Interpretation
In this study, a total of 555 pregnant women had a short cervix. About 6000 deliveries are recorded yearly in our hospital with a short cervix incidence of about 9.3%. A previous study conducted in our hospital between May 2010 and May 2015 found that the incidence of short cervix was 0.45% for a gestation period of 20 and 24 weeks15. It is possible that a variation in the number of subjects studied is responsible for the large difference in the recorded incidence. In the current study, we included patients with a short cervix found at 11-35 weeks of gestation. To minimize severe complications of preterm birth, programs that promote early detection of this condition are often implemented in our hospital. Among such programs, transabdominal ultrasonography is the use to measure the cervical length for pregnant women who agree to undergo antenatal ultrasound examination. Subjects with a cervical length of less than 25mm as well as those that showing signs of miscarriage including bleeding and contraction were subjected to transvaginal ultrasonography for a more accurate assessment. We observed that, among women with a short cervix, BMI before pregnancy was related to PTB. In addition, women who were obese or overweight before pregnancy were at higher risk of PTB compared to those with normal BMI, which is consistent with previous studies10,16,17. Of note, we found that autoimmune disease (SLE and APS) increased the risk of PTB < 37 weeks13. However, PCOS and hypothyroidism previously associated with PTB were not significantly correlated with occurrence of PTB18,19. In the current study, prepregnancy hypertension was associated with PTB < 34 weeks but not PTB < 37 weeks. Analysis of other complications including polyhydramnios, gestational diabetes mellitus and blood pressure state, showed that they were not significant risk factors of PTB among patients with a short cervix (Table 1) . These findings were differed from those reported in a previous two-year retrospective study. This may be due to the fact that the population used in the latter included general pregnant women16. This further indicates that patient’s baseline information can be used to establish a prediction model for PTB. Among the factors defined in the risk history variable, only PTB was a significant predictor and this is in agreement with a previous report17. It is should be noted that induced abortion has also been reported as a risk factor for PTB20. We reasoned that the majority of patients (73.0%) in this study were primipara, and this may explain the discrepancy. Moreover, all patients in this study had a short cervix, unlike in other studies. We further observed that LEEP did not increase the risk of PTB in line with what has previously been reported21. However, a previous meta-analysis found that LEEP is a risk factor for PTB (<32/34, <28 weeks) 22. Numerous studies have demonstrated a relationship between HPV infection and PTB23. In the current study, however, this could not be clarified owing to the small data collected. Analysis of obstetric data showed that in the 65% of patients that underwent IVF-ET, no collinearity was observed between twin pregnancy and IVF-ET. This suggested that twin pregnancy and IVF-ET are both independent predictors of PTB < 37 weeks among patients with a short cervix. However, IVF-ET was not a predictor of PTB < 34 weeks. In this study, parity was not a risk factor of PTB, and its relationship with PTB is still unclear, and hence requires a more systematic assessment in the future17,24.
Cervical length (CL) detected by ultrasound is one of the most commonly used parameters for early detection of PTB4. In the current study, we analyzed the relationship between CL, gestational age, amniotic fluid sludge and overall PTB. We found that the risk of PTB (< 37 weeks or < 34 weeks) increased with decline in CL and with the gestational age at 1st diagnosis of short cervix, however sludge was not a predictor of PTB. Previous works have focused on CL measurements in the second trimester of pregnancy with a short cervix during this period found to be significantly associated with PTB6. However, prediction potential of CL in the first or third trimester of pregnancy remains unclear25. Because a high rate of short cervix (< 25mm) occurring at 36 weeks of gestation and the low rate of short cervix at 16 weeks of gestation26, we included pregnancies with a short cervix at first and third trimesters. Considering severe complications of preterm birth, we estimated the risk of PTB at first and third trimesters. Our results showed that CL during this period was a significant predictor of PTB. Particularly, we observed a low and high risk of preterm at third and first trimesters, respectively. This could be due to; (i) the population with a short cervix screened under this study was at high risk of PTB, in which PTB < 37 weeks was 33.7% and PTB < 34 weeks was 16.9%, (ii) a combination of factors including CL and other factors such as gestation age played an important role in the prediction of PTB16. This is in line with a previous study that implicated a decrease in CL and the gestational age as a risk factor of PTB < 35 weeks27.In our study, the predictors of PTB < 37 weeks and PTB < 34 weeks were not consistent. Notably, PTB < 37 weeks was influenced by more factors than PTB < 34 weeks. It was also evident that CL and gestational age of 1st short cervix were both significant predictors of PTB < 37 weeks and PTB < 34 weeks.
In the current study, patients were diagnosed with a short cervix (CL ≤ 25mm) using transvaginal ultrasonography (TVCL). An obstetrician was able to assess a patient’s risk of PTB < 37 weeks or PTB < 34 weeks using nomograms based on her BMI before pregnancy, autoimmune disease, prepregnancy hypertension, history of PTB, twin pregnancy or singleton pregnancy, mode of fertilization, frequency of pregnancy, gestational age, and CL. TVCL screening at 17-23 weeks allows efficient interventions including potential cost-effectiveness of screening with limited harm28. A combination of TVCL screening and our nomogram predictions during the second trimester may be more helpful to an obstetrician’s decision regarding intervention. A routine measure of cervical length through transvaginal sonographs is controversial and may not be suitable. However, our hospital’s protocol for cervical length measurement (as described in the methods of this report) is recommended during the first and third trimesters. This protocol, together with our nomograms could help obstetricians discover high-risk populations of preterm births during this period thereby allowing drug therapy or monitoring of changes in the cervical length for prevention of preterm births.
In the current study, we did not analyze CL changes over time although has been hypothesized to be related to PTB risk. A previous study found that changes in transvaginal sonographic CL over time was not a clinically useful test to predict PTB in women29. Therefore, a continuous assessment of CL after our nomogram prediction is recommended in order to improve the sensitivity of prediction. Some factors including gestational diabetes mellitus, polyhydramnios, and gestational hypertension have been implicated in PTB risk although the current study did not find them to be significant predictors of overall PTB16. Future studies may benefit from a prospective cohort design that allows researchers to collect more detailed information on characteristics of study subjects and to analyze the subtypes of PTB. Moreover, multiple-center studies are further suggested in the future to improve the accuracy of nomogram prediction.