To assess the effectiveness and safety of sublingual Misoprostol comparing with vaginal Misoprostol for cervical ripening and labor induction in women with viable fetus at term, 120 women were randomized prospectively to receive Misoprostol 50ug vaginally (VG) (n=57) or 50 ug sublingually (SG) (n=63), every 4 hours three times maximum. The mean induction to delivery time was 11.76 ± 6.5 hours in the vaginal group (VG) and 10.46 ± 6.22 hours in the sublingual group (SG). Women delivering vaginally within 24h was 43 (73.6%) in VG vs 51 (80.9%) in SG. Oxcytocin use was needed in 29 cases in VG (50.9%) vs 31 cases in SG (49.2%). The Sublingual group experienced more hyperstimulation syndrome (n=7, 11.11%) vs vaginal group (n=2, 3.5%) (p=0.67). The Apgar score and intensive care unit admission were similar in the two groups. Sublingual Misoprostol is as efficacious and safety as vaginal Misoprostol for induction of labor at term.
1. Gynecology obstetrics department, University Hospital Mohammed VI Marrakech, Morocco.
RecievedSep 2 2013 AcceptedOct 11 2013 PublishedOct 30 2013
CitationBouchra Fakhir, Abderrahim Aboulfalah, Hamid Asmouki, Abderraouf Soummani (2013) Sublingual versus vaginal misoprostol for labor induction at term: a prospective randomized trial. Science Postprint 1(1): e00003. doi:10.14340/spp.2013.10C0003
Copyright©2013 The Authors. Science Postprint published by General Healthcare Inc.. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs 2.1 Japan (CC BY-NC-ND 2.1 JP) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
FundingOur research was not supported by any funds.
Competing interestsNo conflict of interest.
Ethics statementStudy design was approved by gynecology and obstetrics department staff, and by Ethics committee of the university hospital Mohammed VI.
Patients were clearly informed about the aim of the study and about safety of the use of the tow ways of administration of Misoprostol according to previous studys, and about that they will be closely followed along induction and labor.
B.F: Writed the article and designed the discussion.
A.A: Designed the study, realized randomization and statistics results.
H.A: Correction of the article
A.S: Department chief, Approved the quality of the study, and coordination of the team work.
Corresponding authorFakhir Bouchra
AddressApt 4 resid Ifrane Lot Bouizgaren 40000 Marrakech, Morocco.
E-mailIf you want to contact author,Please register as a member.
Misoprostol is a synthetic prostaglandin E1 analogue. Actually, it is more frequently used for cervical ripening and labor induction than natural prostaglandin, particularly in developing countries regarding its low cost. The most favorable method for the administration and the optimal dose of Misoprostol has not yet been established. Several studies indicate that oral misoprostol is less effective and results in more side effects than intravaginal doses because of systemic diffusion and digestive passage 1-2. Sublingual misoprostol is another route of administration that may perhaps be compared with vaginal administration, as both require mucosal uptake of the drug. Since the pharmacokinetic is different for sublingual and vaginal Misoprostol, differences in efficacy and side effects need to be compared.
The aim of this study is to compare complications and efficacy of sublingual vs vaginal administration of Misoprostol for labor induction in pregnancy at term.
Study was performed in gynecology obstetrics department of Mohammed VI University Hospital of Marrakech, Morocco.
We utilized a randomize prospective study during the one year from June 2008 to May 2009, and compared the two groups of patients: first group receiving Vaginal Misoprostol for labor induction (VG) and second group receiving sublingual Misoprostol (SG). Patients were randomized into the two groups using tow random numbers sets (VG, SG) corresponding to patients numbers. The size of sample was calculated according to the study of vaginal Misoprostol efficacy in 1996 with 5% range of error between the tow ways of administration. Inclusion criteria for our study were: singleton viable pregnancy, 37weeks or more, cephalic presentation, artificial labor induction for medical or obstetrical indication, with Bishop cervical score less than 5, sonographic weight evaluation less than 4500g and normal non stress test. Excluded from the study were: twin pregnancy, other fetus presentations, previous uterine scars, cephalopelvic disproportions and if any first try of labor induction was attempted. Patients meeting inclusion criteria were counseled about participating in the study and then randomized in the two groups: VG, SG. Labor induction protocol was vaginal or sublingual administration of 50 μg of Misoprostol ( quarter of 200 μg divisible tablet of Misoprostol prepared by hospital pharmacologist ) every 4 hours until three or more uterine contractions occurred during ten minutes, or cervical modifications appeared, or when the maximum of three doses was reached. Patients not entering in the active phase of labor 4 hours after the last dose were diagnosed as failed induction. Oxytocin progressive perfusion was performed after misoprostol induction failure or when necessary for dynamic dystocia in active phase of labor. We waited for a 4hours interval between last Misoprostol dose and Oxytocin perfusion placement. Nonstop tococardiogram was performed for surveillance and we evaluate efficacy and tolerance criteria for both ways of administration of Misoprostol, also neonatal outcome with Apgar score and NICU admission. Statistical analysis was performed using C2test and fisher test. Significance level of 5% was adopted.
