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Background: Intensive care unit (ICU) outcome prediction models, such as Acute Physiology And Chronic Health Evaluation (APACHE), were designed in general critical care populations and their use in obstetric populations is contentious. The aim of the CIPHER (Collaborative Integrated Pregnancy High-dependency Estimate of Risk) study was to develop and internally validate a multivariable prognostic model calibrated specifically for pregnant or recently delivered women admitted for critical care., Methods: A retrospective observational cohort was created for this study from 13 tertiary facilities across five high-income and six low- or middle-income countries. Women admitted to an ICU for more than 24 h during pregnancy or less than 6 weeks post-partum from 2000 to 2012 were included in the cohort. A composite primary outcome was defined as maternal death or need for organ support for more than 7 days or acute life-saving intervention. Model development involved selection of candidate predictor variables based on prior evidence of effect, availability across study sites, and use of LASSO (Least Absolute Shrinkage and Selection Operator) model building after multiple imputation using chained equations to address missing data for variable selection. The final model was estimated using multivariable logistic regression. Internal validation was completed using bootstrapping to correct for optimism in model performance measures of discrimination and calibration., Results: Overall, 127 out of 769 (16.5%) women experienced an adverse outcome. Predictors included in the final CIPHER model were maternal age, surgery in the preceding 24 h, systolic blood pressure, Glasgow Coma Scale score, serum sodium, serum potassium, activated partial thromboplastin time, arterial blood gas (ABG) pH, serum creatinine, and serum bilirubin. After internal validation, the model maintained excellent discrimination (area under the curve of the receiver operating characteristic (AUROC) 0.82, 95% confidence interval (CI) 0.81 to 0.84) and good calibration (slope of 0.92, 95% CI 0.91 to 0.92 and intercept of -0.11, 95% CI -0.13 to -0.08)., Conclusions: The CIPHER model has the potential to be a pragmatic risk prediction tool. CIPHER can identify critically ill pregnant women at highest risk for adverse outcomes, inform counseling of patients about risk, and facilitate bench-marking of outcomes between centers by adjusting for baseline risk.

Introduction and Hypothesis: Shoulder dystocia is an obstetric emergency that occurs in 0.2-3% of all cephalic vaginal deliveries. We hypothesized that because of the difficult nature of deliveries complicated by shoulder dystocia, the condition may be associated with anal sphincter injury. We sought to identify risk factors for obstetric anal sphincter injury in women with shoulder dystocia., Methods: This retrospective analysis included all cases of shoulder dystocia from 2007 to 2011 at two large tertiary referral centers, in the USA and Ireland. Details of maternal demographics, intrapartum characteristics, and delivery outcomes in cases of shoulder dystocia were analyzed. Univariate and multivariate analyses were used to describe the association between shoulder dystocia and anal sphincter injury., Results: There were 685 cases of shoulder dystocia, and the rate of shoulder dystocia was similar at both institutions. The incidence of anal sphincter injury was 8.8% (60 out of 685). The rate was 14% (45 out of 324) in nulliparas and 4.2% (15 out of 361) in multiparas. Women with sphincter injury were more likely to be nulliparous (75% [45 out of 60] vs 45% [279 out of 625]; p < 0.0001), have had an operative vaginal delivery (50% [30 out of 60] vs 36% [226 out of 625]; p = 0.03) and require internal maneuvers (50% [30 out of 60] vs 32% [198 out of 625], p = 0.004) than those with an intact sphincter. On multivariate regression analysis, these predictors of sphincter injury remained significant when adjusted for other risk factors. Episiotomy was negatively associated with sphincter injury on multivariate regression analysis., Conclusions: In a retrospective cohort of 685 women with shoulder dystocia, the risk of anal sphincter injury is 9%. Risk factors include nulliparity, operative vaginal delivery, and use of internal maneuvers, whereas episiotomy was found to have a protective effect against anal sphincter injury during cases of shoulder dystocia.

Iodine deficiency is known to result in deficits in neuropsychological development in children born to iodine deficient mothers. However, a remedy in terms of iodisation of table salt as is the norm in most countries, has not been embraced by Ireland. The borderline iodine status of the Irish population persists unchanged over the past 20 years with the annual median urinary iodine (UI) varying from 62.9 to 105 μg/L; overall median 72.4 μg/L (WHO recommended 100 μg/L). Exposure to a seaweed rich environment allowing for intake by respiration of seaweed derived gaseous iodine, rather than simple proximity to the sea, confers advantages in terms of iodine intake with 21/46 (45.6%) of schoolchildren in seaweed rich coastal areas having UI values > 150 μg/L compared to 1/28 (3.6 %) and 2/93 (2.2%) in low seaweed abundant coastal and inland areas respectively. The corresponding values for adult females were 31/72 (43%), 7/60 (11.6%) and 21/132 (16.0%). The findings support introduction of iodine prophylaxis through Universal Salt Iodisation (USI), to ensure that women of child bearing age have access to sufficient dietary iodine.

