Objective
We sought to assess pregnancy outcome along a continuum of cervical lengths (CLs) ≥25 mm.
Study Design
We conducted planned secondary analysis of a randomized cerclage trial of women with prior spontaneous preterm birth 17 0 -34 6/7 weeks. Outcomes of women who maintained CLs ≥25 mm were analyzed. Women with CLs <25 mm randomized to no cerclage comprised an internal comparison group.
Results
Of 1014 screened, 153 had CL <25 mm, and 672 had CL ≥25 mm. Birth <35 weeks occurred in 16% of the ≥25 mm cohort. The relationship between CLs ≥25 mm and birth gestational age was null ( P = .15). In the <25 mm group, progressively shorter CLs predicted birth <35 weeks ( P < .001); this relationship was null in the ≥25 mm group ( P = .17).
Conclusion
The continuum of CLs ≥25 mm measured between 16 0/7 -22 6/7 weeks does not predict gestational length in women with prior spontaneous preterm birth.
A prior spontaneous preterm birth is one of the strongest historical predictors of recurrence, and sonographic evaluation of the cervix, especially shortened cervical length (CL), has consistently been shown to be an effective predictor of preterm birth. Although not recommended for routine use in low-risk or unselected populations, CL screening appears to have the most clinical utility in high-risk populations. Previous reports have described the association between shortened CL below a prescribed cutoff and the risk of preterm birth. The use of a 25-mm cutoff in the midtrimester has been utilized by investigators and clinicians to identify women at the highest risk of preterm birth. This cutoff threshold value is the lower 10th percentile in both unselected and high-risk populations. The 25-mm threshold has also been utilized as the basis for cerclage intervention trials.
Systematic reviews confirm a consistent relationship between short cervix and earlier birth in various populations, but, using the native reports that populated the reviews, these investigators primarily sought to summarize and compare sensitivities, specificities, and likelihood ratios for preterm birth at various CL and gestational age thresholds. None specifically evaluated the continuum of CLs above a specified threshold for the prediction of preterm birth, as the outcomes of patients with longer CLs were simply pooled to calculate the screening test characteristics. Iams et al in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network evaluated nearly 3000 unselected women at 24 weeks’ gestation and found increasing relative risks of preterm birth with cervical shortening using the upper quartile >40 mm as the referent group; however, the trend in rates of preterm birth associated with CLs above a 25-mm threshold was not formally evaluated.
To improve clinical decision making, patient selection for intervention trials, and our understanding of the preterm birth syndrome, the risks of preterm birth associated with longer CLs in high-risk women requires further characterization. Our null hypothesis was that the continuum of CLs above a 25-mm CL threshold would not be associated with pregnancy duration in women with prior preterm birth.
Materials and Methods
This is a planned secondary analysis of a randomized clinical trial performed by a consortium of 15 US Centers from January 2003 through November 2007. Multiparous women carrying a singleton and who had experienced at least 1 prior spontaneous preterm birth between 17 0/7 -33 6/7 weeks’ gestation, confirmed by a review of the patient’s medical records, underwent serial vaginal sonographic assessment of CL. Exclusion criteria were fetal anomaly, planned history-indicated cerclage for a clinical diagnosis of cervical insufficiency, and clinically significant maternal-fetal complications. Other details of the study protocol are described elsewhere.
Sonologists underwent a uniform certification process by a single investigator (J.O.) to ensure uniformity in sonographic equipment, measurement technique, completion of study forms, and adherence to protocol. Specifics of this sonographic evaluation based on the technique of Iams et al have been previously described: the CL at each visit was measured along a closed endocervical canal, where minimal degrees of apparent dilation (ie, echolucency along the entire canal) <5 mm were considered closed. Fundal pressure was also applied for 30 seconds by the sonologist as a provocative maneuver, and each scan included an evaluation period of at least 5 minutes to detect spontaneously occurring cervical shortening. The shortest CL for each examination that clearly displayed the internal and external cervical os with equivalent thickness of the anterior and posterior cervix was recorded as the CL, regardless of whether the measurement was obtained with pressure or was the result of spontaneous dynamic shortening. Managing physicians were masked to the results of the sonographic evaluations except in cases of complete placenta previa, oligohydramnios, or fetal death.
