COMPARISON OF ORAL (20 uG 2 HOURLY) VERSUS VAGINAL (25 uG 6 HOURLY) MISOPROSTOL FOR INDUCTION OF LABOUR IN TERM PREGNANCIES.
Keywords: Induction of Labour, Misoprostol, Oral and vaginal route.
Induction of labour is defined as the process of artificially stimulating the uterus to initiate the process of labour. Over the past several decades, the incidence of labour induction has continued to rise. In developed countries, the proportion of infants delivered at term following induction of labour, is as high as one in four deliveries1. Induction is widely carried out all over the world, in cases where continuation of pregnancy is considered hazardous to both the mother or to the fetus or both2. Labour induction is considered as successful when it results in vaginal delivery. However when induction is performed on a patient with an unfavorable cervix, it is often difficult and can result in cesarean delivery3.
There is wide variety of techniques available for induction of labour, however prostaglandins remain the single most effective means of achieving cervical ripening and labour induction. When combined with amniotomy, it provides good clinical effectiveness and patient satisfaction4. Prostaglandin E2 is registered for labour induction in many countries, however it is expensive for routine use in developing countries. It is sensitive to temperature changes so has to be kept under refrigeration. Misoprostol (a prostaglandin E1 analogue) has several potential advantages with few systemic side effects. Advantages include its stability at room temperature, it is relatively inexpensive and it can be given via several routes (oral vaginal, sublingual, buccal). These properties make it an ideal agent for induction of labour, particularly in settings where the use of prostaglandin E2 is not possible owing to lack of availability, facilities for storage, or financial constraints5.
Although misoprostol is not registered for such use, it has been widely used for obstetric indications such as induction of abortion and of labor. In 2011, World Health Organization (WHO) issued recommendation for induction of labour, which compared the use of low dose oral and vaginal misoprostol for induction of labour. However, owing to concerns about the risk of uterine hyper stimulation with vaginal misoprostol, more recent trials have focused on lower doses of vaginal misoprostol and the oral route for misoprostol administration. In a study conducted in China, low dose oral was compared with low dose vaginal misoprostol for labor induction at term and it concluded a cesarean rate of 4% in oral route and 17% in vaginal route6. A number of studies had been performed to compare oral versus vaginal misoprostol for induction of labour but with a higher dose regimen.
Few studies are available in previous literature in which low dose (25ug) misoprostol has been used for comparison. These studies have compared 25ug vaginal with 100ug oral misoprostol, but no significant difference has been observed regarding mode of delivery7. Similarly another study compared 50ug vaginal with 50ug oral misoprostol without any significant difference in the mode of deliveries8. It was therefore suggested that dose can be reduced to avoid the side effects associated with higher doses of misoprostol, without affecting the mode of delivery.
The rationale of this study is to utilize lower dose protocol of misoprostol (25 ug) for induction of labour in term pregnancies and compare the outcome of oral route with vaginal route.
MATERIAL AND METHODS
This randomized clinical trial study was conducted at the department of Gynaecology and Obstetrics, Unit II, Maternal and Child Health Centre, Pakistan Institute of Medical Sciences, Islamabad, form one year from, January 2015 to December 2015.
Total 190 females were selected for this study. Sample size calculated by using WHO sample size calculator taking level of significance 5%; power of test 90%; anticipated population proportion is equal to (P1) 4%10, anticipated population proportion (P2) is equal to 17%10; sample size 95 in each group.
Group A was oral, group B was vaginal, technique used was non-probability convenience sampling.
The inclusion criteria of this study was all term pregnant women (upto parity 4) with obstetric and medical Indication of induction for labour and bishop score a$?6.
Parity [greater than or equal to]4, previous history of obstetric and gynaecological surgery e.g: C-section, myomectomy. Women with genital tract anomalies and suspected cephalopelvic disproportion were exlusion of this study.
Mode of delivery was the main outcome, measured in term of frequency of vaginal delivery and cesarean section.
Data were collected on a pre-designed proforma. Permission from the hospital ethical committee was sought. Patients admitted for induction of labour were recruited after informed consent. Lottery method was used to randomize and allocate the patients to oral or vaginal group. The women randomized to group A received 20 microgramoral misoprostol 2 hourly orally up to a maximum of 12 doses. The women randomized to group B receive 25 microgrammisoprostol vaginally and was repeated at 6 hours interval up to a maximum of 4 doses. Oral misoprostol is currently available in the form of 200ug tablets. The recommended dose of oral misoprostol for induction of labour is 20ug, 2-hourly.
It was suggested that rather than breaking the 200ug tablet into eight pieces, the tablet should be dissolved into 200 ml of water and 20 ml of that solution be administered as a single dose. The primary outcome measure was mode of delivery, (vaginal, instrumental or C-section) and number of doses required for initiation of labour. Secondary outcome was uterine hyperstimulation. Data were entered and analyzed using the SPSS version 10. Descriptive statistics were calculated for both qualitative and quantitative variables. For quantitative variables (age, parity, gestational age and no. of doses) mean +- S.D was calculated and for qualitative variable (mode of delivery) frequency and percentage was calculated. Qualitative variables like mode of delivery were compared by using chi square test. A p-value of 25years###55 (28.9%)###45 (23.6%)
###Primigravida###60 (31.57%)###61 (32.1%)
Gravidity.###1.02 +- 1.19###0.89
###Multigravida###35 (18.4%)###34 (17.8%)
Gestational 38 weeks###45 (23.6%)###47 (24.7%)
###38.91 +- 1.02###0.78
age.###>38weeks###50 (26.3%)###48 (25.2%)
Table-II: Mode of delivery (n=190).
