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Objective To compare the effect of induction of labour with a policy of expectant monitoring for intrauterine growth restriction near term.

Design Multicentre randomised equivalence trial (the Disproportionate Intrauterine Growth Intervention Trial At Term (DIGITAT)).

Setting Eight academic and 44 non-academic hospitals in the Netherlands between November 2004 and November 2008.

Participants Pregnant women who had a singleton pregnancy beyond 36+0 weeks’ gestation with suspected intrauterine growth restriction.

Interventions Induction of labour or expectant monitoring.

Main outcome measures The primary outcome was a composite measure of adverse neonatal outcome, defined as death before hospital discharge, five minute Apgar score of less than 7, umbilical artery pH of less than 7.05, or admission to the intensive care unit. Operative delivery (vaginal instrumental delivery or caesarean section) was a secondary outcome. Analysis was by intention to treat, with confidence intervals calculated for the differences in percentages or means.

Results 321 pregnant women were randomly allocated to induction and 329 to expectant monitoring. Induction group infants were delivered 10 days earlier (mean difference −9.9 days, 95% CI −11.3 to −8.6) and weighed 130 g less (mean difference −130 g, 95% CI −188 g to −71 g) than babies in the expectant monitoring group. A total of 17 (5.3%) infants in the induction group experienced the composite adverse neonatal outcome, compared with 20 (6.1%) in the expectant monitoring group (difference −0.8%, 95% CI −4.3% to 3.2%). Caesarean sections were performed on 45 (14.0%) mothers in the induction group and 45 (13.7%) in the expectant monitoring group (difference 0.3%, 95% CI −5.0% to 5.6%).

Conclusions In women with suspected intrauterine growth restriction at term, we found no important differences in adverse outcomes between induction of labour and expectant monitoring. Patients who are keen on non-intervention can safely choose expectant management with intensive maternal and fetal monitoring; however, it is rational to choose induction to prevent possible neonatal morbidity and stillbirth.

Trial registration International Standard Randomised Controlled Trial number ISRCTN10363217.

Background

Hypertensive disorders, i.e. pregnancy induced hypertension and preeclampsia, complicate 10 to15% of all pregnancies at term and are a major cause of maternal and perinatal morbidity and mortality. The only causal treatment is delivery. In case of preterm pregnancies conservative management is advocated if the risks for mother and child remain acceptable. In contrast, there is no consensus on how to manage mild hypertensive disease in pregnancies at term. Induction of labour might prevent maternal and neonatal complications at the expense of increased instrumental vaginal delivery rates and caesarean section rates.

Methods/Design

Women with a pregnancy complicated by pregnancy induced hypertension or mild preeclampsia at a gestational age between 36+0 and 41+0 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant management for spontaneous delivery. The primary outcome of this study is severe maternal morbidity, which can be complicated by maternal mortality in rare cases. Secondary outcome measures are neonatal mortality and morbidity, caesarean and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be by intention to treat. In total, 720 pregnant women have to be randomised to show a reduction in severe maternal complications of hypertensive disease from 12 to 6%.

Discussion

This trial will provide evidence as to whether or not induction of labour in women with pregnancy induced hypertension or mild preeclampsia (nearly) at term is an effective treatment to prevent severe maternal complications.

Trial Registration

The protocol is registered in the clinical trial register number ISRCTN08132825.

Objective

Pregnancies complicated by intrauterine growth retardation (IUGR) beyond 36 weeks of gestation are at increased risk of neonatal morbidity and mortality. Optimal treatment in IUGR at term is highly debated. Results from the multicenter DIGITAT (Disproportionate Intrauterine Growth Intervention Trial At Term) trial show that induction of labor and expectant monitoring result in equal neonatal and maternal outcomes for comparable cesarean section rates. We report the maternal health-related quality of life (HR-QoL) that was measured alongside the trial at several points in time.

Methods

Both randomized and non-randomized women were asked to participate in the HR-QoL study. Women were asked to fill out written validated questionnaires, covering background characteristics, condition-specific issues and the Short Form (SF-36), European Quality of Life (EuroQoL 6D3L), Hospital Anxiety and Depression scale (HADS), and Symptom Check List (SCL-90) at baseline, 6 weeks postpartum and 6 months postpartum. We compared the difference scores of all summary measures between the two management strategies by ANOVA. A repeated measures multivariate mixed model was defined to assess the effect of the management strategies on the physical (PCS) and mental (MCS) components of the SF-36. Analysis was by intention to treat.

Results

We analyzed data of 361 randomized and 198 non-randomized patients. There were no clinically relevant differences between the treatments at 6 weeks or 6 months postpartum on any summary measures; e.g., on the SF-36 (PCS: P = .09; MCS: P = .48). The PCS and the MCS were below norm values at inclusion. The PCS improved over time but stayed below norm values at 6 months, while the MCS did not improve.

Conclusion

In pregnancies complicated by IUGR beyond 36 weeks, induction of labor does not affect the long-term maternal quality of life.

Background

Preterm prelabour rupture of the membranes (PPROM) is an important clinical problem and a dilemma for the gynaecologist. On the one hand, awaiting spontaneous labour increases the probability of infectious disease for both mother and child, whereas on the other hand induction of labour leads to preterm birth with an increase in neonatal morbidity (e.g., respiratory distress syndrome (RDS)) and a possible rise in the number of instrumental deliveries.

