Objective
The purpose of this study was to determine the pregnancy outcome of asymptomatic patients in the second trimester with a nonmeasurable cervical length (0 mm).
Study Design
This retrospective cohort study included 78 patients with singleton pregnancies and a sonographic nonmeasurable cervix that was detected at 14-28 weeks of gestation. Patients with cervical cerclage were excluded.
Results
We found that (1) 75.3% of the patients delivered before 32 weeks of gestation; (2) the median diagnosis-to-delivery interval was 20.5 days, and the delivery rate within 7 and 14 days was 28.2% and 35.6%, respectively; and (3) patients with a nonmeasurable cervix that was diagnosed at <24 weeks of gestation had a shorter median diagnosis-to-delivery interval than patients who were diagnosed at 24-28 weeks of gestation (17.5 vs 41 days; P = .009).
Conclusion
Asymptomatic women with a nonmeasurable cervix in the second trimester have a median diagnosis-to-delivery interval of approximately 3 weeks. Almost 65% of these patients will not deliver within 2 weeks, yet 75% of them will deliver before 32 weeks of gestation. The earlier a nonmeasurable cervix is identified, the shorter the diagnosis-to-delivery interval.
Preterm birth is the leading cause of perinatal morbidity and death worldwide. A short cervical length is recognized as a powerful predictor of spontaneous preterm birth; and transvaginal cervical sonography is the most objective and reliable method to assess cervical length. However, there is no agreement as to the definition of a sonographic short cervix. Iams et al reported that a sonographic cervical length of ≤25 mm at 24 weeks of gestation is associated with a prevalence of 4.3% of spontaneous preterm delivery at <35 weeks of gestation and a positive predictive value of only 17.8%. Subsequently, a cutoff of 15 mm has been proposed. The prevalence of a sonographic cervical length of ≤15 mm ranges from 0.6% at 14-24 weeks of gestation to 1-1.7% at 20-24 weeks of gestation. The rate of preterm delivery in these patients varies according to the gestational age at diagnosis. In asymptomatic women with a sonographic cervical length of ≤15 mm between 14 and 24 weeks of gestation, the rate of spontaneous preterm delivery at ≤32 weeks of gestation is 48%.
For Editors’ Commentary, see Table of Contents
Despite the broad range of criteria for the definition of a sonographic short cervix, it is generally accepted that the shorter the sonographic cervical length in the midtrimester, the higher the risk of spontaneous preterm labor/delivery. However, data regarding pregnancy outcome of asymptomatic patients with a nonmeasurable cervical length (usually described as a “0 mm” cervix) are limited and based on a small number of patients. These patients are considered to be at a very high risk of preterm delivery. Furthermore, therapeutic interventions such as vaginal progesterone, cervical cerclage, antibiotics, or indomethacin are of limited success in women with an extremely short cervix.
The aim of this study was to determine the pregnancy outcome of asymptomatic patients with a nonmeasurable cervical length (0 mm) that was diagnosed in the second trimester of pregnancy (14-28 weeks of gestation) by transvaginal sonography.
Materials and Methods
Study population
This retrospective cohort study included pregnant women with a singleton pregnancy whose cases were followed at our cervix clinic between January 2002 and December 2008. With a computer-based search of our clinical and sonographic databases, consecutive asymptomatic patients between 14 and 28 weeks of gestation with a nonmeasurable cervical length (0 mm), as determined by a documented transvaginal ultrasound (TVUS) examination, were identified. Patients with ≥1 of the following conditions were excluded: (1) multifetal pregnancy; (2) premature contractions, preterm labor, or preterm prelabor rupture of membranes at the time of diagnosis; (3) cervical cerclage (placed before or after the diagnosis of a short cervix); (4) placenta previa, and (5) fetuses with chromosomal and/or congenital anomalies.
Patients were diagnosed with a nonmeasurable cervical length during TVUS evaluation of the cervix. Digital assessment of the cervix was performed in all patients. The ultrasound findings were recorded and stored in a dedicated database. After the diagnosis of a short cervix, the patients were referred to the labor and delivery ward for further evaluation and treatment. Both the sonographic cervical length and the result of the digital vaginal examination were available to the managing physicians. The standard obstetrics practice in our institution is to offer amniocentesis to determine the microbial status of the amniotic cavity to patients with an asymptomatic short cervix, based on previous observations that suggest an association between a sonographic short cervix and histologic chorioamnionitis and intraamniotic infection.
All participating women provided written informed consent before inclusion in this study. The use of clinical and ultrasound data for research purposes was approved by the Institutional Review Boards of Wayne State University and the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Department of Health and Human Services.
Definitions and study procedures
Gestational age was determined by the last menstrual period or by ultrasound if the sonographic determination of gestational age was not consistent with the menstrual dating by >1 week in the first trimester and by >2 weeks in the second trimester of pregnancy. Gestational age at diagnosis was defined as the earliest gestation at which a cervical length of 0 mm was documented by TVUS examination. Data regarding pregnancy outcomes were obtained from the clinical and research records. Patients who were lost to follow-up and for whom delivery data were not available were censored from the last available follow-up visit.
Patients with an a priori increased risk for spontaneous preterm delivery included those patients with a history of at least 1 of the following conditions: (1) ≥1 previous spontaneous preterm deliveries (≤35 weeks of gestation), (2) ≥1 late midtrimester spontaneous miscarriages (≥16 weeks of gestation), (3) ≥2 curettage procedures, and (4) previous cervical surgery (loop electrosurgical excision procedure or cone biopsy).
