Long-term indomethacin therapy and cervical stabilization in dichorionic twin pregnancies

To evaluate the effect of long-term indomethacin therapy (LIT) in stabilizing cervical length in dichorionic-diamniotic (DCDA) twin pregnancies with a short cervix.

This retrospective cohort study included 54 dichorionic-diamniotic twin pregnancies with a short cervix (≤25 mm), managed with LIT between 18 and 26 weeks of gestation age (GA) at a single quaternary medical center from 2014 to 2024. LIT was initiated with a 100 mg oral loading dose, followed by 50 mg every 6 h for 48 h, and continued at 25 mg every 6 h until 32 weeks or delivery. Weekly monitoring included transvaginal ultrasound, amniotic fluid assessment, and fetal Doppler studies. The expected cervical length (E_LCL) was modeled by applying an assumed physiologic cervical shortening rate of 0.9 mm per week to the observed first cervical length (O_FCL) in twin pregnancies without intervention. E_CL = O_FCL - [(GA at O_LCL - GA at O_FCL (weeks)) × 0.9 (mm/week)]. Cervical stabilization was defined as the observed last cervical length (O_LCL) exceeding the expected last cervical length (E_LCL) at the last examination. The primary outcome was cervical stabilization, while the secondary outcome was gestational age at delivery.

LIT was successful in stabilizing the cervix in 81.5% (n = 44/54) of cases. The mean GA at LIT onset was 22.9 ± 1.9 weeks, with a median O_FCL of 14.5 mm (IQR: 10.0-18.0). The mean duration of LIT was 48 days (IQR: 25-61). Final O_LCL was significantly longer than E_LCL (15.9 ± 6.1 mm vs. 9.3 ± 5.9 mm, p < .001). Median gestational age at delivery was higher in stabilized vs. non-stabilized patients (34.6 weeks [IQR: 31.7-36.6] vs. 30.8 weeks [IQR: 26.1-32.3], p = .004). No difference was observed in initial cervical length between groups (p = .282). LIT was discontinued in 11.2% due to ductus arteriosus constriction or oligohydramnios; no adverse neonatal outcomes were reported.

These findings suggest an association between LIT and cervical stabilization in DCDA twin pregnancies with a short cervix; this exploratory, hypothesis-generating analysis warrants confirmation in prospective studies.