Methods/Design

We aim to determine the effectiveness and cost-effectiveness of immediate delivery after PPROM in near term gestation compared to expectant management. Pregnant women with preterm prelabour rupture of the membranes at a gestational age from 34+0 weeks until 37+0 weeks will be included in a multicentre prospective randomised controlled trial. We will compare early delivery with expectant monitoring.

The primary outcome of this study is neonatal sepsis. Secondary outcome measures are maternal morbidity (chorioamnionitis, puerperal sepsis) and neonatal disease, instrumental delivery rate, maternal quality of life, maternal preferences and costs. We anticipate that a reduction of neonatal infection from 7.5% to 2.5% after induction will outweigh an increase in RDS and additional costs due to admission of the child due to prematurity. Under these assumptions, we aim to randomly allocate 520 women to two groups of 260 women each. Analysis will be by intention to treat. Additionally a cost-effectiveness analysis will be performed to evaluate if the cost related to early delivery will outweigh those of expectant management. Long term outcomes will be evaluated using modelling.

Discussion

This trial will provide evidence as to whether induction of labour after preterm prelabour rupture of membranes is an effective and cost-effective strategy to reduce the risk of neonatal sepsis.

Controlled clinical trial register

ISRCTN29313500

Intrauterine growth restriction (IUGR) is an important perinatal syndrome that poses several serious short- and long-term effects. We studied cytokine production by maternal peripheral blood lymphocytes stimulated by trophoblast antigens. 36 women with a diagnosis of IUGR and 22 healthy women with normal fetal growth were inducted. Peripheral blood mononuclear cells were stimulated with trophoblast antigens and levels of the proinflammatory cytokines IL-6, IL-8, IL-12, IL-23, IFNγ, and TNFα and the anti-inflammatory cytokines IL-4, IL-10, and IL-13 were measured in culture supernatants by ELISA. IL-8 was produced at higher levels by blood cells of the IUGR group than normal pregnant women, while IL-13 was produced at lower levels. IL-8, IFNγ, and TNFα were higher in IUGR with placental insufficiency than in normal pregnancy. IL-12 levels were higher and IL-10 levels were lower in IUGR with placental insufficiency than in IUGR without placental insufficiency. We suggest that a stronger pro-inflammatory bias exists in IUGR as compared to normal pregnancy and in IUGR with placental insufficiency when compared to IUGR without placental insufficiency. Several ratios of proinflammatory to anti-inflammatory cytokines also support the existence of an inflammatory bias in IUGR.

OBJECTIVE--To compare the effects on fetal and maternal morbidity of routine active management of third stage of labour and expectant (physiological) management, in particular to determine whether active management reduced incidence of postpartum haemorrhage. DESIGN--Randomised trial of active versus physiological management. Women entered trial on admission to labour ward with allocation revealed just before vaginal delivery. Five months into trial high rate of postpartum haemorrhage in physiological group (16.5% v 3.8%) prompted modification of protocol to exclude more women and allow those allocated to physiological group who needed some active management to be switched to fully active management. Sample size of 3900 was planned, but even after protocol modification a planned interim analysis after first 1500 deliveries showed continuing high postpartum haemorrhage rate in physiological group and study was stopped. SETTING--Maternity hospital. PARTICIPANTS--Of 4709 women delivered from 1 January 1986 to 31 January 1987, 1695 were admitted to trial and allocated randomly to physiological (849) or active (846) management. Reasons for exclusion were: refusal, antepartum haemorrhage, cardiac disease, breech presentation, multiple pregnancy, intrauterine death, and, after May 1986, ritodrine given two hours before delivery, anticoagulant treatment, and any condition needing a particular management of third stage. INTERVENTIONS--All but six women allocated to active management actually received it, having prophylactic oxytocic, cord clamping before placental delivery, and cord traction; whereas just under half those allocated to physiological management achieved it. A fifth of physiological group received prophylactic oxytocic, two fifths underwent cord traction and just over half clamping of the cord before placental delivery. ENDPOINT--Reduction in incidence of postpartum haemorrhage from 7.5% under physiological management to 5.0% under active management. MEASUREMENTS AND MAIN RESULTS--Incidence of postpartum haemorrhage was 5.9% in active management group and 17.9% in physiological group (odds ratio 3.13; 95% confidence interval 2.3 to 4.2), a contrast reflected in other indices of blood loss. In physiological group third stage was longer (median 15 min v 5 min) and more women needed therapeutic oxytocics (29.7% v 6.4%). Apgar scores at one and five minutes and incidence of neonatal respiratory problems were not significantly different between groups. Babies in physiological group weighed mean of 85 g more than those in active group. When women allocated to and receiving active management (840) were compared with those who actually received physiological management (403) active management still produced lower rate of postpartum haemorrhage (odds ratio 2.4;95% CI1.6 to 3.7). CONCLUSIONS--Policy of active management practised in this trial reduces incidence of postpartum haemorrhage, shortens third stage, and results in reduced neonatal packed cell volume.

Objective To compare oral misoprostol solution with vaginal prostaglandin gel (dinoprostone) for induction of labour at term to determine whether misoprostol is superior.

