VBAC and Prostaglandin Induction

Prostaglandin gel or tablets can be used to induce labour. The usual form is Prostaglandin E2, also known as Prostin, dinoprostone, or Prepidil. Prostaglandin E2 is the substance discussed on this page. It should be distinguished from Prostaglandin E1, known as Cytotec or Misoprostol, because the two drugs have some important differences and have different implications for women planning a VBAC.

Different women react differently to prostaglandin gel. In particular, 'hypertonic uterine activity' is more common with this drug than with other methods of induction[1], and some people worry that this may increase the possibility of uterine rupture [2]. Laura Brockman's uterus was left 'in shreds', and her baby died, after her labour was induced with Prostin; her local hospital has discontinued its use for all women with prior caesarean sections after her tragic experience.

One midwife told me that she always starts off with half the suggested dose, because if the woman reacts strongly to the gel then that is enough. If she doesn't react strongly, you can always add more later. But, unlike an oxytocin drip which can be turned down, you cannot reduce the effect of gel already given; you can only add more. If your midwife or doctor suggests using this drug and you agree, perhaps starting with a half dose would be an option to consider.

Information on Prostaglandins for Induction of Labour:

Prepidil: RX-Med information for doctors - says this product should not be used on women with a history of caesarean section or other uterine surgery. See also entry for Prostin.

Cervidil Manufacturer's Information - detailed.

E-Doc

WebMD

RX-List

Studies on VBAC and Prostaglandin Gel

Some of these studies found increased risks associated with the use of prostaglandin gel, while others did not. It is difficult for any study to cover enough cases to allow all the results to be statistically significant - ideally one study would look at tens of thousands of cases. To quote one researcher:

"Uterine rupture is rare; it occurs in between 0.3% to 0.7% of labours. The terms "rupture" and "dehiscence" are not used consistently, which hinders further assessment of these events. Assuming a background risk of 0.5%, prospective studies would have to include 10 000 women in order to show a twofold increased relative risk. It is unlikely that a such a large comparative study would be feasible." [2]

Some meta-analyses lump together the results from a number of smaller studies to try to draw further conclusions, but it can be hard to know whether the component studies were really comparable.

The fact that some studies have found increased risks associated with the use of prostaglandin gel for mothers attempting VBAC, suggests that it has not been proven safe in this situation, although it has not conclusively been proven dangerous either. While there are still questions over its safe use, it would seem sensible to treat it with extreme caution.

Here are the studies I have found - if you know of any more, please email angela@horns.freeserve.co.uk

Uterine Rupture During Induced Trials Of Labour In Women With A Previous Cesarean Delivery

American Journal of Obstetrics and Gynecology, January 2000, in two parts, part 2, volume 182, number one

D. Ravasiax S. Woodx J. Pollard
University of Calgary, Foothills Hospital, Calgary, AB, Canada

This is the most recent of the VBAC induction studies.

This study of women attempting VBAC found that labour induced with prostaglandin gel was more than six times more likely to end in uterine rupture, than spontaneous labour.

"The relative risk of uterine rupture with PGE2 use versus spontaneous trial of labour was 6.41 ."

The full abstract of this study is on the VBAC and Induction page.

Use of prostaglandins to induce labour in women with a caesarean section scar

British Medical Journal 1999; 318: 1056-1058
Sarah Vause, specialist registrar, Mary Macintosh, consultant.
Department of Obstetrics and Gynaecology, Leeds General Infirmary, Leeds LS1 3EK

A mother planning VBAC in this hospital suffered a ruptured uterus, and lost her baby, following induction with prostaglandins. It is pointed out in the correspondence that the early warning signs of uterine rupture were not acted upon appropriately.

After this sad event, the authors undertook a review of the literature on prostaglandin use in VBAC attempts. Their paper and the following correspondence gives a good overview of the subject, although they did not draw any firm conclusions. Note that they do not appear to have reviewed several of the studies which are mentioned on this page - some were published after the review. They only found trials covering small numbers of women.

Read the full article in the British Medical Journal

Uterine rupture during induced or augmented labor in gravid women with one prior cesarean delivery.

