Background
The main reason to avoid trial of labor after cesarean delivery is the possibility of uterine rupture. Identifying women at risk is thus an important aim, for it would enable women at low risk to proceed with a secure planned vaginal birth.
Objective
To evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the lower uterine segment thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous cesarean delivery.
Study Design
This multicenter, randomized, controlled, parallel-group, unmasked trial was conducted at 8 referral university hospitals with a neonatal intensive care unit and enrolled 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor. Women in the study group had their lower uterine segment thickness measured by ultrasound. Those with measurements >3.5 mm, were encouraged to choose a planned vaginal delivery, and those with measurements ≤3.5 mm, were encouraged to choose a planned repeat cesarean delivery. This measurement was not taken in the control group; their mode of delivery was decided according to standard management. The primary outcome was a composite criterion comprising maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, perinatal death, or neonatal encephalopathy. Prespecified secondary outcomes were repeat cesarean deliveries, elective or after trial of labor.
Results
The study group included 1472 women, and the control group included 1476 women. These groups were similar at baseline. The primary outcome occurred in 3.4% of the study group and 4.3% of the control group (relative risk, 0.78; 95% confidence interval, 0.54–1.13: risk difference, −1.0%; 95% confidence interval, −2.4 to 0.5). The uterine rupture rate in the study group was 0.4% and in the control group 0.9% (relative risk, 0.43; 95% confidence interval, 0.15–1.19). The planned cesarean delivery rate was 16.4% in the study group and 13.7% in the control group (relative risk, 1.21; 95% confidence interval, 1.00–1.47), whereas the rates of cesarean delivery during labor were 25.1% and 25.0% (relative risk, 1.01; 95% confidence interval, 0.89–1.14) in the study and control groups, respectively.
Conclusion
Ultrasound measurements of lower uterine segment thickness did not result in a statistically significant lower frequency of maternal and perinatal adverse outcomes than standard management. However, because this study was underpowered, further research should be encouraged.
Introduction
The cesarean delivery (CD) rate has dramatically increased in many countries over the past 3 decades, reaching 31.9% in the United States and 26.9% in Western Europe. , The most common indication for CD is a history of a previous one; these account for more than one-third of the CDs annually. Among the medical and nonmedical factors contributing to the decline of vaginal birth after CD, one frequently cited as a reason to avoid trial of labor is the possibility of uterine rupture, which can lead to perinatal asphyxia or death and severe maternal complications. However, there are serious concerns about the long-term risks associated with CDs, particularly placenta previa and placenta accreta in later pregnancies. They are responsible for substantial maternal and neonatal mortality and morbidity, and their risks increase with each subsequent CD.
Why was this study conducted?
It is currently unclear whether the choice of mode of delivery based on the ultrasound measurement of the lower uterine segment thickness is useful in reducing maternal-fetal mortality and morbidity among pregnant women with a previous cesarean delivery.
Key findings
In this randomized clinical trial that included 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor, choice of mode of delivery based on the ultrasound measurement of the lower uterine segment thickness did not significantly reduce maternal-fetal mortality and morbidity compared with usual management (relative risk, 0.78; 95% confidence interval, 0.54–1.13).
What does this add to what is known?
Among pregnant women with a previous cesarean delivery, ultrasound measurements of lower uterine segment thickness cannot be recommended in routine practice.
Identifying women at real risk for uterine rupture is thus an important aim in obstetrical care, for it would enable women at low risk to proceed with a secure planned vaginal birth, whereas women at high risk could plan a CD. Several authors have evaluated the interest of ultrasound for predicting the risk of a cesarean scar defect by measuring the thickness of the lower uterine segment (LUS) in women with a history of CD. Their results are concordant: the thinner the LUS on ultrasound, the higher the likelihood of a uterine defect. The most recent meta-analysis concluded that the thickness of this segment should be used as an additional tool to help make an informed decision about a trial of labor after CD (TOLAC).
The Lower Uterine Segment Trial (LUSTrial) aimed to evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the LUS thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous CD.
Materials and Methods
Study design
We conducted a multicenter, randomized, controlled, parallel-group, unmasked trial at 8 hospitals, all referral university hospitals with a neonatal intensive care unit (NICU). The Ethics Committee of Poissy-Saint Germain Hospital (Comité de Protection des Personnes, Saint Germain en Laye, France) approved the study protocol for all centers before participant enrollment. All participants provided written informed consent before randomization. An independent data monitoring committee, whose members had access to unblinded data related to key trial outcomes and reviewed trial safety and progress. The committee, in addition, reviewed a planned interim analysis halfway through the trial and recommended that it be continued. The trial was registered at ClinicalTrials.gov (NCT01916044).
