Serial cervical length determination in twin pregnancies reveals 4 distinct patterns with prognostic significance for preterm birth

Abstract

Background: Women with a twin gestation are at increased risk for preterm birth (PTB), and sonographic cervical length (CL) is a powerful predictor for spontaneous PTB. Obstetricians frequently monitor CL in multiple gestations; yet, the optimal method to integrate and interpret the results of serial sonographic CL has not been determined.

Objective: We sought to determine whether there are different patterns of cervical shortening in twin gestations, and whether such patterns are related to the risk of PTB.

Study design: We conducted a retrospective study of all women with twins followed up in a single tertiary referral center during 2012 through 2014. All women underwent serial measurements of CL every 2-3 weeks starting from 14-18 weeks and until 28-32 weeks of gestation. Changes in CL were analyzed and classified into distinct patterns that were initially identified by visual inspection of all individual cases. Each pattern was then characterized by several parameters including information about when cervical shortening began, the rate of shortening, and whether a plateau was observed. Locally weighted regression mean profiles were generated to describe each pattern of CL over time. The association of these patterns with spontaneous PTB was determined. The specific characteristics of each pattern that further determined the risk of PTB were identified using multivariable logistic regression analysis.

Results: We studied 441 women who had a total of 2826 measurements of CL done. Overall, 4 main patterns of change in CL were identified: pattern I, stable cervix (n = 196); pattern II, early and rapid shortening (n = 18); pattern III, late shortening (n = 109); and pattern IV, early shortening with a plateau (n = 118). The rate of PTB at <34 weeks was lowest in cases of pattern I (11.7%), followed by pattern IV (14.4%) and pattern III (20.2%), and was highest for women with pattern II (44.4%) (P < .001). In cases with pattern III (late shortening), the most important factors affecting the risk of PTB were the shortening rate, the gestational age at the onset of cervical shortening, and the initial plateau of CL. In the case of pattern IV (early shortening with a plateau), it was only the new plateau at which cervical shortening stopped that was associated with the risk of PTB.

Conclusion: Changes in sonographic CL over time in twin gestations can be classified into 4 patterns, each associated with a different risk of PTB.

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

Figure 1. Cervical length as a function of gestational age according to preterm birth prior to 32 weeks

Women who did and those who did not give birth prior to 32 weeks of gestation are represented by the dashed lines and solid lines, respectively. The differences in mean cervical length between the two groups is presented at gestational age of 18, 20, 23, 25 and 28 weeks. The slope of the regression line for women who gave birth prior to 32 weeks (beta=−1.72) is significantly greater than the slope of the regression line for women who did not (beta=−0.85, p<0.001 using ANCOVA).

Figure 2. Patterns of change in sonographic cervical length in twin gestations

Four patterns were identified: Pattern I – stable cervix (A), Pattern II – Early rapid shortening (B), Pattern III – Late shortening (C), and Pattern IV – Early shortening with plateau (D). The proportion of women in the study group having each of the distinct patterns is noted at the lower left corner of each graph. The solid lines are schematic representation of each of the patterns. The dashed lines represent examples of individual cases that were classified under the specific pattern.

Figure 3. Mean and 95% confidence intervals of each pattern of cervical length in twin gestations determined using locally-weighted regression

The colored lines represent locally weighted regression mean profiles (95% confidence interval bands) for each of the four curve types. The regression lines are superimposed on population smoothed quantiles (estimated by longitudinal quantile regression).

Figure 4. The rate of preterm birth associated with each of the four patterns of change in cervical length

PTB, preterm birth

Figure 5. Survival probability expressed as a function of the pattern of cervical length shortening over time

The survival probability differed significantly as a function of the pattern of cervical length change over time when censoring patients who delivered at or after 34 weeks (Log-Rank p<0.0001)