Main findings
This study explores the benefit of implementing universal screening for SPD by transvaginal CL measurement at the 20–24 weeks anomaly scan visit. Both the screening and the no screening groups were examined in two private fetal medicine settings at the same time period. We opted to consider only low risk women because this is the cohort that accounts for the majority of the preterm births while on the other hand they receive less attention regarding their SPD risk. In addition, we included in our outcomes pregnancies resulting in late miscarriage that could potentially have been prevented by CL measurement. Propensity analysis was used in order to minimize the influence of confounding variables in the two groups. This type of analysis creates study cohorts similar to the baseline characteristics defined by the logistic regression analysis and reduces bias.
We observed a significant reduction of about 60% in the SPD32 rate and the SPD20-32 in the women that had SPD screening (Table 2, Fig. 1). This was not accompanied by a difference in the mean gestational age at delivery between the two groups which rather points to a shift of the preterm births after 32 weeks in the screened group. We also observed that assisted conception was a significant risk factor for late miscarriage as well as SPD (Tables 3 and 4).
Strengths and limitations
The strength of our study relies in the large number of subjects and the homogenous population created after the propensity analysis. More robust conclusions would be derived from a randomized trial comparing universal screening to no screening and this is the main limitation of the study. Another limitation is that the treatment for CL shortening was not uniform. However, these results probably reflect more accurately how a policy of SPD screening would work in real life conditions.
Interpretation
In our previous study on universal SPD screening, the rate of SPD was compared before and after implementation of the policy in the same institute.18 A population of 10,506 singleton pregnancies was assessed with a decline rate of 1.32%. High risk women contributed only 16% of the total SPD cases. SPD at less than 34 weeks occurred in women with very short CL ≤ 15mm in 38% of high risk and 18% of low risk women despite treatment. In women with CL ≤ 15mm receiving intervention, a plateau was observed in the increase of the risk for SPD for CL 9–13 mm, whereas below 9 mm the risk increased exponentially. Following the introduction of mid-trimester CL measurement, there was a trend for a reduction in the rate of any SPD < 34 weeks of about 20% in comparison with the pre-screening period.
Likewise, Temming et al evaluated the acceptability of a universal CL screening program, the risk factors associated with declining screening and the subsequent delivery outcomes of women who accepted or declined screening.19 Transvaginal CL measurement was offered at 17–23 weeks of gestation to all women with singleton pregnancies and expectant mothers could choose to opt out. The acceptance rate was high (85%) and stabilized after the first six months of introducing the policy of CL measurement. Patients with CL ≤ 20 mm (1.2% of the screened population) were considered to have clinically significant cervical shortening and were offered treatment. The rate of spontaneous preterm birth < 28 weeks was double in those who declined screening, although delivery at less than 34 and less than 37 weeks were not significantly different. Similarly Son et al reported that the introduction of a universal SPD screening program in women without a history of preterm birth was associated with a reduction in the frequency of prematurity.20 CL was evaluated at 18–24 weeks of gestation in singleton low risk pregnancies and the SPD rates were compared before and after the implementation of the screening program. The authors report that the introduction of the program was associated with a significant decrease in the frequency of preterm birth of about 25% for SPD < 37 and SPD < 34 weeks.
In contrast van Os et al reported a non-significant reduction in SPD < 32 weeks and SPD < 34 weeks in low risk singleton pregnancies identified after universal screening.21 The authors report a very small percentage of short CL in their population probably because of methodological problems (the isthmus was included in the CL measurement).
The magnitude of the benefit in our study is higher than previously reported and higher than the reduction of SPD observed in randomized trials of progesterone versus placebo.22,23 Possible factors accounting for the difference is firstly that we examined only low risk pregnancies and secondly that the median CL in the screened population is lower whereas the percentage of short CL is higher than other studies.20,21 Similarly to our study Son et al examined singleton low risk women but the prevalence of the short cervix, defined by the authors as ≤ 25 mm, was only 0.89% compared to 5% in our data.21 If the sonographer exerts too much pressure to the cervix or the if the uterine isthmus is included in the measurement, the majority of the shorter and commonly softer cervices remains unnoticed. The implication is that women that may benefit from treatment are not identified and there is no benefit from the screening process. In addition in our study the therapeutic options in the intervention group included not only progesterone but cervical cerclage as well if CL was very short. Souka et al have recently presented data showing that if CL is less than 9mm at screening, cerclage is more efficient than progesterone in preventing SPD.24 It is also possible that preventive measures such as progesterone and cerclage are more effective in low risk pregnancies.
The finding that assisted conception pregnancies have a higher risk of preterm birth even in women without relevant history is important and confirms previous reports.25 This increased risk may be the result of multiple procedures such as hysteroscopy that include cervical manipulation or may be inherent to the population that need fertility treatment.
Several analyses were performed regarding the cost-effectiveness of the implementation of universal CL screening and treatment with vaginal progesterone to prevent SPD.26–28 Einerson et al compared three cervical length screening strategies in a population of women with no prior SPD: the risk-based screening and the universal screening were more effective and less costly than no screening at all.25 Comparing between the two screening strategies, universal screening, despite costing more, resulted in being more cost-effective when considering additional costs from the short and long term consequences of prematurity. The benefit persists even after taking into account reduced incidence of CL ≤ 20 mm at initial screening (0.83%), vaginal progesterone supplementation for women with CL ≤ 20 mm, additional ultrasound(s) for women with CL 21-24.9 mm and the assumption that vaginal progesterone reduces the rate of preterm birth < 34 weeks of gestation by 39% if a short CL is diagnosed.