bluuebunny/crossref_metadata_2025 huggingface dataset:
Fetal fibronectin—how useful is it in the prediction of preterm birth?
Authors: Leitich Harald , Kaider Alexandra
Published: December 2003

Objective
To determine the value of cervicovaginal fetal fibronectin as a marker for preterm delivery, a previously published meta‐analysis was updated.

Study design
Selection criteria confined the analysis to English‐language original reports of prospective studies including women at <37 weeks' gestation with intact amniotic membranes. For the outcomes of delivery <37 or <34 weeks' gestation or delivery within 7, 14, or 21 days after fibronectin sampling, we calculated sensitivity and specificity rates for each study, for subgroups of studies, and for all studies combined.

Results
A total of 40 studies were included. Statistical heterogeneity was seen in the majority of calculations of combined results and a random‐effects model was used in these cases. For the outcomes of delivery <37 and <34 weeks' gestation, overall sensitivity rates were 52% and 53%, and overall specificity rates were 85% and 89%, respectively. For the outcomes of delivery within 7, 14, and 21 days, we calculated sensitivity rates of 71%, 67%, and 59% and specificity rates of 89%, 89%, and 92%, respectively. For the subgroup of women with symptoms of preterm labour, sensitivity rates for delivery <37 and <34 weeks' gestation or delivery within 7, 14, and 21 days of 54%, 63%, 77%, 74%, and 70% and specificity rates of 85%, 86%, 87%, 87%, and 90% were calculated.

Conclusion
Cervicovaginal fetal fibronectin is an effective short‐term marker of preterm delivery, especially in women with symptoms of preterm labour. Because results appear to be heterogeneous in different studies, caution should be taken when they are applied to a specific population.
Infection in the prediction and antibiotics in the prevention of spontaneous preterm labour and preterm birth
Authors: Lamont Ronald F.
Published: December 2003

The association between infection and spontaneous preterm labour is now well established and thought to be responsible for preterm birth in up to 40% of cases. Preterm labour that is due to infection is refractory to the use of tocolytic agents. So the knowledge that infection may be the cause is unhelpful once a woman is admitted in spontaneous preterm labour, since by that time there may be irreversible changes in the uterine cervix, which renders futile those attempts to inhibit the process. It would be much more logical to use the association between infection and spontaneous preterm labour to identify a group of women at risk and to intervene using antibiotic prophylaxis. It is important to record, that the earlier in gestation at which abnormal genital tract colonisation is detected, the greater is the risk of an adverse outcome. For example, abnormal genital tract flora at 26–32 weeks gestation is associated with preterm birth with an odds ratio (OR) of 1.4 to 2, whereas abnormal genital tract flora at 7–16 weeks gestation carries an OR of 5 to 7.5. Intervention studies have used different antibiotics in different dosage regimes by different routes of administration to patients of differing risks at different gestational ages. Not surprisingly this has led to differing results. If intervention is to be successful, the antibiotics chosen should be active against bacterial vaginosis or bacterial vaginosis‐related organisms and should be used early in pregnancy in those women with the greatest degree of abnormal genital tract flora. While there is logic in using intravaginal antibiotics to deliver a heavy antibiotic load to the vagina where heavy abnormal colonisation exists, there is also logic in considering systemic antibiotics to eradicate those organisms, which have already gained access to the decidua. It may be that the greatest chance of benefit would exist if both routes of administration were combined. Yet no study has evaluated the combination of both intravaginal and systemic antibiotics to eradicate abnormal genital tract flora for the prevention of preterm birth.
Problems and challenges in the management of preterm labour
Authors: McNamara Helen M.
Published: December 2003

The main problem with preterm labour is our lack of progress in the successful management of this condition. We need to reassess our approach to this problem because preterm labour is not a disease, but an event, which may result from multiple independent pathways. This problem has also been affected significantly by medical advances such as infertility treatments and changes in neonatal survival at the limit of viability. The specific challenges that we face in managing preterm labour include: problems with definition; aetiology, including genetic and infection components; diagnostic problems, such as true versus false labour and role of cervical length and fetal fibronectin; and specific interventions according to the antepartum, intrapartum and postpartum challenges. In order to address the main issue, and make future progress in the management of preterm labour, we should consider the implementation of a ‘Postpartum Preterm Labour Diagnostic Workup Protocol’. These data/workup results could be entered on web‐based databases for each preterm labour ‘event’. An international research team could analyse data relating to specific aetiological patterns and subgroup analyses, leading to the collaborative development of ‘aetiology specific’ management modalities. This approach requires a close collaboration between clinicians and researchers, in order to make significant progress in this difficult area, and ultimately improve perinatal outcomes.
Method of delivery for the preterm infant
Authors: Lumley Judith
Published: December 2003

The principal issue concerning the mode of delivery is that while elective caesarean births may reduce the chances of fetal or neonatal death, this method of delivery might also increase maternal morbidity. Six trials with a total of 122 women investigated the effects of a policy of elective caesarean delivery (ECD) versus expectant management for small babies. A meta‐analysis of these six trials also included additional unpublished data from several of the authors. Babies in the ‘elective’ group were less likely to develop respiratory distress syndrome and were more likely to have a low pH after birth. They were also less likely to have neonatal seizures and there were fewer perinatal deaths, although the studies were too small to detect even very large differences. However, there was significantly more serious maternal morbidity. There is insufficient evidence to evaluate a policy of ECD. All trials described major problems in recruitment and no subsequent trials have been identified. Changes in population‐based data suggest that ECD of very preterm infants has increased markedly in the last 20 years. Given these changes, it seems unlikely that recruitment for future trials will be any easier than it was in the recent past.
The history of tocolysis
Authors: Keirse Marc J.N.C.
Published: December 2003

