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Journal of Obstetrics and Gynaecology (September 2003) Vol. 23, No. 5, 469–478 Evidence-based labour ward guidelines for thediagnosis, management and treatment ofspontaneous preterm labour R. F. LAMONT1 and the INTERNATIONAL PRETERM LABOUR COUNCIL2 1Department of Obstetrics and Gynaecology, Northwick Park Hospital, Harrow, UK and Tressler, 2001). Delaying delivery may reduce the rate Currently, there is considerable variation in the way spontaneous of long-term morbidity by facilitating the growth and preterm labour is diagnosed and managed internationally. As a maturation of developing organs and system. The benefits result, 12 international leading experts from 10 countries met to of administration of antepartum glucocorticoids (Crowley establish consensus on clinical recommendations and guidelines et al., 1990) to reduce the incidence and severity of regarding the diagnosis, management and treatment of spontaneouspreterm labour. The consensus was supported by evidence from respiratory distress syndrome may be exploited by delay.
quality literature published during the last 15 years and graded Delay may also permit transfer of the fetus in utero to a using the National Health Service Executive classification system centre with neonatal intensive care unit facilities (Lamont et (Grades A – C), endorsed by the Royal College of Obstetricians and Gynaecologists. The Council found enough evidence of a lack of a The economic burden of preterm birth includes the consensus across nations to recommend guidelines. It is hoped that immediate neonatal intensive care unit costs together with these international guidelines, while not meant to be prescriptive, the longer-term costs for residential care or support of will initiate discussion and correspondence for a basis for infants born preterm with residual disabilities. In the United implementation on a national level and be adapted for local clinical States, the weekly cost of caring for a baby in the neonatal practice, leading to further meetings around the world, to discuss intensive care unit is estimated to be approximately other areas including infection, mode of delivery and in-uterotransfer.
US$10 000 per baby (Keirse, 1995). Annually this amountsto approximately US$5 000 000 000. If, as a result of disability, an infant needs long-term residential care, thelifelong cost may be as high as US$450 000 each.
Preterm birth, defined as delivery 5 37 completed weeks of pregnancy (World Health Organisation, 1993) has a world- spontaneous preterm labour is diagnosed, managed and wide incidence estimated to be 13 million, occurring in 5 – treated internationally and this variation is outlined in 10% of all pregnancies (Hall et al., 1997). Preterm birth is Table I. The existence of national guidelines varies from not only one of the more common obstetric complications, country to country with little or no agreement on the use of but also one of the most serious causes of perinatal mortality and morbidity. Early preterm birth ( 5 32 weeks’ In this review, the guidelines for diagnosis concentrated gestation) is associated with a high perinatal mortality rate on whether the woman was in true labour and whether it was at a gestational age that required intervention. The The second and third trimesters of pregnancy are vital for diagnostic criteria were based on contractions, cervical maturation of the fetal lungs and other organs in dilatation and cervical effacement, and consideration was preparation for extrauterine life. If this is interrupted by given to the role of oncofetal fibronectin and vaginal very early delivery, the chances of survival of the newborn ultrasound measurements of cervical length. The issues are markedly diminished. Preterm birth is also the leading surrounding the choice of tocolytic focused on licensed cause of long-term morbidity, including neurodevelopmen- drugs including the oxytocin antagonist, atosiban, and b- tal handicap, cerebral palsy, seizure disorders, blindness, agonists, as well as unlicensed drugs. The relative efficacy deafness and non-neurological disorders, such as broncho- and safety of each class were compared, contrasted and pulmonary dysplasia and retinopathy of prematurity (Hole graded with respect to quality of evidence, according to 2International Preterm Labour Council: Dr Anders Atke; Holbæk Sygehus, Denmark; Dr Jim van Eyck; Isala, Klinieken Locatie, Sophia, the Netherlands; Dr Hanns Helmer; University of Vienna, Austria; Professor Ingemar Ingemarsson; Lund University Hospital, Sweden; Dr RonnieLamont (Chair); Northwick Park Hospital, United Kingdom; Dr Line Leduc; University of Montreal, Canada; Professor Jean-Marie Moutquin;University of Montreal, Canada; Professor Nicola Rizzo; University of Bologna, Italy; Dr Jens Svare; University of Copenhagen, Denmark; Professor Arthur Wischnik; Augsburg Central Clinic, Germany. Additional contributions: Professor Cabero Roura; Hospital Materno-InfantilValle Hebro´n Barcelona, Spain; Professor Dominique Cabrol; Groupe Hospitalier Cochin, France.
