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.

Study design: 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.

Conclusion: 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.

Keywords: biomarker; cervical ripening; cervical shortening; cervix; labor; longitudinal study; prediction; pregnancy; prematurity; preterm labor; screening; ultrasound.

Figure 1. Cervical length at each period of gestation in women who did or did not deliver at <32 weeks

^*p<0.001 (Student’s t-test). Data reflect the mean cervical length at each gestational age period. Similar findings were observed for women who did or did not deliver at <34 weeks (data not shown).

Figure 2. Change in cervical length between successive periods of gestation in women who did or did not deliver at <32 weeks

^*p<0.001 ^**p<0.01 Data reflect the change in cervical length between different period of gestation. The change in cervical length was calculated as follows: ([cervical length in later period - cervical length in earlier period] / cervical length in earlier period) x100. Thus, lower (more negative) values reflect greater cervical shortening. Similar findings were observed for women who did or did not deliver at <34 weeks (data not shown).

Figure 3. Effect of serial measurements of cervical length (interpreted as absolute length in mm) on the ROC curve for the prediction of preterm birth <32 weeks

ROC, Receiver operating characteristic; AUC, area under the ROC curve; CL cervical length ROC curves are presented for: single measurement of CL in Period 1 (blue line), combination of CL in periods 1 and 2 (green line), combination of CL in periods 1, 2 and 3 (orange line), and combination of CL in periods 1, 2, 3 and 4 (red line). ^*p<0.001 compared with AUC of single measurement of cervical length in period 1 ^**p=0.004 compared with AUC of single measurement of cervical length in period 1

Figure 4. Effect of serial measurements of cervical length (interpreted as percentage shortening compared with period 1) on the ROC curve for the prediction of preterm birth <32 weeks

ROC, Receiver operating characteristic; AUC, area under the ROC curve; CL cervical length ROC curves are presented for: single measurement of CL in Period 1 (blue line), combination of CL in period1 and percentage shortening between period 1→2 (green line), combination of CL in period1 and percentage shortening between periods 1→2 and 1→3 (orange line), and combination of CL in period1 and percentage shortening between periods 1→2, 1→3 and 1→4 (red line). ^*p<0.001 compared with AUC of single measurement of cervical length in period 1 ^**p=0.007 compared with AUC of single measurement of cervical length in period 1