Am J Obstet Gynecol 1999 Oct;181(4):882-6
Zelop CM, Shipp TD, Repke JT, Cohen A, Caughey AB, Lieberman E
Department of Obstetrics and Gynecology, Massachusetts General Hospital, the Department of Obstetrics and Gynecology, Brigham and Women's Hospital, Harvard Medical School, and the Department of Obtetrics and Gynecology, University of Nebras.

This paper, published in 1999, is among the most recent of the VBAC studies and we can assume that the researchers will have been familiar with previous research on the matter. Its findings are worrying.

The study looked at 2774 women attempting VBAC at term, after 1 prior cesarean delivery and no other births. It compared the rates of uterine rupture associated with spontaneous labour, oxytocin induction or acceleration, and prostaglandin E2 gel induction. The analysis controlled for other factors which might confuse the result, such as birth weight, use of epidural, duration of labour, maternal age, year of delivery, and years since last birth.

Of 2774 women in the analysis, 2214 had spontaneous onset of labor and 560 women had labor induced with oxytocin or prostaglandin E(2) gel. 1072 women had their labours accelerated ('augmented') with oxytocin.

The overall rate of rupture among all patients with induction of labor was 2.3%, in comparison with 0.7% among women with spontaneous labor. Among 1072 patients receiving oxytocin augmentation, the rate of uterine rupture was 1.0%, in comparison with 0.4% in nonaugmented, spontaneously laboring patients.

After adjusting for birth weight, use of epidural, duration of labor, maternal age, year of delivery, and years since last birth, induction with oxytocin was associated with a 4.6-fold increased risk of uterine rupture compared with no oxytocin use. Acceleration with oxytocin made uterine rupture was 2.3 times more likely, and use of prostaglandin E(2) gel made rupture 3.2 times more likely. These differences did not qualify as statistically significant though, because of the small numbers involved.

CONCLUSION: "Induction of labor with oxytocin is associated with an increased rate of uterine rupture in gravid women with 1 prior uterine scar in comparison with the rate in spontaneously laboring women. Although the rate of uterine rupture was not statistically increased during oxytocin augmentation, use of oxytocin in such cases should proceed with caution."

Cervical ripening and labor induction after previous cesarean delivery

Clinical Obstetrics & Gynecology. 38(2):287-92, 1995 Jun.
By Chez, RA.
Institution - Department of Obstetrics and Gynecology, University of South Florida, College of Medicine, Tampa 33606, USA.

The authors of this paper appear to only discuss other studies, rather than presenting new data; the full study would be interesting to read, but the abstract only states that the majority of published data on VBAC candidates suggests that, if it is safe for the woman to go into labour naturally, it is safe for her to be induced and to have her labour accelerated or 'augmented':

"Both conclusions are based on the assumption that treatment and care is provided in a safe, modern obstetric service with staff and resources compatible with national standards."

Prostaglandin E2 for cervical ripening: a multicenter study of patients with prior cesarean delivery.

Am J Perinatol 1997 Mar;14(3):157-60
Flamm BL, Anton D, Goings JR, Newman J
Department of Obstetrics and Gynecology, Kaiser Permanente Medical Centers, Los Angeles, Riverside, CA 92505, USA.

5022 women attempted VBAC at California hospitals after prior cesareans. Of these patients, 453 (9%) were treated with PGE2 gel. There were no significant differences between the rates of uterine rupture in the two groups, and "indicators of maternal and perinatal morbidity were not significantly higher in the prostaglandin treated group".

"The use of PGE2 gel for cervical ripening appears to be relatively safe in patients with prior cesarean delivery."

Uterine rupture after use of a prostaglandin E2 vaginal insert during vaginal birth after cesarean. A report of two cases.

J Reprod Med 1999 Jun;44(6):571-4
Raskin KS, Dachauer JD, Doeden AL, Rayburn WF
Department of Obstetrics and Gynecology, University of Oklahoma Health Sciences Center, Oklahoma City, USA.

The authors describe two cases of uterine rupture among 57 pregnancies undergoing attempted vaginal birth after a single low transverse cesarean section. The women were treated with the insert either at 41 weeks, 4 days, or 39 weeks, 3 days, for postdatism or pre-eclampsia.

"Signs of uterine rupture included persistent suprapubic pain and repetitive fetal heart rate variable decelerations followed by bradycardia. Infant outcomes were favorable, and tears along the prior low transverse uterine scar were repaired without additional morbidity."