Correspondence to: Dr Ronnie Lamont, Department of Obstetrics and Gynaecology, Northwick Park Hospital, Watford Road, Harrow,Middlesex HA1 3UJ, UK. Tel: 0044 20 8869 2862Fax: 0044 20 8869 2864.
ISSN 0144-3615 print/ISSN 1364-6893 online/03/050469-10 ª Taylor & Francis Limited, 2003DOI: 10.1080/0144361031000153666 Table I. Current clinical practice for the prevention of preterm labour in Europe and Canada Gynaecology, since 1997,due to be revised *Societa` Italiana di Ginecologia e Ostetricia (SIGO); {Oesterreichische Gesellschaft fuer Gynaekologie und Geburtshilfe (OeGGG);{Sociedad Espan˜ola de Ginecologı´a y Obstetricia (SEGO); §Royal College of Obstetricians and Gynaecologists (RCOG); **CollegeNational des Gynecologues et Obstetriciens Francais (CNGOF).
recognised definitions. The absolute and relative contra- the literature that supplied evidence of an appropriate indications for prolongation of pregnancy were also quality published during the last 15 years.
To ensure that the evidence used to support the The development of clinical guidelines requires an statements was based on current research, the evidence for evidence-based approach to improve patient outcome and diagnosis and treatment of spontaneous preterm labour was allow more efficient use of resources (Woolf et al., 1999).
graded following the United Kingdom National Health With recent advances in our understanding of the aetiology System Executive classification system (which is endorsed and mechanisms of spontaneous preterm labour and the by the Royal College of Obstetricians and Gynaecologists.
availability of safer, more specific tocolytics, it was felt that guidelines should be developed to achieve, if possible, an Grade A evidence is derived from randomised controlled international consensus in patient diagnosis, management trials or systematic reviews of randomised trials. Meta- and treatment. The aim of this report is to provide evidence- analyses/systematic reviews had to include 50% or more based practical guidelines for the diagnosis, management and treatment of spontaneous preterm labour within a Grade B evidence is from non-randomised controlled labour ward environment. It is hoped that these guidelines trials, other robust experimental or good observational will stimulate thought and debate internationally with respect to the management of spontaneous preterm labour 4 50% randomised controlled studies.
and be used as a basis for the development of national and Grade C evidence is more limited and refers to observational studies with poorer methodology or casereports or the advice relies on consensus amongprofessional groups.
MethodsIn June 2001, a group of 10 obstetricians with a special Within each literature search only certain papers were interest in the management of preterm labour convened selected for grading. Evidence for oncofetal fibronectin and under the auspices of the ‘International Preterm Labour transvaginal ultrasound scanning concentrated on papers Council’ to discuss clinical guidelines for the diagnosis, that investigated these markers for the prediction of preterm birth rather than predicting infection. Evidence for corticosteroid recommendations concentrated on papers Their objective was: ‘to reduce the fetomaternal mortality that examined single and/or repeated doses of therapy and and morbidity associated with spontaneous preterm labour those papers whose outcome measures concentrated on the and preterm birth’. Their discussions focused on the evidence for decreasing fetal mortality and respiratory diagnosis and management of spontaneous preterm labour distress syndrome. Evidence for the benefits of tocolytic within the labour ward. The recommendations were therapy came from those papers that looked at placebo- supported by data collected from a systematic review of controlled trials or comparisons between tocolytics.
