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Preterm labor affects up to 20% of pregnancies, is considered a main cause of associated neonatal morbidity and mortality and is responsible for neonatal care costs of multimillion euros. In spite of that, the commercial market for this clinical indication is rather limited, which may be also related to high liability. Consequently, with only a few exceptions, preterm labor is not in the orbit of great interest of the pharmaceutical industry. Coordinated effort of research community may bring the change and help required to reduce the influence of this multifactorial syndrome on society. Between the novel techniques that are being explored in a SAFE (The Special Non-Invasive Advances in Fetal and Neonatal Evaluation Network) group, there are new research models of preterm labor as well as novel methodology of analysis of biological signals. In this article, we briefly describe new clinical and nonclinical human models of preterm labor as well as summarize some novel methods of data processing and analysis that may be used in the context of preterm labor.

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.

New technologies are rapidly having a great impact on the development of novel rehabilitation interventions. One of the more popular of these technological advances is virtual reality. The wide range of applications of this technology, from immersive environments to tele-rehabilitation equipment and care, lends versatility to its use as a rehabilitation intervention. But increasing access to this technology requires that we further our understanding about its impact on a performer. The International Workshop on Virtual Reality in Rehabilitation (IWVR), now known as Virtual Rehabilitation 2007, is a conference that emerged from the need to discover how virtual reality could be applied to rehabilitation practice. Individuals from multiple disciplines concerned with the development, transmission, and evaluation of virtual reality as a technology applied to rehabilitation attend this meeting to share their work. In this special issue of the Journal of NeuroEngineering and Rehabilitation we are sharing some of the papers presented at the 2006 meeting of IWVR with the objective of offering a description of the state of the art in this research field. A perusal of these papers will provide a good cross-section of the emerging work in this area as well as inform the reader about new findings relevant to research and practice in rehabilitation.

Background

Preterm labour is the main cause of perinatal morbidity and mortality in the Western world. At present, there is evidence that tocolysis for 48 hours is useful in women with threatened preterm labour at least before 32 weeks. This allows transfer of the patient to a perinatal centre, and maximizes the effect of corticosteroids for improved neonatal survival. It is questionable whether treatment with tocolytics should be maintained after 48 hours.

Methods/Design

The APOSTEL II trial is a multicentre placebo-controlled study. Pregnant women admitted for threatened preterm labour who have been treated with 48 hours corticosteroids and tocolysis will be eligible to participate in the trial between 26+0 and 32+2 weeks gestational age. They will be randomly allocated to nifedipine (intervention) or placebo (control) for twelve days or until delivery, whatever comes first.

Primary outcome is a composite of perinatal death, and severe neonatal morbidity up to evaluation at 6 months after birth. Secondary outcomes are gestational age at delivery, number of days in neonatal intensive care and total days of the first 6 months out of hospital. In addition a cost-effectiveness analysis will be performed. Analysis will be by intention to treat. The power calculation is based on an expected 11% difference in adverse neonatal outcome. This implies that 406 women have to be randomised (two sided test, β 0.2 at alpha 0.05).

Discussion

This trial will provide evidence as to whether maintenance tocolysis reduces severe perinatal morbidity and mortality in women with threatened preterm labour before 32 weeks.

Trial Registration

Clinical trial registration: , NTR 1336, date of registration: June 3rd 2008.

Background

The Medical Research Council (MRC) ORACLE trial evaluated the use of co-amoxiclav 375 mg and/or erythromycin 250 mg in women presenting with preterm rupture of membranes (PROM) ORACLE I or in spontaneous preterm labour (SPL) ORACLE II using a factorial design. The results showed that for women with a singleton baby with PROM the prescription of erythromycin is associated with improvements in short term neonatal outcomes, although co-amoxiclav is associated with prolongation of pregnancy, a significantly higher rate of neonatal necrotising enterocolitis was found in these babies. Prescription of erythromycin is now established practice for women with PROM. For women with SPL antibiotics demonstrated no improvements in short term neonatal outcomes and are not recommended treatment. There is evidence that both these conditions are associated with subclinical infection so perinatal antibiotic administration may reduce the risk of later disabilities, including cerebral palsy, although the risk may be increased through exposure to inflammatory cytokines, so assessment of longer term functional and educational outcomes is appropriate.

Methods

The MRC ORACLE Children's Study will follow up UK children at age 7 years born to 4809 women with PROM and the 4266 women with SPL enrolled in the earlier ORACLE trials. We will use a parental questionnaire including validated tools to assess disability and behaviour. We will collect the frequency of specific medical conditions: cerebral palsy, epilepsy, respiratory illness including asthma, diabetes, admission to hospital in last year and other diseases, as reported by parents.

