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The use of cervical sonography to differentiate true from false labor in term patients presenting for labor check Nadia B. Kunzier, DO; Wendy L. Kinzler, MD; Martin R. Chavez, MD; Tracy M. Adams, DO; Donald A. Brand, PhD; Anthony M. Vintzileos, MD

BACKGROUND: Cervical length by transvaginal ultrasound to predict

preterm labor is widely used in clinical practice. Virtually no data exist on cervical length measurement to differentiate true from false labor in term patients who present for labor check. False-positive diagnosis of true labor at term may lead to unnecessary hospital admissions, obstetrical interventions, resource utilization, and cost. OBJECTIVE: We sought to determine if cervical length by transvaginal ultrasound can differentiate true from false labor in term patients presenting for labor check. STUDY DESIGN: This is a prospective observational study of women presenting to labor and delivery with labor symptoms at 37-42 weeks, singleton cephalic gestation, regular uterine contractions (
4/20 min), intact membranes, and cervix 4 cm dilated and 80% effaced. Those patients with placenta previa and indications for immediate delivery were excluded. The shortest best cervical length of 3 collected images was used for analysis. Providers managing labor were blinded to the cervical length. True labor was defined as spontaneous rupture of membranes or spontaneous cervical dilation
4 cm and
80% effaced within 24 hours of cervical length measurement. In the absence of these outcomes, labor status was determined as false labor. Receiver operating characteristic curves were generated to assess the predictive ability of cervical length to differentiate true from false labor and were analyzed separately for primiparous and multiparous patients. The diagnostic accuracies of various cervical length cutoffs were determined. The relationship of cervical length and time to delivery was also analyzed including both use and nonuse of oxytocin. RESULTS: In all, 77 patients were included in the study; the prevalence of true labor was 58.4% (45/77). Patients who were in

Introduction The obstetrical patient presenting to labor and delivery triage for a labor evaluation at term is one of the most common clinical scenarios. Currently, the diagnosis of true labor at term relies on patient symptomatology and very frequently on progressive cervical dilation by digital vaginal exams. However, perception of contractions is a poor predictor of labor and digital exams and

Cite this article as: Kunzier NB, Kinzler WL, Chavez MR, et al. The use of cervical sonography to differentiate true from false labor in term patients presenting for labor check. Am J Obstet Gynecol 2016;215:372.e1-5. 0002-9378/$36.00 ª 2016 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2016.03.031

true labor had shorter cervical length as compared to those in false labor: median 1.3 cm (range 0.5-4.1) vs 2.4 cm (range 1.0-5.0), respectively (P < .001). The area under the receiver operating characteristic curve for primiparous patients was 0.88 (P < .001) and for multiparous patients was 0.76 (P < .01), both demonstrating good correlation. The area under the receiver operating characteristic curves were not significantly different between primiparous and multiparous (P ¼ .23). The area under the receiver operating characteristic curve for primiparous and multiparous patients combined was 0.8 (P < .0001), indicating a good overall correlation between cervical length and its ability to differentiate true from false labor. Overall, a cervical length cutoff of 1.5 cm to predict true labor had the highest specificity (81%), positive predictive value (83%), and positive likelihood ratio (4.2). There were no differences in cervical length prediction between primiparous and multiparous patients. Cervical length was positively correlated with time to delivery, regardless of the use of oxytocin. CONCLUSION: In differentiating true from false labor in term patients who present for labor check, a cervical length of 1.5 cm was the most clinically optimal cutoff with the lowest false positive rateedue to its highest specificityeand highest positive predictive value and positive likelihood ratios. Its use to decide admission in patients at term with labor symptoms may prevent unnecessary admissions, obstetrical interventions, resource utilization, and cost. Key words: cervical length, cervical sonography, false labor, labor

check, term gestation, true labor

therefore Bishop score have large intraobserver and interobserver variabilities,1 providing low accuracy to predict true labor.2,3 There are several studies examining the use of cervical length (CL) surveillance by transvaginal ultrasound (TVUS) to predict spontaneous preterm birth in symptomatic as well as asymptomatic patients.4-12 As a matter of fact, the usefulness of CL to predict preterm labor (PTL) has been documented very well so that it is now routinely used in clinical practice.5-12 In term patients the use of CL has been limited to prediction of spontaneous labor in prolonged pregnancies and also in the prediction of successful labor induction.13-16 To our knowledge, there are no data on CL measurements to differentiate