Objective: To assess continence and anal sphincter integrity during a subsequent pregnancy and delivery in women known to have a previous anal sphincter injury., Design: Prospective observational study., Setting: The National Maternity Hospital, Dublin, Ireland., Population: Antenatal patients with a documented obstetric anal sphincter injury at a previous delivery., Methods: Women underwent symptom scoring, endoanal ultrasound and manometry., Main Outcome Measures: Recommended and actual mode of delivery, continence scores and endoanal ultrasound findings after index delivery., Results: 557 women were studied. 293 (53%) had no symptoms of faecal incontinence, 189 (34%) had mild symptoms and 75 (13%) moderate or severe symptoms. 408 (73%) had an endoanal ultrasound. 383(94%) had a normal or small (<1 quadrant) defect in the internal anal sphincter and 390 (96%) had a scar or small (<1e quadrant) defect in the external anal sphincter. 393 (70%) delivered vaginally. 164 (30%) were delivered by caesarean section. 197/557 (35%) returned for follow-up. There was no significant change in continence following either vaginal or caesarean delivery. 20 (5.1%) women had a recognised second anal sphincter tear during vaginal delivery., Conclusions: The majority of women who sustain a third degree tear have minimal or no symptoms of faecal incontinence when assessed antenatally in a subsequent pregnancy. 70% go on to have a vaginal delivery, with little impact on faecal continence. These findings provide reassurance for patients and clinicians about the safety of vaginal delivery following anal sphincter injury in appropriately selected patients., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: We sought to assess amniotic fluid lactate (AFL) at diagnosis of spontaneous labor at term (≥37 weeks) as a predictor of labor disorders (dystocia) and cesarean delivery (CD)., Study Design: This was a single-institution, prospective cohort study of 905 singleton, cephalic, term (≥37 weeks) nulliparous women in spontaneous labor. A standard management of labor (active management of labor) including a standard oxytocin regimen up to a maximum dose of 30 mU/min was applied. AFL was measured using a point-of-care device (LMU061; ObsteCare, Stockholm, Sweden). Labor arrest in the first stage of labor was defined as the need for oxytocin when cervical dilatation was <1 cm/h over 2 hours and in the second stage of labor by poor descent and rotation over 1 hour. Standard statistical analysis included analysis of variance, Pearson correlations, and binary logistic regression. Unsupervised decision tree analysis with 10-fold cross-validation was used to identify AFL thresholds., Results: AFL was normally distributed and did not correlate with age, body mass index, or gestation. Unsupervised decision tree analysis demonstrated that AFL could be divided into 3 groups: 0-4.9 mmol/L (n = 118), 5.0-9.9 mmol/L (n = 707), and ≥10.0 mmol/L (n = 80). Increasing AFL was associated with higher total oxytocin dose (P = .001), labor disorders (P = .005), and CD (P ≤ .001). Multivariable regression analysis demonstrated that women with AFL ≥5.0-9.9 mmol/L (odds ratio [OR], 1.6; 95% confidence interval [CI], 1.06-2.39) and AFL ≥10.0 mmol/L (OR, 1.72; 95% CI, 1.01-2.93) were independent predictors of a labor disorder. AFL ≥5.0-9.9 mmol/L did not predict CD but multivariable analysis confirmed that AFL ≥10.0 mmol/L was an independent predictor of CD (OR, 3.35; 95% CI, 1.73-6.46). AFL ≥5.0-9.9 mmol/L had a sensitivity of 89% in predicting a labor disorder and a sensitivity of 93% in predicting CD with a 97% negative predictive value. AFL ≥10.0 mmol/L was highly specific but lacked sensitivity for CD. There was no difference in birthweight of infants according to labor disorder and delivery method., Conclusion: AFL at diagnosis of labor in spontaneously laboring single cephalic nulliparous term women is an independent predictor of a labor disorder and CD. These data suggest that women with AFL between 5.0-9.9 mmol/L with a labor disorder may be amenable to correction using the active management of labor protocol., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Umbilical cord prolapse is an acute obstetrical emergency requiring rapid identification and intervention. Its management has undergone significant changes over the past century. This study aims to document the changes in incidence, morbidity, and perinatal mortality over a 69-year period., Design: A retrospective review of the annual clinical reports of the National Maternity Hospital, Dublin, Ireland, was performed., Setting: The National Maternity hospital was founded in 1894 and has nearly 10,000 deliveries each year., Population: All deliveries in the hospital for each year are included in each annual report., Methods: We reviewed the reports from a 69-year period (1940-2009). Information from the reports was collated into a database and analysed using Microsoft excel 2007., Main Outcome Measures: Incidence and outcome of all cases of umbilical cord prolapse were recorded, along with the neurological outcome of all neonatal survivors (available since 1970)., Results: The incidence of cord prolapse has decreased from 6.4/1000 live births in the 1940s to 1.7/1000 [corrected] live births in the last decade. Perinatal survival increased from 46 to 94% in the same period of time. This is inversely related to the use of caesarean section as the recommended method of delivery in this emergency. Short- and long-term neurological impairment remains rare., Conclusions: There has been a large reduction in the incidence of cord prolapse over a period of 69 years. A reduction in grand multiparity and use of caesarean section as the gold standard for delivery are likely to have accounted for the changes seen. Neurological impairment remains unusual., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Objective: To examine the incidence of obstetric anal sphincter injury in women who had a successful vaginal birth after a previous caesarean delivery (VBAC)., Design: Retrospective analysis of prospectively gathered data., Setting: A tertiary referral university institution., Population: All secundiparous women with a previous caesarean delivery who had a VBAC from 2001 to 2011., Methods: Details of maternal demographics, intrapartum characteristics and outcomes were examined in cases of VBAC with accompanying anal sphincter injury., Main Outcome Measures: Rates of obstetric anal sphincter injury and associated risk factors., Results: During the study period there were 3071 trials of labour in secundiparous women with a previous caesarean delivery; 65% (1981/3071) of these had a successful VBAC. Women having a VBAC were at greater risk of anal sphincter injury than nulliparous women having a vaginal delivery over the same period (5% [98/1981] versus 3.5% [1216/34,496], P = 0.001, odds ratio 1.4, 95% CI 1.15-1.75). The rate of instrumental delivery in woman having a VBAC was 39% (771/1981). On multiple logistic regression analysis an increased rate of instrumental delivery was a strong predictor of sphincter injury (P = 0.03, odds ratio 1.15, 95% CI 1.01-1.3). When the first labours of women with sphincter injury in the VBAC group were examined, 70% (60/86) had been in labour before undergoing their caesarean delivery., Conclusion: The incidence of anal sphincter injury in women undergoing VBAC is 5% and birthweight is the strongest predictor of this. The rate of instrumental delivery in this group was also increased., (© 2014 Royal College of Obstetricians and Gynaecologists.)

Background: Maintenance of adequate iodide supply to the developing fetus is dependent not only on maternal dietary iodine intake but also on placental iodide transport. The objective of this study was to examine the effects of different pregnancy-associated hormones on the uptake of radioiodide by the placenta and to determine if iodide transporter expression is affected by hormone incubation., Methods: Primary cultures of placental trophoblast cells were established from placentas obtained at term from pre-labor caesarean sections. They were pre-incubated with 17β-estradiol, prolactin, oxytocin, human chorionic gonadotropin (hCG) and progesterone either singly or in combination over 12 h with (125)I uptake being measured after 6 h. RNA was isolated from placental trophoblasts and real-time RT-PCR performed using sodium iodide symporter (NIS) and pendrin (PDS) probes., Results: Significant dose response increments in (125)I uptake by trophoblast cells (p < 0.01) were observed following incubation with hCG (60% increase), oxytocin (45% increase) and prolactin (32% increase). Although progesterone (50-200 ng/ml) and 17β-estradiol (1,000-15,000 pg/ml) alone produced no significant differences in uptake, they facilitated increased uptake when combined with prolactin or oxytocin, with a combination of all four hormones producing the greatest increase (82%). Increased (125)I uptake was accompanied by corresponding increments in NIS mRNA (ratio 1.52) compared to untreated control cells. No significantly increased expression levels of PDS were observed., Conclusions: Pregnancy-associated hormones, particularly oxytocin and hCG, have a role in promoting placental iodide uptake which may protect the fetus against iodine deficiency.

Objective: Placenta accreta, morbid adherence to the uterus to the myometrium, is commonest in association with placenta previa in women previously delivered by caesarean section (CS). It has become proportionally a greater cause of major maternal morbidity and mortality as the frequency of other serious obstetric complications has declined. The aim of this study was to examine the incidence of placenta accreta in the context of a rising caesarean delivery rate., Study Design: Retrospective review of the incidence of placenta accreta in parous women during the 36 years 1975-2010. Cases were identified from hospital records and then correlated with pathological reports. The incidence of placenta accreta was analysed in the context of women previously delivered by CS., Results: During the 36-year period in our unit, 157,162 multiparous women delivered, of whom 15,151 (9.6%) had a previous CS scar. The institutional incidence of CS rose from 4.1% in 1975 to 20.7% in 2010. Twenty-five parous women, all with a previous CS, had placenta accreta requiring hysterectomy. The overall incidence of placenta accreta was 1.65 per 1000 parous women with a previous CS, but was low (1.06/1000) until 2002. From 2003 to 2010 the incidence rose to 2.37/1000 previous CS deliveries (OR 2.2; 95% CI 1.05-5.1)., Conclusion: The frequency of placenta accreta correlated steadily with the CS rate until 2000. Since then, the incidence has nearly doubled in women with previous CS scars, suggesting an additional causative influence on risk., (Copyright © 2013. Published by Elsevier Ireland Ltd.)

Objective: To compare early home biofeedback physiotherapy with pelvic floor exercises (PFEs) for the initial management of women sustaining a primary third-degree tear., Design: Single centre, randomised trial., Setting: National Maternity Hospital, Dublin, Ireland., Population: A total of 120 women sustaining a primary third-degree tear., Methods: Women were randomised in a one to three ratio: 30 to early postpartum home biofeedback physiotherapy and 90 to PFEs., Main Outcome Measures: Differences in anorectal manometry results, Cleveland Clinic continence scores and Rockwood faecal incontinence quality of life scale scores after 3 months of postpartum treatment., Results: The mean anal resting pressure was 39 ± 13 mmHg in the early biofeedback physiotherapy group and 43 ± 17 mmHg in the PFE group. The mean anal squeeze pressure was 64 ± 17 mmHg in the biofeedback group and 62 ± 23 mmHg in the PFE group. There was no significant difference in anal resting and squeeze pressure values between the groups (P = 0.123 and P = 0.68, respectively). There were no differences in symptom score and quality of life measurements between the groups., Conclusions: This study demonstrates no added value in using early home biofeedback physiotherapy in the management of women sustaining third-degree tears. Poor compliance may have contributed because women found it difficult to designate time to using biofeedback., (© 2013 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2013 RCOG.)