National standard test results will be collected to assess educational attainment at Key Stage 1 for children in England.

Discussion

This study is designed to investigate whether or not peripartum antibiotics improve health and disability for children at 7 years of age.

Trial registration

The ORACLE Trial and Children Study is registered in the Current Controlled Trials registry. ISCRTN 52995660

Background

Screening and monitoring in pregnancy are strategies used by healthcare providers to identify high-risk pregnancies so that they can provide more targeted and appropriate treatment and follow-up care, and to monitor fetal well-being in both low- and high-risk pregnancies. The use of many of these techniques is controversial and their ability to detect fetal compromise often unknown. Theoretically, appropriate management of maternal and fetal risk factors and complications that are detected in pregnancy and labour could prevent a large proportion of the world's 3.2 million estimated annual stillbirths, as well as minimise maternal and neonatal morbidity and mortality.

Methods

The fourth in a series of papers assessing the evidence base for prevention of stillbirths, this paper reviews available published evidence for the impact of 14 screening and monitoring interventions in pregnancy on stillbirth, including identification and management of high-risk pregnancies, advanced monitoring techniques, and monitoring of labour. Using broad and specific strategies to search PubMed and the Cochrane Library, we identified 221 relevant reviews and studies testing screening and monitoring interventions during the antenatal and intrapartum periods and reporting stillbirth or perinatal mortality as an outcome.

Results

We found a dearth of rigorous evidence of direct impact of any of these screening procedures and interventions on stillbirth incidence. Observational studies testing some interventions, including fetal movement monitoring and Doppler monitoring, showed some evidence of impact on stillbirths in selected high-risk populations, but require larger rigourous trials to confirm impact. Other interventions, such as amniotic fluid assessment for oligohydramnios, appear predictive of stillbirth risk, but studies are lacking which assess the impact on perinatal mortality of subsequent intervention based on test findings. Few rigorous studies of cardiotocography have reported stillbirth outcomes, but steep declines in stillbirth rates have been observed in high-income settings such as the U.S., where cardiotocography is used in conjunction with Caesarean section for fetal distress.

Conclusion

There are numerous research gaps and large, adequately controlled trials are still needed for most of the interventions we considered. The impact of monitoring interventions on stillbirth relies on use of effective and timely intervention should problems be detected. Numerous studies indicated that positive tests were associated with increased perinatal mortality, but while some tests had good sensitivity in detecting distress, false-positive rates were high for most tests, and questions remain about optimal timing, frequency, and implications of testing. Few studies included assessments of impact of subsequent intervention needed before recommending particular monitoring strategies as a means to decrease stillbirth incidence. In high-income countries such as the US, observational evidence suggests that widespread use of cardiotocography with Caesarean section for fetal distress has led to significant declines in stillbirth rates. Efforts to increase availability of Caesarean section in low-/middle-income countries should be coupled with intrapartum monitoring technologies where resources and provider skills permit.

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.

Advances in the field of labour analgesia have tread a long journey from the days of ether and chloroform in 1847 to the present day practice of comprehensive programme of labour pain management using evidence-based medicine. Newer advances include introduction of newer techniques like combined spinal epidurals, low-dose epidurals facilitating ambulation, pharmacological advances like introduction of remifentanil for patient-controlled intravenous analgesia, introduction of newer local anaesthetics and adjuvants like ropivacaine, levobupivacaine, sufentanil, clonidine and neostigmine, use of inhalational agents like sevoflourane for patient-controlled inhalational analgesia using special vaporizers, all have revolutionized the practice of pain management in labouring parturients. Technological advances like use of ultrasound to localize epidural space in difficult cases minimizes failed epidurals and introduction of novel drug delivery modalities like patient-controlled epidural analgesia (PCEA) pumps and computer-integrated drug delivery pumps have improved the overall maternal satisfaction rate and have enabled us to customize a suitable analgesic regimen for each parturient. Recent randomized controlled trials and Cochrane studies have concluded that the association of epidurals with increased caesarean section and long-term backache remains only a myth. Studies have also shown that the newer, low-dose regimes do not have a statistically significant impact on the duration of labour and breast feeding and also that these reduce the instrumental delivery rates thus improving maternal and foetal safety. Advances in medical technology like use of ultrasound for localizing epidural space have helped the clinicians to minimize the failure rates, and many novel drug delivery modalities like PCEA and computer-integrated PCEA have contributed to the overall maternal satisfaction and safety.

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.