120 patients have participated to this study, 57 received vaginal Misoprostol and 63 received sublingual Misoprostol. Subjects were similar in mean age, parity, gestational age, corporal masse index (CMI) and initial Bishop score (table 1). Induction indications were also similar in the two groups: post term followed by preeclampsia, prelabor membrane rupture, diabetes and others (table 1).
The mean induction to delivery time was 11.76 ± 6.5 hours in the vaginal group(VG) vs 10.46 ± 6.22 hours in the sublingual group (SG) (p=0.46). Women delivering.
vaginaly within 24h was 43 (73.6%) in VG vs 51 (80.9%) in SG (p=0,107). The mean number of Misoprostol doses required was similar for both of groups, 1.8 in VG and 1.7 in SG (p=0.815). 4 cases (7%) in VG and 7 cases (11%) in SG required emergent cesarean section for abnormal fetal rate monitoring (p=0. 22). 3 cases (5%) in VG vs 2 cases (3%) in SG required cesarean section for induction failure and finally 4 cases vs 2 (7% vs 3%) required cesarean section for progressing labor anomalies . In total difference for cesarean section indications was statistically not significant (p=0.389). Oxcytocin use was needed in 29 cases in VG (50.9%) vs 31 cases in SG (49.2%) p=0.855 (table 2).
Clinical outcomes of induction in both groups
Sublingual group patients experienced more hyperstimulation syndrome (n=7, 11.11%) compared with vaginal group (n=2, 3.5%) but this difference was not significant (p=0.167). In sublingual group mean time to onset of the hyperstimulation syndrome appearance was 4 hours after the first dose in 6 cases and was 30 minutes after the second dose in one case. In the vaginal group the first case of hyperstimulation syndrome occurred 4 hours after the first dose but the second one appeared after beginning of oxcytocin perfusion. This syndrome was treated in one case using Salbutamol. In the other cases cesarean sections were performed regarding sever fetal heart beat anomalies. Minor maternal side effects were similar in both vaginal and sublingual routs. Finally neonatal outcomes including the Apgar score, and intensive care unit admission were similar in the two groups (table 3).
Maternal and fetal complications in both groups
Misoprostol is a synthetic prostaglandine E1 analogue; actually it is used frequently in cervical ripening and labor induction at term especially in developing countries. It is a low cost product, affordable, stable at room temperature and used even not licensed for use in pregnancy 3. Misoprostol can be administrated orally, vaginally and sublingually. Oral and sublingual Misoprostol have a rapid onset action. Sublingual and vaginal routes have prolonged activity and possess the greatest bioavailability 1. Not many studies in the literature evaluated the sublingual route in labor induction at term. In our study, both vaginal and sublingual Misoprostol are efficient. The mean induction to delivery time was 11.76 h vs 10.46h and vaginal delivery within 24h was 73.6% vs 80.9% respectively. No difference between the two groups was found. These results are compared with Nacer randomized trial 2007 4, and with Pernella Geels results in 2010, but this one evaluate 200 μg once in 24h vaginally or sublingually in women with intrauterine fetal death 5. Zahrane’s randomized double blind placebo controlled clinical study, using the same inclusion criteria as us, found that sublingual Misoprostol resulted in a shorter induction to delivery interval, more women delivered within 24h of induction and fewer patients required Oxcytocin augmentation compared with those using vaginal Misoprostol 3. The sublingual route doesn’t increase cesarean section rate, we found almost the same rates for both groups. Feitosa and all 2006 showed a non significant but considerable difference between cesarean section rate due to fetal distress in both groups (15% vs 5% respectively vaginal and sublingual misoprostol) 6. In contradiction with the literature our sublingual group experienced more hyperstimulation syndrome (11% vs 3.5%), statistically not significant but completely opposed to Zahran’s findings that sublingual route is greater safty than vaginal route 3. And also opposed to Danielson and all explanation for a prolonged stimulatory effect of vaginal misoprostol through direct effects on the cervix, initiating the physiological events leading to uterine hyperstimulation 7.Finally no difference was found in side effects or neonatal outcome 3,5,8.
Sublingual Misoprostol is as safe and efficient as vaginal Misoprostol in the induction of labor in viable term pregnancies. No differences were found in induction to delivery time, in cesarean section rate, in maternal side effects or neonatal outcome. More frequent hyperstimulation syndrome may occur with sublingual administration but more studies with larger sample size are recommended to confirm or negate this possibility.