Factors predicting labour onset in patients treated with prostaglandin E2 for cervical ripening

ELSEVIER

European Journal of Obstetrics & Gynecology and Reproductive Biology60 (1995) 129-132

GYNE

Factors predicting labour onset in patients treated with prostaglandin E2 for cervical ripening Fabio Facchinetti*, Isabella Neri, Andrea R. Genazzani Department of Obstetrics and Gynecology, Universityof Modena, Modena, Italy

Accepted 6 February 1995

Abstract

The aim of this study is the evaluation of predictive factors in the onset of labour after pre-induction cervical ripening with prostaglandins. We enrolled 112 consecutive singleton term pregnancies (37-42.3 weeks) with unfavourable cervix and intact membranes, requiring induction of labour because prolonged pregnancy (59%) or maternal/fetal complications (41%). Treatment consisted of the cervical application (once or twice, 12 h apart) of prostaglandin E: gel (Upjohn, Italy). Uterine activity was monitored by external cardio-tocography before and during the next 2 h. Two patients showed uterine hyperstimulation and acute fetal distress requiring caesarean section. Sixty percent of patients went to labour and delivered without further stimulations. In this group the rate of caesarean section (9.1%) was lower than in patients failing to onset labour (68.2%). According to the logistic regression three factors positively predicted the onset of labour: first-hour uterine contractility, basal uterine activity and gestational age. The first-hour contractility in particular, represents the myometrial sensitivity to prostaglandin E2 and may become a practical marker of spontaneous onset of labour in patients undergoing cervical ripening. Keywords: Cervical ripening; Induction of labour; Prostaglandin; Complicated pregnancy

1. Introduction

A ripe uterine cervix is required for successful induction of labour. Indeed, an inadequately ripe cervix resuits in a delayed onset as well as in a prolonged and complicated course of labour [1,21. The cervical ripening process is the result of biochemical changes producing a breakdown of collagen and a change in the glycosaminoglycans and water content of the matrix [3]. Several hormonal changes are involved in this process, including an increased production of prostaglandins which seem to play a major role [4]. In the last 10 years several studies have described the use of local prostaglandin application for cervical ripening by using different routes of administration [5-8]. Keirse, submitting such studies to a meta-analysis, coneluded that the use of prostaglandins in prolonged preg* Corresponding author, Clinica Ostetrica e Ginecologica,via del Pozzo 71, 41100 Modena, Italy. Tel: +39 59 379512; Fax: +39 59 371401.

nancy reduced the incidence of both caesarean sections and instrumental vaginal deliveries [9]. Local prostaglandin therapy is also associated with more favourable neonatal outcome [10]. Either the endocervical or the vaginal route seem to be the useful ways for prostaglandin application. Although the goal of intracervital prostaglandin application is the ripening of the cervix, some authors also described the onset of labour either with a single [8,11] or a double administration, 6-12 h apart [12-14]. The aim of the study is to investigate the clinical features of women developing labour after application of PGE2 for cervical ripening and possibly to define the predictive factors. 2. Materials and methods 2.1. Subjects During the period October 1992 to July 1994 we consecutively enrolled 112 singleton term pregnancies, in vertex presentation with unripe cervix (Bishop score <4), referring to the Department of Obstetrics and

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Gynecology of the University of Modena for the induction of labour. Induction was decided for: a cronological prolongation of pregnancy according to our previous policy (>41.1 week, estimated by early ultrasound examination in the first quarter) (66 cases, 58.9%), oligohydramnios (12 cases, 10.7%), mild hypertension (ranging from 135/85 mmHg to 150/95 mmHg) (19 cases, 16.9%) and other risk factors (either maternal or fetal) including intrauterine growth retardation, mitral valve insufficiency and epilepsia (15 cases, 13.3%). Exclusion criteria were the following: rupture of membranes, previous uterine surgery or classic caesarean section, grand multiparity ( > 6), cephalopelvic disproportion, fetal distress suspected by nonstress test, known hypersensitivity to prostaglandins. 2.2. Protocol