###Oral Misoprostol###Vaginal Misoprostol###p-value
###Vaginal Delivery###91 (47.8%)###79 (41.5%)
Mode of delivery.###0.0045*
###Cesarean Section.###4 (2.1%)###16 (8.4%)
Table-III: Reasons for induction of labour (n=190).
###Oral Misoprostol###Vaginal Misoprostol
Post date###42 (22.1%)###45 (23.6%)
PROM###24 (12.6)###25 (13.1%)
Poor Bishop###15 (7.8%)###13 (6.8%)###0.96
Oligohydramnios###8 (4.2%)###8 (4.2%)
NRCTG###6 (3.1%)###4 (2.1%)
Table-IV: Stratification of mode of delivery in study arms by number of doses (n=190).
Number of doses###p-value
###Mode of delivery###Oral misoprostol###Vaginal Misoprostol
###Vaginal Delivery###52 (27.3%)###47 (24.7%)
###Cesarean section.###2 (1.05%)###12 (6.3%)
###Vaginal Delivery###39 (20.5%)###32 (16.8%)
###Cesarean section.###2 (1.05%)###4 (2.1%)
A total of 190 patients were enrolled for this study. The mean age of participants was 26.93 +- 4.09 years. Mean gravidity of was 1.02 +- 1.19 and 63.7% of women were primigavida and 36.3% were multigravida. Mean gestational age by dates was 38.91 +- 1.02 weeks (table-I). Commonest indication for induction of labour was post dates pregnancy accounting for 87 (45.8%) cases (table-III). Of 190 participants, 113 (59.5%) needed single dose of misoprostol and 77 (40.5%) needed multiple doses (table-IV). Overall, 170 (89.5%) women had spontaneous vaginal delivery and 20 (10.5%) women needed cesarean section (table-II). Stratified analysis of mode of delivery in each study arm by number of doses is summarized in table-IV. No case of uterine hyperstimulation was seen during the study.
Misoprostol is, a cost effective treatment, being increasingly used for induction of labour since past few years. There have been different published reports of misoprostol use through different routes (oral, vaginal and rectal) and in varying doses (25 ug to 200 ug). Higher incidence of tachysystole is reported with higher doses9.
In the present study baseline characteristics such as age, gravidity, gestational age and indication for induction of labour were distributed equally across the treatment arms. This is the impact of randomization which distributes known and unknown confounders across treatment groups.
In this study, oral dosage regimens of 20ug at 2 hourly intervals for maximum of 12 doses and vaginal dose was 25ug 6 hourly up to maximum of 4 doses. Jindal et al used same dose of misoprostolvia oral and vaginal route and found that vaginal route was more effective for inducing labour successfully as compared to oral route. Their findings were contrary to results of our study where oral route was found to be more effective10. Higher doses of misoprostol were used in a study by Blanchard, Clark et al10,11.
In this study the percentage ofprimigravida women in oral group was 31.5% and in vaginal group 32.1% (p-0.50). Literature has reported higher percentage of primiparous women in the treatment arms which was consistent with our resuts12-14.
Cesarean section rate in group A was 2.1% as compared to 8.4% (p-0.004) in group B. Darney et al reported (4% and 17%) and Kambhampati et al reported (6% and 14%) in both groups15,16. In another study by Ratnakhatri et al the rates of operative delivery in both groups were 14% and 30% which were higher in comparison to our study17. In contrast, other studies reported that no difference in the rate of cesarean delivery in oral vs. vaginal misoprostol. The proportion of cesarean delivery in oral group was 41% and vaginal group was 42% (p-0.63)18-21. In a study by Sultana et al need for cesarean section in oral misoprostol was 30% as compared to 34% in vaginal misoprostol (p-0.78)21.
Commonest indication for induction of labour in the present study was postdates pregnancy (22.1% and 23.6%) in both groups, followed by prelabour rupture of membranes. Jindal et al and Osmundson et al reported hypertensive disorders as the most common indication whereas oligohydramnios, intrauterine growth restriction and medical disorders in pregnancy are the indications reported in previous studies, for inducing labour at term10,22.
Misoprostol effectively induces labour, with the vaginal route of administration and has a faster action than with the oral route in equivalent doses. However frequent occurrence of hyperstimulation and the higher intervention rate in the vaginal group mean that the preferred route might be oral. More trials are needed to find the right oral dosage that combines efficacy with safety.
Misoprostol is especially relevant for Pakistan where economic resources are scarce and high temperatures prevail. This drug ischeap as compared to other prostaglandins licensed for pregnancy termination, induction of labour and treatment and prevention of post-partum hemorrhage. It is heat stable so is easily stored at room temperatures and it had few systemic side effects. Although formulated for oral usage, but rapidly absorbable via sublingual, vaginal and per rectal route.
It is concluded that women randomized to oral misoprostol had better obstetrics outcome as compared to vaginal misoprostol.
Although our contribution to the existing literature is small, but it is significant addition to studies comparing lower dose regimen and provides comparison of oral and vaginal routes in terms of mode of delivery.
LIMITATIONS OF STUDY
This study was performed on limited number of patients. To reach the consensus about the lowest effective dose of oral and vaginal misoprostol, we need further trials on larger scale. However, any increase in dose, while improving clinical efficacy must be balanced against a potential increase in side effects and adverse complications for the women and her infant.
CONFLICT OF INTEREST
This study has no conflict of interest to be declared by any author.
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|Publication:||Pakistan Armed Forces Medical Journal|
|Date:||Apr 30, 2019|
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