Aim: To describe the natural history, management and outcomes of peripartum cardiomyopathy (PPCM) in an unselected Northern European population., Methods: A retrospective single-center observational study was performed at a tertiary referral heart failure and transplantation unit. Outcomes measured were baseline demographics, clinical presentation, course, and treatment. Echocardiographic findings were compared at baseline, 2 months, and 6 months., Results: Twelve cases of PPCM were identified between 2002 and 2008. Mean age was 34.7 years. Nine patients were multiparous and nine had preeclampsia. Ten patients presented in the first week postpartum. Two patients required inotropic support. Mean ejection fraction (EF) at presentation was 27% (SD = 8%) which improved to 47% (SD = 13%) at 6 months. At this time, 10 patients were asymptomatic and 6 had recovered normal cardiac function. Left ventricular (LV) function improved but did not reach normal limits in five cases. One case with persistent severe LV dysfunction required cardiac transplantation. One patient suffered an arrhythmic death several years after the 6 months follow-up period., Conclusions: PPCM is a rare condition. With appropriate therapy, a good clinical outcome is common but not universal. Continued deterioration requiring ventricular support and cardiac transplantation can occur. In our cohort, older maternal age, multiparity, and preeclampsia appeared to be risk factors.

The aim of this study was to compare the efficacy of endometrial aspiration biopsy (EAB) with the more traditional dilatation and curettage (D&C) for the procurement of lymphoid progenitor cells and uterine natural killer (NK) populations in endometrial tissue. This prospective observational study conducted in a tertiary referral university hospital examined endometrium obtained from 32 women admitted for laparoscopic gynaecological procedures. Each participant had endometrium sampled using both EAB and D&C. Both methods were assessed as a source of uterine NK and lymphoid progenitor cells. Similar proportions of mature CD45+CD56+ NK cells (range 25.4-36.2%) and CD45+CD34+ lymphoid progenitors (range 1.2-2.0%) were found in tissue obtained using both EAB and D&C. These cells were adequate for flow cytometric analysis, magnetic bead separation and culture. Colony formation by the CD34+ population demonstrated maturational potential. Tissues obtained via endometrial biopsy and D&C are equivalent, by analysis of uterine NK and lymphoid progenitor cells. The aim of this study was to compare two methods of endometrial sampling - endometrial aspiration biopsy and traditional dilatation and curettage - for the procurement of haematopoietic stem cells and uterine natural killer (NK) populations in endometrial tissue. Thirty-two women who had gynaecological procedures in a tertiary referral hospital participated in this study and had endometrial tissue collected via both methods. Similar populations of mature NK cells and haematopoietic stem cells were found in tissue obtained using both endometrial aspiration biopsy and dilatation and curettage. Tissue obtained via endometrial aspiration biopsy was adequate for the culture and growth of haematopoietic stem cells. We conclude that tissue obtained via endometrial biopsy and dilatation and curettage is equivalent, by analysis of uterine NK and haematopoietic stem cells using flow cytometry. This has implications for further more extensive study of endometrial haematopoietic stem cell populations, as these samples can be collected in a clinical setting without a requirement for general anaesthesia., (Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background:   The rat external anal sphincter (EAS) and external urethral sphincter (EUS) are voluntary muscles of continence that can display similar synchronous electromyographic (EMG) activity patterns. However, the two sphincters are quite different in structure and function. The EUS is a fast twitch muscle and contains fibers expressing type 2B myosin. In contrast, the EAS exhibits slower kinetics and lacks type 2B fibers. This striking contrast in kinetics and fiber type profiles may be shaped by differences in the basal motor drive that each sphincter receives., Methods:   A double EMG approach was used to obtain spontaneously active single motor unit action potentials from the EUS and EAS simultaneously and compare their basal discharge frequencies in urethane anaesthetized rats., Key Results:   The basal firing rates of motor units of the EUS and EAS were not significantly different (3.9 ± 0.9 Hz vs. 3.1 ± 1.6 Hz, respectively, n = 7 animals, P = 0.32, paired Student's t-test). However, auto-correlogram analysis showed that EUS is driven by neurons with faster instantaneous firing frequencies: 30.5 ± 2.4 Hz vs 14.3 ± 0.9 Hz in the EAS (P = 0.03, paired Student's t-test)., Conclusions & Inferences:   The oscillator(s) driving the EUS operate(s) at a frequency twice that of the EAS. This may explain the presence of type 2B fibers in the EUS. In the inter-micturition periods no cross correlation was found in motor discharge to the sphincters suggesting that the two muscles do not share a common central drive to sustain the continent tonus of the two outlet tracts., (© 2012 Blackwell Publishing Ltd.)

Background: Childbirth, in particular, when it involves instrumental vaginal delivery, can result in direct trauma to the external anal sphincter muscle. In addition, a global injury to the pelvic floor, including neurovascular injury to the anal sphincter complex, may occur., Objective: The aims of this study were to determine whether sensory drive from the anal canal and oxygenation of the external anal sphincter were compromised during simulated labor in a validated animal model of obstetric trauma., Design: Fifteen female Wister rats were operated on. Group 1 (n = 5) underwent pelvic balloon compression for 1 hour to simulate increased pelvic pressure during childbirth. Somatosensory cortical potentials, evoked by electrically stimulating the anal canal, were tracked. In group 2 (sham), the balloons were not inflated. In group 3, tissue PO2 values of the external anal sphincter and femoral arterial blood flow were measured simultaneously during the period of balloon inflation., Results: The peak amplitude of cortical evoked potentials was reduced (from 11.8 ± 1.5 μV to 3.1 ± 1.1 μV) during pelvic compression (p = 0.002, ANOVA). During this period, arterial blood flow to the hindlimb and the external anal sphincter tissue PO2 decreased by 20% (p < 0.001) and 60% (p < 0.001)., Conclusion: Pelvic compression that mimics obstetric trauma is associated with diminished anocortical drive. This neural insult may be compounded by concomitant ischemia of the external anal sphincter.

Objective: To examine the obstetric and perinatal outcomes of women presenting with reduced fetal movement (RFM) during the third trimester, specifically in relation to the diagnostic capacity of non-stress cardiotocography (CTG) used as the primary investigation in this clinical scenario., Study Design: This was a retrospective population-based cohort study of pregnancy outcomes of all women ≥ 28 weeks' gestation with singleton pregnancies presenting during one calendar year with maternal perception of RFM, all of whom underwent CTG at presentation. Main outcome measures included: obstetric intervention (induction of labour, spontaneous vaginal delivery, operative vaginal delivery, emergency caesarean section), and perinatal outcome (subsequent perinatal death, low Apgar scores (<7(5)), neonatal resuscitation and NICU admission)., Results: In all, 524 women presented with RFM and a live fetus, representing 7% of the antenatal obstetric population; 284 women (54%) were nulliparous. The reassuring CTG group comprised 482 (92%) women in whom initial CTG was reassuring and 15 (3%) where a repeat tracing within 1h was reassuring. The non-reassuring/abnormal CTG group (n=27, 5%) either underwent emergency delivery or comprehensive serial fetal assessment; this group had significantly higher rates of emergency caesarean delivery, neonatal resuscitation and NICU admission; the incidence of small-for-gestational-age infants did not differ significantly. No perinatal death occurred in either group following CTG., Conclusion: Normal non-stress CTG is a reliable screening indicator of fetal wellbeing in women presenting with perception of RFM in the third trimester; abnormal pregnancy outcomes were more common when initial CTG was abnormal or persistently non-reassuring., (Copyright © 2011. Published by Elsevier Ireland Ltd.)