Design Randomised double blind placebo controlled trial.

Setting Maternity departments in three hospitals in Australia.

Population Pregnant women with a singleton cephalic presentation at ≥ 36+6 weeks' gestation, with an indication for prostaglandin induction of labour.

Interventions 20 μg oral misoprostol solution at ourly intervals and placebo vaginal gel or vaginal dinoprostone gel at six hourly intervals and placebo oral solution.

Main outcome measures Vaginal birth within 24 hours; uterine hyperstimulation with associated changes in fetal heart rate; caesarean section (all); and caesarean section for fetal distress.

Results 741 women were randomised, 365 to the misoprostol group and 376 to the vaginal dinoprostone group. There were no significant differences between the two treatment groups in the primary outcomes: vaginal birth not achieved in 24 hours (misoprostol 168/365 (46.0%) v dinoprostone 155/376 (41.2%); relative risk 1.12, 95% confidence interval 0.95 to 1.32; P = 0.134), caesarean section (83/365 (22.7%) v 100/376 (26.6%); 0.82, 0.64 to 1.06; P = 0.127), caesarean section for fetal distress (32/365 (8.8%) v 35/376 (9.3%); 0.91, 0.57 to 1.44; P = 0.679), or uterine hyperstimulation with changes in fetal heart rate (3/365 (0.8%) v 6/376 (1.6%); 0.55, 0.14 to 2.21; P = 0.401). Although there were differences in the process of labour induction, there were no significant differences in adverse maternal or neonatal outcomes.

Conclusions This trial shows no evidence that oral misoprostol is superior to vaginal dinoprostone for induction of labour. However, it does not lead to poorer health outcomes for women or their infants, and oral treatment is preferred by women.

Trial registration National Health and Medical Research Council, Perinatal Trials, PT0361.

BACKGROUND: As the interval between rupture of the fetal membranes at term and delivery increases, so may the risk of fetal and maternal infection. Recently the TERMPROM (Term Prelabor Rupture of the Membranes) Study Group reported the results of a randomized controlled trial comparing 4 management strategies: induction with oxytocin (IwO), induction with prostaglandin (IwP), and expectant management and induction with either oxytocin (EM-O) or prostaglandin (EM-P) if complications developed. The study found no statistically significant differences in neonatal infection and cesarean section rates between any of the 4 groups. OBJECTIVE: To conduct an economic evaluation comparing the cost of (a) IwO and EM-O, (b) IwP and EM-P and (c) IwO and IwP. DESIGN: An economic analysis, conducted alongside the clinical trial, using a third-party payer perspective. Analysis included all treatment costs incurred for both the mother and the baby. Information on health care utilization and outcomes was collected for all study participants. Three countries (Canada, the United Kingdom and Australia), corresponding to the largest study recruitment, were chosen for calculation of unit costs. For each country, the base, low and high estimates of unit cost for each service item were generated. Intention-to-treat analysis. Extensive statistical and sensitivity analyses were performed. RESULTS: The median cost of IwO per patient was significantly lower statistically than that of EM-O and IwP. This result held in all 3 countries compared -$114 and -$46 in Canada, -113 Pounds and -63 Pounds in the UK, and -A$30 and -A$49 in Australia) and after an extensive sensitivity analysis. There was no statistically significant difference in median cost per patient between IwP and EM-P. CONCLUSION: Although the clinical results of the TERMPROM study did not find IwO to be preferable to the other treatment alternatives, the economic evaluation found it to be less costly. However, these cost differences, even though statistically significant, are not likely to be important in many countries. When this is the case, the authors recommend that women be offered a choice between management strategies.

Objective

To examine whether cervical favourability (measured by cervical length and the Bishop score) should inform obstetricians’ decision regarding labour induction for women with gestational hypertension or mild pre-eclampsia at term.

Design

A post hoc analysis of the Hypertension and Pre-eclampsia Intervention Trial At Term (HYPITAT).

Setting

Obstetric departments of six university and 32 teaching and district hospitals in the Netherlands.

Population

A total of 756 women diagnosed with gestational hypertension or pre-eclampsia between 36 + 0 and 41 + 0 weeks of gestation randomly allocated to induction of labour or expectant management.

Methods

Data were analysed using logistic regression modelling.

Main outcome measures

The occurrence of a high-risk maternal situation defined as either maternal complications or progression to severe disease. Secondary outcomes were caesarean delivery and adverse neonatal outcomes.

Results

The superiority of labour induction in preventing high-risk situations in women with gestational hypertension or mild pre-eclampsia at term varied significantly according to cervical favourability. In women who were managed expectantly, the longer the cervix the higher the risk of developing maternal high-risk situations, whereas in women in whom labour was induced, cervical length was not associated with a higher probability of maternal high-risk situations (test of interaction P = 0.03). Similarly, the beneficial effect of labour induction on reducing the caesarean section rate was stronger in women with an unfavourable cervix.

Conclusion

Against widely held opinion, our exploratory analysis showed that women with gestational hypertension or mild pre-eclampsia at term who have an unfavourable cervix benefited more from labour induction than other women.

Trial registration

The trial has been registered in the clinical trial register as ISRCTN08132825.

