The efficacy of two different doses of vaginal isosorbide mononitrate in pre induction cervical ripening: a double blind randomised controlled trial

Abstract

Objective: Nitric oxide donors have been shown to cause cervical ripening. The aim of this study was to evaluate the effects on the mother and the fetus when isosorbide mononitrate (ISMN) 40 mg or the sustained release ISMN (ISMN - SR) 60 mg was administered vaginally for preinduction cervical ripening.

Methods: A double blind randomised controlled trial. Consecutive women (n=156) with uncomplicated singleton pregnancies between 40 weeks +5 days and 41 weeks' gestation with modified Bishop Scores (MBS) <5 were allocated by stratified (primp/multip) block randomisation to receive ISMN 40 mg, ISMN - SR 60 mg or the placebo vitamin C 100 mg vaginally.

Results: At the commencement of the study the parity and mean age, MBS, pulse rate (PR), systolic and diastolic blood pressure (SBP and DBP), umbilical artery resistance index (RI) and pulsatility index (PI) were similar among the three treatment groups. There was significant increase (p<0.001) of mean MBS by 1.3 (95% CI 0.8, 1.7) in primips and by 1.7 (95% CI 1.3, 2.0) in multips at 6 hours and by 2.4 (95% CI 1.9, 2.7 ) in primips and by 2.3 (95% CI 2.0, 2.6) in multips at 48 hours. Greater proportions of primips (42% with ISMN - SR 60 mg and 31% with ISMN 40 mg, p<0.05) were favourable for induction of labour (IOL) after 48 hours in comparison with the controls (7.6%). Greater proportions of multips (46% with ISMN - SR 60 mg and 40% with ISMN 40 mg, p<0.05) were favourable for IOL after 48 hours in comparison with the controls (16%). A mean increase of PR by 6.7-10.2 bpm (95% CI 5.0 - 12.5, p<0.001) in both ISMN groups at 180 minutes persisted up to 360 minutes. A mean reduction of SBP by 7.3 - 10 mmHg (95% CI = 8.0-11.5, p<0.001) in both ISMN groups at 180 minutes persisted up to 360 mins. No significant change was seen in DBP, RI or PI. Frequency of maternal side effects (mainly headache) were higher in ISMN groups.

Conclusions: When compared with the placebo Vitamin C 100 mg, vaginal ISMN 40 mg and ISMN - SR 60 mg lead to significantly greater cervical ripening after 6 hours and 48 hours respectively. Therefore vaginal ISMN leads to more women becoming favourable for IOL. Vaginal ISMN does not affect placental blood flow but causes headaches and clinically insignificant maternal haemodynamic changes.