Intrathoracic pressure and volume changes were measured during the spontaneous first breath in 11 healthy term neonates delivered by emergency caesarean section (CS). Although inspiratory and expiratory rates were higher than those found among babies delivered by elective CS, inspiratory volume was very similar and these babies, unlike those delivered by elective CS, had all formed a functional residual capacity at the end of the first breath. We obtained cord arterial and venous samples for catecholamine analysis concurrently, and found that most of the babies had concentrations of plasma noradrenaline similar to babies delivered by elective CS--high values were found only among infants who had suffered fetal distress. Both catecholamine excretion and method of delivery may be important in the formation of the functional residual capacity at birth.

Fifty twin pregnancies in which the mother received epidural analgesia in labour were compared with 92 in which the mother received standard parenteral analgesia. The duration of the first and second stages of labour; the incidence of assisted deliveries when the head presented; the proportion of breech extractions when either the first or second twin presented by the breech; the incidence of low Apgar scores; and the perinatal mortality were not significantly different in the two groups. These findings suggest that lumbar epidural analgesia is safe for providing pain relief in labour for patients with a twin pregnancy. Moreover, an epidural block is preferable to conventional analgesia in these cases as it allows prompt intervention to effect delivery of the second twin.

Objective. We performed a prospective observational audit study to compare neonatal and maternal outcomes of the primary cesarean sections performed in first stage versus second stage of labour. Methods. One thousand three hundred and eighty-nine nullipara women who had undergone cesarean section in a tertiary teaching hospital between February 1, 2009 and January 31, 2010 were included in the study. Primary maternal outcomes of interest were uterine atonia, transfusion requirement, urinary system injury, requirement for hysterectomy, and duration of hospital stay. Results. A total of 1389 women underwent cesarean section at this 12 month time period. Of these 1389 cesarean sections, 1271 were in the first stage of the labour and 171 were in the second stage of the labour. Urinary injuries, transfusion requirement, and uterine atonia hysterectomy were significantly more frequent in women who underwent cesarean section in the second stage of the labour compared to women undergoing cesarean section in the first stage of the labour. Conclusion. Cesarean section in the second stage of the labour is associated with increased maternal and neonatal morbidities. Special attention is required to the patients undergoing cesarean section in the second stage of the labour.

Objective

To investigate the effect of maternal obesity on mode of delivery following induction of labour (IOL) for prolonged pregnancy and subsequent intrapartum and neonatal complications.

Design

Retrospective (historical) cohort study.

Setting

Liverpool Women's Hospital NHS Foundation Trust, UK.

Population

A total of 29 224 women with singleton pregnancies between 2004 and 2008 of whom 3076 had a prolonged pregnancy (defined as ≥290 days or 41+3 weeks of gestation) and received IOL.

Methods

Kruskal–Wallis test, chi-square test and multivariable logistic regression.

Main outcome measures

Mode of delivery and risk of delivery and neonatal complications in obese verses non-obese women following IOL.

Results

Obese women had a significantly higher rate of IOL ending in caesarean section compared with women of normal weight following IOL (38.7% versus 23.8% primiparous; 9.9% versus 7.9% multiparous women, respectively); however, length of labour, incidence of postpartum haemorrhage and third-degree tear, rate of low cord blood pH, low Apgar scores and shoulder dystocia were similar in all body mass index categories. Complications included a higher incidence of fetal macrosomia and second-degree, but not third-degree, tear in primiparous women.

Conclusions

Higher maternal body mass index at booking is associated with an increased risk of prolonged pregnancy and increased rate of IOL. Despite this, more than 60% of obese primiparous and 90% of multiparous women with prolonged pregnancies who were induced achieved vaginal delivery and labour complications in the obese women with prolonged pregnancies were largely comparable to those of normal weight women with prolonged pregnancies. Our data suggest that IOL for prolonged pregnancy in obese women is a reasonable and safe management option.

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.

Young, unrelated queens may cooperate in colony founding (pleometrosis) in many species of ants. Whereas the founding queens of many 'advanced' species rely completely on body reserves in order to rear their first young, queens of the ponerine Pachycondyla 'inversa' forage for food. In founding associations, only one queen specializes in this risky task. Here we show that the division of labour is strongly affected by aggressive interactions between cofounding queens: the dominant remains in the nest and guards the brood, whereas the subordinate is forced to leave and forage. The frequency of queen antagonism increased with the duration since food was last added to the foraging arena. Egg-laying rates did not differ significantly between nest-mate queens, but dominant queens destroyed and ate some of the eggs laid by subordinates.