International preterm labour council guidelines fibronectin has a high negative predictive value of 86.6% The following databases were used to ensure that the for preterm delivery before 37 weeks’ gestation so may prevent unnecessary intervention but has a low positive MEDLINE (1986 – present), EMBASE (1986 – present), predictive value of 45.2% for delivery (Grade A) (Rozen- BIOSIS (1986 – present), Current Contents (1995 – present), Derwent Drugfile (1986 – present), Reactions Database When compared with digital examination and transab- (1986 – present). The search terms were: ‘steroid’/‘cortico- dominal scanning, transvaginal ultrasound has a high steroid’, ‘preterm labour’/‘labour premature’, ‘randomised’, sensitivity for the detection of cervical shortening and the ‘meta-analysis’, ‘controlled trial’, ‘utero AND transfer risk of preterm birth (Vause and Johnston, 2000). Grade A AND guideline’, ‘fetal fibronectin AND ultrasound’, evidence indicates that ultrasound measurement of cervical ‘tocolysis’/‘tocolytic AND efficacy’, ‘safety AND mater- length is more valuable than the Bishop score for predicting the onset of spontaneous labour within 7 days, whenmeasured close to term (Rozenberg et al., 1999). There isstill debate with respect to the length of the cervix below which the risk of preterm birth is increased and by how The discussion and data from the systematic literature much this risk is increased, if at all, with shorter cervical review are presented in the form of the following subheadings: the diagnosis of spontaneous preterm labour, It was concluded that fetal fibronectin and transvaginal the management and treatment of spontaneous preterm ultrasound used for the diagnosis of spontaneous preterm labour (tocolytic therapy, the administration of antepartum labour as an adjuvant to clinical parameters but without glucocorticoids, the role of infection and preterm labour further research should not be recommended for routine and other measures) and finally the contraindications for use. It was resolved to consider the use of fetal fibronectin the intervention of spontaneous preterm labour.
and transvaginal ultrasound in the diagnosis of spontaneouspreterm labour and their place in the prediction andprevention of preterm birth, as part of future guidelines.
The diagnosis of spontaneous preterm labour An algorithm describing the diagnosis of preterm labour is On admission with suspected spontaneous preterm labour, the accuracy of the expected date of confinement should bere-checked scrupulously because the best estimate willinfluence whether or not intervention should take place. If the mother is sure of the last day of her last menstrual period, had a regular monthly cycle and an early These guidelines are based on the acute management of ultrasound scan confirmed the date then menstrual dates spontaneous preterm labour 5 34 weeks’ gestation. As a should be used. If the dates are uncertain, or the cycle consequence, the main management focus is centred on the irregular, or there is a discrepancy of 4 10 days between inhibition of preterm labour and therefore the administra- the scan and the menstrual dates, then the scan dates tion of tocolytics forms the majority of the recommenda- tions obtained from the systematic literature review.
The diagnosis of spontaneous preterm labour on clinical (1) contractions that are painful, palpable, last longer than 30 seconds duration and occur at least four times every The primary aims of tocolytic therapy are to delay delivery to allow the administration of a complete course of (2) there should be evidence of change in the position, antepartum glucocorticoids in order to reduce the incidence consistency, length and/or dilatation of the cervix.
and severity of idiopathic respiratory distress syndrome and Where there is doubt using clinical parameters, then in to arrange in-utero transfer to a centre with neonatal centres where the technique is available, oncofetal fibro- nectin may be considered in addition to clinical assessment.
The secondary aim of tocolytic therapy is to delay Fetal fibronectin is an extracellular matrix glycoprotein delivery to permit significant growth and maturity of the produced by the chorion and concentrated in the amniotic fetus and to reduce the perinatal mortality and morbidity fluid. It is normally present in cervicovaginal secretions until about 20 weeks and then disappears to reappear before the Because some of the currently used tocolytic agents have onset of labour at term. If the adhesive fibronectin interface the potential to cause serious fetomaternal adverse effects, between the chorion and the decidua is disturbed, fetal informed consent from the patient, and/or partner should fibronectin may reappear in the vaginal secretions at an earlier gestation. As a result, the detection of fetalfibronectin in cervicovaginal secretion after 22 weeks’gestation has been proposed as an indicator of spontaneous preterm labour (Lockwood et al., 1991).
