Spontaneous preterm birth predictors in asymptomatic twin pregnancies

We appreciate the opportunity to address the concerns raised in the recent Letter to the Editor by Sathian et al.¹ about our recent study. We value constructive feedback and believe it contributes to the improvement of scientific knowledge. In response to the questions highlighted, we would like to clarify the following points:

Regarding the generalizability of our study, we acknowledged in our discussion that the small number of cases of sPTB is the principal limitation of our work, as they may impact the diagnostic accuracy of all the markers evaluated, especially the predictive value of parameters other than uterocervical angle and cervical length that may be underestimated. For this reason, we concluded that these other parameters (CCI, cervical texture and cervical inflammatory biomarkers/fetal fibronectin) did not achieve an association with sPTB <34 weeks in our study, but further prospective series are needed to confirm these findings, as they cannot be completely excluded due to the small number of sPTB <34 weeks cases observed in our cohort.²

This is of special importance due to the differences observed by other authors like Van der Merwe et al.,³ regarding CCI as an sPTB predictor in twins. Regarding cervical texture, our results are in line with Van der Merwe et al.,³ but contrast with what is found in singletons. The role of this biomarker in sPTB in twins has yet to be elucidated, as some authors found differences between cervical stiffness and tissue composition and microstructure between singleton and multiple pregnancies.⁴ On the other hand, the role of inflammatory biomarkers and intraamniotic inflammation in the pathogenesis of sPTB in twins must be interpreted with caution, as stated in our discussion. An association between cervical inflammatory biomarkers and sPTB could not be demonstrated in our study, but this does not mean that intraamniotic inflammation does not play a relevant role in sPTB later than midtrimester, as other authors like Wennerholm et al.⁵ find an association with IL-8 levels at 28 weeks and an association with PTB in twin pregnancies. Regarding the study by Amabebe et al.,⁶ they excluded multiple pregnancies, stating once again the differences in the mechanisms of sPTB between singletons and twins, suggesting a more significant role of intraamniotic inflammation in singletons and perhaps a more mechanical one in twins.

Finally, uterocervical angle's contribution to sPTB prediction in twins has been observed in previous publications,⁷ indeed, in our study, uterocervical angle remained statistically significant after adjusting for potential confounders like cervical length, maternal age, ethnicity, risk factor for preterm birth, chorionicity, assisted reproductive technology, use of progesterone/cerclage placement with the following result: [OR 1.06 (1.01–1.12); p-value 0.017]. However, acknowledging once more the low sPTB rate <34 weeks in our study, prospective multicenter studies are needed in order to add higher-quality evidence to this finding.

We hope that these clarifications address the concerns raised, and our work may help as a starting point in raising awareness in evaluating novel sPTB predictors in twin pregnancies.