Background

Preterm birth is a global problem, with a prevalence of 8 to 12% depending on location. Several large trials and systematic reviews have shown progestogens to be effective in preventing or delaying preterm birth in selected high risk women with a singleton pregnancy (including those with a short cervix or previous preterm birth). Although an improvement in short term neonatal outcomes has been shown in some trials these have not consistently been confirmed in meta-analyses. Additionally data on longer term outcomes is limited to a single trial where no difference in outcomes was demonstrated at four years of age of the child, despite those in the “progesterone” group having a lower incidence of preterm birth.

Methods/Design

The OPPTIMUM study is a double blind randomized placebo controlled trial to determine whether progesterone prophylaxis to prevent preterm birth has long term neonatal or infant benefit. Specifically it will study whether, in women with singleton pregnancy and at high risk of preterm labour, prophylactic vaginal natural progesterone, 200 mg daily from 22 – 34 weeks gestation, compared to placebo, improves obstetric outcome by lengthening pregnancy thus reducing the incidence of preterm delivery (before 34 weeks), improves neonatal outcome by reducing a composite of death and major morbidity, and leads to improved childhood cognitive and neurosensory outcomes at two years of age. Recruitment began in 2009 and is scheduled to close in Spring 2013. As of May 2012, over 800 women had been randomized in 60 sites.

Discussion

OPPTIMUM will provide further evidence on the effectiveness of vaginal progesterone for prevention of preterm birth and improvement of neonatal outcomes in selected groups of women with singleton pregnancy at high risk of preterm birth. Additionally it will determine whether any reduction in the incidence of preterm birth is accompanied by improved childhood outcome.

Trial registration

ISRCTN14568373

Many ant species have morphologically distinct worker sub-castes. This presumably increases colony efficiency and is thought to be optimized by natural selection. Optimality arguments are, however, often lacking in detail. In ants, the benefits of having workers in a range of sizes have rarely been explained mechanistically. In Atta leafcutter ants, large workers specialize in defence and also cut fruit. Fruit is soft and can be cut by smaller workers. Why, therefore, are large workers involved? According to the geometry hypothesis, cutting large pieces from three-dimensional objects like fruit is enhanced by longer mandibles. By contrast, long mandibles are not needed to cut leaves that are effectively two-dimensional. Our results from Atta laevigata support three predictions from the geometry hypothesis. First, larger workers cut larger fruit pieces. Second, the effect of large size is greater in cutting fruit than leaves. Third, the size of fruit pieces cut increases approximately in proportion to the cube of mandible length. Our results are a novel mechanistic example of how size variation among worker ants enhances division of labour.

A workshop on the Clinical Practice Guidelines (CPG) Network was held in Ottawa on Oct. 31 and Nov. 1, 1994. Five plenary sessions focused on CPGs and the roles of organizations, priority setting, dissemination and implementation, evaluation, and establishment of a network of individuals and organizations active in the CPG field. In general, the participants identified consumers as important stakeholders in CPG processes and agreed that there was a role for national coordination and information gathering, however, local and regional bodies have a role in CPG development, dissemination and implementation. Burden of illness and likeliness that the guidelines would affect the burden were key criteria for setting priorities. Eighteen high-priority topics were identified for CPG development and dissemination. Methods to enhance the effectiveness of dissemination and implementation were identified: improved funding, enhanced research and decreased duplication of effort. Barriers to CPG evaluation were lack of funding and inadequate data sources. Voluntary self-audit was the preferred evaluation method. The participants agreed on three important functions of the network: facilitation, cooperation and communication, operation of a central CPG information centre, and provision of expertise in CPG processes. They also agreed to the use of an existing organization as a secretariat for the network, with a voluntary, informal membership of all those interested.

Abstract

The current Labour Government has embarked on radical public sector reform in England. A so-called ‘Modernisation Agenda’ has been developed that is encapsulated in the NHS Plan—a document that details a long-term vision for health care. This plan involves a five-fold strategy: investment through greater public funding; quality assurance; improving access; service integration and inter-professional working; and providing a public health focus.

The principles of Labour's vision have been broadly supported. However, achieving its aims appears reliant on two key factors. First, appropriate resources are required to create capacity, particularly management capacity, to enable new functions to develop. Second, promoting access and service integration requires the development of significant co-ordination, collaboration and networking between agencies and individuals. This is particularly important for health and social care professionals. Their historically separate professions suggest that a significant period of change management is required to allow new roles and partnerships to evolve.

In an attempt to secure delivery of its goals, however, the Government has placed the emphasis on further organisational restructuring. In doing so, the Government may have missed the key challenges faced in delivering its NHS Plan. As this paper argues, cultural and behavioural change is probably a far more appropriate and important requirement for success than a centrally directed approach that emphasises the rearrangement of structural furniture.