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true from false labor in term patients presenting for a labor check. Consequences from false-positive diagnosis of true labor at term are unnecessary hospital admissions, unnecessary obstetrical interventions, increased resource utilization, and increased cost.17,18 Therefore, the primary objective of this prospective study was to determine if CL by TVUS can differentiate true from false labor in term patients who present to the hospital for labor check. Our secondary objective was to determine the relationship between CL and time to delivery in these patients.

Materials and Methods This was an institutional review boardeapproved prospective observational study from 2013 through 2016 in

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ajog.org term (37-42 weeks) patients presenting to labor and delivery triage at Winthrop University Hospital, Mineola, NY, with labor symptoms. A history and physical was performed as standard of care. Informed consent was obtained after determining eligibility. Recruitment was not consecutive secondary to time constraints because of a very busy labor and delivery unit where the study was conducted. Inclusion criteria were: singleton, live intrauterine pregnancy in cephalic presentation, gestational age 3742 weeks, regular uterine contractions (defined as
4 contractions/20 min on the tocometer), intact membranes, and cervix <4 cm dilated and <80% effaced. Exclusion criteria were: clinical chorioamnionitis (defined as temperature >100.4 F and 2 of the following: malodorous discharge, maternal leukocytosis, maternal tachycardia, fetal tachycardia, uterine tenderness), maternal or fetal indications for immediate delivery, placenta previa, and previous cesarean delivery. TVUS was performed by residents previously trained on proper CL technique.19 Three images per patient were collected and the shortest best image was chosen to be analyzed in the study. Providers making management decisions were blinded to the CL measurements. True labor was defined as spontaneous rupture of membranes or spontaneous cervical dilation
4 cm and
80% effaced within 24 hours of CL measurement. False labor was defined as cases that did not fulfill the above definition of true labor. Patient’s demographics and obstetrical variables were collected and included: patient’s age, prepregnancy body mass index, race, gravidity, parity, gestational age, cervical exam, CL measurement upon presentation, date and time of CL measurement, date of admission to or discharge from hospital, time of active labor, induction or augmentation of labor, spontaneous or artificial rupture of membranes and timing, time of birth, birthweight, and mode of delivery. Several statistical analyses were performed. The demographic and clinical characteristics of true vs false labor patients were compared with parametric

TABLE 1

Comparison of demographic and obstetric variables for true vs false labor patients True labor n ¼ 45 [58.4%]

False labor n ¼ 32 [41.6%]

P value

Age, y

28.7  6.0

27.7  5.7

.47

BMI, kg/m2

29.9  5.5

30.1  5.0

.85

Race

.71

White

20 (44.4)

12 (37.5)

Black

13 (28.9)

12 (37.5)

Hispanic

12 (26.7)

5 (15.6)

0 (0.0)

3 (9.4)

Gravidity

2 (1e5)

2 (1e6)

.54

Parity

0 (0e3)

0 (0e2)

.30

39.3  0.9

38.7  1.1

<.01

7 (15.6)

5 (15.6)

1.00

Other

Gestational age, wk Cesarean delivery Birthweight, g Cervical length, cm

3285  434

3413  375

1.3 (0.5e4.1)

2.4 (1.0e5.0)

.18 <.001

Data expressed as n (%), mean  SD, or median (range). BMI, body mass index. Kunzier et al. Cervical length to predict true labor at term. Am J Obstet Gynecol 2016.

and nonparametric analysis. Receiver operating characteristic (ROC) curves of CL in the prediction of true labor were generated and the diagnostic accuracy of CL was determined for various CL cutoffs for both primiparous and multiparous patients. The diagnostic accuracy of the various CL cutoffs was expressed by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and positive and negative likelihood ratios for both primiparous and multiparous patients separately as well as combined. Lastly, the relationship between CL and time to delivery was determined by linear regression and scatter plot and the correlation coefficient (r) was calculated. CL vs time to delivery was analyzed individually for patients who received oxytocin augmentation and those who did not.