After the evaluation of Bishop score, prostaglandin E 2 gel (PGE2) (Prepidil Gel 0.5mg, Upjohn, Milan, Italy) was applied deep into the cervical canal to the level of the internal os under direct cervical visualization using a speculum. Gel preparations were applied by two members of the staff, carefully trained in order to avoid extra-amniotic instillation. The external cardiotocograph was applied in every women for 60 min before the prostaglandin application and for 120 min thereafter. A pelvic examination was performed before treatment and 6 and 12 hours later. Bishop score was assigned by the same examiner. A second application of the same dose of PGE 2 was performed if Bishop score remained below 4 and/or no regular contractions were observed. Twelve hours after the second prostaglandin application, the cervical ripening was evaluated again; where cervical conditions ramained unchanged, the induction of labour with PGE2 was considered unsuccessful and the patient was managed individually by the attending obstetrician. Labour was defined as the onset of regular uterine contractions resulting in the effacement of > 80% and dilation > 3 cm of the cervix. Statistical analysis was performed by using Chisquare and one-way ANOVA when appropriate. Logistic regression with Enter method was also applied. 3. Results

Out of 112 pregnancies consecutively enrolled in this study, two patients dropped out because an increased

uterine activity, associated with a persistent fetal bradycardia, occurred immediately after gel application. Such cases, showing oligoidramnios and prolonged pregnancy as indications for induction, were delivered by caesarean section on the decision of the attending obstetrician. No other side effects were reported. Sixty-six patients (labour group) out of 110 went into labour with one (38 cases) or two (28 cases) intracervical applications of PGE2 gel. The remaining 44 women (failure group), having receiving one (8 cases) or two (36 cases) applications, were further supported by oxytocin infusion (37 cases) or by 2 mg of PGE2 gel administered vaginally (7 cases). In the failure group, the Bishop score significantly increased after the second application (2.1 + 0.96 vs. 3.6 ± 1.9, P = 0.001). The labour group was characterized by an older maternal age (29.4 ± 5.3 vs. 27.2 ± 3.4 years, mean ± S.D., P = 0.003) and a lower rate of nulliparity (72.7% vs. 90.95, P < 0.05), whereas no differences were observed in the basal Bishop score (median 2.0 vs. 2.0, range 0 - 4 in both groups). The indications for induction were different in the two groups. Indeed, a higher rate of pregnancy complications was reported in the failure group than in labour group (59.1% vs. 27.3%, P = 0.001). Table 1 reports the frequency of uterine contractions before and after PGE 2 gel application. The labour group showed a higher uterine activity at baseline and after both the first and second hour following application. Obviously, the labour group had a higher Bishop score at the sixth and twelfth hour from the first application than the failure group and, of course, the former had a shorter delay to delivery with respect to the latter (16.3 ± 9.3 h vs. 28.5 ± 10.6 h). Moreover, in the labour group there was a reduced rate of caesarean section with respect to the failure group (9.1% vs. 68.2%, chi square = 39.22, P < 0.001). In both groups the indications for emergency caesarean section were failure to progress (57.8%) (the largest part of failure group) and prolonged pregnancy (meaning patients failing to go into labour despite repeated inductions), followed by acute fetal distress (42.2%). Birthweight showed a higher trend in labour group than in failure group (3601 ± 527 g vs. 3439 ± 406 g, mean ± S.D., P = 0.08). The group receiving only one application of PGE2 gel showed the highest Bishop score after 12 h and more frequent uterine contractions in the first (17. l 4- 9.4 vs.

Table 1 Frequency(number/hour)of uterine contractionsin the two groups in basal condition(before)and after PGE2 application (mean ± S.D., ranges are reported in brackets)

Labour group Basal

First hour Second hour

5.5 ± 6.5

(0-18)

18.4 ± 9.1 20.8 ±9.4

(0-32) (0-38)

Failure group 2.1 ± 4.4

(0-28)

8.1 ± 8.0 (0-32) 10.6 ± 7.1 (0-38)

P-value 0.007 <0.0001 <0.O001

F. Facchinetti et al. /European Journal of Obstetrics & Gynecology and Reproductive Biology 60 (1995) 129-132

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Fig. 1. Factors predicting the onset of labour in patients treated with cervical prostaglandin E 2 gel. Upper box reported tested variables not entering in the model.