Preterm labour continues to be a major contributor to neonatal and infant morbidity. Recent data from the USA indicate that the number of preterm deliveries (including those associated with preterm labour) has risen in the last 20 years by 30%. This increase is despite considerable efforts to introduce new therapies for the prevention and treatment of preterm labour and highlights the need to assess research in this area from a fresh perspective. In this paper we discuss i) the limitations of our knowledge concerning prediction, prevention and treatment of preterm labour and ii) future multidisciplinary strategies for improving our approach.

Preterm birth remains a major cause of perinatal mortality and long term handicap in surviving infants. This is one of the most important clinical problems in Europe and across the world. While some preterm births are iatrogenic, associated with severe complications of pregnancy (e.g. hypertensive disorders, antepartum haemorrhage, infection), or the result of multiple pregnancies following assisted reproduction, a high proportion of preterm births occur following spontaneous preterm labour of unknown cause. Early intervention in this group of women would have a significant impact on neonatal mortality and morbidity figures. However, the endocrine changes preceding parturition in women remain elusive and this makes it difficult to predict spontaneous labour at term, let alone preterm labour. Moreover our understanding of myometrial physiology remains rudimentary, limiting our options to devise improved pharmacological strategies to control uterine contractility when this is indicated. There is a need for concerted European and international research efforts to improve our knowledge of the mechanism of labour in women, to identify diagnostic markers to predict preterm labour and to develop uterine selective drugs to inhibit uterine contractions in a safe and efficient manner. This aim will be achieved by multidisciplinary research efforts from academics and industry, using traditional laboratory and clinical research methods, as well as novel technologies.

Background

Preterm birth is the primary cause of the neonatal mortality and morbidity. There will be no preterm birth without a cervical softening. Nitric oxide (NO) is shown to be a mediator of term cervical ripening. The aim of this study was to investigate mRNA expression of the three isomers of NO synthases (NOS) and to identify them by immunohistochemistry in the human cervix at preterm birth compared to term.

Methods

The three isomers of NOS- inducible (iNOS), endothelial (eNOS) and neuronal (bNOS) – were investigated in the human cervix. The expression of mRNA was determined using Real-Time Multiplex RT-PCR. The localisation of synthases in the cervical tissue was analysed using immunohistochemistry. Cervical biopsies were obtained from 4 groups of women without clinical signs of infection: preterm (PTL), term labour (TL), preterm not in labour (PTnotL) and term not in labour (TnotL) patients. One-Way ANOVA, Kruskal-Wallis, Student t-test or Mann-Whitney test were applied as appropriate to determine statistically significant differences among the groups.

Results

Patients in preterm labour had significantly (p < 0.01) higher mRNA levels of all the three NOS isomers compared to those in term labour. Women not in labour, irrespective of gestational age, thus with unripe cervices, had significantly lower eNOS mRNA levels compared to those in labour (p < 0.01). Immunoreactivity for all three NO synthases was observed in each examined sample in all groups. The bNOS staining was the most prominent.

Conclusion

The mRNA levels were higher in the preterm labour group compared to the women at term labour. The significant increase of the eNOS mRNA expression, from the unripe to the favourable cervical state during labour, may indicate a role of eNOS and supports the role of NO in the cervical ripening process. All the three synthases were identified by immunohistochemistry in all the groups of study.

The labour stencil representing the expected cervimetric progress of normal labour was used in 741 consecutive spontaneous labours to identify high-risk labours which needed oxytocic stimulation. Uterine contractions were stimulated if progress extended two hours past the nomogram, which resulted in shorter labours, fewer instrumental deliveries and caesarean sections, and babies with higher Apgar scores than in those dysfunctional labours which were not stimulated. According to the protocol used 36% of primigravid and 13% of multigravid labours needed acceleration. The remaining patients did not need any oxytocic interference during the first stage. This selection of patients is important to prevent a major obstetric advance being abused and discredited at a time when the profession and public are questioning the safety of active labour.

The management and outcome of 242 infants delivered between 26 and 34 weeks' gestation in an obstetrical and neonatal regional referral centre as a result of spontaneous preterm labour were recorded prospectively. Results of the survey show that the decision to intervene and delay delivery will depend on the availability of neonatal intensive care facilities. Infants likely to require intensive neonatal care should be transferred in utero to a centre with these facilities. The use of steroids reduces the mortality of preterm infants. The maximum effect occurs between 30 and 32 weeks' gestation, and there is no benefit after 34 weeks. If the weight is over 1500 g the mode of delivery of the preterm infant presenting by the breech does not influence outcome; if under 1500 g a caesarean section improves survival over those infants born by vaginal breech delivery.

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