Background: The most common indication for cesarean section (CS) in nulliparous women is dystocia secondary to ineffective myometrial contractility. The aim of this study was to identify a molecular profile in myometrium associated with dystocic labor., Methods: Myometrial biopsies were obtained from the upper incisional margins of nulliparous women undergoing lower segment CS for dystocia (n = 4) and control women undergoing CS in the second stage who had demonstrated efficient uterine action during the first stage of labor (n = 4). All patients were in spontaneous (non-induced) labor and had received intrapartum oxytocin to accelerate labor. RNA was extracted from biopsies and hybridized to Affymetrix HuGene U133A Plus 2 microarrays. Internal validation was performed using quantitative SYBR Green Real-Time PCR., Results: Seventy genes were differentially expressed between the two groups. 58 genes were down-regulated in the dystocia group. Gene ontology analysis revealed 12 of the 58 down-regulated genes were involved in the immune response. These included (ERAP2, (8.67 fold change (FC)) HLA-DQB1 (7.88 FC) CD28 (2.60 FC), LILRA3 (2.87 FC) and TGFBR3 (2.1 FC)) Hierarchical clustering demonstrated a difference in global gene expression patterns between the samples from dystocic and non-dystocic labours. RT-PCR validation was performed on 4 genes ERAP2, CD28, LILRA3 and TGFBR3, Conclusion: These findings suggest an underlying molecular basis for dystocia in nulliparous women in spontaneous labor. Differentially expressed genes suggest an important role for the immune response in dystocic labor and may provide important indicators for new diagnostic assays and potential intrapartum therapeutic targets.

Background: An experimental model of neuropathic faecal incontinence has recently been established. This study aimed to quantify and compare the effect of crush and compression injury on first-order sensory neurones of the inferior rectal nerve (IRN) using a nuclear marker of axonal injury, activating transcription factor (ATF) 3., Methods: Eighteen Wistar rats were allocated to three groups: an unoperated control group, an IRN crush group (positive control) and a retrouterine balloon compression group. Five days after surgery, all animals were anaesthetized and perfused with fixative, and S1 dorsal root ganglia (DRG) were harvested. The tissue was sampled and neuronal nuclear ATF-3 expression calculated., Results: Estimated total S1 DRG ATF-3 nuclear labelling was higher in the nerve crush (median (interquartile range) 171 (60-824) cells) and balloon compression (59 (20-274) cells) groups, compared with that in the unoperated control group (9 (3-24) cells) (P = 0.001 and P = 0.008 respectively). In all groups, most neurones displaying the marker of injury were of the C-fibre class., Conclusion: This study confirmed the presence of axonal injury in a pelvic compression model of obstetric injury. C-fibre afferent pathways appeared to be most vulnerable. Neuromodulation may function through augmentation of residual C-fibre pathways., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: Delivery of iodine to the foetus depends not only on maternal dietary iodine intake but also on the presence of a functioning placental transport system. A role for the placenta as an iodine storage organ has been suggested, and this study compares the iodine content of placentas from women giving birth at term in Ireland and Iran, areas with median urinary iodine of 79 and 206 μg/l respectively., Design: Placental cotyledon iodine was measured using an alkaline ashing technique with Sandell-Kolthoff kinetic colorimetry. Samples were taken from six sites from the centre and periphery of each cotyledon. Placentas (Ireland n = 58; Iran n = 45) were obtained from consecutive euthyroid women delivering at term., Results: The median placental iodine (μg/g wet weight) was significantly higher in Iranian than in Irish women (187·2 μg/g vs 34·3 μg/g; P < 0·001). The distribution of individual placental iodine values showed that values >50μg/g were found in 71·0% of Iranian and in only 21·0% of Irish samples. In Irish subjects, the relationship of placental iodine to pregnant population urinary iodine (UI) (ng/g:μg/l) was 1:2 (40:79), while in Iranians this ratio is closer to 1:1 (211:206)., Conclusions: These findings, by demonstrating an apparent ability of the placenta to store iodine in a concentration-dependent manner, suggest a hitherto undetected role for the placenta. Whether placental iodine has a role in protecting the foetus from inadequacies in maternal dietary iodine intake is as yet unknown., (© 2011 Blackwell Publishing Ltd.)

Background: Sacral and posterior tibial nerve stimulation may be used to treat faecal incontinence; however, the mechanism of action is unknown. The aim of this study was to establish whether sensory activation of the cerebral cortex by anal canal stimulation was increased by peripheral neuromodulation., Methods: A multielectrode array was positioned over the right primary somatosensory cortex of anaesthetized rats. A brief burst of electrical stimulation was applied to either the left sacral root or the left posterior tibial nerve, and evoked potentials from anal canal stimulation were signal-averaged at intervals over 1 h. At the end of the experiment, the cerebral cortex was removed and probed for polysialylated neural cell adhesion molecule (PSA-NCAM)., Results: Sacral nerve root and posterior tibial nerve stimulation significantly increased the peak amplitude of primary cortical evoked potentials by 54.0 and 45.1 per cent respectively. This change persisted throughout the period of observation. The density of PSA-NCAM-positive cells in the somatosensory cortex underlying the electrode array was increased by approximately 50 per cent in the sacral nerve-stimulated group., Conclusion: Brief sacral neuromodulation induces profound changes in anal canal representation on the primary somatosensory cortex, providing a plausible hypothesis concerning the mechanism of action of neuromodulation in the treatment of faecal incontinence., (Copyright © 2011 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.)

Objective: To assess the influence of body mass index (BMI) on labor outcome in both induced and actively managed spontaneous nulliparous labors., Methods: This is a prospective observational study of all consecutive nulliparous women who delivered in the National Maternity Hospital, Dublin in 2008. Labor outcome variables examined in relation to BMI included duration of labor, oxytocin requirements, epidural use, mode of delivery, and infant birthweight., Results: Of 4162 nulliparous women who labored during the study period, accurate BMI data were available on 3158, who constituted the study group. Of these women, 2143 (68%) were in spontaneous labor and 1015 (32%) had labor induced. A statistically significant association was found between maternal BMI at first antenatal visit and the need for intrapartum cesarean section (CS) in both spontaneous and induced labors (p < 0.05). A significantly poorer response to oxytocin augmentation was observed in women with a higher BMI, as indicated by an increased intrapartum CS rate for dystocia despite oxytocin augmentation. There was a linear relationship between maternal BMI and gestational age at onset of spontaneous labor., Conclusion: Our results in a large consecutive series of nulliparous labors confirm the potent influence of increasing maternal BMI on intrapartum events.

Background: The production of iodine-containing thyroid hormones necessary for brain development in the fetus depends not only on maternal dietary intake but also on placental iodine transport. The optimum level of iodine nutrition during pregnancy and the proportion of the pregnant population reaching this level have previously been evaluated. Little information exists on the ability of the placenta to either accumulate or store iodine. This study aims to investigate iodine uptake and tissue iodine content within placental tissue obtained from women delivering at term., Methods: Samples (∼1 cm(3)) obtained from placental cotyledons (n = 19), thyroid (n = 4), and uterine myometrial (n = 4) tissue were incubated for 6 hours with (125)I in the presence and absence of potassium perchlorate. To account for variation in tissue composition, results were expressed in cpm (125)I/μg DNA., Results: Placental uptake of (125)I (375 cpm/μg DNA) was significantly higher than that of control myometrial tissue (226 cpm/μg DNA) (p < 0.05) and was ∼25% that of thyroid tissue (1702 cpm/μg DNA). Uptake of (125)I could be partially blocked in the thyroid and placenta, respectively, by potassium perchlorate (100 μM), which had no effect on uptake by myometrial tissue. Iodine content of tissue samples measured using an alkaline ashing technique with Sandell-Kolthoff colorimetry gave a mean value for total iodine of 30.4 ng/g placental tissue (range 21-50 ng/g), 1.74 ng/g myometrial tissue, and 1037 ng/g thyroid tissue., Conclusions: Placental iodine content was only ∼3% that of the thyroid, but on the basis that neonatal iodine stores are very low and highly sensitive to fluctuations in maternal iodine supply, we postulate that placental iodine bioavailability makes a significant contribution to protection against neonatal hypothyroidism. These findings suggest that the placenta has a role not only in uptake but also in storing iodine as a possible means of protecting the fetus from inadequacies in maternal dietary iodine intake.

