Labour induction with 25 micrograms versus 50 micrograms intravaginal misoprostol in full term pregnancies

Introduction

The advent of misoprostol, a prostaglandin E1 analogue, has revolutionized labour induction. It can be used orally, vaginally and sublingually. ¹ There are many studies of misoprostol regarding labour induction but concerns still exist regarding the safe and effective dosing schedule due to the increased incidence of fetal distress, ² meconium-stained liquor and hyperstimulation at higher doses.

This study was undertaken in order to assess the safety and efficacy of the use of 25 µg versus 50 µg of misoprostol administered intravaginally for the induction of labour at term.

Material and methods

After obtaining written consent, 120 pregnant women attending the Department of Obstetrics and Gynaecology of the Lady Hardinge Medical College and SSK Hospital, New Delhi, India were screened for possible recruitment into the study. They all presented with period of gestation >37 weeks, with a singleton pregnancy in cephalic presentation, a Bishop's scoring of <6, a reassuring non-stressed pattern, with either an obstetric or a medical indication for the induction of labour induction. The study was undertaken over a three-month period. At our institute approximately 200 term pregnancies are subjected to induction per month. We excluded from the study any pregnant woman who had a non-vertex presentation, a previous uterine scar, a multifetal pregnancy, clinical evidence of cardiopulmonary, hepatic or renal disease, contraindication to prostaglandins and those with significant maternal and fetal compromise or who failed to supply written informed consent.

Approval was obtained from the hospital ethical committee. All patients were subjected to detailed history taking, a complete physical examination and investigations including a complete haemogram, random blood sugar, blood urea, serum creatinine, an obstetric ultrasonography and a cardiotocography.

Enrolled subjects were randomized (simple randomization) into two groups (A and B). Group A received 25 µg of vaginal misoprostol while group B received 50 µg of intravaginal misoprostol 4 hourly to a maximum of five doses. Therapy was continued until the cervix was favourable for amniotomy, a spontaneous rupture of the membranes or an active labour. Further dosing was withheld if there was hyperstimulation or a nonreassuring heart rate pattern.

All subjects were monitored hourly for blood pressure, pulse rate and temperature; the fetal heart rate was monitored every 15 minutes in the first stage and every 5 minutes in second stage of labour; uterine contractions and their intensity, frequency and duration were monitored every 2 hours and their cervical dilatation was monitored every 4 hours.

All those who had an uncomplicated course of labour were discharged 48 hours after delivery. Patients with complicated labour were retained in the wards for a week after delivery.

The collected information was tabulated and subjected to appropriate statistical analysis using Microsoft Excel package on a personal computer. Figures and tables were drawn on Microsoft Excel and Microsoft Word (Windows 2000 based). The rejection criteria for null hypothesis were fixed at P < 0.05 (two-tailed significance).

Results

One hundred and twenty pregnant women who fulfilled the inclusion criteria were randomized into two groups, A and B, each group consisted of 60 women. Group A received 25 µg of misoprostol intravaginally and group B received 50 µg. The demographic characteristics and obstetric details of the two groups were similar (Table 1).

Postdatism was the most common induction followed by pregnancy-induced hypertension in both the groups. Other indications were term pregnancy with leaking per vaginum, oligohydramnios and intrauterine growth retardation.

The comparison of the primary and secondary outcomes is as shown in Table 2. The most common indications for an emergency caesarean section were fetal heart rate abnormalities, in the form of late decelerations, and meconium stained liquor.

Group A patients required 60±25.9 µg of misoprostol whereas group B women required 138.33±63.34 µg. This was found to be statistically significant (P < 0.001). The average dose requirement was found to be equal in both the groups (2.4±1.04 in group A versus 2.76±1.26 in group B).

In patients with fetal distress the main finding on cardiotocography was fetal heart rate deceleration. Although the difference in the meconium passage during labour was not significant statistically, four patients had a passage of thick meconium at an early stage of labour and, therefore, underwent a caesarean section. Potential adverse effects of misoprostol, such as nausea, vomiting, diarrhoea and fever, were not noted in either group. There was no significant difference in neonatal outcome. None of the neonates required admission to the neonatal intensive care unit.

Discussion

Although the efficacy of misoprostol for the induction of labour is confirmed by many studies, the optimal dose, regimen and route of administration needs further research. The result of this study indicates that 25 µg every 4 h is as efficacious as 50 µg for cervical ripening and labour induction at term and there was a reduction in the rate of caesarean sections.

We found no significant difference in the induction delivery interval with 25 µg or 50 µg of vaginal misoprostol at term shown by Meydanli et al. ³ The number of women delivering within the first 12 h was greater in group B. It has previously been reported that plasma concentrations of vaginal misoprostol rose gradually and reached maximum levels between 60–120 minutes. ⁴ It was expected that the 50 µg dose vaginally would reach the threshold plasma misoprostol acid concentration level earlier than the 25 µg group. This may also be due to the possibility that higher concentrations of intravaginal misoprostol may have more effect locally on the cervix. It may also be possible that this might be the reason that more patients in group B delivered within the first 12 h.

The vaginal and operative delivery rates in our study were comparable to other studies ^3,5 and we found no significant difference between either group.

Although the rate of abnormal fetal heart rate patterns in our study is comparable to the other studies, ^3,5 we did not find any significant difference in the incidence of fetal distress in either group. There was a greater incidence of meconium staining in our study compared to other studies. ⁶ Four patients in group B had a thick meconium at an early stage of labour. It might be that the vaginal administration of 50 µg causes higher cumulative levels which may lead to abnormal fetal heart rate patterns and passage of meconium.

As in other studies ^7,8 we did not find any increase in uterine contraction abnormalities among those receiving the 50 µg dose.

There was a significant increase in the need for oxytocin infusion in 25 µg group which is comparable to that reported in other studies. ⁵ According to our results, the intravaginal administration of 25 µg of misoprostol is as effective as 50 µg in inducing labour, and has a higher success rate of vaginal delivery and a lower caesarean section rate than the group who received 50 µg.