Background

Gestational Diabetes (GDM) is one of the most common complications of pregnancies affecting around 7% of women. This clinical condition is associated with an increased risk of developing fetal macrosomia and is related to a higher incidence of caesarean section in comparison to the general population. Strong evidence indicating the best management between induction of labour at term and expectant monitoring are missing.

Methods/Design

Pregnant women with singleton pregnancy in vertex presentation previously diagnosed with gestational diabetes will be asked to participate in a multicenter open-label randomized controlled trial between 38+0 and 39+0 gestational weeks. Women will be recruited in the third trimester in the Outpatient clinic or in the Day Assessment Unit according to local protocols. Women who opt to take part will be randomized according to induction of labour or expectant management for spontaneous delivery. Patients allocated to the induction group will be admitted to the obstetric ward and offered induction of labour via use of prostaglandins, Foley catheter or oxytocin (depending on clinical conditions). Women assigned to the expectant arm will be sent to their domicile where they will be followed up until delivery, through maternal and fetal wellbeing monitoring twice weekly. The primary study outcome is the Caesarean section (C-section) rate, whilst secondary measurement4s are maternal and neonatal outcomes. A total sample of 1760 women (880 each arm) will be recruited to identify a relative difference between the two arms equal to 20% in favour of induction, with concerns to C-section rate. Data will be collected until mothers and newborns discharge from the hospital. Analysis of the outcome measures will be carried out by intention to treat.

Discussion

The present trial will provide evidence as to whether or not, in women affected by gestational diabetes, induction of labour between 38+0 and 39+0 weeks is an effective management to ameliorate maternal and neonatal outcomes. The primary objective is to determine whether caesarean section rate could be reduced among women undergoing induction of labour, in comparison to patients allocated to expectant monitoring. The secondary objective consists of the assessment and comparison of maternal and neonatal outcomes in the two study arms.

Trial Registration

The study protocol has been registered in the ClinicalTrials.gov Protocol Registration System, identification number NCT01058772.

Objective To compare the effectiveness of an algorithm for diagnosis of active labour in primiparous women with standard care in terms of maternal and neonatal outcomes.

Design Cluster randomised trial.

Setting Maternity units in Scotland with at least 800 annual births.

Participants 4503 women giving birth for the first time, in 14 maternity units. Seven experimental clusters collected data from a baseline sample of 1029 women and a post-implementation sample of 896 women. The seven control clusters had a baseline sample of 1291 women and a post-implementation sample of 1287 women.

Intervention Use of an algorithm by midwives to assist their diagnosis of active labour, compared with standard care.

Main outcomes Primary outcome: use of oxytocin for augmentation of labour. Secondary outcomes: medical interventions in labour, admission management, and birth outcome.

Results No significant difference was found between groups in percentage use of oxytocin for augmentation of labour (experimental minus control, difference=0.3, 95% confidence interval −9.2 to 9.8; P=0.9) or in the use of medical interventions in labour. Women in the algorithm group were more likely to be discharged from the labour suite after their first labour assessment (difference=−19.2, −29.9 to −8.6; P=0.002) and to have more pre-labour admissions (0.29, 0.04 to 0.55; P=0.03).

Conclusions Use of an algorithm to assist midwives with the diagnosis of active labour in primiparous women did not result in a reduction in oxytocin use or in medical intervention in spontaneous labour. Significantly more women in the experimental group were discharged home after their first labour ward assessment.

Trial registration Current Controlled Trials ISRCTN00522952.

Objective

To compare the annual incidence rates of caesarean delivery between induction of labour and expectant management in the setting of macrosomia.

Design

This is a retrospective cohort study.

Setting

Deliveries in the USA in 2003.

Population

Singleton births of macrosomic neonates to low-risk nulliparous women at 39 weeks of gestation and beyond.

Methods

Women who had induction of labour at 39 weeks of gestation with a neonatal birthweight of 4000 ± 125 g (3875–4125 g) were compared with women who delivered (either induced or spontaneous labour) at 40, 41 or 42 weeks (i.e. expectant management), assuming an intrauterine fetal weight gain of 200 g per additional week of gestation. Similar comparisons were made at 40 and 41 weeks of gestation. Chi-square test and multivariable logistic regression analysis were used for statistical comparison.

Main outcome measures

Method of delivery, 5-minute Apgar scores, neonatal injury.

Results

There were 132 112 women meeting the study criteria. In women whose labours were induced at 39 weeks and who delivered a neonate with a birthweight of 4000 ± 125 g, the frequency of caesarean was lower compared with women who delivered at a later gestational age (35.2% versus 40.9%; adjusted OR 1.25, 95% CI 1.17–1.33). This trend was maintained at both 40 weeks (36.1% versus 42.6%; adjusted OR 1.31, 95% CI 1.23–1.40) and 41 weeks (38.9% versus 41.8%; adjusted OR 1.16, 95% CI 1.06–1.28) of gestation.

Conclusions

In the setting of known birthweight, it appears that induction of labour may reduce the risk of caesarean delivery. Future research should concentrate on clinical and radiological methods to better estimate birthweight to facilitate improved clinical care. These findings deserve examination in a large, prospective, randomised trial.

