Objective
The objective of the study was to determine whether risk of recurrent preterm birth differs based on the clinical presentation of a prior spontaneous preterm birth (SPTB): advanced cervical dilatation (ACD), preterm premature rupture of membranes (PPROM), or preterm labor (PTL).
Study Design
This retrospective cohort study included singleton pregnancies from 2009 to 2014 complicated by a history of prior SPTB. Women were categorized based on the clinical presentation of their prior preterm delivery as having ACD, PPROM, or PTL. Risks for sonographic short cervical length and recurrent SPTB were compared between women based on the clinical presentation of their prior preterm birth. Log-linear regression was used to control for confounders.
Results
Of 522 patients included in this study, 96 (18.4%) had prior ACD, 246 (47.1%) had prior PPROM, and 180 (34.5%) had prior PTL. Recurrent PTB occurred in 55.2% of patients with a history of ACD compared with 27.2% of those with PPROM and 32.2% with PTL ( P = .001). The mean gestational age at delivery was significantly lower for those with a history of ACD (34.0 weeks) compared with women with prior PPROM (37.2 weeks) or PTL (37.0 weeks) ( P = .001). The lowest mean cervical length prior to 24 weeks was significantly shorter in patients with a history of advanced cervical dilation when compared with the other clinical presentations.
Conclusion
Patients with a history of ACD are at an increased risk of having recurrent preterm birth and cervical shortening in a subsequent pregnancy compared with women with prior preterm birth associated PPROM or PTL.
Spontaneous preterm birth is a leading cause of perinatal morbidity and mortality. Long-term sequelae of preterm birth include cerebral palsy, cognitive and developmental abnormalities, and chronic respiratory disease; increased risks for these conditions are particularly high when delivery occurs at very early gestational ages. Because of the neonatal risks associated with preterm birth, extensive research has focused on improving screening for preterm birth risk and optimizing the interventions that reduce preterm birth rates.
Although the causes of preterm birth are only partially understood, preterm delivery is thought to occur by multiple mechanisms and may manifest in a variety of clinical presentations. Spontaneous preterm labor (PTL) with intact membranes, preterm premature rupture of membranes (PPROM), and advanced cervical dilatation (ACD) may all represent distinct pathways resulting in early delivery.
The specific presentation of a prior preterm birth may be of clinical importance in a subsequent pregnancy, both in terms of guiding interventions and in terms of prognosticating risk. In particular, clinical management may differ for ACD; interventions such as cerclage are supported specifically for a history of this condition. However, there are few data comparing subsequent obstetric outcomes based on clinical presentation of prior preterm delivery, both in terms of subsequent preterm birth rates and whether related risk factors, such as short transvaginal sonographic cervical length, are present.
Given the importance of elucidating preterm birth risk factors, both for guiding interventions and for patient surveillance and counseling, the purpose of this study was to compare subsequent pregnancy outcomes of women who had a prior preterm birth based on whether they had a history of PTL, PPROM, or ACD. We hypothesized that patients with a history of preterm delivery because of advanced cervical dilatation are at higher risk of recurrent preterm birth and cervical shortening in a subsequent pregnancy compared with those with a history of PPROM or PTL.
Materials and Methods
This retrospective cohort study evaluated women with a current singleton pregnancy and an obstetric history significant for a prior spontaneous preterm birth. Patients were identified from an ultrasound database from a single tertiary center (Columbia University Medical Center, New York, NY). This database includes midtrimester transvaginal ultrasound cervical length measurements because cervical length screening is standard practice at our institution for all women with prior spontaneous preterm birth <37 weeks. Cervical length measurements take place every 2 weeks between 16 weeks onward or more frequently if short cervical length is detected.
Patients were included if they received care between 2009 and 2014. Patients with multiple gestations, major fetal anomalies, abdominal cerclage, physical examination–indicated cerclage, missing delivery data, a history of iatrogenic preterm birth, or evidence of placental abruption at the time of delivery or by placental pathology were excluded. Additionally, patients were excluded if documentation of the clinical presentation of the prior preterm birth was unclear and thus could not be categorized. This included patients who presented for evaluation of PPROM but were found have cervical dilation because we considered the potential for misclassification among these patients. Approval for this study from the Columbia University Institutional Review Board was obtained.
Review of the electronic medical record was performed to obtain individual demographic, obstetric, and medical information. Documentation of receipt of vaginal or intramuscular progesterone administration was abstracted, as was whether a patient received a history or ultrasound-indicated cerclage. Women were categorized based on whether their prior preterm birth presentation was most compatible with 1 of 3 specific diagnoses: advanced cervical dilation, PPROM, or preterm labor. This designation was based on at least one of the following sources: review of inpatient hospital records for the index preterm birth, obstetric history obtained at a first prenatal visit, and/or a maternal-fetal medicine consultation.
