gestational week Table 1. Clinical and obstetrical characteristics of women presenting with preterm parturition at 28–32 weeks’ gestation (56 women). Parameter Parity Gestational week at presentation (weeks) Cervical length (mm) Gestational week at delivery (weeks)
Mean ± SD 1.13 ± 1.25 29.88 ± 1.13 35.04 ± 10.87 37.05 ± 2.86
Cervical length nd PTD at 28–32 weeks
DOI: 10.3109/14767058.2014.972929
at presentation and history of prior PTD (p ¼ 0.027, r ¼ 0.502). There was also a correlation between cervical length and the latency interval from gestational week at presentation to gestational week at delivery (p ¼ 0.006, r ¼ 0.392; Figure 2). A univariate logistic regression analysis demonstrated that cervical length was associated with PTD before 34 weeks of gestation (p ¼ 0.045) and before 37 weeks of gestation (p ¼ 0.046). However, in a multivariate logistic regression model, controlling for cervical length, parity, gestational week at presentation and history of PTD, the association between cervical length and PTD before 34 and 37 weeks of gestation was not significant.
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Discussion In this study, we have demonstrated a direct association between cervical length measurement and gestational week at delivery and between cervical length and the latency period to delivery, in women between 28 and 32 weeks of gestation presenting with PTC. However, in our study, PTD before 34 and before 37 weeks of gestation was not found to be independently associated with cervical length. Measurement of cervical length at mid-trimester has been proposed as an effective tool for the assessment of the risk for preterm birth. This was established by large-scale populationbased prospective studies which showed that the risk of PTD is inversely related to cervical length [7,14,15]. It was also demonstrated that a combination of maternal risk factors for PTD with cervical length measurement, had a higher detection rate for subsequent preterm birth than cervical length alone [14,15,22,23]. A short cervix, measuring less than 25 mm, was found to have the best predictive accuracy for preterm birth in asymptomatic women with prior PTD [5,22,24,25]. Measurements of cervical length below 15 mm in a low-risk population were found in approximately 2% of women [26]. When detected before 20 weeks of gestation, this was found to be associated with a 50% risk of spontaneous early PTD [27], and a shorter diagnosis-to-delivery interval, as well as a lower median gestational age at delivery [28].
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Recent studies have suggested that screening for cervical length at mid-trimester should be used as an important, costeffective tool for the detection of PTD [4,29,30]. Other studies have examined an earlier cervical length screening strategies during the first trimester, especially when there is a history of prior PTD, but their utility is still debatable [31,32]. To date such screening strategies have not been routinely implemented [33,34]. As previously mentioned, the utility of cervical length measurements during early third trimester is less established than in mid-trimester. The findings of the current study are consistent with the previous studies showing an association between cervical length and PTD in symptomatic women in the early third trimester [17–19]. The population in our study was comprised of a relatively high proportion of nulliparous women, especially when considering the multiparous population in our district. Of the remaining multiparous women (n ¼ 32), six had a history of PTD. Only one woman with a history of PTD delivered preterm at 36 weeks of gestation. The present study is underpowered for deducing conclusions about the relationship between a history of PTD and the risk for current PTD. Multivariate logistic regression using this variable also failed to show statistical significance. The high proportion of nulliparous women found in this study might be the result
Figure 2. Latency interval to delivery according to cervical length at admission (Pearson’s r linear ¼ 0.392).
Figure 1. Distribution of cervical length, mean length 35.04 ± 10.87 mm.
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of a selection bias, namely since nulliparous women tend to pay more attention to uterine discomfort and seek more medical attention. Notably, the use of tocolytic agents was not common in our study population, and such agents were used only in four (7.1%) of women, among them only one women with a cervical length of less than 25 mm. The scarce use of tocolytic agents, left to the decision of the attending physician, leads to lack of power in the statistical analysis of their influence. The current study is a prospective study, with pre-defined inclusion and exclusion criteria, designed to shed light on the role of cervical length measurement in a specific everyday clinical situation in the third trimester. However, the relatively small sample size does not allow conducting significant subgroup analysis, as in the case of patients with a history of prior PTD, or evaluating the significance of delivery within 48 h or 7 d from cervical length measurement. Another drawback of this study is that the cervical length measurement was conducted by several examiners. Although a selected group of examiners was chosen for this study, inter-observer variability is still a possible bias in this set-up [35]. In summary, early third trimester cervical length measurements in symptomatic women is associated with gestational age at delivery, as well as with the latency period to delivery. This knowledge might help physicians in their management of these patients, deciding on administration of antenatal corticosteroids, bed rest or administration of tocolytic agents. We encourage physicians to use this simple, available sonographic tool, alongside with physical examination. Further studies using larger populations are needed in order to assess the utility of cervical length measurements in early third trimester, as well as the optimal cervical length cut-off requiring medical intervention. Moreover, measurement of cervical length in third trimester is probably cost-effective; however, this remains to be evaluated.
Declaration of interest None of the authors have a conflict of interest.
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