In 1950, the World Health Organisation (WHO) defined prematurity as a birthweight of 2500 g or less and in 1961 as a gestational age of less than 37 weeks. The time in between marks an era in which there was growing recognition of the importance of gestational age at birth and how to influence it. The latter was facilitated too by the development of tocography, which permitted some semi‐objective measurement of uterine contractility. Along with it, came a growing interest in agents that could control uterine contractility beyond the earlier classical approaches of hormones and gastrointestinal spasmolytics. Hence, the early 1960s saw much research interest in agents, such as nylidrine, isoxsuprine, and orciprenaline that could suppress uterine contractility as one of their many beta‐agonist properties. Subsequently, two approaches would be used to shift the balance towards uterine function over and above the influence on other bodily functions. One consisted of supplementing these drugs with agents, such as calcium antagonists and beta‐receptor blockers that were hoped to suppress non‐uterine actions. The other was a search for drugs in the same class with greater uterospecificity and more selective binding to uterine as opposed to other receptors. Neither of these approaches has ever fully fulfilled the hopes that were pinned on them, but they resulted in the availability of a large number of agents to suppress uterine contractility. The advent of prostaglandins as regulators of uterine contractility and the ability to suppress their biosynthesis saw another range of attempts to suppress uterine activity. They included aspirin, sodium salicylate, flufenamic acid, sulindac and indomethacin, but some were clearly based on a defective understanding of how uterine prostaglandin synthesis can be influenced. In the meantime, a flurry of other agents came and went, often more than once, testifying to the ingenuity of clinicians in trying to solve a problem that is poorly understood. Some, such as relaxin and ethanol, came and disappeared. Others, such as calcium antagonists, entered the scene as protectors against the non‐uterine effects of other agents, went, and re‐entered the scene in their own right. Still others, such as magnesium sulphate, came, lingered around, and became credited with effects in preterm labour that do not depend on affecting uterine contractility. Amidst this all arose the term tocolysis, coined in 1964 by Mosler from the Greek stems ‘τκζ’ and ‘λυɛιν’, to epitomise all of this ingenuity.
Role of cytokines and other inflammatory mediators
Authors: Winkler Matthias
Published: December 2003

In spite of impressive advances in biochemistry and molecular biology, it has not yet been possible to fit the individual biochemical components of cervical ripening and dilatation to a uniform clinical moiety or to uncover any regulatory mechanisms. The production of interleukin‐8 by activated fibroblasts and macrophages plays a key role in cervical ripening, since this cytokine induces chemotaxis, activation, and degranulation of neutrophilic granulocytes with the consequent release of various proteases, including collagenase. In addition, the extravasation of neutrophilic granulocytes is mediated—as in the early stage of an acute inflammatory reaction—by a brief increase in adhesiveness of vascular endothelium. This is known to be modulated by the cytokine‐induced increase in the expression of endothelial adhesion molecules. Furthermore, an increase in pro‐inflammatory cytokine and proteinase concentrations in preterm delivery seems to occur at earlier stages of cervical dilatation than in term delivery. It is also well known that in patients with chorioamnionitis, the levels of pro‐inflammatory cytokines are elevated in amniotic fluid, maternal serum, cervical secretion, placenta, and other compartments of the placento‐maternal unit, and are associated with preterm uterine contractions. We have demonstrated for the first time that cytokine concentrations in the lower uterine segment in patients with chorioamnionitis are strongly elevated. We conclude from our data that increased concentrations of pro‐inflammatory cytokines may also play a pivotal role in cervical softening and dilatation during chorioamniotic infection. Our data agree with the hypothesis of Liggins who stated nearly 20 years ago that cervical ripening may be an inflammatory reaction, which leads to increased prostaglandin synthesis, preterm labour and finally to preterm delivery.
Intrauterine infection and the development of cerebral palsy
Authors: Yoon Bo Hyun , Park Chan‐Wook , Chaiworapongsa Tinnakorn
Published: December 2003

Cerebral palsy is a serious motor disorder that appears in early life. The expectation that improved obstetrical and neonatal care would decrease the rate of this condition has not been realised. Recent evidence indicates that white matter brain lesions, often termed periventricular leukomalacia (PVL), are the most important identifiable risk factors for the development of cerebral palsy. The hypothesis under examination is that inflammatory cytokines released during the course of intrauterine infection play a central role in the genesis of preterm parturition, fetal PVL, and cerebral palsy. We examined the relationship between umbilical cord plasma concentrations of cytokines at birth and the occurrence of PVL in preterm gestation and demonstrated that umbilical cord plasma concentrations of interleukin (IL)‐6 was a significant independent predictor of PVL‐associated lesions. We also demonstrated that preterm neonates born to mothers with elevated amniotic fluid concentrations of pro‐inflammatory cytokines were at increased risk for the subsequent development of PVL and cerebral palsy. Histological chorioamnionitis and congenital neonatal infection‐related morbidity were more common in neonates with PVL than those without PVL in this study. We have also been able to induce PVL‐like brain white matter lesions in the fetal rabbit after experimental ascending intrauterine infection. In support of this hypothesis, we were able to demonstrate overexpression of tumour necrosis factor‐alpha and IL‐6 in histological sections of neonatal brains with PVL. Moreover, the presence of funisitis, a histological counterpart of the fetal inflammatory response syndrome, and elevated concentrations of amniotic fluid IL‐6 and IL‐8 were strong and independent risk factors for the subsequent development of cerebral palsy at the age of 3 years in our recent study. Therefore, clinical and experimental data provide strong support for the hypothesis. There are significant implications of our findings. First, cytokine determinations in amniotic fluid provide information about the risk of PVL and cerebral palsy before birth. Second, the process responsible for some cases of PVL and cerebral palsy begins during intrauterine life, implying that effective strategies for the prevention of cerebral palsy associated with PVL must begin in utero.
Massive perivillous fibrinoid causing recurrent placental failure
Authors: Bane A.L. , Gillan J.E.
Published: December 2003