Patients were categorized as having a history of advanced cervical dilation if they reported that in the absence of contractions they were found to have a dilated cervix on examination for spotting, increased pelvic pressure, or increased discharge or were otherwise incidentally diagnosed with cervical dilatation. Patients were considered to have a history of PPROM if they reported preterm rupture of membranes in the absence of contractions. Patients were allocated to the preterm labor group if they reported presenting for evaluation for painful contractions or reported painful contractions with concomitant rupture of membranes at the time of presentation to labor and delivery. Whether patients did or did not have additional prior term deliveries was also abstracted.
The shortest cervical length measurement between 16 and 24 weeks’ gestation was determined for each patient. Based on our institution’s protocol, cervical length measurements take place every 2 weeks for women with a history of prior preterm birth or more frequently if short cervical length is detected. Each transvaginal cervical length assessment was obtained using the technique published by Iams et al, wherein sonographers record the shortest cervical length for each examination that clearly displays the internal and external os with equivalent thickness of the anterior and posterior cervix.
Sonographer training at our site was performed in conjunction with a Maternal-Fetal Medicine Units Network study by Grobman et al and involved a didactics series and image submission. Additionally, the obstetrical ultrasound guidelines at Columbia University Medical Center require 3 measurements of the cervix, including at least 1 assessment while the patient performs the Valsalva maneuver. The shortest of the 3 cervical length values is reported clinically, and this measurement was recorded into our database for each visit.
Sonographic assessments were performed for clinical use; therefore, the gestational age at the initiation of cervical length surveillance as well as the frequency of surveillance was variable between patients. During the study period, ultrasound machines from multiple manufacturers were used to collect clinical data including General Electric (Fairfield, CT), Philips (Andover, MA), Medison (Seoul, South Korea), and Acuson (Mountain View, CA) ultrasound machines. Transvaginal probes (5–9 mHz) were used to obtain cervical length measurement.
The primary outcome for this study was preterm delivery <37 weeks. Secondary outcomes included mean gestational age at delivery, preterm delivery <34 weeks, preterm delivery <28 weeks, shortest mean cervical length, and the presence of a short cervix <25 mm prior to 24 weeks.
Categorical variables were analyzed with the χ 2 test, whereas continuous variables were compared using an analysis of variance. A Kruskal-Wallis test was used to compare the median differences for nonparametric data. Pregnancy duration was analyzed with Kaplan-Meier curves and the log-rank test. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC). A value of P < .05 was considered statistically significant.
Adjusted analyses were performed using log linear regression and included the following factors: age, race/ethnicity, the number of prior full-term deliveries, the number of prior preterm deliveries, gestational age of last preterm delivery, and a history of cervical procedures (loop electrosurgical excision procedure, cold-knife cone, and/or prior dilation and evacuation procedure). We chose a log linear model over a logistic regression model because the former permits estimating the true relative risks instead of odds ratios. Because the design of this study is a retrospective cohort study, we estimated the relative risks directly using a log linear model.
Results
Of 595 cases potentially eligible for inclusion, 44 patients were excluded because the etiology of the prior preterm birth could not be established, 18 patients were excluded because of missing delivery data, 6 patients were excluded because of a history of suspected placental abruption, and 5 patients were excluded because of major fetal anomalies, resulting in 522 patients remaining in the analysis. Of patients included in the analysis, 96 (18.4%) had a history of advanced cervical dilation, 246 (47.1%) had a history of PPROM, and 180 (34.5%) had a history of preterm labor. Demographic characteristics and risk factors for preterm delivery are summarized in Table 1 .
| Demographic | ACD (n = 96) | PPROM (n = 246) | PTL (n = 180) | P value |
|---|---|---|---|---|
| Maternal age, y (SD) | 33.0 (5.7) | 32.3 (5.9) | 32.0 (5.8) | .37 |
| Parity, median (IQR) | 2 (1-3) | 2 (1-2) | 2 (1-3) | < .01 |
| Prior full-term births, median (IQR) | 0 (0-1) | 0 (0-1) | 1 (0-1) | < .01 |
| Prior preterm births, median (IQR) | 1 (1-2) | 1 (1-1) | 1 (1-2) | < .01 |
| Government-insured clinic, n (%) | 34 (35.4) | 128 (52.0) | 89 (49.4) | .02 |
| Race/ethnicity, n (%) | .04 | |||
| White | 25 (26.0) | 40 (16.3) | 34 (18.9) | |
| African American | 17 (17.7) | 26 (10.5) | 14 (7.8) | |
| Hispanic | 18 (18.8) | 53 (21.5) | 44 (24.4) | |
| Other/unknown | 36 (37.5) | 127 (51.6) | 88 (48.9) | |
| Mean GA of earliest PTB, wks (SD) | 24.4 (6.2) | 28.1 (5.9) | 29.5 (6.0) | < .01 a |
| History-indicated cerclage, n (%) | 42 (43.8) | 11 (4.5) | 9 (5.0) | < .01 |
| History of LEEP, CKC, or D&E, n (%) | 16 (16.7) | 26 (10.6) | 14 (7.8) | .07 |
| 17OHP-C, n (%) | 77 (80.2) | 206 (83.7) | 155 (86.1) | .60 |
a The P value represents the difference between the ACD group and both the PPROM and PTL groups; the P value for the Student t test comparing the mean GA at delivery of the earliest PTB between the PPROM and PTL groups was .02. All other P values represent the difference between the ACD group and both the PPROM and PTL groups; however, the PPROM and PTL groups were similar.