OBJECTIVE: To determine the cost-effectiveness of induction of labour versus serial fetal monitoring while awaiting spontaneous labour in postterm pregnancies. DESIGN: Cost-effectiveness and cost-minimization analyses conducted as part of a Canadian multicentre randomized clinical trial. SETTING: Twenty-two Canadian hospitals, of which 19 were teaching hospitals and 3 were community hospitals. PATIENTS: Women with uncomplicated pregnancies of 41 or more weeks' gestation were randomly assigned to induction of labour or serial antenatal monitoring. Of the 3418 women enrolled, no data were received on 11. Therefore, results were based on data from 1701 women in the induction arm of the study and 1706 women in the monitoring arm. MAIN OUTCOME MEASURES: Perinatal mortality and neonatal morbidity, rates of cesarean section and health care costs. Hospital costing models were developed specifically for the study. Data on use of major resources (e.g., length of hospital stay, surgical procedures, major diagnostic tests and procedures, and medications) for all trial participants were collected and combined with data on minor tests and procedures (e.g., laboratory tests) abstracted from a detailed review of medical records of a sample of patients. RESULTS: Because the results of the clinical trial showed a nonsignificant difference in perinatal mortality and neonatal morbidity between the induction and monitoring arms, the authors conducted a cost-minimization rather than a cost-effectiveness analysis. The mean cost per patient with a postterm pregnancy managed through monitoring was $3132 (95% confidence interval [CI] $3090 to $3174) and per patient who underwent induction of labour was $2939 (95% CI $2898 to $2981), for a difference of $193. The significantly higher (p < 0.0001) mean cost per patient in the monitoring arm was due mainly to the costs of additional monitoring and the significantly higher rates of cesarean section among these patients. Estimated conservatively, the savings resulting from a universal policy of managing postterm pregnancies by induction of labour in Canada may be as high as $8 million a year. CONCLUSIONS: A policy of managing postterm pregnancy through induction of labour not only results in more favourable outcomes than a monitoring strategy but does so at a lower cost.

Objective To determine neonatal outcomes (perinatal mortality and special care unit admission) and maternal outcomes (mode of delivery, delivery complications) of elective induction of labour compared with expectant management.

Design Retrospective cohort study using an unselected population database.

Setting Consultant and midwife led obstetric units in Scotland 1981-2007.

Participants 1 271 549 women with singleton pregnancies of 37 weeks or more gestation.

Interventions Outcomes of elective induction of labour (induction of labour with no recognised medical indication) at 37, 38, 39, 40, and 41 weeks’ gestation compared with those of expectant management (continuation of pregnancy to either spontaneous labour, induction of labour or caesarean section at a later gestation).

Main outcome measures Extended perinatal mortality, mode of delivery, postpartum haemorrhage, obstetric anal sphincter injury, and admission to a neonatal or special care baby unit. Outcomes were adjusted for age at delivery, parity, year of birth, birth weight, deprivation category, and, where appropriate, mode of delivery.

Results At each gestation between 37 and 41 completed weeks, elective induction of labour was associated with a decreased odds of perinatal mortality compared with expectant management (at 40 weeks’ gestation 0.08% (37/44 764) in the induction of labour group versus 0.18% (627/350 643) in the expectant management group; adjusted odds ratio 0.39, 99% confidence interval 0.24 to 0.63), without a reduction in the odds of spontaneous vertex delivery (at 40 weeks’ gestation 79.9% (35 775/44 778) in the induction of labour group versus 73.7% (258 665/350 791) in the expectant management group; adjusted odds ratio 1.26, 1.22 to 1.31). Admission to a neonatal unit was, however, increased in association with elective induction of labour at all gestations before 41 weeks (at 40 weeks’ gestation 8.0% (3605/44 778) in the induction of labour group compared with 7.3% (25 572/350 791) in the expectant management group; adjusted odds ratio 1.14, 1.09 to 1.20).

Conclusion Although residual confounding may remain, our findings indicate that elective induction of labour at term gestation can reduce perinatal mortality in developed countries without increasing the risk of operative delivery.

Background

British women are increasingly delaying childbirth. The proportion giving birth over the age of 35 rose from 12% in 1996 to 20% in 2006. Women over this age are at a higher risk of perinatal death, and antepartum stillbirth accounts for 61% of all such deaths. Women over 40 years old have a similar stillbirth risk at 39 weeks as women who are between 25 and 29 years old have at 41 weeks.

Many obstetricians respond to this by suggesting labour induction at term to forestall some of the risk. In a national survey of obstetricians 37% already induce women aged 40–44 years. A substantial minority of parents support such a policy, but others do not on the grounds that it might increase the risk of Caesarean section. However trials of induction in other high-risk scenarios have not shown any increase in Caesarean sections, rather the reverse. If induction for women over 35 did not increase Caesareans, or even reduced them, it would plausibly improve perinatal outcome and be an acceptable intervention. We therefore plan to perform a trial to test the effect of such an induction policy on Caesarean section rates.

This trial is funded by the NHS Research for Patient Benefit (RfPB) Programme.

Design

The 35/39 trial is a multi-centre, prospective, randomised controlled trial. It is being run in twenty UK centres and we aim to recruit 630 nulliparous women (315 per group) aged over 35 years of age, over two years. Women will be randomly allocated to one of two groups:

Induction of labour between 390/7 and 396/7 weeks gestation.