To maintain an interpretable temporal relationship between the results of amniocentesis and pregnancy outcome, only the results from amniocentesis that had been performed within 7 days of diagnosis of a nonmeasurable cervical length were included in the statistical analyses. Intraamniotic infection was defined as a positive amniotic fluid culture for microorganisms (aerobic/anaerobic bacteria or genital mycoplasmas). Intraamniotic inflammation was defined as an amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL. Amniotic fluid IL-6 concentrations were determined using a specific and sensitive immunoassay (R&D Systems, Minneapolis, MN) after all patients were delivered and were not used in clinical management.
From a clinical perspective, the gestational age at delivery is more important than the diagnosis-to-delivery interval per se. For example, an interval to delivery of 6 weeks for a patient whose condition was diagnosed at 16 weeks of gestation is not associated with a better outcome than an interval of only 2 weeks in a patient whose condition was diagnosed at 26 weeks of gestation. To overcome this limitation and to take into account the relative wide range (14-28 weeks) of gestational age at diagnosis that was included in this study, an “interval ratio” was calculated for each patient according to the following formula: diagnosis-to-delivery interval (days)/diagnosis-to-37-week interval (days). Ratios of ≥1 represent patients who delivered at term (≥37 weeks of gestation). The lower the ratio, the shorter the time the patient remained pregnant after diagnosis relative to expected remaining time to term.
Sonographic assessment of the cervix
Transvaginal ultrasound examination was conducted with commercially available 2-dimensional and 3-dimensional ultrasound systems (Acuson Sequoia: Siemens Medical Systems, Mountain View, CA; and Voluson 730 Expert or Voluson E8: GE Healthcare, Milwaukee, WI) that were equipped with endovaginal transducers with frequency ranges of 5-7.5 MHz and 5-9 MHz, respectively. All sonographic examinations of the cervical length were performed by registered diagnostic medical sonographers who used a technique previously described and were reviewed by an experienced physician. Amniotic fluid sludge was identified by the presence of dense aggregates of particulate matter in proximity to the internal cervical os, as previously described. Two experienced sonographers who were blinded to clinical outcome reviewed the 2-dimensional images and 3-dimensional volume datasets of the cervix for the presence of amniotic fluid sludge, which was considered to be present only when identified by both examiners.
Statistical analysis
The main outcome variables were the diagnosis-to-delivery interval, the rate of delivery within 7 and 14 days from diagnosis, and the rate of early preterm delivery (<32 weeks of gestation). Patients were further stratified by gestational age at diagnosis (<24 weeks vs 24-28 weeks of gestation). Subjects who had an indicated preterm delivery because of a diagnosis that could not be attributed directly to the initial diagnosis of a short cervix (eg, preeclampsia, fetal growth restriction, fetal death, etc) were censored from the statistical analyses at the corresponding gestational age at induction of labor.
Comparisons among groups were performed with the Fisher’s exact test for categoric variables and the Mann-Whitney U test for comparisons of continuous variables. Correlation between continuous variables was assessed by Spearman’s rho correlation test. Multivariable logistic regression (backward-stepwise) analyses were performed to determine the relationship between maternal age, gestational age at the time of ultrasound diagnosis, cervical dilation (as continuous variables), nulliparity, an a priori risk for preterm delivery, 17-hydroxyprogesterone caproate prophylactic treatment and the presence of amniotic fluid sludge (as categoric variables), and pregnancy outcomes (delivery within 7-14 days and at <32 weeks of gestation). A Kaplan-Meier survival analysis was performed to assess the diagnosis-to-delivery interval according to the cervical length and presence or absence of amniotic fluid sludge. A probability value of < .05 was considered statistically significant. SPSS statistical package (version 14.0; SPSS Inc, Chicago, IL) was used for analysis.
Results
During the study period, 78 asymptomatic patients with a sonographic cervical length of 0 mm during the second trimester of pregnancy met the inclusion criteria of this study. The earliest gestational age at which an asymptomatic nonmeasurable cervical length was recorded by TVUS examination was 17 weeks and 4 days. There was a high correlation between the gestational age at diagnosis and the gestational age at delivery (Spearman’s rho, 0.73; P < .0001).
Demographic and clinical characteristics of the study population are listed in Table 1 . Women who received a diagnosis of a nonmeasurable cervical length at 24-28 weeks of gestation had a higher median prepregnancy body mass index than did the women who received the diagnoses at <24 weeks of gestation ( P = .027). Both the median gestational age at delivery and the median neonatal birthweight were lower in patients whose condition was diagnosed at <24 weeks of gestation than in patients whose case was diagnosed between 24 and 28 weeks of gestation ( P < .001 for both; Table 1 ). The median cervical dilation was slightly greater in patients whose condition was diagnosed at 24-28 weeks of gestation than in the women whose condition was diagnosed earlier in the midtrimester ( P = .041). Yet, the median diagnosis-to-delivery interval was shorter among the group of patients whose condition was diagnosed earlier in pregnancy ( P = .009; Table 2 ). Similarly, the interval ratio (diagnosis-to-delivery interval/diagnosis-to-37 weeks of gestation interval) was significantly lower in patients whose condition was diagnosed at <24 weeks of gestation than in those women who received the diagnosis at 24-28 weeks of gestation ( P = .001; Table 2 )
