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  7Induction of labour with an unfavourable cervix G. Justus Hofmeyr*  MRCOG Consultant, East London Hospital Complex, South Africa; Director, Effective Care Research Unit East London Hospital Complex, South AfricaEffective Care Research Unit, Frere Maternity Hospital, University of the Witwatersrand, Post Bag X9047, East London 5201, South Africa Labour induction is undertaken when the advantages for the mother and/or the baby areconsidered to outweigh the disadvantages. When the uterine cervix is unfavourable, oxytocin,with or without amniotomy, is frequently ineffective. Vaginal prostaglandin E 2  is most commonlyused if it is affordable. Evidence regarding many alternative methods is discussed in this chapter.Of particular interest are misoprostol and extra-amniotic saline infusion.Misoprostol, an orally active prostaglandin E 1  analogue, has been used widely by the vaginal andoral routes for labour induction at or near term. Several recent trials have confirmed that it ishighly effective. Overall Caesarean section rates appear to be reduced, despite a relative increasein Caesarean sections for fetal heart rate abnormalities. Concern remains regarding increasedrates of uterine hyperstimulation and meconium-stained amniotic fluid, although dataon perinataloutcome have been reassuring. Postpartum haemorrhage may be increased following labourinduction with misoprostol, and isolated reports of uterine rupture, with or without previousCaesarean section, have appeared. Using small dosages appears to reduce adverse outcomes.Very large trials are needed to evaluate rare adverse outcomes.Extra-amniotic saline infusion is an effective method which appears to reduce the risk of uterine hyperstimulation that occurs with the use of exogenous uterotonics. Key words:  labour induction; unfavourable cervix; prostaglandins; misoprostol; extra-amnioticsaline. Induction of labour refers to the use of artificial methods to bring about labour after theage of fetal viability (24 weeks in the UK) and before the spontaneous onset of labour.Similar methods used before fetal viability are called induction of abortion ortermination of pregnancy, and after the onset of labour are called augmentation of labour. The distinction between induction and augmentation of labour is sometimesblurred by uncertainty concerning the diagnosis of early labour.Labour induction is one of the most frequent procedures in pregnant women. In theUnited States of America, the rate increased during the 1990s from about 10 to 20%. 1 A distinction is sometimes drawn between methods used with the intention of ‘ripening’ the uterine cervix, and similar methods used with the intention of inducinglabour. The former may progress unavoidably to the latter. 1521-6934/$ - see front matter Q 2003 Elsevier Ltd. All rights reserved.Best Practice & Research Clinical Obstetrics & GynaecologyVol. 17, No. 5, pp. 777–794, 2003 doi:10.1016/S1521-6934(03)00037-3, *Address for Correspondence: Effective Care Research Unit, Frere Maternity Hospital, University of theWitwatersrand, Post Bag X9047, East London 5201, South Africa. Tel.: þ 27-43-709-2483. E-mail address: (G. J. Hofmeyr).  The decision to induce labour is usually a matter of rather complex clinical judgement which takes into account a number of factors: †  Anticipated benefits to the mother—for example, improving a medical conditionwhich is caused or aggravated by pregnancy, such as pre-eclampsia, placentalabruption, certain respiratory, hepatic and cardiac disorders; relieving discomfort,such as from multiple pregnancy, polyhydramnios or spontaneous symphysiotomy;relieving emotional distress after intrauterine death; or alleviating anxiety about thebaby’s wellbeing. †  Estimated risks to the mother—for example, increased pain and need for analgesia,increased chance of requiring Caesarean section, infection, other complications of the procedures, postpartum haemorrhage, (rarely) uterine rupture, anxiety if theinduction is protracted or unsuccessful, and loss of self-esteem because of perceivedfailure to give birth normally. †  Anticipated benefits to the fetus—for example, improved growth and developmentwhen intrauterine growth is suboptimal, reduced risk of intrauterine death fromcomplications such as diabetes, prolonged pregnancy (beyond 41 weeks) 2 ,amnionitis, ruptured membranes, rhesus immunization, fetal distress and cholestasisof pregnancy. †  Estimated risks to the fetus—for example, prematurity and uterinehyperstimulation.Several factors influence the decision: †  The condition of the mother. †  The condition of the baby. †  The gestational age of the baby, and level of certainty about the baby’s age. Whenfetal lung maturity is uncertain, amniocentesis may be performed to assess markersfor lung maturity such as the alcohol ‘shake’ test, lecithin/sphingomyelin ratio andphosphatidyl glycerol level. †  Previous Caesarean section. †  The preference of the mother (and sometimes the care provider). †  The likelihood that induction of labour will be easy and vaginal delivery successful.The last factor is dependent mainly on the state of the uterine cervix. Where otherfactors are equivocal, the state of the cervix may influence the decision whether or notto proceed with labour induction. THE UNFAVOURABLE UTERINE CERVIX The process of softening, shortening and partial dilation of the cervix usually takes placein the days or weeks prior to the onset of labour, but the timing of this process isextremely variable. An unfavourable or ‘unripe’ cervix is one which has undergoneminimal change and is more resistant to attempts at induction of labour. In the firsttrimester, 50% of the dry weight of the cervix is tightly aligned collagen, 20% smoothmuscle and the rest is ground substance composed of elastin and glycosaminoglycans(chondroitin, dermatan sulphate and hyaluronidase). 