The authors vouch for the accuracy and completeness of the data and for the fidelity of the trial, to the protocol.
Participants
Women were potentially eligible for inclusion if they were ≥18 years, at 36 weeks 0 days to 38 weeks 6 days of gestation with a live singleton fetus in vertex presentation and had previously had 1 low transverse CD. They were ineligible if they had ≥2 previous CDs, an indication for a repeat CD, a classic CD scar, a multiple pregnancy, placenta previa, or if they requested an elective repeat CD.
Eligible women were informed of the risks of both planned vaginal birth and CDs. They were, in addition, informed that ultrasound measurement of the thickness of the LUS can be used to assess the risk of uterine rupture, but that the value of this examination was controversial.
Randomization and masking
After verification of the inclusion and exclusion criteria, eligible consenting women were randomly assigned by the physician-investigator in a 1:1 ratio to 1 of the 2 following groups:
- 1.
The study group, with a proposed mode of delivery determined by ultrasound measurement of the LUS thickness.
- 2.
The control group, with a proposed mode of delivery decided according to the usual management at the center, without an ultrasound measurement of the LUS.
An independent, centralized, computer-generated randomization sequence (CleanWEB, Télémedecine Technologies, Boulogne, France) was used for this allocation, based on a randomization list established by the study statistician, according to a permuted block method stratified by center.
Procedures
Each center selected 1 expert sonographer to be responsible for all ultrasound measurements of the LUS thickness for women randomized to the study group. Each expert sonographer was a maternal-fetal medicine specialist with at least 5 years of experience. The sonographers received uniform training and certification by the principal investigator who had previously published this method to ensure that the same measurement technique was used in each participating center.
This measurement was performed transabdominally by a standardized technique between 36 weeks 0 days to 38 weeks 6 days of gestation, with the bladder moderately filled. This examination of the LUS in the sagittal plane looked for the thinnest area of the upper third of this segment. The image was then frozen, and the measurements were taken with the cursor placed at the bladder and urine, and amniotic fluid and decidua interfaces. The LUS was at an angle of 0° to 30° with the horizontal plane and was then enlarged such that any movement of the cursor induced a measurement variation of only ±0.1 mm. Of note, 3 successive measurements were taken, and the lowest value was recorded. All centers performed ultrasounds with General Electric Voluson E8 (GE Medical System Europe, Vélizy, France) ultrasound machines with a 2 to 5 MHz convex transabdominal transducer or a 4.0 to 8.5 MHz 4D convex volumetric transabdominal transducer or Voluson E10 (GE Medical System Europe) ultrasound machines with a 1.5 to 6.0 MHz convex transabdominal transducer or a 1 to 7 MHz 4D convex volumetric transabdominal transducer (GE Medical System Europe).
Validation of 10 ultrasound images was required before these sonographers started the study. Because this was a pragmatic trial, the quality of the images was not verified later.
After this ultrasound assessment, the obstetrician and the study subject discussed the decision about planned mode of delivery. The LUS thickness was used as a tool to help her make an informed decision. She received the following information:
- 1.
If the LUS thickness was >3.5 mm, she was considered at low risk of uterine rupture and was encouraged to choose a planned vaginal delivery.
- 2.
If this measurement was ≤3.5 mm, she was considered at risk for uterine rupture and was encouraged to choose a planned repeat CD.
The 3.5-mm threshold value was chosen based on previously published results.
Women in the control group did not have an ultrasound measurement of the LUS thickness. Mode of delivery was decided according to the center’s standard management and the patient preference. The risk of contamination was limited in the control group because this examination was performed by only 1 referent sonographer-investigator, aware of the randomization arm.
For all included women, the final decision was specified in the medical file by the attending physician and in the study electronic file by a research midwife.
Obstetrical providers managing the labor of women who underwent ultrasound measurement were aware of the value of the LUS measurement and therefore were not blinded to group assignment.
Outcomes
The primary outcome measure applied the maternal and perinatal outcomes and definitions used by Landon et al to compare outcomes after trial of labor or elective CD in women with a previous CD. It was a composite criterion of maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, antepartum stillbirth, intrapartum stillbirth, neonatal death, and neonatal hypoxic-ischemic encephalopathy.