Objective
To establish the incidence, recurrence rate and consequences of massive perivillous fibrinoid.

Design
Retrospective analysis of the histology of all placentas with a diagnosis of massive perivillous fibrinoid between 1991 and 1998, together with the maternal case records.

Setting
The histopathology department of the Rotunda Hospital, Dublin, Ireland.

Population
A relatively homogeneous group of pregnant women in the northern part of Dublin City, which is the catchment area for the Rotunda Hospital, delivered between 1991 and 1998.

Methods
Retrospective review of archival placental pathology and maternal charts.

Main outcome measures
The incidence of massive perivillous fibrinoid, perinatal outcome and recurrence rate.

Results
The incidence of massive perivillous fibrinoid was 0.028%, with a recurrence rate of approximately 18%. All the infants suffered intrauterine growth restriction; there was a 31% fetal loss rate and a 33% preterm delivery rate.

Conclusions
Massive perivillous fibrinoid is associated with intrauterine death, intrauterine growth restriction and preterm delivery. It has a significant recurrence rate and both the clinical findings of intrauterine growth restriction and the postmortem findings imply a syndrome of chronic placental insufficiency.
Magnetic resonance spectroscopy in pre‐eclampsia: evidence of cerebral ischaemia
Authors: Rutherford Jane M. , Moody Alan , Crawshaw Sarah , Rubin Peter C.
Published: December 2003

ObjectiveTo establish whether there are changes in the maternal brain in pre‐eclampsia detectable by magnetic resonance angiography and spectroscopy.

DesignA prospective, observational study.

SettingObstetric and Radiology Departments, Queen's Medical Centre, Nottingham.

SampleFourteen healthy, nulliparous non‐pregnant women, 9 healthy primiparous pregnant women and 10 women with pre‐eclampsia.

MethodsMagnetic resonance angiography and proton magnetic resonance spectroscopy of the brain was performed on each woman. Non‐pregnant women were each studied twice. Healthy pregnant women were studied three times during pregnancy and once postnatally. Subjects with pre‐eclampsia were studied once antenatally and twice postnatally. Magnetic resonance angiograms were examined for signs of vessel narrowing. On magnetic resonance spectroscopy, the ratios of the dominant peaks of the spectrum:N‐acetyl aspartate (NAA), choline, creatine and lactate were compared.

Main outcome measuresComparison of spectroscopic indices in non‐pregnant, normal pregnant and pre‐eclamptic women.

ResultsOn magnetic resonance angiography, there was no evidence of vessel narrowing in any of the three groups. NAA/choline ratio was higher at all stages of pregnancy compared with the non‐pregnant group (P< 0.05) associated with lower choline. NAA/choline increased gradually during healthy pregnancy associated with a decrease in choline. NAA/choline was significantly lower in the pre‐eclampsia group compared with the healthy pregnant women at similar gestation (P< 0.01), associated with higher choline. There were no differences between the groups postnatally. Lactate was not detected. These changes are similar to those found in patients with carotid stenosis without cerebral infarction.

ConclusionsNarrowing of vessels detectable on magnetic resonance angiography does not occur commonly in pre‐eclampsia. Magnetic resonance spectroscopy results suggest that there is relative cerebral ischaemia in pre‐eclampsia compared with healthy pregnancy.
Triple compartment prolapse: sacrocolpopexy with anterior and posterior mesh extensions
Authors: Marinkovic Serge Peter , Stanton Stuart L.
Published: December 2003

Post‐hysterectomy vault prolapse may be accompanied by anterior (cystocele) and posterior (rectocele) pelvic compartment prolapse. We describe our results with sacrocolpopexy with anterior and posterior polytetrafluoroethylene mesh (SCAPM) extensions. A prospective on‐going study is presented of 12 consecutive, complicated patients referred to our tertiary referral unit with a median age of 60 years (range 39–69) who underwent SCAPM between April 1997 and June 1999. All patients had a history and physical examination, International Continence Society Prolapse Staging (ICS) and pre‐operative multichannel urodynamics testing with their prolapse reduced. All patients had an ICS grade 2, triple compartment prolapse or worse for inclusion into this study. The operative results were assessed with a 10‐point visual analogue scale (VAS) for personal satisfaction and the (non‐validated) St George's Hospital symptom questionnaire assessing urgency, urge incontinence, stress incontinence, splinting, digitation, sexual activity and function. All patients were reviewed during February 2002 by an independent observer (B.G. gynaecologist) no longer associated with the Department of Urogynaecology. All patients were followed post‐operatively for a median of 39 months (range 32–58). One patient had a recurrent grade 1 cystocele and another a grade 1 rectocele. The median VAS score for personal satisfaction with the operative results was 8 (range 6–10). There was one patient with de novo urgency and one with de novo stress incontinence. Four of the five patients who needed to splint or digitate to empty the rectum no longer required these measures post‐operatively. There were no reports of de novo dyspareunia, and two patients had improved vaginal lubrication. Two patients, each with more than five prior vaginal procedures, had a total of three episodes of mesh erosion through the posterior vaginal wall. The SCAPM is an effective treatment for triple compartment prolapse and incomplete rectal emptying. Patient satisfaction is good.
Absence of Factor V Leiden, thrombomodulin and prothrombin gene variants in Black South African women with pre‐eclampsia and eclampsia
Authors: Hira B. , Pegoraro R.J. , Rom L. , Moodley J.
Published: December 2003

