Our Experience with Vaginal Prostaglandin-E2
for Induction of Labor in Qatar: Six Months Review

Alsakka M., Dauleh W. and Al Tamimi H.
Department of Obstetrics and Gynecology Hamad Medical Corporation, Doha, Qatar

Abstract:

In order to review our experience with prostaglandin-E2 for the induction of labour and to evaluate its safety and outcomes, a retrospective study was carried out at the Women’s Hospital, Hamad Medical Corporation, over a six-month period. Three hundred and thirty four patients (7% of total deliveries) were induced by PGE2 (Dinoprostone), including 105 (30%) nulliparae and 229 (70%) multiparae. Patients with a history of one previous lower segment caesarean section were also included. Post date pregnancy and diabetes were the most common indications for induction.

There were significant differences in the two groups regarding the number of doses and the mean total dose of PGE2 used. The need for syntocinon augmentation was more in the nulliparae (41% vs 22%). Failed induction occurred only in nulliparae. The rate of caesarean section in induced labour remained significantly low compared with a spontaneous labour (11.6% vs 10.7%). The caesarean section rate was higher in the nulliparae (16.0% vs 9.6%) but this was not statistically significant. The caesarean section rate was higher when Bishop score 0-4 (76% vs 24%). Only two of the babies in the study group had an Apgar score less than 7 at 5 minutes. There was one caesarean hysterectomy because of postpartum hemorrhage associated with the PGE2 induction.

Conclusion: The calculated induction rate with PGE2 was 7% of total deliveries. Induction of labour with PGE2 in a grandmultiparae and previous caesarean section is relatively safe but further multicentre studies are needed to confirm our findings.

Key words: Prostaglandin E2, cervical ripening, labour induction.

Introduction:

Labour induction has become commonplace in modern obstetrics and is indicated in medical, obstetrical and foetal conditions in which prolongation of pregnancy would jeopardize maternal and foetal well-being and in which there are no contraindication to the use of amniotomy, oxytocin and prostaglandin (PG).

PGE2’s have been used vaginally for induction of labour for the last two decades. Over the last decade induction of labour has become one of the most common procedures performed in delivery room services⁽¹⁾.

A pregnancy requiring induction of labour with an unfa-vorable cervix presents a management dilemma. The rapid increase in induction rate is not well understood. Introduction of newer methods of cervical ripening, more accurate gestational dating, and antepartum foetal surveillance may all contribute to a rising induction rate. PGE2 has been shown to be efficacious in promoting pre-induction cervical ripening and in initiating labor(2). Various routes, forms, and doses of PGE2 have been tried yet the optimum dose and frequency of its applications has not been determined. Traditionally induction of labour has been thought to increase the risk of operative delivery and iatrogenic prematurity(3). The purpose of this study is to review retrospectively the use of PGE2 for induction of labour in our hospital and to determine whether the outcome was adversely affected by the PGE2 induction.

Materials and Methods:

The hospital record files were reviewed of prostaglandin-induced patients over a six-month period (1st January, 1999 to 30th June, 1999). Three hundred and thirty four patients were induced with PGE2 vaginal tablets or PGE2 vaginal gel. Of the 334 patients, 105 were nulliparae and 229 multiparae; parity ranged from 1-10, the grand multiparae (para > 5) were 28 patients (12.2%) of the multiparae group. Twenty six (12%) of the multiparae had a history of one previous lower segment caesarean section. Seventeen patients were excluded from the subsequent analysis of neonatal outcome because there was a congenital lethal anomaly in the foetus or there was intrauterine foetal death (IUFD).

Demographic data and details of the induction of labour and delivery were obtained from hospital records. Maternal ages of the nulliparae ranged 17-36 years, and for the multiparae ranged 19-46 years. Diabetes and post-term pregnancy were the most common indications for induction of labour (nearly 45% of the inductions) with pre-eclampsia, hypertension, intrauterine growth restriction, premature rupture of membranes (PROM), RH-isoimmunization and suspected macrosomia being other primary indications for induction.

Some cases were induced for relatively minor indications such as increased body weight, oligohydramnios, previous IUFD and less foetal movement. No elective induction of labour was performed. The gestational age ranged from 26 to 42 weeks for both nulliparae and multiparae.

Once the decision was made to induce, digital examination for scoring of cervical favorability was performed by a senior obstetrician using the scoring system of Bishop. The dose of PGE2 was either 1.5 mg or 3 mg vaginal tablets or 2 mg intravaginal gel. The permitted PGE2 gel is placed in ready-to-use syringes and is chemically stable at 4°C. The interval for repeating the dose was eight hours or twelve hours after cervical assessment if the patient did not go into labour after a single dose. No need to repeat induction by PGE2 if regular contractions ensued or the cervix was deemed favorable for artificial rupture of the membranes and oxytocin augmentation. A maximum of four doses of PGE2 were allowed in any one induction. If the patient has failed to respond to induction it can be repeated after interval of 24 hours with a maximum of four doses.