"CONCLUSION: This prostaglandin compound is not exempt from being associated directly or indirectly with uterine rupture and requires informed consent and continuous monitoring."


This study compares Prostaglandin E2 with Misoprostol:

Comparison of the safety and efficacy of intravaginal misoprostol (prostaglandin E1) with those of dinoprostone (prostaglandin E2) for cervical ripening and induction of labor in a community hospital.

Am J Obstet Gynecol 1999 Jun;180(6 Pt 1):1551-9
Blanchette HA, Nayak S, Erasmus S
MetroWest Medical Center, Department of Obstetrics and Gynecology, British Columbia, Canada.

Eighty-one mothers whose labour was induced with prostaglandin E2, were compared with one hundred and forty-five who were induced with misoprostol (prostaglandin E1).

The mean time between induction and birth was approximately a third shorter with misoprostol: 19.8 hours compared to 31.3 with prostaglandin E2. There was no significant difference in the cesarean delivery rate with misoprostol (25.6% vs 22.2%). The incidence of uterine hyperstimulation was higher with prostaglandin E2 (7.4% vs 0.7%).

There were no uterine ruptures among the 81 women induced with prostaglandin E2. However, among the 145 induced with misoprostol, there were 2 uterine ruptures and 1 dehiscence among mothers attempting VBACs, and 1 rupture in a mother with no prior caesarean. One baby died as a result of uterine rupture after misoprostol induction, but otherwise outcomes for the babies were similar.

CONCLUSIONS: "Compared with prostaglandin E2, misoprostol is more effective in cervical ripening and induction of labor, is as safe for patients who do not have a history of cesarean birth, may carry a higher incidence of uterine rupture, and should not be used for patients attempting vaginal birth after previous cesarean delivery"

Rupture of an unscarred uterus at full term after an intracervical application of dinoprostone (Prepidil) gel

VERNACULAR TITLE: Rupture d'un uterus non cicatriciel a terme, apres application intracervicale d'un gel de dinoprostone (Prepidil).

Rev Fr Gynecol Obstet 1993 Mar;88(3):162-4
Heckel S; Ohl J; Dellenbach P
C.M.C.O. Schiltigheim, Strasbourg.

"The authors report a case of uterine rupture following intra-cervical application of dinoprostone (two doses at an interval of 6 hours). No oxytocic had been administered and recording of the contractions had revealed no hyperkinesia or hypertonia one hour before rupture occurred"

Induced labor with prostaglandin E2 gel after previous cesarean section

VERNACULAR TITLE: Geburtseinleitung mit Prostaglandin-E2-Gel bei Zustand nach Sectio.

Geburtshilfe Frauenheilkd 1994 Mar;54(3):144-50
AUTHORS: Behrens O; Goeschen K; Jakob H; Kauffels W
Frauenklinik der Medizinischen Hochschule Hannover.

The authors analysed data from 385 trials of vaginal labour induction in a total of 522 patients with previous Caesarean section. Single or multiple cervical doses of prostaglandin-E2-gel were administered because of an unripe cervix in 161 women for induction of labour for medical indications.

The VBAC rates in this study were impressive: 84.9% of women delivered vaginally, and 70% of the mothers who had two prior Caesareans gave birth vaginally.

The highest success rates were seen after previous Caesarean for breech presentation, while there was still a vaginal delivery rate above 60% even after Caesarean for cephalopelvic disproportion or failure to progress.

There was no difference in complications for mother or baby between the induced and non-induced groups. There was a 0.5% incidence of uterine rupture, only in the NON-induced group. However, because of the small numbers involved, it is difficult to draw any further conclusions without reading the full study.

"Taking into consideration contraindications, intracervical application of PGE2-gel is a safe and effective method, even in patients after previous Caesarean section with clear advantages in case of an unripe cervix."

Read this abstract on Medline

References

[1] Keirse MJNC, van Oppen ACC. Comparison of prostaglandins and oxytocin for inducing labour. In: Chalmers I, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and childbirth. Oxford: Oxford University Press, 1989:1080-1111.

[2] Vause and Mackintosh, Use of prostaglandins to induce labour in women with a caesarean section scar, BMJ 1999, detailed on this page.

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