It has been suggested that gene aberrations may contribute to vascular endothelial dysfunction of pre‐eclampsia in Caucasian and Japanese women. This study was undertaken to examine the association between pre‐eclampsia in Black Zulu speaking South African women and the Factor 5 Leiden mutation. 100 patients with pre‐eclampsia comprised the study group. The control group comprised 110 normotensive pregnant women of the same population group. Genotyping was performed to detect the G or A allele at residue 506 of the Factor V gene, and the C or T allele at residue 455 of the thrombomodulin gene. Our findings demonstrate that these particularly genetic loci are of little use in disease association studies for pre‐eclampsia in homogenous Zulu speaking Africans.
Gene expression of nitric oxide synthase by human umbilical vein endothelial cells: the effect of fetal plasma from pregnancy with umbilical placental vascular disease
Authors: Wang Xin , Wang Jian , Trudinger Brian
Published: December 2003

Objective
To determine whether endothelial cell injury would be produced by factor(s) released into the fetal circulation, manifested by altered messenger RNA expression of nitric oxide synthase.

Design
Case–control study.

Setting
University teaching hospital.

Samples
Fetal plasma was collected from 34 normal pregnancies, 44 pregnancies with umbilical placental vascular disease identified by an abnormal umbilical Doppler and 11 pregnancies with maternal pre‐eclampsia but with normal umbilical Doppler studies.

Methods
Aliquots from a common culture of human umbilical vein endothelial cells (HUVECs) were incubated with fetal plasma from the members of the three patient groups. The total RNA was extracted from the endothelial cells and mRNA for nitric oxide synthase was measured by reverse transcription and semi‐quantitative polymerase chain reaction (RT‐PCR). This was standardised by comparison of the amplified inducible nitric oxide synthase (iNOS) or endothelial constitutive nitric oxide synthase (ecNOS) to glyceraldehyde 3‐phosphate dehydrogenase (GAPDH).

Main outcome measure
Endothelial cell gene expression of iNOS and ecNOS.

Results
The mRNA expression of iNOS and ecNOS were significantly higher (P < 0.05) in HUVECs stimulated by fetal plasma from pregnancies with umbilical placental vascular disease [iNOS 1.12 (0.16); ecNOS 1.78 (0.18)] when compared with normal pregnancies [iNOS 0.56 (0.06); ecNOS 1.06 (0.10)]. In the maternal pre‐eclampsia group, the NOS expression [iNOS 0.76 (0.11); ecNOS 1.39 (0.26)] did not differ from normal pregnancy. In the vascular disease group, there was no difference in NOS expression between the subgroups with and without maternal pre‐eclampsia.

Conclusions
Our study demonstrates that umbilical placental vascular disease is associated with a factor(s) in fetal plasma that produces an increase in the expression of iNOS and ecNOS mRNA by endothelial cells. Our findings raise the possibility that the release of factors causing an up‐regulation of iNOS and ecNOS in the endothelium in the fetal placenta may occur as part of an inflammatory response of the vascular endothelium to injury.
Cohort study of operative delivery in the second stage of labour and standard of obstetric care
Authors: Murphy Deirdre J. , Liebling Rachel E. , Patel Roshni , Verity Lisa , Swingler Rebecca
Published: December 2003

Objective
To assess the maternal and neonatal morbidity following operative delivery in the second stage of labour in relation to the standard of obstetric care.

Design
Cohort study.

Setting
Maternity units in two teaching hospitals in Bristol, United Kingdom.

Population
Three hundred and ninety‐three women with term, singleton, cephalic pregnancies who required operative delivery in theatre at full dilatation between February 1999 and February 2000.

Methods
Morbidity was compared for completed instrumental delivery, failed instrumental delivery and immediate caesarean section in relation to duration of second stage of labour, number of pulls at attempted instrumental delivery, number of instruments used and operator experience.

Main outcome measures
Maternal trauma, admission to special care baby unit, neonatal trauma.

Results
Failed instrumental delivery after a long second stage of labour was associated with increased maternal trauma (adjusted odds ratios [OR] 4.1, 95% confidence interval [CI] 1.1, 16.5). More than three pulls at attempted instrumental delivery was associated with increased neonatal trauma for completed (adjusted OR 4.2, 95% CI 1.6, 9.5) and failed deliveries (adjusted OR 7.2, 95% CI 2.1, 24.0). Babies delivered after failed instrumental delivery with more than three pulls were at increased risk of admission to special care baby unit (adjusted OR 6.2, 95% CI 1.6, 22.8) The use of multiple instruments was associated with increased neonatal trauma (adjusted OR 3.1, 95% CI 1.5, 6.8; adjusted OR 4.4, 95% CI 1.3, 14.4, for completed and failed deliveries, respectively). Excessive pulls and multiple instrument use were associated with an initial attempt at vaginal delivery by an inexperienced operator, 25/48 (52%) and 34/75 (45%).