agonists are related structurally to adrenalin and nora-drenalin and include such drugs as ritodrine, terbutaline,albuterol, These b2-agonists act on receptors in the uterus to increase cAMP in smooth muscle cells, which decreases The systematic review produced six of 30 references that intracellular free calcium and phosphorylation of myosin studied the predictive value of fetal fibronectin and cervical light chain kinase, which in turn inhibits myometrial length for preterm delivery. The detection of fetal contraction (Hearne and Nagey, 2000). Within 48 hours Contractions — painful, detectable, last Figure 1. Diagnosis of preterm labour (PTL) algorithm.
of administration, the b-agonists are able to reduce the indirectly by stimulating the release of prostaglandins in number of women who deliver preterm (King et al., decidual and fetal membranes, contributing further to 1998), but have not been found to produce a reduction myometrial contractions and cervical ripening (Bossmar, in perinatal mortality or morbidity (Rozenberg et al., Compared with b-agonists, in randomised double-blind Several randomised clinical studies have shown the most placebo-controlled trials atosiban (oxytocin antagonist, widely used b-agonist, ritodrine, is equally as active as the partial vasopressin antagonist) offers comparable effective- calcium channel blocker, nifedipine, but with poorer ness (i.e. the proportion of women remaining undelivered at tolerability (Kupfermine et al., 1993; Papatsonis et al., 48 hours and 7 days) as well as comparable efficacy and 1997; Garcia-Velasco and Gonzalez-Gonzalez, 1998; Koks tolerability (non-delivery and no alternative tocolysis) at et al., 1998; Al-Qattan et al., 2000; Papatsonis et al., 2000) 48 hours (European Atosiban Study Group, 2001) (Grade A, Table II). Due to more favourable safety and tolerability The maternal adverse events of b-agonists include atosiban, assessed at 7 days, is significantly superior to b- palpitations, tremor, nausea, vomiting, headache and agonists. The likelihood of prolongation of pregnancy is restlessness (RCOG, 1997). Pulmonary oedema occurs with increased (Worldwide Atosiban versus Beta-agonists Study an incidence of approximately one in 400 (Black et al., 1999; Group, 2001) (Grade A, Table II). In addition, atosiban had a significantly lower rate of cardiovascular side effects and a The risk of these adverse events associated with b- reduced need to discontinue therapy due to unacceptable agonists in the management of spontaneous preterm labour side effects. Significantly fewer patients required alternative requires close monitoring of the mother in a high tocolytic therapy following allocation to atosiban due to the dependency unit. These have been addressed by the Royal superior tolerability profile (Romero et al., 2000; Moutquin College of Obstetrics and Gynaecology (RCOG, 1997) and et al., 2000) (Grade A, Table II). Atosiban represents an their recommendations for monitoring are shown in Table advance in currently available tocolytics, and should be considered a first-line tocolytic for the management ofspontaneous preterm labour (Worldwide Atosiban versusBeta-agonists Study Group, 2001) (Grade A, Table II).
Oxytocin is believed to initiate myometrial contractility by adirect effect on membrane-bound receptors that leads to an Unlicensed tocolytic therapy: calcium channel increase in intracellular calcium. It is also understood to act Calcium channel blockers, such as nifedi- International preterm labour council guidelines Table II. Grade A evidence for the efficacy and tolerability of the b-agonists in comparison with other tocolytics.