Results In all, 101 patients were enrolled; 24 patients were excluded because of: induction prior to active labor (22), breech presentation after the CL measurement (delivered by scheduled cesarean) (1),

and spontaneous rupture of membranes after the vaginal exam and before the TVUS (1). Analysis was performed on the remaining 77 patients. Of the 77 patients analyzed, 45 were in true labor (prevalence of true labor 45/77 or 58.4%) and 32 (41.6%) were in false labor. The groups were similar in regards to maternal age, body mass index, race, gravidity, parity, and mode of delivery (Table 1). Patients who were in true labor had shorter CL measurements at the time of presentation as compared to those in false labor: median 1.3 cm (range 0.5-4.1) vs 2.4 cm (range 1.0-5.0), respectively (P < .001). Those who were in true labor were also of more advanced gestational age compared to the false labor patients (P < .01) (Table 1). ROC curves were generated separately for primiparous and multiparous (Figure 1). There was no statistically significant difference in the area under the ROC curves between primiparous and multiparous (0.88 vs 0.76, respectively, P ¼ .23), therefore, the data were combined (Figure 2). Table 2 shows the sensitivity, specificity, PPV, NPV, and

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FIGURE 1

CL differentiating true from false labor: Primiparous and multiparous gestations CL ≤ 2.5 cm

CL ≤ 3.0 cm

Primiparous AUC= 0.88

100 CL ≤ 2.0 cm CL ≤ 3.0 cm

80

CL ≤ 2.5 cm

CL ≤ 1.5 cm

MulƟparous AUC= 0.76

Sensitivity (%)

CL ≤ 2.0 cm

60

CL ≤ 1.5 cm

Area under the curves do not differ significantly (p=0.23)

40

20

0 0

20

40

60

80

100

1 - Specificity (%)

Area under receiver operating characteristic (AUC) curves for cervical length (CL) in differentiating true from false labor at term. Primiparous and multiparous gestations analyzed individually. Kunzier et al. Cervical length to predict true labor at term. Am J Obstet Gynecol 2016.

positive and negative likelihood ratios of various CL cutoffs. Overall, the CL cutoff of 1.5 cm had the highest specificity (and thus lowest false positive rate [FPR]), PPV, and positive likelihood ratio. Utilizing a CL of 1.5 had a specificity of 81% (thus, FPR of 19%),

FIGURE 2

Comment

CL differentiating true from false labor: Primiparous and multiparous combined 100 CL ≤ 3.0 cm CL ≤ 2.5 cm

Sensitivity (%)

80

CL ≤ 2.0 cm CL ≤ 1.5 cm

60

Area under curve = 0.80 P<0.0001

40

20

0 0

20

40

60

80

PPV of 83% and a positive likelihood ratio of 4.2. The sensitivity, specificity, PPV, NPV, and positive likelihood ratios were not significantly different for primiparous vs multiparous patients. Time to delivery was positively correlated with CL (P < .001), regardless of labor augmentation (Figure 3) with a correlation coefficient (r) of 0.48.

100

1 - Specificity (%)

Receiver operating characteristic curve of cervical length (CL) in differentiating true from false labor at term. Primiparous and multiparous gestations combined. Kunzier et al. Cervical length to predict true labor at term. Am J Obstet Gynecol 2016.