Conclusion
Guidelines for safe operative delivery in the second stage of labour should be developed and adhered to in order to reduce morbidity, particularly neonatal trauma.
The prognostic significance of HPV‐16 genome status of the lymph nodes, the integration status and p53 genotype in HPV‐16 positive cervical cancer: a long term follow up
Authors: Hernádi Zoltán , Szarka Krisztina , Sápy Tamás , Krasznai Zoárd , Veress György , Póka Róbert
Published: December 2003

Objective
Prognostic evaluation of HPV‐16 genome status of the pelvic lymph nodes, the integration status of HPV‐16 and p53 codon 72 polymorphism in cervical cancer.

Design
Prospective cohort study.

Setting
Department of Gynaecological Oncology, University of Debrecen, Hungary.

Sample
Thirty‐nine patients with HPV‐16 positive cervical cancer.

Methods
Primary tumour specimens of 39 cervical cancer patients with HPV‐16 positive primary tumour were subjected to multiplex polymerase chain reaction using HPV‐16 E1/E2, E7 and p53 codon 72 allele‐specific primers. Pelvic lymph nodes of the same patients were also tested for the presence of HPV‐16 DNA and for its integration status using HPV‐16 E7 and E1/E2 ORF specific primers, respectively.

Main outcome measures
Progression‐free survival.

Results
Metastatic lymph nodes carried HPV‐16 DNA more frequently than nodes with no evidence of disease (100.0% vs 35.7%, P= 0.001). Cases with HPV‐16 positive nodes had higher recurrence rate than those with HPV‐16 negative nodes (42.9% vs 11.1%, P= 0.009). There was no difference between cases with and without histologically proven nodal disease with regard to integration status of HPV‐16 DNA in the primary tumour (integrated 90.9% vs 71.4%, episomal 9.1% vs 21.4%, mixed 0% vs 7.1%) and p53 codon 72 polymorphism (Arg/Arg 54.5% vs 67.9%, Pro/Pro 0 vs 7.1%, Arg/Pro 45.5% vs 21.4%).

Conclusion
Regardless of the presence of nodal metastasis, HPV‐16 status of the nodes is a significant predictor of recurrent disease. HPV‐16 integration status and p53 codon 72 genotype do not seem to have a bearing on disease outcome in cervical cancer with HPV‐16 positive primary.
Serum profile of isosorbide mononitrate after vaginal administration in the third trimester
Authors: Bates Catharine D. , Nicoll Antony E. , Mullen Alexander B. , Mackenzie Fiona , Thomson Andrew J. , Norman Jane E.
Published: December 2003

Vaginally administered nitric oxide donors such as isosorbide mononitrate have been used to ripen the uterine cervix in pregnancy. The pharmacokinetics of isosorbide mononitrate following vaginal administration are unknown. Serum levels of isosorbide mononitrate were determined at baseline and 60, 180 and 360 minutes after vaginal administration of 20 or 40 mg isosorbide mononitrate to pregnant women scheduled for induction of labour at term. Serum levels of isosorbide mononitrate continued to rise up to 360 minutes after isosorbide mononitrate insertion, with mean (SD) final levels of 337 (94) μg/L following isosorbide mononitrate 40 mg and 144 (47) μg/L following isosorbide mononitrate 20 mg, P < 0.01.
Virtual reality laparoscopic simulator for assessment in gynaecology
Authors: Gor Mounna , McCloy Rory , Stone Robert , Smith Anthony
Published: December 2003

A validated virtual reality laparoscopic simulator minimally invasive surgical trainer (MIST) 2 was used to assess the psychomotor skills of 21 gynaecologists (2 consultants, 8 registrars and 11 senior house officers). Nine gynaecologists failed to complete the VR tasks at the first attempt and were excluded for sequential evaluation. Each of the remaining 12 gynaecologists were tested on MIST 2 on four occasions within four weeks. The MIST 2 simulator provided quantitative data on time to complete tasks, errors, economy of movement and economy of diathermy use—for both right and left hand performance. The results show a significant early learning curve for the majority of tasks which plateaued by the third session. This suggests a high quality surgeon–computer interface. MIST 2 provides objective assessment of laparoscopic skills in gynaecologists.
No recurrence of mature ovarian teratomas after laparoscopic cystectomy
Authors: Mais Valerio , Ajossa Silvia , Mallarini Giorgio , Guerriero Stefano , Oggiano Marco P. , Melis Gian B.
Published: December 2003

Recurrence of ovarian teratomas was evaluated in a randomised trial to determine whether laparoscopic cystectomy had the same efficacy as laparotomy. Forty premenopausal non‐pregnant women with a unilateral teratoma no larger than 10 cm were randomised to laparoscopy or laparotomy. Post‐operative pain, duration of stay in hospital and duration of convalescence were compared. Women were reviewed every six months for five years. A higher proportion had milder pain, faster hospital discharge and faster recovery following laparoscopy than laparotomy. There were no recurrences of teratomas in both arms of the study, suggesting that laparoscopy has the same efficacy as laparotomy.
Laparoscopic colposuspension: a systematic review
Authors: Moehrer Birgit , Carey Marcus , Wilson Don
Published: December 2003

Objective
To determine the effectiveness of laparoscopic colposuspension for the treatment of stress urinary incontinence.

Design
Systematic review.

Setting
Teaching hospitals.

Population
Women with symptoms or urodynamic diagnosis of stress, urge or mixed incontinence.