NB: in terms of efficacy, 4 implies a greater efficacy and in terms of tolerability, 4 implies a greater tolerability Table III. The recommended guidelines for monitoring fewer patients who have to discontinue treatment due to IV administration with b-agonists produced by the drug-associated side effects (Grade A). Since the Interna- Guidelines from the Royal College of Obstetricians Cochrane meta-analysis (King et al, 2003) also suggestedthat calcium antagonists (mainly nifedipine) were more effective than other tocolytic agents (mainly b-agonists) in terms of fewer births within 7 days of initiation of treatment Maternal pulse and BP should be monitored every 15 and before 34 days’ gestation), with improvement in some neonatal outcomes and a reduction in adverse maternal side Chest auscultation should be performed every effects (Grade A). Side effects commonly associated with nifedipine include flushing, headache and rarely hypoten- Strict input/output charts should be measured for sion in the hypovolaemic patient (Childress and Katz, Urea and electrolytes and haematocrit should be Recent reviews of the evidence pertaining to the use of nicardipine suggest that the safety profiles of these drugs are Maternal blood glucose should be measured incomplete and should lead to careful consideration before use. It has been recommended that nicardipine should onlybe used in a clinical trial setting (King, 2001).
pine and nicardipine, inhibit the influx of calcium ionsinto myometrial cells, and the decreased intracellular calcium results in decreased myometrial activity (Hearne glandin synthetase inhibitors (e.g. indomethacin, sulindac and ketorolac) decrease prostaglandin synthetase and Calcium channel blockers, when compared with b- block conversion of free arachidonic acid to prostaglan- agonists, have a comparable tocolytic efficacy with a din. As the prostaglandin E and F series are mediators of reduction in neonatal morbidity (Papatsonis et al., 2001; uterine contractions, a decrease in production results in Tsatsaris and Carbonne, 2001) (Grade A, Table II).
decreased contractile activity (Hearne and Nagey, 2000).
As tocolytic agents calcium channel blockers, especially Indomethacin is a potent inhibitor of prostaglandin nifedipine, are more effective than b-agonists and there are synthesis and has been used as a tocolytic agent since the early 1970s. Indomethacin is effective in delaying preterm infant (Grade A). They suggested that any further trials labour and increases birth weight, results in shorter stays in should be of high quality, large enough to assess serious neonatal intensive care units and shorter intervals of morbidity and mortality, compare different dose regimens mechanical ventilation (Grades A or B, depending on study and provide information about the neurodevelopmental quoted) (Table IV). Conversely, contradictory evidence shows that indomethacin fails to prolong gestation andinfants are delivered prematurely (Merrill et al., 1994)(Grade A).
In one study, indomethacin was associated with a reduced risk of neonatal complications in infants born Prolonging gestation with tocolytic therapy allows for the between 24 and 31 weeks’ gestation (Gardner et al., 1996) administration of antepartum glucocorticoids to reduce the (Grade B). Morales and Madhav (1993) reported that incidence and severity of respiratory distress syndrome and indomethacin used to treat spontaneous preterm labour, hence reduce neonatal morbidity and mortality. The caused oligohydramnios and was associated with maternal systematic literature review concentrated on those papers side effects such as chest pain, shortness of breath, malaise that studied the single and multiple administrations of and pulmonary oedema (Grade A). Potential fetal adverse effects include premature closure of the ductus arteriosus, Ten of 63 references in the literature search provided necrotising enterocolitis, respiratory distress syndrome and Grade A evidence for the use of single rather than multiple bronchopulmonary dysplasia (Highby and Suiter, 1999) courses of antepartum glucocorticoids. The administration of a single course of antepartum glucocorticoids to pregnantwomen, between 24 – 34 weeks’ gestation, at risk of pretermdelivery within 7 days, reduces the risk of death, respiratory distress syndrome and intraventricular haemorrhage in the magnesium sulphate is believed to be via competitive preterm infant (Schmitz et al., 2000; Crowley 2001). This antagonism to calcium for entry into myometrial cells.
has been reflected in the National Institutes of Health Decreased intracellular free calcium results in decreased Consensus Statement, 1994. The treatment should consist of myometrial contractility (Hearne and Nagey, 2000).