The main finding of this study was that that in term patients who present for labor check there was a good correlation between CL and its ability to differentiate true from false labor and that the most optimal cutoff was 1.5 cm. This cutoff of 1.5 cm provides the lowest FPR because of its highest specificity and it has the same accuracy for both primiparous and multiparous patients. We also demonstrated a positive relationship between CL and time to delivery, regardless of oxytocin use. Cervical surveillance has been mainly used to predict spontaneous PTL.5-12 In using CL to detect or predict PTL, a high sensitivity should be the driver in deciding the most optimal CL cutoff20 because failure to diagnose PTL carries

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significant consequences of withholding interventions such as vaginal progesterone, cervical cerclage, betamethasone, and magnesium sulfate for neuroprotection.21-24 This concept leads to the typically used CL cutoffs of 20 mm or 2.5 cm in the preterm population.24 However, the importance of differentiating true from false labor at term should have different clinical considerations. High false-positive diagnosis (of true labor) may lead to unnecessary hospital admissions, unnecessary obstetrical interventions, increased resource utilization, and increased cost.17,18 Therefore, in choosing the optimal cutoff, the FPR should be minimized (or the specificity should be maximized), thus making the CL cutoff of 1.5 cm appropriate with accuracies being similar for both primiparous and multiparous patients. In term patients the consequences from falsenegative diagnosis are not as important as in preterm gestations; however, they may include patient inconvenience or the worst rare case scenario is delivery en route to a hospital setting. Given the known inaccuracy of digital cervical exams1 in predicting true labor, CL by TVUS, along with the overall clinical assessment of the patient presenting for labor check, can provide an objective measurement to help patient management. However, the decision of hospital admission cannot rely only on CL but it should take into consideration the individual factors of each case. Our sample size did not allow for stratification by each gestational age from 37-42 weeks to investigate any differences in the accuracy of the CL cutoffs. Future, larger studies are needed to examine if the CL accuracy varies according to each gestational week. Some caution should be exercised in extrapolating our findings to other populations. In our study we used a strict definition of “labor” and as a result our prevalence of disease (true labor) was 58.4% (45/77), which may not be representative of other populations. Therefore, real-life scenarios or settings may carry different PPV and NPV for the diagnosis of true labor. However, our positive and negative likelihood ratios may be applicable to other populations

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TABLE 2

Diagnostic accuracy of cervical length to predict true labor at term CL 1.5 cm n (%)

CL2 n (%)

CL2.5 n (%)

CL3 n (%)

Sensitivity

30/45 (67)

37/45 (82)

41/45 (91)

43/45 (96)

Specificity

26/32 (81)

20/32 (63)

12/32 (38)

7/32 (22)

Positive predictive value

30/36 (83)

37/49 (76)

41/61 (67)

43/68 (63)

Negative predictive value

26/41 (63)

20/28 (71)

12/16 (75)

7/9 (78)

Positive likelihood ratio

67/16 (4.2)

82/37 (2.2)

93/62 (1.5)

96/78 (1.2)

Negative likelihood ratio

33/84 (0.39)

18/63 (0.29)

Sensitivity

20/31 (65)

Specificity

All subjects, n ¼ 77

7/38 (0.18)

4/22 (0.18)

26/31 (84)

31/31 (100)

31/31 (100)

14/16 (88)

10/16 (63)

6/16 (38)

5/16 (31)

Positive predictive value

20/22 (91)

26/32 (81)

31/41 (76)

31/42 (74)

Negative predictive value

14/25 (56)

10/15 (67)

6/6 (100)

5/5 (100)

Positive likelihood ratio

66/12 (5.5)

84/37 (2.3)

100/63 (1.6)

100/69 (1.4)

Negative likelihood ratio

34/88 (0.39)

16/63 (0.25)

0/38 (0)

0/31 (0)

11/15 (73)

13/15 (87)

Primiparous, n ¼ 47

Multiparous, n ¼ 30 Sensitivity

9/15 (60)

Specificity

11/15 (73)

12/15 (80)

9/15 (60)

7/15 (47)

2/15 (13)

Positive predictive value

9/12 (75)

11/17 (65)

11/19 (58)

13/26 (50)

Negative predictive value

12/18 (67)

9/13 (69)

7/11 (64)

2/4 (50)

Positive likelihood ratio

60/20 (3)

73/40 (1.8)

73/53 (1.4)

87/87 (1)

Negative likelihood ratio

40/80 (0.50)

27/60 (0.45)

27/47 (0.57)

13/13 (1.00)

CL, cervical length. Kunzier et al. Cervical length to predict true labor at term. Am J Obstet Gynecol 2016.