Expectant management i.e. awaiting spontaneous onset of labour unless a situation develops necessitating either induction of labour or Caesarean Section.

The primary purpose of this trial is to establish what effect a policy of induction of labour at 39 weeks for nulliparous women of advanced maternal age has on the rate of Caesarean section deliveries. The secondary aim is to act as a pilot study for a trial to answer the question, does induction of labour in this group of women improve perinatal outcomes? Randomisation will occur at 360/7 – 396/7 weeks gestation via a computerised randomisation programme at the Clinical Trials Unit, University of Nottingham. There will be no blinding to treatment allocation.

Discussion

The 35/39 trial is powered to detect an effect of induction of labour on the risk of caesarean section, it is underpowered to determine whether it improves perinatal outcome. The current study will also act as a pilot for a larger study to address this question.

Trial registration

ISRCTN11517275

In a prospective randomised study of mothers referred for prolonged pregnancy (around the 42nd week) 214 (group 1) were submitted to attempted induction of labour and 195 (group 2) assigned to continue for a further week without intervention. Strict selection criteria were used for the certainty of term. Mothers in group 2 were given regular non-stress tests to ensure fetal wellbeing, as were those in group 1 in whom induction failed. In group 1, 48 (23%) out of 210 first attempted inductions failed. In group 2, 135 (69%) of the births started spontaneously as compared with 38 (18%) in group 1. The mean duration of labour was 7.5 hours in each group. There was no significant difference in incidence of operative delivery, use of analgesics, or signs of perinatal asphyxia. Significantly more children in group 1 needed phototherapy for hyperbilirubinaemia. There was a clustering of births in the late afternoon and evening, which was most pronounced in group 1. A policy of vigilant non-intervention up to the 44th completed week of pregnancy does not appear to jeopardize mother or fetus.

OBJECTIVE--To compare intramuscular oxytocin alone and intramuscular oxytocin with ergometrine (Syntometrine) for their effect in reducing the risk of postpartum haemorrhage when both are used as part of the active management of the third stage of labour. DESIGN--Double blind, randomised controlled trial. SETTING--Two metropolitan teaching hospitals in Perth, Western Australia. SUBJECTS--All women who expected a vaginal birth during the period of the trial. Informed consent was obtained. MAIN OUTCOME MEASURES--Postpartum haemorrhage, nausea, vomiting, and increased blood pressure. RESULTS--3497 women were randomly allocated to receive oxytocin-ergometrine (n = 1730) or oxytocin (n = 1753). Rates of postpartum haemorrhage (> or = 500 ml or > or = 1000 ml) were similar in both arms (odds ratio 0.90 (0.82); 95% confidence interval 0.75 to 1.07 (0.59 to 1.14) at 500 ml (1000 ml) threshold). The use of oxytocin-ergometrine was associated with nausea, vomiting, and increased blood pressure. CONCLUSIONS--There are few advantages but several disadvantages for the routine use of oxytoxinergometrine when prophylactic active management of the third stage of labour is practised. Further investigation of dose-response for oxytocin may be warranted.

Objectives To evaluate the impact of labouring in water during first stage of labour on rates of epidural analgesia and operative delivery in nulliparous women with dystocia.

Design Randomised controlled trial.

Setting University teaching hospital in southern England.

Participants 99 nulliparous women with dystocia (cervical dilation rate < 1 cm/hour in active labour) at low risk of complications.

Interventions Immersion in water in birth pool or standard augmentation for dystocia (amniotomy and intravenous oxytocin).

Main outcome measures Primary: epidural analgesia and operative delivery rates. Secondary: augmentation rates with amniotomy and oxytocin, length of labour, maternal and neonatal morbidity including infections, maternal pain score, and maternal satisfaction with care.

Results Women randomised to immersion in water had a lower rate of epidural analgesia than women allocated to augmentation (47% v 66%, relative risk 0.71 (95% confidence interval 0.49 to 1.01), number needed to treat for benefit (NNT) 5). They showed no difference in rates of operative delivery (49% v 50%, 0.98 (0.65 to 1.47), NNT 98), but significantly fewer received augmentation (71% v 96%, 0.74 (0.59 to 0.88), NNT 4) or any form of obstetric intervention (amniotomy, oxytocin, epidural, or operative delivery) (80% v 98%, 0.81 (0.67 to 0.92), NNT 5). More neonates of women in the water group were admitted to the neonatal unit (6 v 0, P = 0.013), but there was no difference in Apgar score, infection rates, or umbilical cord pH.

Conclusions Labouring in water under midwifery care may be an option for slow progress in labour, reducing the need for obstetric intervention, and offering an alternative pain management strategy.