3 During pregnancy, hyaluronidaseincreases from 6 to 33%, whereas dermatin and chodroitin, which bind collagen more 778 G. J. Hofmeyr  tightly, decrease. Collagenase and elastase enzymes increase, as do the vascularity andwater content.A standardized method of semi-quantitative clinical scoring of the cervix wasdescribed by Bishop in 1964 4 , and has since been modified (see Table 1). A score of sixor more predicts the likelihood of successful induction of labour. A score offive or lessis regarded as being unfavourable for induction of labour, and use of artificial rupture of the amniotic sac and/or oxytocin infusion is unlikely to be successful.More recently, measurement of fibronectin in cervicovaginal secretions has been used to predict the imminence of labour 5 , with variable success. 6 The mainstay of induction of  labour with an unfavourable cervix is the use of exogenousprostaglandins 7,8 , or methods to stimulate the release of endogenous prostaglandins,in order to ‘ripen’ the cervix. ROYAL COLLEGE OF OBSTETRICIANS AND GYNAECOLOGISTS’GUIDELINES Guidelines developed by the Royal College of Obstetricians and Gynaecologists(RCOG) 9 recommend offering an ultrasound scan before 20 weeks to confirm thegestational age; membrane ‘sweeping’ after 40 weeks; labour induction after 41 weeks;if declined, fetal monitoring from 42 weeks with induction of labour recommended if the monitoring is abnormal. In the case of pregnancy complications, membranesweeping or labour induction are offered at the appropriate gestation. METHODS OF INDUCTION OF LABOUR WITH AN UNFAVOURABLECERVIXProstaglandin E 2  (PGE 2 ) and oxytocin Vaginal prostaglandins Labour induction with prostaglandin F 2 a  was introduced in the 1960s. Subsequently,formulations of prostaglandin E 2  were developed which largely replaced the use of F 2 a  in countries such as the UK. The most common route of administration is vaginal,and tablets, suppositories, gels and pessaries have been developed. A recentrandomized comparison found similar effectiveness for a 10 mg PGE 2  sustained-releasevaginal insert compared with 3 mg PGE 2  vaginal tablets twice at a 6-hour interval. Inseven out of eight women with uterine hyperstimulation, removal of the vaginal insert Table 1.  Modified ‘Bishop’ cervical score.Score 0 1 2 3Cervical dilation (cm) 0 1–2 3–4 5 þ Cervical length (cm) 3 2 1  , 1Station of the presenting part  2 3  2 2  2 1, 0  þ 1 or moreConsistency Firm Moderate SoftPosition Posterior Midposition AnteriorInduction of labour with an unfavourable cervix 779  was sufficient to normalize uterine activity. In the PGE 2  tablet group eight of nine withuterine hyperstimulation required medical treatment. 10 Awide variety of dosages and dosing intervals are in use. A limiting factor for the useof prostaglandin E 2  preparations in many countries has been the cost.Systematic review of vaginal prostaglandin E 2  compared with placebo or notreatment showed that prostaglandins were clearly effective in bringing about delivery(relative risk  of failure to deliver within 24 hours 0.03, 95% confidence interval0.02–0.05). 11 The RCOG recommends the use of intravaginal PGE 2  irrespective of the woman’sparity or cervical status. PGE 2  tablets (3 mg 6–8 hourly to a maximum dose of 6 mg)are recommended in preference to PGE 2  gel (2 mg for nulliparous women withmodified Bishop cervical score , 4, 1 mg to all others, repeated 6 hourly to a maximumdose of 4 mg).In the case of ruptured membranes, intravenous oxytocin is recommended as analternative initiating agent. If oxytocin is used after PGE 2 , 6 hours should elapse afterthe last dose of PGE 2  to reduce the riskof hyperstimulation. Oxytocin is recommendedas an intravenous infusion of 30 iu in 500 ml normal saline, in titrated dosages from 1 to32 mIU per minute, for up to 5 hours. The effectiveness of oxytocin is optimized withruptured membranes. Comparison of methods of induction of labour with an unfavourable cervix As vaginal PGE 2  with or without oxytocin infusion is widely recognized and accepted asa standard method of labour induction, this chapter focuses on alternative methodswhich areless well established, comparing them with PGE 2  as the conventional method.Particular attention is paid to misoprostol because of the controversy surrounding itsuse and the volume of recent research.Comparisons of alternative methods are most reliably based on the results of well-conducted randomized clinical trials. To manage the complexity of several hundredreported randomized trials comparing various combinations of 25 methods of labourinduction, the Pregnancy and Childbirth Group of the Cochrane Collaboration, incollaboration with the Clinical Effectiveness Support Unit, RCOG, developed astrategy to review well-defined clusters of comparisons in a series of ‘primary’systematic reviews using standardized outcomes and clinical sub-groups. 12 Thisenables comparisons across reviews for specific clinical categories to be made. Forthe purposes of this chapter, data have been extracted from these reviews fromavailable trials in all women (Table 2), and in all women with unfavourable cervices(Table 3), comparing PGE 2  administered vaginally (as the ‘gold standard’) with anyother method. Intracervical prostaglandins PGE 2  may be administered into the cervical canal, in smaller dosages than those usedvaginally, with the objective of optimizing the local effect on the cervix. Administrationis somewhat more cumbersome, and no clear advantages over vaginal administrationhave emerged. 780 G. J. Hofmeyr
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