FIGURE 3

Cervical length versus time to delivery 700

600

Time to Delivery (hours)

500

400 Correla on coefficient (r)=0.48 300 p<0.001 200

100

0 0.0

1.0

2.0 3.0 Cervical Length (cm)

4.0

5.0

Cervical length vs time to delivery. Kunzier et al. Cervical length to predict true labor at term. Am J Obstet Gynecol 2016.

since these metrics are not influenced by different prevalences of disease (true labor). Another potential limitation of our study may be related to generalizability given the fact that it was performed in a single institution. We identified several strengths of the study. First, to our knowledge, this is the first study using CL to differentiate true from false labor in patients presenting at term for labor check. Second, the prospective observational study design reduced bias between the study groups. Third, the data were obtained in a reallife setting with residents who were trained in CL measurements performing the TVUS. Having residents undergo specific educational intervention has been shown to affect competence in performing accurate examinations.19 Fourth, the practitioners making

management decisions were blinded to the CLs measured, thereby decreasing bias in admissions and interventions. In summary, we analyzed various CL cutoffs and showed that the use of the CL cutoff of 1.5 is the optimal in an attempt to prevent unnecessary admissions with resulting obstetrical interventions, resource utilization, and increased costs in term patients presenting for labor check. Further studies are needed to include a larger number of patients of a diverse population to confirm our results. n References 1. Phelps JY, Higby K, Smyth, et al. Accuracy and intraobserver variability of stimulated cervical dilation measurements. Am J Obstet Gynecol 1995;173:942. 2. Berghella V, Tolosa JE, Kuhlman KA, et al. Cervical ultrasonography compared to manual examination as a predictor of preterm delivery. Am J Obstet Gynecol 1997;177:723-30. 3. Miller ES, Grobman WA. When to expect when you’re expecting: a mystery unsolved by cervical length. BJOG 2016;123:23. 4. Khalifeh A, Berghella V. Universal cervical length screening in singleton gestations without a previous preterm birth: ten reasons why it should be implemented. Am J Obstet Gynecol 2016;214:603-6. 5. Einerson BD, Grobman WA, Miller ES. Cost effectiveness of risk-based screening for cervical length to prevent preterm birth. Am J Obstet Gynecol 2016;214(Suppl):S257. 6. Temming LA, Durst JK, Tuuli MG, et al. Universal cervical length screening: implementation and outcomes. Am J Obstet Gynecol 2016;214: 523.e1-8. 7. Conde-Agudelo A, Romero R. Vaginal progesterone to prevent preterm birth in pregnant women with a sonographically short cervix: clinical and public health implications. Am J Obstet Gynecol 2015;214:235-42. 8. Gordon MC, McKenna DS, Stewart TL, et al. Transvaginal cervical length scans to prevent prematurity in twins: a randomized controlled trial. Am J Obstet Gynecol 2015;214:277.e1-7. 9. Conde-Agudelo A, Romero R. Predictive accuracy of changes in transvaginal sonographic cervical length over time for preterm birth: a systemic review and metaanalysis. Am J Obstet Gynecol 2015;213:789-801. 10. Tsoi E, Akmal S, Rane S, et al. Ultrasound assessment of cervical length in threatened preterm labor. Ultrasound Obstet Gynecol 2003;21:552-5. 11. Iam JD, Goldenburg RL, Meis PJ, et al; The length of the cervix and the risk of spontaneous premature delivery. National Institute of Child Health and Human Development Maternal Fetal Medicine Unit Network. N Engl J Med 1996;334: 567-72.