Prespecified secondary outcomes were each element of the composite principal criterion; repeat CDs, elective or after trial of labor, separately; and third- and fourth-degree perineal lacerations.
Maternal and neonatal data were collected from inclusion to their discharge. To ensure accurate diagnoses, all cases identified with uterine rupture or dehiscence or neonatal encephalopathy were reviewed and, if necessary, reclassified by an independent blinded adjudication committee, from reports that deleted all information about their randomization group.
Statistical analysis
The sample size calculation was based on the data from Landon et al, which reported a 6.41% rate for the composite principal criterion in the trial of labor group and 4.07% in the elective repeat CD group. On the assumption that measuring the LUS thickness would reduce fetal and maternal mortality and morbidity to levels similar to those with elective CDs, each group required 1423 women for a power of 80% with a 2-sided 5% significance level. Because an intermediate analysis was planned midtrial with O’Brien-Fleming boundaries, the tests for the primary outcome at the final analysis used a 4.67% significance level. The planned sample size was increased to 1471 per arm, to take the interim analysis and potential loss to follow-up into account.
The primary analysis applied the intention-to-treat principle, that is, all randomized women were analyzed in the group to which they had been allocated, regardless of protocol deviations. Missing outcome data were handled by multiple imputation by chained equations; 20 datasets with complete data were generated and analyzed separately, and the resulting estimates pooled. Log-binomial models adjusted for parity (randomization stratification variable), were used to estimate relative risks (RRs). To account for clustering by center, we fit models with generalized estimating equations with an exchangeable correlation matrix and derived risk difference estimates from them. For the primary outcome, sensitivity analyses used complete cases only and did not impute missing data or adjust for parity or center clustering.
The trial was open label, but the data analysts were blinded to allocated treatment group, until the entire analysis was completed. Analyses were performed with R version 3.4.4. (The R Foundation for Statistical Computing, Vienna, Austria).
Results
Patient characteristics
From August 2013 to February 2018, 2948 women underwent randomization: 1472 were assigned to the study group and 1476 to the control group ( Figure ). These groups were similar at baseline ( Table 1 ). Timing of and indications for the previous CD in each group are reported in Table 2 . Overall, 25 women in the study group and 17 in the control group were lost to follow-up or withdrew consent.
| Characteristic | Study group (n=1472) | Control group (n=1476) |
|---|---|---|
| Maternal age, median (Q 1 –Q 3 ), y | 32.5 (29.4–35.7) | 32.4 (29.2–35.4) |
| Missing data | 0 | 0 |
| Body mass index, median (Q 1 –Q 3 ), kg/m 2 | 24.2 (21.6–28.1) | 24.2 (21.2–28.4) |
| Missing data | 8 (0.5) | 11 (0.7) |
| Mother’s country of birth | ||
| France | 769 (55.6) | 782 (56.8) |
| Other country in Europe | 48 (3.5) | 52 (3.8) |
| North Africa | 315 (22.8) | 261 (19.0) |
| Sub-Saharan Africa | 135 (9.8) | 171 (12.4) |
| Other | 117 (8.2) | 110 (7.9) |
| Missing data | 88 (6.0) | 100 (6.8) |
| Gestational age, median (Q 1 –Q 3 ), wk | 37.0 (36.4–37.6) | 36.9 (36.4–37.4) |
| Missing data | 0 | 0 |
| Smoking during pregnancy, n (%) | 150 (10.3) | 160 (11.0) |
| Missing data | 19 (1.3) | 18 (1.2) |
| Parity, n (%) | ||
| 1 | 1176 (80.8) | 1178 (80.7) |
| ≥2 | 280 (19.2) | 281 (19.3) |
| Missing data | 16 (1.1) | 17 (1.2) |
| Previous IUFD, n (%) | 17 (1.2) | 25 (1.7) |
| Missing data | 2 (0.1) | 2 (0.1) |
| Previous PPH, n (%) | 85 (5.8) | 84 (5.7) |
| Missing data | 4 (0.3) | 4 (0.3) |
| Chronic hypertension, n (%) | 31 (7.8) | 33 (8.2) |
| Missing data | 0 | 0 |
| Diabetes mellitus, n (%) | 28 (7.0) | 18 (4.5) |
| Missing data | 0 | 0 |
| Preeclampsia, n (%) | 11 (0.7) | 20 (1.4)] |
| Missing data | 3 (0.2) | 7 (0.5) |
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