Objective: To test the hypothesis that women from Eastern European countries have lower caesarean delivery rates and higher spontaneous labour rates relative to Irish women in a setting in which the management of labour is standardised., Design: A retrospective review of prospectively collected data., Setting: Tertiary referral centre, Dublin, Ireland., Population: All Irish and Eastern European term nulliparous women who laboured and delivered in 2008., Methods: A comparison of labour outcomes between women from Ireland and women from Eastern European countries., Main Outcome Measures: The principal outcomes measured were the gestational age at onset of labour, whether labour was spontaneous or induced, the need for oxytocin augmentation, duration of labour, mode of delivery, epidural use and birthweight., Results: Of 2556 Irish (n = 2041) and Eastern European (n = 511) term cephalic singleton labours in the calendar year 2008, women from Eastern Europe were significantly more likely to labour spontaneously (74.6% versus 65.9%, P < 0.001), required less epidural analgesia (68.4% versus 59.7%) and were significantly less likely to require delivery by caesarean section (8.6% versus 15.7%, P < 0.001) than Irish women. This is despite no significant difference between the two groups with regard to mean birthweight (3581 g versus 3569 g, P = 0.6) or macrosomia (birthweight over 4000 g) (18% versus 16%, P = 0.4). There were significant differences in maternal age at delivery (27.2 years versus 29.2 years, P < 0.001) and body mass index (BMI) (24.1 kg/m² versus 25.4 kg/m², P < 0.001) between the two groups., Conclusion: These findings confirm our hypothesis that economic migrants from Eastern European countries exhibit a so-called 'healthy migrant effect' in terms of obstetric outcomes., (© 2011 The Authors BJOG An International Journal of Obstetrics and Gynaecology © 2011 RCOG.)

Objective: We sought to compare the incidence and antecedents of neonatal brachial plexus injury (BPI) in 2 different 5-year epochs a decade apart following the introduction of specific staff training in the management of shoulder dystocia., Study Design: All infants with BPI were prospectively identified during 2004 through 2008. Injuries were correlated with maternal details and intrapartum events and compared with the earlier series., Results: Of 41,828 deliveries during 2004 through 2008, 72 infants with BPI were identified (1.7/1000), compared to 54 cases (1.5/1000) from 1994 through 1998 (P = .4); 9 injuries (12.5%) were persistent from 2004 through 2008, compared with 10 (18.5%) earlier (P = .4). There were no significant differences between the 2 time periods with respect to maternal parity, obesity, or prolonged pregnancy, although the cesarean section rate had increased from 10.7 to 18.4%., Conclusion: Despite training in the management of shoulder dystocia and a rising institutional cesarean section rate, the incidence of BPI has remained unchanged compared with 10 years earlier., (Copyright © 2011 Mosby, Inc. All rights reserved.)

In the triennium 2006-2008, 261 women in the UK died directly or indirectly related to pregnancy. The overall maternal mortality rate was 11.39 per 100,000 maternities. Direct deaths decreased from 6.24 per 100,000 maternities in 2003-2005 to 4.67 per 100,000 maternities in 2006–2008 (p = 0.02). This decline is predominantly due to the reduction in deaths from thromboembolism and, to a lesser extent, haemorrhage. For the first time there has been a reduction in the inequalities gap, with a significant decrease in maternal mortality rates among those living in the most deprived areas and those in the lowest socio-economic group. Despite a decline in the overall UK maternal mortality rate, there has been an increase in deaths related to genital tract sepsis, particularly from community acquired Group A streptococcal disease. The mortality rate related to sepsis increased from 0.85 deaths per 100,000 maternities in 2003-2005 to 1.13 deaths in 2006-2008, and sepsis is now the most common cause of Direct maternal death. Cardiac disease is the most common cause of Indirect death; the Indirect maternal mortality rate has not changed significantly since 2003-2005. This Confidential Enquiry identified substandard care in 70% of Direct deaths and 55% of Indirect deaths. Many of the identified avoidable factors remain the same as those identified in previous Enquiries. Recommendations for improving care have been developed and are highlighted in this report. Implementing the Top ten recommendations should be prioritised in order to ensure the overall UK maternal mortality rate continues to decline.

Objective: To examine the contribution of singleton, cephalic, term (37 weeks or later) nulliparous cesarean rates to overall cesarean incidence in a single institution during a 35-year period., Methods: Cesarean rates were examined for 1974, 1984, 1994, 1999, 2005, and 2008, applying a 10-group classification system. Groups 1 (spontaneously laboring, term nulliparous women) and 2 (prelabor cesarean and induced term nulliparous women) were combined as a composite variable-the term, singleton, cephalic nulliparous woman., Results: Overall and term, singleton, cephalic nulliparous cesarean rates correlated throughout the 35-year period (r=0.93, P<.001). Between 1974 and 2008, overall cesarean rates increased from 5% to 19.1% and from 4.4% to 15.8% among term, singleton, cephalic nulliparous women. Term, singleton, cephalic nulliparous inductions increased from 19.7% to 32.7% (P<.001) and the intrapartum cesarean rate in term, singleton, cephalic nulliparous inductions rose from 4.1% to 27.3%. The cesarean rate in group 1 increased from 2.3% to 7.2%., Conclusion: The increase in term, singleton, cephalic nulliparous cesarean rates correlated with the increase in overall cesarean rates throughout 35 years in an institution with standard management of labor. This relationship was due to an increase in both the incidence and rate of cesarean delivery within term, singleton, cephalic nulliparous inductions. Examination of the different term, singleton, cephalic nullipara components (spontaneous labor, induction, or prelabor cesarean) can help to identify major variations in practice between institutions., Level of Evidence: III.

Objective: To assess whether women who underwent forceps delivery were more likely than those who delivered either normally (spontaneous vaginal delivery [SVD]) or by cesarean to experience deterioration in fecal continence as they aged., Methods: The study investigated fecal continence assessment among women who gave birth to their first child 10, 20, or 30 years previously. Women who had undergone forceps delivery in the selected years were matched with women who had SVD in the same year. Two additional cohorts (1 premenopausal, 1 postmenopausal), who had only ever delivered by pre-labor cesarean, were identified for comparison., Results: Of the 85 women who participated, 36 had undergone forceps delivery, 35 SVD, and 14 cesarean delivery only. The mode of vaginal delivery had no significant effect on continence scores or manometry pressures. Premenopausal women who had undergone cesarean delivery had significantly higher manometry pressures than those who delivered vaginally, but this protective effect was lost after the menopause. Multivariate analysis of pudendal nerve conduction found that the adverse effect of duration since delivery was greater than the adverse effect of forceps compared with vaginal delivery., Conclusion: Mode of delivery and aging affect pelvic floor function. Women who deliver via cesarean are not immune to age-related deterioration of anal sphincter function., (Copyright © 2010 International Federation of Gynecology and Obstetrics. All rights reserved.)

Objective: To compare levator ani muscle injury rates in primiparous women who had a forceps delivery owing to fetal distress with women delivered by forceps for second stage arrest; and to compare these injury rates with a historical control group of women who delivered spontaneously., Methods: Primiparous women who delivered by forceps were recruited retrospectively into 2 groups: forceps for fetal distress with short second stage (25±11 minutes; n=19); and forceps delivery for second stage arrest (137±26 minutes; n=19). MR images of the levator ani muscles were compared with a historical control group of women from a previous study who had delivered spontaneously (n=129)., Results: Major defect rates were: 42% for forceps and short second stage; 63% for forceps and second stage arrest; and 6% for spontaneous delivery. The odds ratios for major injury were: 11.0 for forceps and short second stage compared with spontaneous delivery; 25.9 for forceps and second stage arrest compared with spontaneous delivery; and 2.3 for forceps and second stage arrest compared with short second stage (P=0.07)., Conclusion: Women delivered by forceps have a higher rate of levator ani injury compared with spontaneous delivery controls; the difference between the forceps groups did not reach significance., (Copyright © 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