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SMFM Papers 12. Sonek JD, Iams JD, Blumenfeld M, et al. Measurement of cervical length in pregnancy: comparison between vaginal ultrasonography and digital examination. Obstet Gynecol 1990;76:172-5. 13. Rao A, Celik E, Poggi S, Poon L, Nicolaides KH. Cervical length and maternal factors in expectantly managed prolonged pregnancy: prediction of onset of labor and mode of delivery. Ultrasound Obstet Gynecol 2008;32:646-51. 14. Strobel E, Sladkevicius P, Rovas L, De Smet F, Karlsson E, Valentin L. Bishop score and ultrasound assessment of the cervix for prediction of time to onset of labor and time to delivery in prolonged pregnancy. Ultrasound Obstet Gynecol 2006;28:298-305. 15. Ware V, Raynor BD. Transvaginal ultrasonographic cervical measurement as a predictor of successful labor induction. Am J Obstet Gynecol 2000;182:1030-2. 16. Comas M, Cochs B, Martí L, et al. Ultrasound examination at term for predicting the outcome of delivery in women with a previous cesarean section. J Matern Fetal Neonatal Med 2016;1:1-21. 17. Osmundson S, Ou-Yang RJ, Grobman WA. Elective induction compared with expectant management in nulliparous women with an

ajog.org unfavorable cervix. Obstet Gynecol 2011;117: 583-7. 18. Clark SL, Miller DD, Belfort MA, Dildy GA, Frye DK, Meyers JA. Neonatal and maternal outcomes associated with elective term delivery. Am J Obstet Gynecol 2009;200:156.e1-4. 19. Vahanian SA, Gallagher K, Chavez MR, Kinzler WL, Vintzileos AM. Does educational intervention affect resident competence in sonographic cervical length measurement? J Matern Fetal Neonatal Med 2015:1-4. 20. Anderson HF, Nugent CE, Wanty SD, Hayashi RH. Prediction of risk for preterm delivery by ultrasonographic measurement of cervical length. Am J Obstet Gynecol 1990;163:859-67. 21. Schoen CN, Tabbah S, Iams JD, Caughey AB, Berghella V. Why the United States preterm birth rate is declining. Am J Obstet Gynecol 2014;213:175-80. 22. Hassan SS, Romero R, Vidyadhari D, et al. Vaginal progesterone reduces the rate of preterm birth in women with a sonographic short cervix: a multicenter, randomized, double-blind, placebo-controlled trial. Ultrasound Obstet Gynecol 2011;38:18-31. 23. Romero R, Nicolaides K, Conde-Agudelo A, et al. Vaginal progesterone in women with an asymptomatic sonographic short cervix in the midtrimester decreases preterm delivery and

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neonatal morbidity: a systematic review and metaanalysis of individual patient data. Am J Obstet Gynecol 2012;206:124.e1-19. 24. Society for Maternal-Fetal Medicine Publications Committee, with assistance of Vincent Berghella. Progesterone and preterm birth prevention: translating clinical trials data into clinical practice. Am J Obstet Gynecol 2012;206: 376-86.

Author and article information From the Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine (Drs Kunzier, Kinzler, Chavez, Adams, and Vintzileos), and Office of Health Outcomes Research, (Dr Brand), Winthrop University Hospital, Mineola; Department of Preventive Medicine (Dr Brand) and Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Stony Brook Medicine, Stony Brook (Drs Kunzier and Adams), NY. Received March 2, 2016; revised March 9, 2016; accepted March 17, 2016. The authors report no conflict of interest. Presented as a poster at the 36th annual meeting of the Society for Maternal-Fetal Medicine, Atlanta, GA, Feb. 1-7, 2016. Corresponding author: Nadia B. Kunzier, DO. [email protected]