The first sonographic assessment was scheduled in the gestational age window 16 0/7 -21 6/7 weeks. Subsequent evaluations were scheduled every 2 weeks. If the CL was observed to be 25-29 mm, scans were scheduled weekly. If on any evaluation the CL was <25 mm, the woman became eligible for randomization to cerclage or to a no-cerclage group. Women with a CL that remained at least 25 mm at the final sonographic evaluation, scheduled to be no later than 22 6/7 weeks, were ineligible for randomization and comprised the ≥25 mm cohort. We also compared their outcomes to an internal control group of women who qualified for the trial based on a CL <25 mm and were randomized to no cerclage. The protocol and consent forms received local institutional review board approval at all centers.
Categorical variables were analyzed with χ 2 or the Mantel-Haenszel test of trend, while continuous variables were compared using a t test or Wilcoxon rank sum test. Linear regression modeled the association between 2 continuous variables. Differences in time to birth were assessed by Kaplan-Meier curves and the log rank test. Multivariable Cox proportional hazard models considered possible confounders for time to birth. An alpha level of 0.05 was selected to represent statistical significance. Analyses were performed using SAS 9.2 (SAS Institute Inc, Cary, NC).
Results
A total of 1014 eligible women gave consent and underwent their initial sonographic assessment of CL. From this cohort, we observed 318 (31%) who experienced CL shortening <25 mm. Sixteen patients did not consent to randomization, and 302 (95%) entered the randomized trial; 153 were assigned to the no-cerclage cohort. Of the 696 who underwent their initial scan and failed to shorten to <25 mm, delivery outcomes were available in 672 (96.6%); these comprised the ≥25 mm cohort ( Figure 1 ). Selected characteristics of the 2 study cohorts are shown in the Table . As anticipated, the cohorts differed with regard to several characteristics.
| Variable | <25 mm (n = 153) | ≥25 mm (n = 672) | P value |
|---|---|---|---|
| Maternal age, y | 26.6 ± 5.1 | 26.7 ± 5.3 | .72 |
| No. of prior births | 2 (1-4) a | 2 (1-4) a | .33 |
| ≥1 prior induced abortion, n (%) | 25 (16) | 62 (9) | .01 |
| Body mass index, kg/m 2 | 29.9 ± 7.5 | 28.7 ± 7.1 | .07 |
| Race/ethnicity, n (%) b | < .0001 | ||
| Black (non-Hispanic) | 93 (61) | 217 (32) | |
| White (non-Hispanic) | 28 (18) | 128 (19) | |
| Hispanic | 17 (11) | 208 (92) | |
| Asian | 0 (0) | 11 (2) | |
| Other | 15 (9.8) | 108 (16) | |
| Marital status, n (%) | |||
| Single/never married | 99 (65) | 337 (50) | .002 |
| Married | 42 (27) | 294 (44) | |
| Divorced | 10 (6.5) | 36 (5.4) | |
| Widowed | 1 (0.7) | 4 (0.6) | |
| Other | 1 (0.7) | 1 (0.2) | |
| Prior cerclage, n (%) | 12 (7.8) | 17 (2.5) | .001 |
| Education, y | 11.9 ± 2.4 | 11.6 ± 4.4 | .35 |
| Gestational age of qualifying birth, wk | 24.9 ± 4.7 | 26.8 ± 4.4 | < .0001 |
| Gestational age at first vaginal sonogram, wk | 17.4 ± 1.4 | 17.8 ± 1.4 | .002 |
| Cervical length at first vaginal sonogram, mm | 29.5 ± 12.9 | 40.6 ± 10.1 | < .0001 |
| Gestational age at randomization or final sonogram, wk | 19.5 ± 2.0 | 21.3 ± 1.4 | < .0001 |
| Cervical length at randomization or final sonogram, mm | 19.5 ± 5.3 | 37.9 ± 8.2 | < .0001 |
| Total vaginal sonograms, n | 2 (1–4) a | 3 (1–4) a | < .0001 |
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