Methods
Randomised and ‘quasi‐randomised trials’ in women with symptoms or urodynamic diagnoses of stress, urge or mixed incontinence including laparoscopic surgery in at least one arm of the trial were identified from the Cochrane Incontinence Review Group's Specialised Register of Controlled Trials.

Main outcome measures
Subjective cure, objective cure, quality of life measurements and surgical outcome measures.

Results
Eight trials met the inclusion criteria. Five trials compared laparoscopic (n= 233) with open (n= 254) colposuspension. Risk of a positive stress test at follow up was significantly less in the open group (relative risk [RR] 0.89, 95% confidence interval [CI] 0.82 to 0.98). When one poor quality trial was excluded from the analysis, the relative risk was still less in the open group, but was no longer significant (RR 0.91, 95% CI 0.82 to 1.01). If considered as risk difference there is a 9% significantly higher risk of failure for laparoscopic colposuspension, however, excluding one poor quality trial, this risk of failure is non‐significant at 8%. Analysis of subjective cure showed no difference between the groups. A trend was shown towards a higher complication rate, less post‐operative pain, shorter hospital stay and time to return to normal function for laparoscopic compared with open colposuspension. Three trials compared different methods of laparoscopic colposuspension. Data from these trials could not be combined in view of the differences in the trials. Based on a single trial, two sutures were better than one. Sutures were as effective as mesh/staples. No conclusion could be drawn about the benefits of transperitoneal or extraperitoneal access.

Conclusions
It is difficult to make valid conclusions as the evidence is limited by short term follow up and small numbers of trials and participants. However, it is possible that no difference exists between laparoscopic and open colposuspension for either objective or subjective cure. Further, well designed and adequately powered randomised controlled trials are required.
Perinatal mortality: clinical value of postmortem magnetic resonance imaging compared with autopsy in routine obstetric practice
Authors: Alderliesten Marianne E. , Peringa Jan , van der Hulst Victor P.M. , Blaauwgeers Hans L.G. , van Lith Jan M.M.
Published: December 2003

Objective
To compare postmortem magnetic resonance imaging (MRI) with autopsy in perinatal deaths. To determine the acceptance and feasibility of postmortem perinatal MRI.

Design
Cohort study.

Setting
Large teaching hospital.

Population
Fetuses and neonates from 16 weeks gestational age until 28 days after birth, stillbirths as well as intrapartum and neonatal deaths.

Methods
MRI was performed prior to autopsy in a consecutive cohort of perinatal deaths after full parental consent. Agreement between MRI and autopsy was calculated. The consent rate for both examinations was recorded separately, as well as the time between the perinatal death and the MRI.

Main outcome measure
Full agreement between MRI and autopsy.

Results
Of 58 cases, 26 parents consented to both examinations (45%). Autopsy showed 18 major malformations, of which 10 were detected with MRI. The positive predictive value of MRI was 80% (4/5) and the negative predictive value was 65% (13/20). Additional consent for MRI was given in eight cases (14%). In 84%, the MRI could be performed within 48 hours.

Conclusions
MRI is of value if autopsy is refused, but diagnostic accuracy is insufficient to recommend substitution of full autopsy. The acceptance rate of MRI only is better than that of autopsy.
Maternal complications following amniocentesis and chorionic villus sampling for prenatal karyotyping
Authors: Cederholm Maria , Haglund Bengt , Axelsson Ove
Published: December 2003

Objective
To investigate whether amniocentesis and chorionic villus sampling increase the risk of bleeding, placental abruption, complications related to amniotic cavity and membranes, abnormal labour, operative deliveries and to investigate the impact of gestational length at the time of the procedure.

Design
A population‐based cohort study.

Setting
Sweden, 1991–1996.

Population
All women, 35 to 49 years old, with single births (N= 71,586). The women were classified as exposed to amniocentesis (N= 21,748) or chorionic villus sampling (n= 1984) or not exposed (N= 47,854).

Methods
Maternal outcomes were collected from the Swedish Medical Birth Register and the Swedish Hospital Discharge Register. With Logistic regression analyses odds ratios were calculated.

Main outcome measures
Crude and adjusted odds ratios of bleeding, complications related to amniotic cavity and membranes, abnormal labour and operative deliveries. Women exposed to amniocentesis or chorionic villus sampling were compared with women non‐exposed.

Results
Neither amniocentesis nor chorionic villus sampling was associated with severe pregnancy complications such as placental abruption or placenta praevia. Women in the amniocentesis group had a lower chance of normal delivery (OR = 0.93, 95% CI 0.90–0.97), an increased risk of complications related to amniotic cavity and membranes (OR = 1.15, 95% CI 1.06–1.24) and hypotonic uterine dysfunction (OR = 1.12, 95% CI 1.06–1.18). The risks were higher for amniocentesis before 15 weeks of gestation. Women in the amniocentesis group were more often delivered by forceps or vacuum extractions (OR = 1.11, 95% CI 1.03–1.19) and elective caesarean sections (OR = 1.09, 95% CI 1.02–1.16). For the chorionic villus sampling group, no significant associations were found.