The external urethral sphincter (EUS) and external anal sphincter (EAS) are the principal voluntary striated muscles that sustain continence of urine and faeces. In light of their common embryological origin, shared tonic sphincteric action and synchronized electrical activity in vivo, it was expected that they would exhibit similar physiological and structural properties. However, the findings of this study using paired observations of both sphincters isolated from the rat show clearly that this is not the case. The anal sphincter is much more fatigable than the urethral sphincter. On completion of a fatigue protocol, the amplitude of the last twitch of the EAS had declined to 42 +/- 3% of the first twitch, whereas the last twitch of the EUS was almost identical to that of the first (95 +/- 3%). Immunocytochemical detection of myosin heavy-chain isoforms showed that this difference was not due to the presence of more slow-twitch oxidative type 1 fibres in the EUS compared with the EAS (areal densities 4 +/- 1% and 5 +/- 1%, respectively; P = 0.35). In addition, the fatigue difference was not explained by a greater contribution to force production by fast oxidative type 2A fibres in the urethral sphincter. In fact, the anal sphincter contained a higher areal density of type 2A fibres (56 +/- 5% vs. 37 +/- 4% in the EUS, P = 0.017). The higher oxidative capacity of the EUS, measured histochemically, explained its fatigue resistance. These results were surprising because the fatigue-resistant urethral muscle exhibited faster single-twitch contraction times compared with the anal sphincter (56 +/- 0.87 ms vs. 72.5 +/- 1.16 ms, P < 0.001). Neither sphincter expressed the type 2X myosin isoform but the fast-twitch isoform type 2B was found exclusively in the EUS (areal density 16 +/- 2%). The type 2B fibres of the EUS were small (diameter 19.5 +/- 0.4 mum) in comparison to typical type 2B fibres of other muscles. As a whole the EUS is a more oxidative than glycolytic muscle. In conclusion, analysis of the twitch mechanics and fatigue of two sphincters showed that the EUS contained more fatigue-resistant muscle fibres compared with the EAS.

Functional magnetic resonance imaging (fMRI) techniques highlight cerebral vascular responses which are coupled to changes in neural activation. However, two major difficulties arise when employing these techniques in animal studies. First is the disturbance of cerebral blood flow due to anaesthesia and second is the difficulty of precise reproducible quantitative measurements. These difficulties were surmounted in the current study by using propofol and quantitative arterial spin labelling (QASL) to measure relative cerebral blood volume of labelled water (rCBV(lw),) mean transit time (MTT) and capillary transit time (CTT). The ASL method was applied to measure the haemodynamic response in the primary somatosensory cortex following forepaw stimulation in the rat. Following stimulation an increase in signal intensity and rCBV(lw) was recorded, this was accompanied by a significant decrease in MTT (1.97+/-0.06s to 1.44+/-0.04s) and CTT (1.76+/-0.06s to 1.39+/-0.07s). Two animals were scanned repeatedly on two different experimental days. Stimulation in the first animal was applied to the same forepaw during the initial and repeat scan. In the second animal stimulation was applied to different forepaws on the first and second days. The control and activated ASL signal intensities, rCBVlw on both days were almost identical in both animals. The basal MTT and CTT during the second scan were also very similar to the values obtained during the first scan. The MTT recorded from the animal that underwent stimulation to the same paw during both scanning sessions was very similar on the first and second days. In conclusion, propofol induces little physiological disturbance and holds potential for longitudinal QASL fMRI studies., (Copyright 2010 Elsevier Inc. All rights reserved.)

Background: Pudendal nerve injury during childbirth may result in external anal sphincter (EAS) atrophy. Recently, balloon compression of the pelvic side wall has been shown to result in EAS atrophy in an experimental model. The aim of this study was to determine whether other sphincters of continence are similarly affected., Method: Sixteen adult female virgin Wistar rats (eight controls) were studied 4 weeks after surgery. Anal and urethral canals were dissected, snap frozen and sectioned using a cryostat (100 microm thickness). Masses of EAS, internal anal sphincter (IAS) and external urethral sphincter (EUS) were calculated stereologically and stained with succinate dehydrogenase histochemistry to differentiate striated from smooth muscle. Sphincter length was determined and total sphincter mass calculated. Data were analysed with an unpaired Student's t-test., Results: Atrophy of EAS (30.9 +/- 1.7 to 21.3 +/- 1.7 mg/ kg, P = 0.001), IAS (98.1 +/- 11.3 to 67.1 +/- 5.0 mg/kg, P = 0.01) and EUS (9.6 +/- 0.98 to 7.4 +/- 0.8 mg/kg, P = 0.05) was found 4 weeks after the injury., Conclusion: In an experimental model of obstetric pudendal nerve injury, significant atrophy of striated and smooth muscle sphincters of continence occurs and may contribute to altered continence following vaginal childbirth.

Objective: To determine the utilisation of antenatal corticosteroid administration in women presenting at risk of preterm birth (PTB) in a centre where tocolytics are not prescribed., Design: A prospective cohort study., Setting: Tertiary referral centre, Dublin, Ireland., Population: Four hundred and fourteen consecutive women presenting at risk of PTB., Methods: Clinical details were collated prospectively on all booked patients who presented at risk of PTB (i.e. at <34 weeks of gestation) during 2008., Main Outcome Measure: Rate of administration of antenatal corticosteroids in PTB., Results: Of 8985 deliveries, 414 women (5%) presented at <34 weeks of gestation with a clinical potential for PTB, of whom 277 (67%) received antenatal corticosteroids. Amongst women delivering at <34 weeks of gestation, 93% (80/86) received any corticosteroids and 76% (65/86) received a complete course. The ratio of women given a complete course of corticosteroids to the number who actually delivered before 34 weeks of gestation was 4:1 overall. Analysis by indication for PTB revealed this ratio to be 15:1 in suspected preterm labour (PTL), 8:1 in antepartum haemorrhage (APH), and 2:1 in both preterm prelabour rupture of membranes (PPROM) and medically indicated PTB (MIPTB). Seven of ten multiparae (70%) who delivered prematurely during the study period following PTL had a history of previous PTL before 34 weeks of gestation., Conclusion: The ratio of maternal antenatal corticosteroid administration for potential versus actual PTB at <34 weeks of gestation was high in categories such as PTL and substantial APH, whereas selection in PPROM and MIPTB approached 100%. There should be a low threshold for single course therapy for women with prior PTL before 34 weeks of gestation.

This was a retrospective review of normally formed perinatal deaths among 176,620 births at the National Maternity Hospital (1984-2007). Prelabor stillbirths were categorised by presumed cause of death including unexplained, intrauterine growth retardation (IUGR), placental abruption, red cell alloimmunisation (RCA) and deaths related to prematurity. Peripartum deaths included intrapartum and first week neonatal deaths. The post-mortem rate, initially almost 100%, fell to 60%. Data were analysed using the Mantel-Haenszel chi square test for trends. In the study period there was a significant reduction in the PNM, largely because of a fall in death related to prematurity, term peripartum death, death at 42 weeks or greater, placental abruption, death related to IUGR and RCA (P < 0.01). Overall the unexplained still birth rate was unchanged throughout the study period (p = 0.8) despite a highly significant (p < 0.001) increase in obstetric intervention particularly induction of labor and caesarean section.

Background: Our group previously reported that tumour-specific expression of the rate-limiting enzyme in the mevalonate pathway, 3-hydroxy-3-methylglutharyl-coenzyme A reductase (HMG-CoAR) is associated with more favourable tumour parameters and a good prognosis in breast cancer. In the present study, the prognostic value of HMG-CoAR expression was examined in tumours from a cohort of patients with primary epithelial ovarian cancer., Methods: HMG-CoAR expression was assessed using immunohistochemistry (IHC) on tissue microarrays (TMA) consisting of 76 ovarian cancer cases, analysed using automated algorithms to develop a quantitative scoring model. Kaplan Meier analysis and Cox proportional hazards modelling were used to estimate the risk of recurrence free survival (RFS)., Results: Seventy-two tumours were suitable for analysis. Cytoplasmic HMG-CoAR expression was present in 65% (n = 46) of tumours. No relationship was seen between HMG-CoAR and age, histological subtype, grade, disease stage, estrogen receptor or Ki-67 status. Patients with tumours expressing HMG-CoAR had a significantly prolonged RFS (p = 0.012). Multivariate Cox regression analysis revealed that HMG-CoAR expression was an independent predictor of improved RFS (RR = 0.49, 95% CI (0.25-0.93); p = 0.03) when adjusted for established prognostic factors such as residual disease, tumour stage and grade., Conclusion: HMG-CoAR expression is an independent predictor of prolonged RFS in primary ovarian cancer. As HMG-CoAR inhibitors, also known as statins, have demonstrated anti-neoplastic effects in vitro, further studies are required to evaluate HMG-CoAR expression as a surrogate marker of response to statin treatment, especially in conjunction with current chemotherapeutic regimens.