The patient was instructed to stay in bed for one hour, while a non-stress cardiotocography was performed for 30 minutes, if tetanic contractions (a contraction frequency of six or more in 10 minutes) were noted.

The PGE2 was retrieved from the posterior fornix and the patient was prescribed retrodrine (Yutopar) 5 mg I.V. slowly. Failed induction was defined as inability to achieve the active phase of labour despite an adequate exposure to cervical priming and oxytocin stimulation either after spontaneous rupture of membranes or amniotomy. Neonatal outcomes are shown in Table 1.

Table 1: Neonatal outcomes excluding 17 cases of abnormal babies and IUFD

Results:

Over the six-month study period, a total of 5174 mothers were delivered, 337 deliveries (elective caesarean section) were omitted from analysis because of contraindication to induction and 14 deliveries (ARM and syntocinon) as the Bishop score was high. Of the remaining 4823 patients, 334 patients (7%) were induced by PGE2, (105 nulliparae; 31% and 229 multiparae; 69%).

There were 26 patients (12%) of the multiparae group with a history of one previous lower segment caesarean section. The grand multiparae (>5) were 28 patients (12.2% of the multiparae). The overall indications for induction of labour were diabetes 22.5%, postdate 21.6%, preeclampsia and hypertension 16.2%, premature rupture of membranes (PROM) 6%, intrauterine growth restriction (IUGR) 17.1%, suspected microsomia 2.4%, miscellaneous group of relatively minor indications 8.1%, intrauterine foetal death and abnormal foetus 5.1%, are RH-isoimmunization, 0.9% (Figure 1).

Figure 1: Indication for Induction of Labor



There were no cases of ruptured uterus. One case of antepartum hemorrhage necessitated immediate caesarean section and ended by caesarean hysterectomy for postpartum hemorrhage.

A single dose of PGE2 was used for induction of labour in each of 187 patients (82%) of the multiparae compared to 63 atients (60%) of the nulliparae group. The single dose used in nulliparae was 2 mg gel in 58 of the patients (55%), and 3 mg tablets in five patients. A lower dose 1.5 mg of PGE2 tablet, as opposed to the recommended 3 mg, was used in 36 multiparae patients (11%) because we felt that complications would be minimized when smaller doses were used. Of the total study population labour was induced in 74.8% with a single dose.

The PGE2 dose had to be repeated up to four times in 43 patients (19%) of the multiparae compared to 41 patients (39%) of the nulliparae. According to the treatment protocol, only in four cases of the total patients the dose of PGE2 was repeated 5-7 times, two primiparas and two multiparas.

The amount of PGE2 used was 306 doses of 2 mg gel of which 181 single doses (59%) were needed; fifty 3 mg tablets of which 33 (66%) single doses were used; one hundred and twenty four 1.5. mg tablets were used of which only 36 (29%) were used as single doses. At the time of the survey these represented costs of QR.23,000 for the gel and QR.5,000 for the 112 (3 mg) tablets (US$ = 3.65 Qatari Riyal).

Syntocinon was needed in 43 (41%) of the nulliparae compared to 51 (22%) of the multiparae (statistically significant; p = 0.005).

Failed induction (inability to achieve the active phase of labour) occurred in four patients (1.2%), all of whom were nulliparae; Bishop score ranged between 1-4 and doses of PGE2 were repeated up to five times.

Of the multiparae, 90.4% achieved vaginal delivery compared to 79% of the nulliparae.
The caesarean rates in multiparae and nulliparae were 9.6% and 16.2% respectively.

The overall caesarean rate was 11.7%, which is similar to the caesarean rate for women who presented in a spontaneous labour; 10.7% during the same study period (479 caesarean sections out of 4486 spontaneous labour). The caesarean rate was higher when Bishop score ranged 1-4 (74.4%) compared to 25.6% when Bishop score was > 5.

Maternal complications associated with induction of labour and deliveries were infrequent and did not differ by Bishop category or repeat dose. Complications occurred in two cases of antepartum hemorrhage, both delivered by caesarean section, one of them complicated with postpartum hemorrhage necessitating caesarean hysterectomy, another two cases of atonic postpartum hemorrhage managed without other complications. One case of precipitated labour was complicated by retained placenta and manual removal of the placenta (MRP) was performed.