Race and insurance status differed significantly between the groups. Additionally, patients with a history of preterm labor were significantly more likely to have had a full-term birth, and patients with history of advanced cervical dilation were more likely to have had multiple prior preterm births and more likely to be treated with a history-indicated cerclage. The mean gestational age of the prior preterm delivery was significantly earlier in the prior ACD group compared with the prior PPROM and PTL groups. Use of 17-alpha-hydroxyprogesterone caproate was similar among all three groups.
Table 2 demonstrates primary and secondary outcomes. Women with a history of ACD were significantly more likely to have recurrent preterm delivery <37 weeks compared with women with a history of PPROM or PTL (55.2% vs 27.2% vs 32.2%, respectively; P < .01). The mean gestational age at delivery for women with prior ACD was 34.0 weeks compared with 37.2 for women with a history of PPROM and 37.0 weeks for women with a history of preterm labor ( P < .01). Delivery at <34 weeks and 28 weeks was also significantly higher in the prior ACD group.
| Outcome | Prior ACD (n = 96) | Prior PPROM (n = 246) | Prior PTL (n = 180) | P value | |
|---|---|---|---|---|---|
| All patients (including patients with history-indicated cerclage) | |||||
| Mean GA at delivery, wks (SD) | 34.0 (5.8) | 37.2 (3.8) | 37.0 (3.5) | < .01 | |
| Preterm delivery <37, n (%) | 53 (55.2) | 67 (27.2) | 58 (32.2) | < .01 | |
| Preterm delivery <34 wks, n (%) | 34 (35.4) | 23 (9.4) | 21 (11.7) | < .01 | |
| Preterm delivery <28 wks, n (%) | 17 (17.7) | 11 (4.5) | 6 (3.3) | < .01 | |
| Mean shortest CL prior to 24 wks, mm (SD) | 24.0 (13) | 35.3 (11) | 34.7 (12) | < .01 | |
| Short cervix prior to 24 wks, n, (%) a | 48 (50) | 36 (14.6) | 28 (15.6) | < .01 | |
| Subgroup analysis excluding patients with history or ultrasound-indicated cerclage | |||||
| Mean GA at delivery, wks (SD) | 33.6 (6.0) | 37.3 (3.4) | 37.3 (3.0) | < .01 | |
| Preterm delivery <37 wks, n (%) | 21 (60) | 60 (27.4) | 48 (29.5) | < .01 | |
| Preterm delivery <34 wks, n (%) | 14 (40) | 19 (8.7) | 15 (9.2) | < .01 | |
| Preterm delivery <28 wks, n (%) | 6 (17.1) | 7 (2.8) | 3 (1.8) | < .01 | |
| Mean CL prior to 24 wks, mm (SD) | 24.6 (13.0) | 37.0 (9.9) | 36.0 (11.2) | < .01 | |
| Short cervix prior to 24 wks, n (%) a | 16 (46) | 16 (7) | 15 (9) | < .01 | |
a Short cervix was defined as a transvaginal sonographic cervical length of <25 mm. P values represent the difference between the ACD group and both the PPROM and PTL groups, but the PPROM and PTL groups were similar.
The mean cervical length prior to 24 weeks was significantly shorter in patients with a history preterm delivery because of advanced cervical dilation when compared with those with a history of preterm birth because of PPROM or preterm labor; these patients were also more likely to have a short cervix <25 mm prior to 24 weeks. A subgroup analysis was performed excluding patients treated with cerclage because this treatment may have affected the obstetric outcome ( Table 2 ). For all of the primary and secondary outcomes, results were similar to the initial analysis.
In an unadjusted analysis, patients with a history of ACD had a relative risk for preterm birth <37, <34, and <28 weeks of 2.0, 3.8, and 4.0 respectively, with prior PPROM as the referent ( Table 3 ). This elevated risk remained statistically significant in a sensitivity analysis eliminating patients with cervical cerclage. In a multivariate analysis including such factors as the number of prior preterm births, the gestational age of prior preterm birth, and demographic factors, ACD continued to be associated with significantly elevated risk for recurrent preterm birth at <37 weeks, <34 weeks, and <28 weeks ( Table 4 ).