Purpose: Obstetric injury to the pudendal nerve contributes significantly to fecal incontinence. The inferior rectal nerve, a terminal branch of the motor division of the pudendal nerve, innervates the external anal sphincter. Animal models have been developed to establish the scientific basis of sacral neuromodulation. The aims of this study were to determine the spinal location of inferior rectal nerve motoneurons projecting to the external anal sphincter and whether the inferior rectal nerve carries sensory fibers., Methods: Ten female virgin Wistar rats were used; 7 underwent bilateral inferior rectal nerve section and application of the neuronal tracer fluorogold. Five days later dorsal root ganglia L5 to S2 and the lumbosacral spinal cord were harvested and stained for activating transcription factor 3, a molecular marker of nerve injury. Three animals were used to confirm the specificity of activating transcription factor 3 nuclear labeling as a marker of axotomy., Results: Fluorogold-labeled motoneurons were found exclusively at L6 in the dorsomedial sections of Onuf's nuclei (left and right), which contained 30 +/- 9 motoneurons with a median diameter of 28.3 microm (24.4-31.0) (25th-75th centiles). Double-labeled sensory neurons (fluorogold-labeled cytoplasm and activating transcription factor 3-labeled nuclei) were found in dorsal root ganglia L6 to S2 and were smaller in diameter (20.5 microm (17.8-26.7); median (25th-75th centiles)) than motoneurons (P < .0,001)., Conclusions: The external anal sphincter receives both motor and sensory innervation from the inferior rectal nerve. Activating transcription factor 3 nuclear staining may prove useful for quantifying the degree of nerve injury in animal models of fecal incontinence.

Objective: Cesarean section (CS) rates continue to rise throughout the developed world. The aim of this study was to highlight variations in obstetric populations and practices and to identify variations in CS rates in different institutions., Study Design: Data from 9 institutional cohorts (total, 47,402; range, 1962-7985) from 9 different countries were examined using a 10-group classification system based on 4 characteristics of every pregnancy, namely single/multiple, nulliparity/multiparity, multiparity with CS scar, spontaneous/induced labor onset and term (>or=37 weeks) gestation., Results: Overall CS rates correlated with CS rates in singleton cephalic nullipara (r = 0.992; P < .001). Whereas CS rates in induced labor were similar, greatest institutional variation were seen in spontaneously laboring multiparas (6.7-fold difference) and nulliparas (3.7-fold difference)., Conclusion: Ten-group analysis of international obstetric cesarean practice identifies wide variations in women in spontaneous cephalic term labor, a low-risk cohort amenable to effective intrapartum corrective intervention.

This was a retrospective review of term singleton neonates (> 37 weeks) with early onset seizures, with and without encephalopathy, from 1989 through 2000. Our aim was to examine the relationship between antepartum and intrapartum obstetric events, neonatal hypoxic seizures and subsequent neurological impairment of 77,838 infants, the incidence of seizures was significantly higher among primiparas (2.4/1000; 67/31,729) compared with multiparas (0.35/1000; 16/46,109)(p < 0.001). Compared with multiparas, seizures with encephalopathy occurred more frequently among primiparas (0.8/1000; 26/31,729) vs. multiparas (0.2/1000; 8/46,109), were more commonly associated with unexplained intrapartum hypoxia (0.6/1000, n = 20 vs.0.04/ 1000, n = 2) and the incidence of cerebral palsy, 45% (9/20) vs. 0% (0/2) was significantly higher(p < 0.001). Seizures with encephalopathy (0.2/1000 vs.0.13/1000) and cerebral palsy (33%) had a similar incidence in primiparas and multiparas following a sentinel event. Neonatal seizures with encephalopathy, related to intrapartum events, were 4 times more common following first delivery and associated with a 9 fold higher incidence of cerebral palsy, implicating primiparous labor in the development of cerebral palsy.

Purpose: Alteration in cortical awareness may be the underlying abnormality in patients with neuropathic fecal incontinence. The cortical effects of inferior rectal nerve injury were determined using somatosensory evoked cortical potential recordings in an experimental model of neuropathic fecal incontinence., Methods: Eighteen female virgin Wistar rats were assigned equally to one of three groups: an unoperated control group, a nerve crush group (positive control), and a nerve balloon compression group. Four weeks following the injury, all animals underwent somatosensory evoked cortical potential recordings. Following this, the inferior rectal nerve was harvested, resin-embedded, sectioned (1 microm thickness), and axonal counts and axonal cross-sectional areas were analyzed using Scion Image software., Results: Somatosensory evoked cortical potentials were reduced in the nerve crush and balloon compression groups compared with controls (P = 0.024, P = 0.03, respectively). The inferior rectal nerve was harvested in 14 of the 18 animals (4 control, 5 nerve crush, 5 balloon compression). There were no differences in median inferior rectal nerve total axonal counts (P = 0.69) or in the frequency distribution of axonal cross-sectional area between groups (control vs. nerve crush and control vs. balloon compression: P = 0.92, P = 0.17, respectively)., Conclusions: Somatosensory evoked cortical potential amplitude is reduced following crush or compression injury to the inferior rectal nerve. In neuropathic fecal incontinence, alteration in cortical awareness may be the result of processing modification at a central and not peripheral level.

Background: Current prognostic molecular markers for epithelial ovarian cancer (EOC) are insufficient. The aim of the current study was to investigate the role of Sox11 in EOC., Methods: Using an in silico transcriptomic screen, Sox11 was identified as a potential EOC biomarker. Sox11 protein expression was evaluated using immunohistochemistry (IHC) in 76 EOC cases, which were analysed using automated algorithms to develop a quantitative scoring model., Results: Sox11 mRNA expression was upregulated in EOC compared to normal tissues. Automated analysis of Sox11 in the EOC cohort revealed high expression of Sox11, in 40% of tumours, who had an improved recurrence-free survival (RFS) (p=0.002). Multivariate analysis confirmed that Sox11 was an independent predictor of improved RFS after controlling for stage and grade., Conclusions: These data suggest that Sox11 is a new prognostic marker in EOC. Loss of Sox11 is associated with a decreased RFS and a more aggressive phenotype.

Problem: Cycle-dependent fluctuations in natural killer (NK) cell populations in endometrium and circulation may differ, contributing to unexplained infertility., Method of Study: NK cell phenotypes were determined by flow cytometry in endometrial biopsies and matched blood samples., Results: While circulating and endometrial T cell populations remained constant throughout the menstrual cycle in fertile and infertile women, circulating NK cells in infertile women increased during the secretory phase. However, increased expression of CD94, CD158b (secretory phase), and CD158a (proliferative phase) by endometrial NK cells from infertile women was observed. These changes were not reflected in the circulation., Conclusion: In infertile women, changes in circulating NK cell percentages are found exclusively during the secretory phase and not in endometrium; cycle-related changes in NK receptor expression are observed only in infertile endometrium. While having exciting implications for understanding NK cell function in fertility, our data emphasize the difficulty in attaching diagnostic or prognostic significance to NK cell analyses in individual patients.