two doses of 12 mg betamethasone given intramuscularly In a study by Mittendorf et al. (1997), the Magnesium 24 hours apart or four doses of 6 mg dexamethasone given and Neurologic Endpoints Trial (MagNET) showed that magnesium sulphate was as effective, but no more effective There is still debate about the use of repeated doses of as a tocolytic agent than ritodrine, terbutaline, indometha- antepartum glucocorticoids. Multiple doses of antepartum cin or nifedipine (Grade A). This finding appears to reflect glucocorticoids may be associated with early-onset neonatal other evidence (see Table IV) that magnesium sulphate is sepsis and death (Vermillion et al., 2000) (Grade B) or have comparable to b-agonists and prostaglandin synthetase no effect on these outcomes or others such as intraven- inhibitors in prolonging gestation. The authors state that tricular haemorrhage, bronchopulmonary dysplasia, necro- safety and efficacy has not been demonstrated sufficiently tising enterocolitis and birth weight (Aghajafari et al., 2001) with magnesium sulphate. High doses (exceeding a total (Grade B). A recent consensus panel (National Institutes of dose of 48 g) have been associated significantly with Health Consensus Development Panel, 2001) concluded increased perinatal mortality (Scudiero et al., 2000) (Grade that data from currently available studies assessing the benefits and risks of the use of repeated courses of Since the International Preterm Labour Council, the antepartum glucocorticoids remains unanswered at this Cochrane Database has also investigated the use of Furthermore, there is evidence that delaying the use of concluded that magnesium sulphate is ineffective at delaying antepartum glucocorticoids in women with preterm prema- birth or preventing preterm birth after preterm labour, and ture rupture of the membranes (PPROM) may significantly its use is associated with an increased mortality for the increase the risk of fetomaternal infection (Crowley, 2001) Table IV. Grade A and B evidence for the efficacy and tolerability for prostaglandin synthetase inhibitors andmagnesium sulphate in spontaneous preterm labour Prostaglandin synthetase inhibitors and magnesium sulphate International preterm labour council guidelines (Grade A). At earlier gestation, the benefits may outweigh The expected benefit in survival and reduced disability the risks but at later gestations, the risk – benefit analysis from prolonging gestation comes from three recent sources.
Magowan et al. (1999), showed that mortality fell from 80%at 24 weeks’ gestation to 10% at 30 weeks’ gestation andthat while 50% of preterm births occur after 35 weeks’ gestation, almost all the mortality occurs before this time The Council agreed that the following investigations would (Magowan et al., 1999). Secondly, between the gestational ages of 23 and 27 weeks, neonatal survival increases in alinear fashion at a rate of 3% per day with a concomitant (1) full blood count and group and save serum; reduction in neonatal morbidity from 31% at 23 weeks to (2) midstream specimen of urine examined for bacteruria; 7% at 27 weeks (Finnstro¨m et al., 1997). Thirdly, the contribution of preterm birth to morbidity was highlighted in the recently reported Epicure study (Costeloe et al., (4) low vaginal swab and rectal swab to be cultured in 2000). This study was designed to describe the survival and selective broth medium for screening for Group B health problems for all infants born before 26 weeks’ completed gestation in the United Kingdom and the The role of infection in the aetiology of preterm labour and Republic of Ireland. A total of 276 maternity hospitals the implication this has on the choice of investigation on provided information showing that 65% of these babies admission will be the subject of a separate set of guidelines.
died in the delivery suite or in the neonatal intensive careunit, before discharge from hospital.
The most frequently cited cause of death was pulmonary insufficiency. Data from the babies that survived showed As soon as possible after the diagnosis of spontaneous that failure to administer antenatal steroids and failure for postnatal transfer for intensive care within 24 hours of birth paediatricians involved in management decisions are were predictive of major abnormalities based on cerebral informed to ensure that a neonatal intensive care cot is available on site or that in-utero transfer to a centre with Follow-up data at 30 months from the Epicure study showed that 49% of survivors had some form of disability (mental and psychomotor development, neuromotor func- Finnstro¨m et al. (1997) have shown that the level of care tion, sensory and communication function) and nearly 50% at birth and the level of subsequent neonatal care in the of these met the criteria for severe disability using neonatal intensive care unit are related directly to a lower neurological and developmental assessment (Wood et al., rate of neonatal morbidity and mortality when compared 2000). Only 13% of infants survived to 30 months without with babies born in hospitals without specialised staff and equipment (Finnstro¨m et al., 1997) (Grade B). Hospitals Absolute contraindications are those in which prolonga- that had full resources for obstetric and neonatal intensive tion of pregnancy is contraindicated per se, e.g. clinically care had significantly lower infant mortality than those apparent intrauterine infection, known lethal fetal congeni- without. In-utero transfer is safer for the baby and tal malformation, fulminating proteinuric pre-eclampsia and any other urgent fetomaternal indication for delivery.
