Objective
The purpose of this study was to assess funnel type and pregnancy duration in women with previous spontaneous preterm birth and cervical length <25 mm.
Study Design
We performed a secondary analysis of a multicenter randomized trial of cerclage. At the randomization scan that documented short cervix, the presence and type of funnel (U or V) were recorded.
Results
One hundred forty-seven of 301 women (49%) had funneling: V-shaped funnel, 99 women; U-shaped funnel, 48 women. U-shaped funnel was associated significantly with preterm birth at <24, <28, <35, and <37 weeks of gestation. In multivariable models that controlled for randomization cervical length and cerclage, women with U-shaped funnel delivered earlier than women with either V-shaped funnel or no funnel. Interaction between cerclage and U-shaped funnel was observed, and analyses that were stratified by cerclage showed that women with a U-shaped funnel and cerclage delivered at a mean of 33.8 ± 6.6 weeks of gestation, compared with women who did not receive cerclage (28.9 ± 6.9 weeks of gestation).
Conclusion
U-shaped funnels in high-risk women with a short cervix are associated with earlier birth.
Preterm birth (PTB) is the leading cause of perinatal morbidity and death. Most PTBs occur spontaneously and are not due to maternal-fetal indications. The incidence of PTB continues to rise largely because of our poor understanding of the pathophysiologic condition and the paucity of effective interventions, which, combined, has limited our ability to select patients properly for specific therapy. The relationship between shortened cervical length and PTB has been well characterized in both unselected and high-risk women. Cervical length assessment has been well standardized and is reproducible. Other lower uterine segment and cervical characteristics, in addition to cervical length, can be assessed by mid-trimester ultrasound scans. One of these characteristics is the presence of a cervical funnel. The presence of a funnel has been shown to be a significant risk factor for adverse perinatal outcome and is best measured as a categoric variable (present or absent). Other investigators have suggested that the finding of a funnel at the internal os is a poor independent predictor of PTB once the effect of short cervix is considered. The shape of the funnel (U or V), percent funneling, and the depth and width of the funnel have all been described as methods of assessing cervical funneling. In high-risk women, the progression to a U-shaped funnel has been associated with an increased risk of preterm delivery. Thus, the relationship between cervical funneling and PTB remains unclear.
In women with a previous early spontaneous PTB and shortened cervical length of <25 mm, cerclage has been shown to reduce PTB to <37 weeks of gestation, previable birth of <24 weeks of gestation, and perinatal death. However, the relationship between funneling and ultrasound-indicated cerclage has also not been well characterized.
We postulated that funnel shape would be associated with different effects on gestational length and might respond differently to cerclage intervention. The aim of this study was to assess the relationship between the type of cervical funneling and pregnancy duration in women with previous spontaneous PTB and cervical length of <25 mm who were enrolled in a randomized intervention trial of ultrasound-indicated cerclage.
Materials and Methods
This was a planned, secondary analysis of the National Institute of Child Health and Human Development–sponsored randomized trial of cerclage for PTB prevention that was performed by a consortium of 15 U. Clinical Centers between January 2003 and November 2007. Healthy, multiparous women who enrolled for prenatal care before 22 weeks of gestation were screened to identify the women with at least 1 previous spontaneous PTB between 17 0/7 and 33 6/7 weeks of gestation.
Exclusion criteria were fetal anomaly, planned history-indicated cerclage for a clinical diagnosis of cervical insufficiency, acute cervical insufficiency (defined as 2-cm dilation and visible membranes at the external os), and clinically significant maternal-fetal complications. Eligible women were invited to consent for the ultrasound screening phase of the trial. Other details of the study protocol are described elsewhere.
Consenting women underwent serial transvaginal sonographic evaluations, the first of which was scheduled in the temporal window of 16 0/7 to 21 6/7 weeks of gestation. Subsequent scans were scheduled every 2 weeks, unless the cervical length was observed to be 25-29 mm, after which scans were scheduled on a weekly basis. Women with a cervical length that remained at least 25 mm by the final sonographic evaluation, which was scheduled to be no later than 22 6/7 weeks, were ineligible for random assignment and resumed their obstetric care. If on any evaluation the cervical length was <25 mm, the woman became eligible for the random assignment to either receive a McDonald cerclage or to enter a no cerclage group. Women who were assigned to no cerclage could receive a physical examination–indicated cerclage after random assignment for the clinical diagnosis of acute cervical insufficiency.