Conclusions
Among women aged 35–49 years, amniocentesis is not associated with important adverse outcomes such as abruption or placenta praevia. Minor associations were found for other maternal complications when amniocentesis was performed before 15 weeks of gestation. Improved methods to identify women with increased risk of chromosomally abnormal pregnancies might minimise the number of women exposed to invasive procedures.
Aspirin (100 mg) used for prevention of pre‐eclampsia in nulliparous women: the Essai Régional Aspirine Mère–Enfant study (Part 1)
Authors: Subtil Damien , Goeusse Patrice , Puech Francis , Lequien Pierre , Biausque Serge , Breart Gérard , Uzan Serge , Marquis Pierre , Parmentier Dominique , Churlet Alain ,   Essai Régional Aspirine Mère–Enfant (ERASME) Collaborative Group,   Collaborators and participating centres are listed at the end of the report
Published: December 2003

Objective
To reduce the incidence of pre‐eclampsia in nulliparous women, in accordance with the suggestion of a recent meta‐analysis that low dose aspirin might decrease this incidence by more than half if used early enough in and at a sufficient dose during pregnancy (more than 75 mg).

Design
Multicentre randomised double‐blinded placebo‐controlled trial.

Setting
Twenty eight centres in Northern of France and one in Belgium.

Population
Three thousand and two hundred ninety‐four nulliparous women recruited between 14 and 20 weeks.

Methods
Randomisation to either 100 mg aspirin or placebo daily from inclusion through 34 weeks.

Main outcome measures
Preeclampsia was defined as hypertension (≥140 and or 90 mmHg) associated with proteinuria (≥0.5 g/L).

Results
The aspirin (n= 1644) and placebo (n= 1650) groups did not differ significantly in the mothers' incidence of pre‐eclampsia (28 of 1632 [1.7%] vs 26 of 1637 [1.6%]; relative risk, RR, 1.08, 95% CI 0.64–1.83), hypertension, HELLP syndrome or placental abruption, or in the children's incidence of perinatal deaths or birthweight below the 10th centile. The incidence of babies with birthweight below the third centile was significantly higher in the aspirin group, with no explanation. The incidence of maternal side effects was higher in the aspirin group, principally because of a significantly higher rate of haemorrhage.

Conclusions
Aspirin at a dose of 100 mg does not reduce the incidence of pre‐eclampsia in nulliparous women. Aspirin (100 mg) is associated with an increase in bleeding complications.
Postnatal morbidity after childbirth and severe obstetric morbidity
Authors: Waterstone Mark , Wolfe Charles , Hooper Richard , Bewley Susan
Published: December 2003

Objective
To identify the impact of pregnancy and childbirth, and severe obstetric morbidity on outcome 6 to 12 months postpartum.

Design
Questionnaire assessment of postnatal outcome in a cohort study.

Setting
South East Thames, UK.

Population
All women resident in South East Thames and delivering between 1st March 1997 and 28th February 1998.

Methods
Questionnaire study of a cohort of women who experienced a severe obstetric morbidity during pregnancy or labour (cases), compared with a cohort of women who did not (controls).

Main outcome measures
Assessment of postnatal depression risk [Edinburgh Postnatal Depression Scale (EPDS)], general health [Short Form 36 (SF‐36)], sexual activity and use of health services between 6 and 12 months postpartum.

Results
There were 331 cases and 1339 controls out of 48,262 deliveries. Six to 12 months after delivery, 77 (23.3%) of cases and 272 (20.5%) of the controls were at risk of postnatal depression (P= 0.25; 95% CI for difference −2.2% to 7.9%), 43.1% of cases were having problems with sexual relations compared with 18.7% of controls (P < 0.001; 95% CI for difference 8.9% to 21.9%). There was evidence of poorer general health in cases. Some 31.5% of cases attended outpatients in the first six months and 9.4% required emergency admission to hospital compared with 17.0% (P < 0.001; 95% CI for difference 9.1% to 19.9%) and 3.7% (P < 0.001; 95% CI for difference 2.4% to 9.0%), respectively, in controls.

Conclusion
Both control pregnancy and childbirth and severe obstetric morbidity are associated with significant postnatal morbidity. A severe obstetric morbid event significantly influences women's sexual health and wellbeing and increases health services utilisation. Prevention and appropriate management of severe obstetric morbid events may reduce these outcomes.
Changes in nuchal translucency thickness in normal and abnormal karyotype fetuses
Authors: Zoppi Maria A. , Ibba Rosa M. , Floris Marcella , Manca Fabiola , Axiana Carolina , Monni Giovanni
Published: December 2003

Objective
To investigate the dynamic trend of the nuchal translucency thickness between fetuses with normal and abnormal karyotype.

Design
Prospective observational study.

Setting
Ospedale Microcitemico, Cagliari, Italy.

Population
A cohort of 305 first trimester fetuses.

Methods
Fetuses with a nuchal translucency greater than or equal to the 95th centile were invited for a second nuchal translucency measurement. The finding of an ‘increased or unchanged’ or ‘diminished’ thickness was compared in fetuses with normal and abnormal karyotype.

Main outcome measures
Nuchal translucency and karyotype.

Results
Median maternal age was 35 years (min 17, max 44) and median crown–rump length at first visit was 50 mm (min 38, max 80). A second nuchal translucency measurement was carried out in 292 fetuses, resulting in increased or unchanged values in 95 cases and decreased nuchal translucency in 197 cases. Two hundred and twenty‐six (77.4%) fetuses had normal karyotype and 66 (22.6%) had abnormal karyotype (44 trisomies 21, 10 trisomies 18, 5 trisomies 13, 4 cases of 45 X0, 1 case of 47,XXY, 1 case of 47,XXX and 1 translocation). In the 66 chromosomally abnormal fetuses, the second nuchal translucency measurement was enlarged or unchanged in 37 (56%), and diminished in 29 (44%), while in the 226 normal fetuses the second nuchal translucency measurement was enlarged or unchanged in 58 cases (25%) and diminished in 168 (75%) (relative risk 2.6, 95% confidence interval 1.7–4.0).