Hyperstimulation occurred in three cases (<1%); one was delivered normally and two by caesarean section. There was no uterine dehiscence or rupture and 19 of 26 patients (73%) achieved vaginal birth after caesarean section (VBAC). None of our study patients developed maternal systemic side effects of PGE2 that required treatment.

After excluding 17 cases (5.1%) induced because of foetal anomaly or intrauterine foetal death, neonatal complications included two admissions (0.6%) to the neonatal intensive care unit (NICU) because the Apgar scores were less than 7 at 5 minutes. No neonatal deaths were recorded in our study.

Neonatal morbidity was recorded in 16 babies, seven in the multipara group, one was a case of Erb’s palsy due to shoulder dystocia and was temporary, one was meconium aspiration syndrome and was discharged home after four days, seven babies of low birth weight (1.8-2.2 kgs), four babies of diabetic mothers, one with an abnormal heart and one baby of anaemia (mother of RH-isoimmunisation). No neonatal morbidity could be attributed directly to the use of the prostaglandin.

Discussion:

This study has shown that in our environment it may be safe to use prostaglandin E2 for induction of labour as there was no serious maternal or neonatal side effect referable to the use of prostaglandin. The vaginal delivery rate of 87% in our study is comparable with that previously reported by Xenkis et al using different methods⁽⁵⁾. In women who require delivery regardless of the Bishop score, strong consideration should be given to the induction of labour instead of elective caesarean delivery because the majority of women induced achieved vaginal delivery. A single dose of PGE2 was used for induction of labour in about 75% of the study population. The dose ranged between 1.5-3 mg, 73% being 2 mg.

The most dangerous complication of induction of labour by PGE2 is rupture of the uterus; although rare it is seen most commonly where there is a previous lower segment scar. The posterior and lateral uterine wall rupture has been described in both the intact and scarred uteri, in addition to rupture of the previous scar^(6,7). The risk of rupture appears to be between 0.7%-2.3% in women with a previous scar⁽⁸⁾.

The greatest risk factors being the previous scar in the uterus, the use of syntocinon infusion, multiparity and the state of the cervix; the presence of an unfavorable cervix is thought to influence the generation of pressure within the uterus hence rupturing the uterus⁽⁹⁾.

There were no cases of rupture of the uterus in our patients of whom 21% were grand multiparae (Para > 5), and syntocinon was used to augment labour in 22% of our multiparae. This corresponds to other reports by MacKenzie et al⁽¹⁰⁾ and Abat et al⁽⁹⁾ which recorded no rupture of uterine scar following PGE2 induction, and contradicts Ramsey et al⁽¹¹⁾ and Raskin et al⁽¹²⁾ who reported uterine rupture in women receiving PGE2 for labour induction.

Eleven percent of our multiparae had a previous lower segment caesarean section scar, 73% of them underwent vaginal birth after caesarean (VBAC). Similarly a review of the literature regarding the use of oxytocin and cervical ripening agents in women undergoing a trial of VBAC supported the view that these modalities for labour induction in a VBAC candidate are safe and are not associated with an increased risk of uterine rupture^(13,14).

The caesarean rate was higher when the Bishop score was low; this is comparable to the findings of a significant reduction in successful VBAC trials in women with a poor Bishop score that was reported by McNelly and Turner⁽¹⁵⁾.

The absorption of PGE2 vaginal tablets or gel and therefore its efficacy and safety is influenced by the vehicle and possibly by vaginal pH, humidity and oily lubrications. These factors might have contributed to the repeated doses of PGE2. In our series 25% of the patients had two to four doses of PGE2.

Induction of labour failed in 1.2% of our patients who therefore required caesarean section, this favorably compared to the findings of 1.7% by Albar et al⁽⁹⁾.

It has been suggested that prostaglandin gel may be safer than tablets, and more effective in multiparous women, but still there is controversy regarding the appropriate dose and route for maximum efficacy(15 -19).

Conclusion:

Induction of labour is increasing by approximately 25% in the United States⁽⁸⁾. Clearly the favorability of the cervix has a substantial impact on the potential success of any labour induction. An unfavorable cervix can result in a prolonged induction, prolonged hospitalization, failed induction and an increased caesarean delivery rate.

In this modern era of health care reform and cost containment, the identification of therapeutic strategies to enhance the success and cost effectiveness (misopristol use vs PGE2) of labour induction are of great interest. Further research is needed to evaluate the most appropriate dosing regimen of all the available agents.

Acknowledgment:

We would like to thank Dr. Ahmed Al-Alousi, Head of Statistics Department for his kind help and support.

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