Cervical length was measured by the standard technique as described by Iams et al. Trial 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. The cervical length at each visit was measured along a closed endocervical canal. Minimal degrees of apparent dilation <5 mm were considered closed. After a baseline cervical length was measured, fundal pressure was applied for 30 seconds as a provocative maneuver; each scan included an evaluation period of at least 5 minutes to detect spontaneous cervical shortening. The shortest cervical length at each examination was recorded as the cervical length, regardless of whether the measurement was obtained with pressure or was the result of spontaneous dynamic shortening.
During the ultrasound examination, the presence and type of funnel (U- or V-shaped) were recorded. Cervical funneling was defined as the protrusion of the amniotic membranes of ≥5 mm into the internal os, as measured along the lateral border of the funnel. Care was taken to differentiate between a true funnel and a pseudo-funnel. A pseudo-funnel may occur when the lower uterine segment forms what appears to be a funnel above an otherwise normal-length cervix.
Study outcomes included gestational age at birth, rates of PTB at several gestational age cutoffs, and time to birth that was assessed by survival analysis. Gestational age at delivery was modeled as a function of funnel type in a simple linear regression model. The cervical length and funnel type at the qualifying evaluation for randomization were recorded. Women were classified as having U-funnel, V-funnel, or no cervical funneling. For this study, we considered actual cerclage placement, not assigned randomization group.
Multiple and pairwise comparisons for the rates of PTB in these funnel classification groups were evaluated with χ 2 tests and logistic regression. Time to delivery was estimated with the Kaplan-Meier method, and group differences were evaluated with the log-rank statistic. Descriptive statistics for these 3 groups of patients were compared using analysis of variance for continuous measures and chi-square tests for categoric measures. Multivariable linear regression, logistic regression, and Cox proportional hazards models were then considered for gestational age, rates of PTB, and time to delivery, respectively. An alpha level of .05 was selected to represent statistical significance for main effects and .10 for interactions. All analyses were performed using SAS software (version 9.2; SAS Institute Inc, Cary, NC).
The protocol and data forms were reviewed and approved by the human-use committees at all participating centers.
Results
Of the 1044 women who had a qualifying previous PTB, 1014 women (99%) gave informed consent and underwent their initial sonographic assessment of cervical length. From this cohort, we observed 318 women who experienced cervical length shortening of <25 mm. Sixteen patients were excluded (13 women did not consent to randomization; 2 women were ruled ineligible at the randomization visit, and 1 woman withdrew from the trial), which left 302 (95%) who were assigned randomly to the no-cerclage (n = 153) or cerclage groups (n = 149). Primary outcome information was available for all 153 women in the no-cerclage group and for 148 of 149 women in the cerclage group, which left a total of 301 women in the analysis. As depicted in Figure 1 , of the 153 women who were assigned to the no-cerclage group, 14 women underwent cerclage placement; 4 cerclage placements were at the discretion of their treating physicians (off-protocol treatment crossover) , and 10 cerclage placements were undertaken for a diagnosis of acute cervical insufficiency (protocol-sanctioned treatment crossover). Similarly, of the 149 women who were assigned to receive cerclage, 11 women did not undergo surgery; 8 women declined to undergo surgery, whereas 3 procedures were contraindicated because of obstetric complications (intraamniotic infection, fetal death, and cervicitis). Thus, the study cohorts included 152 women who did and 149 women who did not receive cerclage.
Of the 301 women who comprised the study population, 147 women (49%) had a funnel present at their qualifying sonogram: 99 funnels were V-shaped, and 48 funnels were U-shaped. Selected characteristics for each of the 3 groups are presented in Table 1 . Of note, the shortest observed cervical length ( P < .0001) and actual cerclage placement ( P = .015) differed among the funnel groups. To control for differences in cerclage placement and shortest cervical length, statistical models that incorporated these 2 covariates and possible interactions were considered.