BACKGROUND: Meta-analyses of randomized controlled trials suggest that elective induction of labour at 41 weeks' gestation, compared with expectant management with selective labour induction, is associated with fewer perinatal deaths and no increase in the cesarean section rate. The authors studied the changes over time in the rates of labour induction in post-term pregnancies in Canada and examined the effects on the rates of stillbirth and cesarean section. METHODS: Changes in the proportion of total births at 41 weeks' and at 42 or more weeks' gestation, and in the rate of stillbirths at 41 or more weeks' (versus 40 weeks') gestation in Canada between 1980 and 1995 were determined using data from Statistics Canada. Changes in the rates of labour induction and cesarean section were determined using data from hospital and provincial sources. RESULTS: There was a marked increase in the proportion of births at 41 weeks' gestation (from 11.9% in 1980 to 16.3% in 1995) and a marked decrease in the proportion at 42 or more weeks (from 7.1% in 1980 to 2.9% in 1995). The rate of stillbirths among deliveries at 41 or more weeks' gestation decreased significantly, from 2.8 per 1000 total births in 1980 to 0.9 per 1000 total births in 1995 (p < 0.001). The stillbirth rate also decreased significantly among births at 40 weeks' gestation, from 1.8 per 1000 total births in 1980 to 1.1 per 1000 total births in 1995 (p < 0.001). The magnitude of the decrease in the stillbirth rate at 41 or more weeks' gestation was greater than that at 40 weeks' gestation (p < 0.001). All hospital and provincial sources of data indicated that the rate of labour induction increased significantly between 1980 and 1995 among women delivering at 41 or more weeks' gestation. The associated changes in rates of cesarean section were variable. INTERPRETATION: Between 1980 and 1995 clinical practice for the management of post-term pregnancy changed in Canada. The increased rate of labour induction at 41 or more weeks' gestation may have contributed to the decreased stillbirth rate but it had no convincing influence either way on the cesarean section rate.

Glucocorticoids are administered to pregnant women at risk of preterm labour to promote fetal lung surfactant maturation. Intrauterine growth restriction (IUGR) is associated with an increased risk of preterm labour. Hence, IUGR babies may be exposed to antenatal glucocorticoids. The ability of the placenta or blood brain barrier to remove glucocorticoids from the fetal compartment or the brain is compromised in the IUGR fetus, which may have implications for lung, brain, and heart development. There is conflicting evidence on the effect of exogenous glucocorticoids on surfactant protein expression in different animal models of IUGR. Furthermore, the IUGR fetus undergoes significant cardiovascular adaptations, including altered blood pressure regulation, which is in conflict with glucocorticoid-induced alterations in blood pressure and flow. Hence, antenatal glucocorticoid therapy in the IUGR fetus may compromise regulation of cardiovascular development. The role of cortisol in cardiomyocyte development is not clear with conflicting evidence in different species and models of IUGR. Further studies are required to study the effects of antenatal glucocorticoids on lung, brain, and heart development in the IUGR fetus. Of specific interest are the aetiology of IUGR and the resultant degree, duration, and severity of hypoxemia.

Objective To determine if a complex nursing and midwifery intervention in hospital labour assessment units would increase the likelihood of spontaneous vaginal birth and improve other maternal and neonatal outcomes.

Design Multicentre, randomised controlled trial with prognostic stratification by hospital.

Setting 20 North American and UK hospitals.

Participants 5002 nulliparous women experiencing contractions but not in active labour; 2501 were allocated to structured care and 2501 to usual care.

Interventions Usual nursing or midwifery care or a minimum of one hour of care by a nurse or midwife trained in structured care, consisting of a formalised approach to assessment of and interventions for maternal emotional state, pain, and fetal position.

Main outcome measures Primary outcome was spontaneous vaginal birth. Other outcomes included intrapartum interventions, women’s views of their care, and indicators of maternal and fetal health during hospital stay and 6-8 weeks after discharge.

Results Outcome data were obtained for 4996 women. The rate of spontaneous vaginal birth was 64.0% (n=1597) in the structured care group and 61.3% (n=1533) in the usual care group (odds ratio 1.12, 95% confidence interval 0.96 to 1.27). Fewer women allocated to structured care (n=403, 19.5%) rated staff helpfulness as less than very helpful than those allocated to usual care (n=544, 26.4%); odds ratio 0.67, 98.75% confidence interval 0.50 to 0.85. Fewer women allocated to structured care (n=233, 11.3%) were disappointed with the amount of attention received from staff than those allocated to usual care (n=407, 19.7%); odds ratio 0.51, 98.75% confidence interval 0.32 to 0.70. None of the other results met prespecified levels of statistical significance.

Conclusion A structured approach to care in hospital labour assessment units increased satisfaction with care and was suggestive of a modest increase in the likelihood of spontaneous vaginal birth. Further study to strengthen the intervention is warranted.

Trial registration Current Controlled Trials ISRCTN16315180.

Intrauterine growth restriction is one of the most common and complex problems in modern obstetrics. The cut off value mainly used for defining an IUGR is at the 10th percentile. There are many evidence demonstrating that the adverse perinatal outcome are mainly confined to infants below the 5th or 3th percentile. The mains causes for the onset of IUGR can be divided into three categories: maternal, fetal and placental. Aim of this study is to obtain a review from which speculate useful indication in clinical practice. Evidence from randomized controlled trials finds few interventions beneficial in preventing or treating IUGR.

Background

Gestational hypertension (GH) and pre-eclampsia (PE) can result in severe complications such as eclampsia, placental abruption, syndrome of Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP) and ultimately even neonatal or maternal death. We recently showed that in women with GH or mild PE at term induction of labour reduces both high risk situations for mothers as well as the caesarean section rate. In view of this knowledge, one can raise the question whether women with severe hypertension, pre-eclampsia or deterioration chronic hypertension between 34 and 37 weeks of gestation should be delivered or monitored expectantly. Induction of labour might prevent maternal complications. However, induction of labour in late pre-term pregnancy might increase neonatal morbidity and mortality compared with delivery at term.