Purpose: Childbirth is the most common cause of fecal incontinence and damage to the pudendal nerve is a major component of childbirth injury. This study was designed to develop an acute animal model of injury to the innervation of the external anal sphincter., Methods: Forty-eight female virgin wistar rats were studied. Two models of neuropathic injury were developed. Bilateral inferior rectal nerve crush (Group A) acted as a positive control. Prolonged intrapelvic retrouterine balloon inflation (Group B) simulated the pelvic compressive forces of labor. Quantitative analysis of external anal sphincter muscle function was performed by using electromyography, external anal sphincter specific force production, and stereologic calculation of external anal sphincter mass., Results: Injury in both groups caused significant atrophy of the external anal sphincter (P = 0.002, ANOVA) and electromyographic evidence of reinnervation at one week. Specific force (mN force per mg mass) was not altered. External anal sphincter muscle mass recovered after four weeks in Group B., Conclusions: Balloon dilation within the boney pelvis results in denervation of the external anal sphincter and offers an experimental model of the effects of childbirth on the continence mechanism in humans.

Perineal outcome in 1000 consecutive term non instrumental second vaginal deliveries was correlated with first delivery method and perineal outcome. Our aim was to determine the relationship between perineal outcome at first and second vaginal deliveries. Overall 75% of first non instrumental vaginal deliveries required sutures. Sutures were required at second delivery in 12% (24 of 199) of cases not sutured at first delivery compared with 60.4% (485 of 801) of those sutured. The rate of second perineal repair correlated with method of first delivery and perineal outcome, instrumental delivery--66.2% (145 of 219), first episiotomy-68.4% (238 of 348) and first sutured tear--43.6% (102 of 234). The incidence of third /fourth degree tear at first delivery was 1.3% (13/1000) (one recurred at second forceps delivery), compared with 0.6% at second delivery. First delivery outcome should be considered when conducting a second delivery as sixty per cent of women require perineal repair following repair at first delivery.

Purpose: The study was designed to determine the effect of further vaginal delivery on anal sphincter function in women after apparently uncomplicated primiparous forceps delivery., Methods: Fifty-two secundigravid women whose first child was forceps-assisted were compared with a control group of 20 women who had undergone spontaneous first vaginal delivery. Both groups were studied antenatally and again at 12 weeks after second delivery using a standardized bowel function questionnaire, endoanal ultrasound, and anal manometry. The primary outcome was fecal incontinence score after second delivery., Results: Before second delivery, 20 of 52 (39 percent) of the forceps group and 3 of 20 (15 percent) control subjects (P = 0.103) reported minor alteration in fecal incontinence. Endoanal ultrasound was more frequently abnormal (38/52 (73 percent) vs. 6/20 (30 percent); P = 0.002), and median anal canal squeeze (71 vs. 104 mmHg; P = 0.004) and resting pressures (43 vs. 58 mmHg; P = 0.004) were lower in the forceps group. There was no difference in continence score between first and second delivery for the forceps group (P = 0.19) group or control subjects (P = 0.18). However, 10 of 38 (26 percent) women with an abnormal endoanal ultrasound after first forceps delivery developed new or worsening symptoms after second delivery., Conclusions: One-quarter of women with occult anal sphincter injury after first forceps delivery experienced some minor alteration in fecal continence after the second delivery.

Background: The distribution of neonatal blood thyroid-stimulating hormone (TSH) concentrations has been used as an index reflecting population dietary iodine intake, with higher concentrations being indicative of lower iodine intake. We examined this distribution in neonates born in Ireland, where the pregnant population has shown a recent decline in urinary iodine (UI) excretion. Our objectives were to determine if any alteration was observed in the percentage of values > 5.0 mIU/L and whether a trend in neonatal blood TSH was apparent., Methods: Samples drawn from the National Neonatal Screening Programme were assessed during the years 1995-2006 from winter (January n = 35,079) and summer (August n = 37,940) months, respectively, in view of the known seasonal variation in Irish dietary iodine intake., Results: Apart from the first years studied (1995-1996), the proportion of individual blood TSH values >5.0 mIU/L did not exceed 3%, a value believed to be indicative of iodine deficiency. A significant declining trend in the proportion of blood TSH >5.0 mIU/L was observed in subsequent years (p < 0.01). While excluding severe iodine deficiency, these analyses failed to detect the slight but highly significant (p < 0.001) tendency toward increasing blood TSH within the 0-5.0 mIU/L interval in the study population between 1999 and 2006, which was greater in summer than in winter months (p < 0.001)., Conclusions: These data support a link between fetal thyroid function and a fall in maternal iodine intake. While the findings of the proportion of blood TSH values >5.0 mIU/L exclude severe maternal or fetal iodine deficiency, a trend toward increasing TSH may provide an early indication of impending iodine deficiency. The findings assume greater importance in the context of declining UI reported from many developed countries even where the proportion of blood TSH values >5.0 mIU/L is <3%, thus excluding severe maternal and fetal iodine deficiency.

Oxidative stress is associated with skeletal muscle fatigue. This study tests the hypotheses that N-acetylcysteine (NAC) reduces fatigue and accelerates recovery of the rat external anal sphincter (EAS). Fifteen female Wistar rats were killed humanely. The EAS was mounted as a ring preparation and electrically stimulated with 50 Hz trains of 200 ms in duration every 4 s for three and a half minutes. Three groups were analysed: a control group (n = 5), a group pretreated with NAC (10(-4) mol L(-1); n = 5) and a group pretreated with NAC (10(-3) mol L(-1); n = 5). A novel fatigue index was formulated and was compared to a conventional method of expressing fatigue. There was no significant difference at concentrations of NAC (10(-4) mol L(-1); P > 0.05). At high concentrations of NAC (10(-3) mol L(-1)) there was a significant depression in peak twitch amplitude before fatigue (P = 0.04). N-acetylcysteine in both concentrations used, did not alter fatigue or recovery of the rat EAS. There was a significant positive correlation between the two methods of expressing fatigue but the conventional method produced a higher fatigue index (22.4% on average). N-acetylcysteine does not ameliorate fatigue or accelerate recovery of the EAS and may not be a useful medical therapy for faecal incontinence.

The Mirena intrauterine system (IUS) has improved the options available to women with menorrhagia. However, in some women, IUS treatment fails to reduce menstrual flow, and surgical treatment, including hysterectomy, is necessary. We have reviewed the histopathological findings on the uteri of 44 women undergoing hysterectomy because of menorrhagia after unsuccessful IUS treatment to assess whether a potentially unresponsive cohort could be identified. A retrospective review of 44 hysterectomy specimens was performed between October 1999 and April 2006 on women who underwent unsuccessful treatment of menorrhagia with the IUS. The patients' ages ranged from 30 to 53 years (median age, 43 years; all were premenopausal). Most women (60%) had the expected appearance of atrophy of the endometrial glands and pseudodecidual stromal reaction. Thirty hysterectomy specimens contained benign leiomyomata with associated reduced reactivity in the uterine cavity and incomplete suppression of the endometrium. In some cases (n = 10), the fibroids had displaced the IUS in the uterine cavity. Fourteen specimens showed adenomyosis, of which 8 also contained fibroids. In addition to leiomyomas, 1 specimen had an atypical polypoid adenomyoma and 1 had a benign adenomatoid tumor. Two specimens had endometrial hyperplasia for which the IUS was unsuccessful in controlling bleeding. Two specimens showed intrauterine misplacement of the IUS. Only 6 women (13.6%) had no histological abnormalities. Most women (86%) undergoing hysterectomy because of abnormal uterine bleeding with a Mirena IUS in situ had uterine abnormalities, as revealed by pathological review. Although recent reports have indicated that the IUS can be used successfully in the treatment of menorrhagia due to uterine fibroids, most cases of hysterectomies in this series after failed IUS suppression of menorrhagia contained uterine fibroids.

This study examines the relationship between maternal weight characteristics and recurrence of macrosomia in 111 non-diabetic women who delivered a second baby following primiparous delivery of a macrosomic infant (> 4500 g). Recurrence of fetal macrosomia was associated with greater maternal body mass index (P = 0.032), greater initial pregnancy weight (P < 0.05) and total weight gain during second pregnancy (P < 0.01). Women delivering a first macrosomic infant should avoid excessive weight gain before and during a subsequent pregnancy.