compared with neonatal transfer (Lamont et al., 1983) Relative contraindications are those in which there is a debate about the risks and benefits of intervention such as If time permits, an ultrasound scan should be arranged to antepartum haemorrhage, ruptured membranes, non-reas- check for fetal viability, fetal morphology, fetal number, suring fetal heart rate pattern on the cardiotocograph, fetal presentation, placental site, an estimate of fetal weight intrauterine growth restriction, insulin-dependent diabetes and amniotic fluid volume index, all of which might affect management. Appropriate analgesia following discussion Tocolytics should not be used if there is a significant with an anaesthetist should be arranged and opiates should antepartum haemorrhage, especially if there are signs and be avoided, if possible, to prevent central fetal and neonatal symptoms of abruptio placentae. Following a mild bleed due to placenta praevia, it is acceptable to use tocolytics If intervention is contraindicated or unsuccessful, then because they may help to stop uterine contraction and the the mode of delivery of a preterm infant should be stretch they induce, leading to further separation of the individualised according to the gestational age, the fetal presentation, the number of fetuses and the presence or Tocolytics are rarely indicated after 32 weeks’ gestation absence of non-reassuring fetal heart tracing on cardiotoco- in the presence of ruptured membranes. At an earlier graph. The debate with respect to the mode of delivery of gestation, they may be administered when the risk – benefit the preterm infant will be the subject of further Council analysis is in favour of delaying delivery to allow a full course of glucocorticoids to be administered or arrange-ments to transfer a woman to a centre with neonatalintensive care unit facilities.
Tocolytics to delay delivery of the preterm infant are contraindicated where non-reassuring fetal heart rate When considering intervention to prolong gestation, certain patterns on the cardiotocograph occur in association with absolute and relative contraindications should be consid- a significant haemorrhage or with signs of fetomaternal ered in order to minimise maternal and fetal morbidity and infection or where the cardiotocograph trace is suggestive of Severe intrauterine growth restriction may be associated professionals such as neonatologists, genitourinary medi- with congenital malformation, and consideration should be cine physicians, microbiologists and geneticists together given to this possibility before intervention. Severe placental with basic scientists, such as molecular biologists, immunol- insufficiency where continued intrauterine existence puts the ogists, physiologists, biochemists and endocrinologists.
fetus at risk, is a contraindication to intervention although It is hoped that, in time, these guidelines will be adopted minor degrees of intrauterine growth restriction where and adapted at a national level to be incorporated into further fetal growth might be anticipated would not be a clinical practice in local settings and to stimulate dialogue contraindication to the use of a tocolytic. In cases where the fetus is thought to be clinically or ultrasonographicallysmall for the dates, the calculation of the estimated date ofconfinement and the dates should be re-checked.
Well-controlled insulin-dependent diabetic women with spontaneous preterm labour can safely be treated with We are grateful to Healthcare Education Services Ltd for tocolytics. Close monitoring is required because both organising the meeting and for Wells Healthcare for assisting withthe manuscript. We are grateful to Ferring Pharmaceuticals who glucocorticoids and particularly b-agonists are likely to supported the meeting with an unrestricted educational grant.
affect diabetic control (Besinger and Lannucci, 1997; Fisheret al., 1997). Poorly controlled diabetes is a relativecontraindication to the use of b-agonist tocolytics andalternative tocolytics should be used where available.