11.7 4- 10.3, P < 0.01) and second hour (20.3 4- 8.6 vs. 13.8 4- 9.9, P < 0.001) after gel application. The data has been also submitted to a logistic regression analysis with onset of labour after PGE2 as the dependent variable. Three variables entered in the model (Chi square = 40.29, d.f. 6.83, P = 0.0001): first-hour uterine contractions (r = 0.34), basal uterine activity (r = 0.20) and increased gestational age (r = 0.13) (Fig. 1). 4. Discussion These data demonstrate that 60% of women treated with a single or a double intracervical prostaglandin gel application experienced a 'spontaneous' onset of labour, without any other support. By using intracervical prostagiandins, the success rate of labour in patients with unfavourable cervix in different studies widely ranged from 16.7% [11] to 84% [14], but it was commonly reported as to be around 50% [10-13]. Even in patients failing labour induction, prostaglandin application was able to prime the cervix by increasing the Bishop score. In our series, the rate of success seems to be influenced by the indications for labour induction. Indeed, the rate of success was significantly higher in patients re-

quiring induction simply for a tendency to prolonged pregnancy in comparison to those affected by pathological conditions [15]. As previous reported by several authors [9,10], no major side effects were observed after the cervical application of 0.5 mg of PGE 2. In agreement with the large study carried out by Noah et al. [16], only two cases (1.7%) of uterine hyperstimulation induced the obstetricians to perform an emergency caesarean section in the presence of acute fetal distress. Conversely, the rate of caesarean section in our study was reduced six-fold for women undergoing labour after cervical prostaglandin application. These data support previous observations demonstrating that, independent of the route of administration, the use of prostaglandins for both ripening the cervix and induction of labour significantly decrease operative deliveries [9,10]. According to the logistic regression neither parity nor cervical effacement and dilation are involved with the success rate. However, onset of labour was positively predicted by the uterine contractile response to prostaglandins: the higher the number of contractions measured in the first hour following treatment, the greater the possibility of initiating labour. The finding that cervical score did not turn out to be a predictable factor can be explained by the major impor-

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tance played by the individual sensitivity of the myometrium to prostaglandins. Two other predictors come out from the analysis: the basal uterine activity before stimulation and the increased gestational age. This latter factor was already recognized by Mainprize et al. who used a lower amount of prostaglandins to induce labour in women with advanced gestational age [17]. We cannot rule out a possible escape of gel beyond the internal os. However it seems unlikely that such an extramniotic application of prostaglandin occurred in a different rate in labour and failure groups. In conclusion, in view of the close (causal) correlation between myometrial activity and prostaglandin application [18], the first-hour contractile response to PGE2 could become a practical marker in predicting the 'spontaneous' onset of labour in patients undergoing cervical ripening. References [I] Calkins LA. The importance of the cervix in prolonged labour. Am J Obstet Gynecol 1954; 77: 801-805. [2] Turnbull AC, Anderson AM. Induction of labour. J Obstet Gynaccol Br Commonw 1967; 74: 849-854. [3] Uidbjerg N, Ekman G, Malmstrocm A. Ripening of the human cervix related to changes in collagen, glycosaminoglycans and collagenolytic activity. Am J Obstet Gynccol 1983; 147: 662-664. [4] Calder AA. Cervical ripening. In: Bygdeman M, Berger GS, Keith LG, editors. Prostaglandins and their inhibitors in clinical obstetrics and gynaecology. Lancaster: MTP Press, 1986; 145-164. [5] Trofatter KF, Bowers D, Gall SA. Preinduction cervical ripening with prostaglandin E 2 (Prepidil) gel. Am J Obstet Gynecol 1985; 153: 268-271. [6] Yonekura ML, Songster G, Smith-Wallace T. Preinduction cervical priming with PGE 2 intracervicai gel. Am J Perinatol 1985; 2: 305-309. [7] Zanini A, Ghidini A, Norchi S, Beretta E, Cortinovis I, Bottino

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