Methods/Design

Pregnant women with severe gestational hypertension, mild pre-eclampsia or deteriorating chronic hypertension at a gestational age between 34+0 and 36+6 weeks will be asked to participate in a multi-centre randomised controlled trial. Women will be randomised to either induction of labour or expectant monitoring. In the expectant monitoring arm, women will be induced only when the maternal or fetal condition detoriates or at 37+0 weeks of gestation. The primary outcome measure is a composite endpoint of maternal mortality, severe maternal complications (eclampsia, HELLP syndrome, pulmonary oedema and thromboembolic disease) and progression to severe pre-eclampsia. Secondary outcomes measures are respiratory distress syndrome (RDS), neonatal morbidity and mortality, caesarean section and vaginal instrumental delivery rates, maternal quality of life and costs. Analysis will be intention to treat. The power calculation is based on an expectant reduction of the maternal composite endpoint from 5% to 1% for an expected increase in neonatal RDS from 1% at 37 weeks to 10% at 34 weeks. This implies that 680 women have to be randomised.

Discussion

This trial will provide insight as to whether in women with hypertensive disorders late pre-term, induction of labour is an effective treatment to prevent severe maternal complications without compromising the neonatal morbidity.

Trial Registration

NTR1792 Clinical trial registration: http://www.trialregister.nl

Background

There is increasing interest in carrying out pre-induction cervical ripening on an outpatient basis. However, there are concerns about the use of prostaglandins, the agents commonly used in hospital settings for this indication, because prostaglandins induce uterine contractions that may lead to fetal hypoxia. Indeed, in a recent study we demonstrated abnormalities in 9% of fetal heart rate tracings performed following prostaglandin induced cervical ripening at term. In contrast, we confirmed in the same study that isosorbide mononitrate (IMN) (administered on an inpatient basis) was both effective in inducing cervical ripening at term, and was associated with no associated fetal heart rate abnormalities.

Methods/design

The aim of this study is to determine whether IMN self administered by women on an outpatient basis improves the process of induction of labour. Specifically, we hypothesise that the use of outpatient IMN will result in a shorter inpatient stay before delivery, decreased costs to the health service and greater maternal satisfaction with ripening and induction of labour, compared with placebo treatment.

In the study described here (the "IMOP" study), women scheduled for induction of labour at term, and who require pre-induction cervical ripening will be randomised to self-administer at home either IMN 40 mg, or a placebo, each vaginally, at 48 hours, 32 hours and 16 hours before scheduled hospital admission.

After admission to hospital, treatment will revert to the usual induction of labour protocol. We will compare the primary outcomes of the elapsed time interval from hospital admission to vaginal delivery, the costs to the health service of induction of labour, and women's experience of induction of labour in the two groups.

Discussion

This trial will provide evidence on the efficacy of outpatient IMN for pre-induction cervical ripening at term. We will study a formulation of IMN which is cheap and widely available. If the treatment is effective, acceptable to women, and cost effective, it could be implemented into obstetric practice worldwide.

Trial registration

The trial has been registered on the International Standard Randomised Controlled Trial Number Register (ISRCTN) and given the registration number ISRTN39772441.

Current therapies for preterm labour (PTL) focus on arresting myometrial contractions but are largely ineffective, thus alternative therapeutic targets need to be identified. Leukocytes infiltrate the uterus around the time of labour, and are in particularly abundant in decidua (maternal-fetal interface). Moreover, decidual inflammation precedes labour in rat pregnancies and thus may contribute to initiation of labour. We hypothesized that chemokines mediate decidual leukocyte trafficking during preterm labour (PTL) and term labour (TL), thus representing potential targets for preventing PTL. Women were recruited into 4 groups: TL, term not in labour (TNL), idiopathic PTL and PTL with infection (PTLI). Choriodecidual RNA was subjected to a pathway-specific PCR array for chemokines. Differential expression of 12 candidate chemokines was validated by real time RT-PCR and Bioplex assay, with immunohistochemistry to confirm cellular origin. 25 chemokines were upregulated in choriodecidua from TL compared to TNL. A similar pattern was detected in PTL, however a distinct profile was observed in PTLI consistent with differences in leukocyte infiltration. Upregulation of CCL2, CCL4, CCL5, CXCL8 and CXCL10 mRNA and protein was confirmed in TL, with CCL8 upregulated in PTL. Significant correlations were detected between these chemokines and decidual leukocyte abundance previously assessed by immunohistochemical and image analysis. Chemokines were primarily expressed by decidual stromal cells. In addition, CXCL8 and CCL5 were significantly elevated in maternal plasma during labour, suggesting chemokines contribute to peripheral inflammatory events during labour. Differences in chemokine expression patterns between TL and idiopathic PTL may be attributable to suppression of chemokine expression by betamethasone administered to women in PTL; this was supported by in vitro evidence of chemokine downregulation by clinically relevant concentrations of the steroid. The current study provides compelling evidence that chemokines regulate decidual leukocyte recruitment during labour. The 6 chemokines identified represent potential novel therapeutic targets to block PTL.