Conclusion
In fetuses with abnormal karyotype, the second nuchal translucency measurement tends to be increased or unchanged, while in normal cases the size of nuchal translucency is generally reduced.
Maternal serum activin A levels in association with intrauterine fetal growth restriction
Authors: Wallace Euan M. , Schneider‐Kolsky Michal E. , Edwards Andrew , Baker Lesleigh , Jenkin Graham
Published: December 2003

Objective
To assess maternal serum activin A as a potential marker of fetal growth restriction.

Design
A cohort study.

Setting
A maternal–fetal medicine unit, university teaching hospital.

Population
Fifty‐seven women with a small fetus (less than 10th centile for gestation) referred for assessment of fetal size by ultrasound biometry.

Methods
At the time of presentation for fetal biometry, maternal blood was collected for activin A measurement. The case records of each woman were independently reviewed after delivery and the pregnancy grouped into one of three groups: constitutionally small fetus, intrauterine growth restricted (IUGR) fetus or IUGR fetus and maternal pre‐eclampsia (IUGR–pre‐eclampsia). Activin A levels in the three groups were compared.

Main outcome measures
Maternal serum activin A levels.

Results
Sixteen of the 57 pregnancies were classified as constitutionally small, 17 as IUGR and 24 as IUGR–pre‐eclampsia. Expressed as multiples of a normal median (MoMs), the median (95% CI) activin A level in the constitutionally small pregnancies was 1.12 (0.72–1.39) MoMs significantly lower than the level in both the IUGR pregnancies, 3.00 (1.84–4.11) MoMs, and the IUGR–pre‐eclampsia pregnancies, 7.96 (5.73–10.62) MoMs (P= 0.002 and 0.0001 for IUGR vs constitutionally small and IUGR–pre‐eclampsia vs constitutionally small, respectively).

Conclusions
Maternal serum activin A may be useful in the assessment of the small for gestational age fetus.
Early invasive cervical adenocarcinoma: its potential for nodal metastasis or recurrence
Authors: Hirai Yasuo , Takeshima Nobuhiro , Tate Shinichi , Akiyama Futoshi , Furuta Reiko , Hasumi Katsuhiko
Published: December 2003

Objective
To investigate the potential for nodal spread or recurrence in patients with early invasive cervical adenocarcinoma. The possible application of the International Federation of Gynecology and Obstetrics (FIGO) classification (1994) to this variant was also examined.

Design
Retrospective observational study.

Setting
Gynaecological oncology division of Cancer Institute Hospital, Japan.

Population
302 patients with FIGO Stage 0‐IIB cervical adenocarcinoma treated surgically at the Cancer Institute Hospital.

Methods
Clinicopathological analysis was performed on 47 patients with early invasive cervical adenocarcinoma in whom the depth of stromal invasion was 5 mm or less. All patients underwent radical hysterectomy and pelvic lymphadenectomy.

Results
In 30 patients with a depth of tumour invasion of 3 mm or less, no lymph node metastasis was found, while two patients developed recurrence; one had a depth of invasion of 3 mm and a horizontal tumour spread of 3 mm, and the other had horizontal spread of more than 7 mm. In 17 patients with a depth of invasion from 3 to 5 mm, there was also no lymph node metastasis, but two patients developed recurrence; one had horizontal tumour spread of 7 mm or less, and the other had horizontal spread of more than 7 mm.

Conclusion
Early invasive cervical adenocarcinoma with a depth of invasion of 3 mm or less and a horizontal spread of 7 mm or less has little potential for nodal metastasis or recurrence. It seems possible that the FIGO definition (1994) of early cervical cancer may be applicable in its present form to early cervical adenocarcinoma.
Psychiatric morbidity following endometrial ablation and its association with genuine menorrhagia
Authors: Wright Barry , Gannon Michael J. , Greenberg Maurice , House Allan , Rutherford Tony
Published: December 2003

Objective
To explore the relation between pre‐operative psychiatric morbidity, menstrual blood loss and psychiatric outcome in women receiving endometrial ablation for heavy periods.

Design
A prospective cohort study.

Setting
The menorrhagia clinic at Leeds General Infirmary.

Population
One hundred and twenty consecutive women referred to the Clinic for endometrial ablation.

Methods
Psychiatric interview and actual menstrual blood loss measurements at presentation pre‐operatively and one year post endometrial ablation.

Main outcome measure
Psychiatric status using the semi‐structured interview, Present State Examination, with measurement of menstrual blood loss.

Results
Endometrial ablation was performed on 92 women. Of the 87 women evaluated 51 (59%) had clinically significant psychiatric symptoms, mainly depression and anxiety. Psychiatric morbidity fell to 21.8% at one year after endometrial ablation. Women with the best psychiatric outcome (6% post‐operative psychiatric morbidity) were those with genuine menorrhagia (≥80 mL) and low psychiatric morbidity pre‐operatively. Those who fared worst (39% post‐operative psychiatric morbidity) were women with high pre‐operative psychiatric morbidity and low menstrual blood loss. Of seven women with very low losses [mean 19 mL (SD 17)] who did not proceed to surgery after counselling, six (86%) had significant psychiatric morbidity.

Conclusions
Pre‐operative psychiatric status and menstrual blood loss are predictors of outcome of surgery for women with reported heavy periods.