Twins and higher-order births are associated with a greater maternal plasma volume expansion (Cambell and MacGillivray, 1997) and secondary hyperaldosteronism Abramov Y., Nadjari M., Weinstein D., Ben-Shachar I., when compared with single pregnancies. Beta-agonists are Plotkin V. and Ezra Y. (2000) Indomethacin for preterm known to increase both aldosterone and renin levels in twin labor: a randomised comparison of vaginal and rectal – oral pregnancies (Lammintausta and Erkkola, 1979), which may routes. Obstetrics and Gynecology, 95, 482 – 486.
potentiate the the risk of pulmonary oedema. Beta-agonists Aghajafari F., Murphy K., Hannah M. and Amankwah K.
are therefore relatively contraindicated in multiple preg- (2001) Repeated courses of antenatal corticosteroids: a nancies, and alternative tocolytics should be used.
systematic review and meta-analysis. American Journal ofObstetrics and Gynecology, 184, S36.
Al-Qattan F., Omu A.E. and Labeeb N. (2000) A prospective randomised study comparing nifedipine versus ritodrine for the suppression of preterm labour. Medical Principles and Preterm birth is the major cause of perinatal mortality and morbidity in the developed world, although the manage- Beall M.H., Edgar B.W., Paul R.H. and Smith-Wallace T.
ment of spontaneous preterm labour varies from unit to unit (1985) A comparison of ritodrine, terbutaline and magnesium and country to country. There is enough evidence based on sulphate for the suppression of preterm labor. American a systematic review to form a basis for consensus using Journal of Obstetrics and Gynecology, 153, 854 – 859.
guidelines produced by a respected committee of experts in Besinger R.E. and Iannucci T.A. (1997) Tocolytic therapy. In: the field who manage spontaneous preterm labour on a Preterm Labour, edited by Elder M.G., Lamont R.F. and daily basis. However, it must be appreciated that definitions Romero R., pp. 243 – 297. New York, Churchill Livingstone.
Bivins H.A., Newman R.B., Fyfe D.A., Campbell B.A. and of spontaneous preterm labour and treatment protocols Stramm S.L. (1993) Randomized trial of oral indomethacin vary across clinical trials and therefore it is not always and terbutaline sulfate for the long-term suppression of possible to compare tocolytic treatment from one clinical preterm labor. American Journal of Obstetrics and Gynecol- trial with another. The International Preterm Labour Council was set up with this in mind and with the hope Black R.S., Lees C., Thompson C., Pickles A. and Campbell S.
that, with the development of preterm labour guidelines, it (1999) Maternal and foetal cardiovascular effects of trans- might contribute to a reduction in the fetomaternal dermal glyceryl trinitrate and intravenous ritodrine. Obste- mortality and morbidity associated with preterm birth.
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The International Preterm Labour Council concluded Bossmar T. (1998) Treatment of preterm labour with the that every case of spontaneous preterm labour is a unique oxytocin and vasopressin antagonist Atosiban. Journal ofPerinatal Medicine, 26, 458 – 465.
situation. The management of each patient has to be Campbell D.M. and MacGillivray I. (1997) Maternal physio- individualised in the light of the clinical circumstances and logical responses and birthweight in singleton and twin the full and informed consent of the pregnant mother and pregnancies by parity. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 7, 17 – 24.
This being the case by necessity the guidelines, although Chau A.C., Gabert H.A. and Miller J.M. (1992) A prospective evidence-based, are generalised and follow a systematic comparison of terbutaline and magnesium for tocolysis.
review that permits individualised variation within a Obstetrics and Gynecology, 80, 847 – 851.
framework. This framework is not rigid, is open to Childress C.H. and Katz V.L. (1994) Nifedipine and its discussion and will change as new evidence becomes indications in obstetrics and gynecology. Obstetrics and Costeloe K., Hennessy E., Gibson A.T., Marlow N. and As our understanding of the mechanism and aetiology of Wilkinson A.R. (2000) The EPICure study: outcomes to spontaneous preterm labour improves, and the remit of the discharge from hospital for infants born at the threshold of group expands to include the prediction and prevention of viability. Pediatrics, 106, 659 – 671.
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