Factors of importance for labor induction

Background: What initiates the onset of labor is still not clarified, and it is debated whether expectant or active management is the best for the woman and the fetus. Active management means induction of labor (IOL) which is a very common obstetric intervention and is used in several situations. During the last five years, 17 % of all singleton pregnancies in Sweden were induced. There are large variations worldwide from less than five percent in some African countries such as Kenya, to extreme cases like for example Iran where IOL is performed in up to 80% of the labors. Both maternal and fetal complications are related to IOL, for instance prolonged labor, postpartum haemorrhage (PPH) and instrumental interventions as vacuum extraction/forceps or Cesarean section (CS).

The increasing rate of CS continues to cause global concerns. The ideal management of the subsequent labor for women who have undergone one previous CS has been intensely debated. The two available options are Trial of Labor after Cesarean section (TOLAC) or an elective CS. Previous CS is the most important risk factor for Uterine rupture (UR). UR is a wellknown but unusual complication in vaginal deliveries with a previous CS in the history. The risk of UR is at least two-fold when labor is induced. In Sweden, women are allowed to deliver vaginally after one previous CS, regardless if labor starts spontaneously or is induced.

Aim: The overall aim of the thesis is to identify factors of importance for the decision of IOL, and to find out which method for IOL is the most effective and safe for women with or without a previous CS.

Study I, a prospective observational study of 52 healthy women with mixed parity examined at their post-term control in gestational week 41+3. CTG, ultrasound assessment of amniotic fluid, a vaginal examination for cervical status and a five-minute skin conductance measurement, including a ‘cold pressor test’ was performed. The aim of the study was to evaluate if altered skin conductance activity could predict spontaneous onset of labor in post-term pregnancies. The probability of having a spontaneous onset of labor increased 4.0 times if the skin conductance score was negative and increased 6,8 times to start within 48 h if the cervix was open ≥2 cm.

Study II, a retrospective cohort study of 4002 women induced to labor with mixed parity. Inclusion criteria were viable singleton fetus in cephalic presentation, gestational age of ≥34 weeks. The women were divided into six groups according to method of IOL; Cytotec®, Minprostin®, Propess®, balloon catheter, amniotomy, or oxytocin. Methods of induction, baseline data, and delivery outcomes were compared. The primary endpoint of the study was the frequency of CS in each method of IOL. The lowest rate of CS overall, for both primi- and multiparous women with an unfavorable cervix Bishop Score (BS) ≤5, was found in the group where Cytotec® was administrated as an oral solution.

Study III, a retrospective cohort study for evaluating the proportion of UR in 208 women with IOL after one previous CS. The women were divided into two subgroups regarding the method of IOL. Group 1 (n=121) was the unexposed group, meaning that the women did not receive Cytotec® as the method of IOL. Group 2 (n=87) serves as the exposed group meaning that most of the women (89%) received Cytotec® as an oral solution. Method of induction, baseline data, and delivery outcomes were recorded. The primary outcome of the study was the frequency of UR in each group. There was no significant difference in the incidence of UR between group 1 and 2 (4.1 vs 4.6%, p=0.9) despite a more favorable cervix in group 1.

Study IV, a retrospective cohort study of 910 women with one previous CS, unfavorable cervix, and IOL. The study was performed at the four largest hospitals in Stockholm, the women were divided into three subgroups according method of IOL (Cytotec®, balloon catheter and Minprostin). The aim of the study was to compare the difference in the proportion of UR between the three methods There was no significant difference in the proportion of UR between Cytotec® and balloon catheter (p=0.64) for IOL after one previous CS. Orally administrated Cytotec® and balloon catheter resulted in a high success rate of vaginal deliveries of almost 70% compared to Minprostin® with the proportion of vaginal deliveries of 57% and which also had more than doubled rate of UR (5%).

Study V, an open label randomized controlled trial of 196 women induced to labor, BS ≤4 and no previous CS divided into two subgroups. Participating women were randomized to receive an oral solution of misoprostol (Cytotec®) or vaginal slow release misoprostol (Misodel®) for IOL. The primary outcome was the induction-to-vaginal-delivery time. Vaginal delivery after IOL with slow release misoprostol resulted in a shorter induction-to-vaginal-delivery time compared with oral misoprostol solution but was associated with a higher risk of hyperstimulation, and fetal distress. There were no differences in mode of delivery or neonatal outcome.

Conclusion: Spontaneous onset of labor is usually preferred, because it generally means lower risk of complications compared to IOL. An oral solution of misoprostol for IOL in women with an unfavourable cervix is safe, cheap, easy to control and can be used in all settings as it gives a high success rate of vaginal deliveries without hyperstimulation. It is also a good method for IOL among women with one previous CS and is as safe as balloon catheter. Both methods give a high success rate of Vaginal Birth after Cesarean Section almost 70% despite an unfavorable cervix. These studies give further support to the feasibility of an oral solution of misoprostol for IOL which is in line with the recommendations from International Federation of Gynecology and Obstetrics.

List of scientific papers

I. Skin conductance activity in post-term pregnancies. Wallstrom T, Hellgren C, Akerud H, Wiberg-Itzel E. J Maternal Fetal Neonatal Med. 2014, 1912–1916.
https://doi.org/10.3109/14767058.2014.972357

II. Labor Induction with Orally Administrated Misoprostol: A Retrospective Cohort Study. Wallstrom T, Jarnbert-Pettersson H, Stenson D, Helena Akerud, Elisabeth Darj, Kristina Gemzell-Danielsson, Eva Wiberg-Itzel. BioMed Research International. 2017; 2017:6840592.
https://doi.org/10.1155/2017/6840592

III. Induction of labor in women with a uterine scar. Stenson D, Wallstrom T, Sjostrand M, Akerud H, Gemzell-Danielsson K, Wiberg-Itzel E. Maternal Fetal Neonatal Med. 2015, 3286-3291.
https://doi.org/10.3109/14767058.2015.1123242

IV. Induction of labor after one previous Cesarean section in an unfavorable cervix: a retrospective cohort study. Tove Wallstrom, Jenny Bjorklund, Joanna Frykman, Hans Jarnbert-Pettersson, Helena Akerud, Elisabeth Darj, Kristina Gemzell-Danielsson, Eva Wiberg-Itzel. PLOS one. July 2, 2018.
https://doi.org/10.1371/journal.pone.0200024

V. Slow release vaginal insert of misoprostol versus orally administrated solution of misoprostol for induction of labor: a randomized controlled trial. Tove Wallstrom, Moa Strandberg, Kristina Gemzell-Danielsson, Christina Pilo, Hans Jarnbert-Pettersson, Matilda Friman-Mathiasson, Eva Wiberg-Itzel. [Accepted]
https://doi.org/10.1111/1471-0528.15796