Coombe Women & Infants University Hospital

Continuing differences of opinion among obstetricians and neonatologists about the place of corticosteroid administration before preterm delivery have prompted us to carry out a systematic review of the relevant controlled trials, using methods designed to minimize systematic and random error. Data from 12 controlled trials, involving over 3000 participants, show that corticosteroids reduce the occurrence of respiratory distress syndrome overall and in all the subgroups of trial participants that we examined. This reduction in respiratory morbidity was associated with reductions in the risk of intraventricular haemorrhage, necrotizing enterocolitis and neonatal death. There is no strong evidence suggesting adverse effects of corticosteroids. The risks of fetal and neonatal infection may be raised if they are administered after prolonged rupture of the membranes, but this possibility is not substantiated by the results of the available trials. The available data on long-term follow-up suggest that the short-term beneficial effects of corticosteroids may be reflected in reduced neurological morbidity in the longer term.

OBJECTIVE: To assess the relative risk of perinatal mortality, severe preterm delivery, and low birth weight associated with previous treatment for precursors of cervical cancer. DATA SOURCES: Medline and Embase citation tracking from January 1960 to December 2007. Selection criteria Eligible studies had data on severe pregnancy outcomes for women with and without previous treatment for cervical intraepithelial neoplasia. Considered outcomes were perinatal mortality, severe preterm delivery (<32/34 weeks), extreme preterm delivery (<28/30 weeks), and low birth weight (<2000 g, <1500 g, and <1000 g). Excisional and ablative treatment procedures were distinguished. RESULTS: One prospective cohort and 19 retrospective studies were retrieved. Cold knife conisation was associated with a significantly increased risk of perinatal mortality (relative risk 2.87, 95% confidence interval 1.42 to 5.81) and a significantly higher risk of severe preterm delivery (2.78, 1.72 to 4.51), extreme preterm delivery (5.33, 1.63 to 17.40), and low birth weight of <2000 g (2.86, 1.37 to 5.97). Laser conisation, described in only one study, was also followed by a significantly increased chance of low birth weight of <2000 g and <1500 g. Large loop excision of the transformation zone and ablative treatment with cryotherapy or laser were not associated with a significantly increased risk of serious adverse pregnancy outcomes. Ablation by radical diathermy was associated with a significantly higher frequency of perinatal mortality, severe and extreme preterm delivery, and low birth weight below 2000 g or 1500 g. CONCLUSIONS: In the treatment of cervical intraepithelial neoplasia, cold knife conisation and probably both laser conisation and radical diathermy are associated with an increased risk of subsequent perinatal mortality and other serious pregnancy outcomes, unlike laser ablation and cryotherapy. Large loop excision of the transformation zone cannot be considered as completely free of adverse outcomes.

BACKGROUND: Respiratory distress syndrome is a serious complication of prematurity causing significant immediate and long-term mortality and morbidity. OBJECTIVES: The objective of this review was to assess the effects of corticosteroids administered to pregnant women to accelerate fetal lung maturity prior to preterm delivery. SEARCH STRATEGY: The Cochrane Pregnancy and Childbirth Group trials register was searched. SELECTION CRITERIA: Randomised and quasi-randomised trials of corticosteroid drugs capable of crossing the placenta compared with placebo or no treatment in women expected to deliver preterm as a result of either spontaneous preterm labour, prelabour rupture of the membranes preterm, or elective preterm delivery. DATA COLLECTION AND ANALYSIS: Eligibility and trial quality were assessed by one reviewer. MAIN RESULTS: Eighteen trials including data on over 3700 babies were included. Antenatal administration of 24 milligrams of betamethasone, of 24 milligrams of dexamethasone, or two grams of hydrocortisone to women expected to give birth preterm was associated with a significant reduction in mortality (odds ratio 0.60, 95% confidence interval 0.48 to 0.75), respiratory distress syndrome (odds ratio 0.53, 95% confidence interval 0.44 to 0.63) and intraventricular haemorrhage in preterm infants. These benefits extended to a broad range of gestational ages and were not limited by gender or race. No adverse consequences of prophylactic corticosteroids for preterm birth have been identified. REVIEWER'S CONCLUSIONS: Corticosteroids given prior to preterm birth (as a result of either preterm labour or elective preterm delivery) are effective in preventing respiratory distress syndrome and neonatal mortality. However there is not enough evidence to evaluate the use of repeated doses of corticosteroids in women who remain undelivered, but who are at continued risk of preterm birth. (This abstract has been prepared centrally.)

BACKGROUND: Expectant management of the third stage of labour involves allowing the placenta to deliver spontaneously or aiding by gravity or nipple stimulation. Active management involves administration of a prophylactic oxytocic after delivery, early cord clamping and cutting, and controlled cord traction of the umbilical cord. OBJECTIVES: The objective of this review was to assess the effects of active versus expectant management on blood loss, post partum haemorrhage and other maternal and perinatal complications of the third stage of labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group trials register. SELECTION CRITERIA: Randomised trials comparing active and expectant management of the third stage of labour in women with singleton pregnancies whose babies were presenting head first and who were expecting a vaginal delivery. DATA COLLECTION AND ANALYSIS: Trial quality was assessed and data were extracted independently by the reviewers. MAIN RESULTS: Four studies were included. Three of the trials were of good quality. Compared to expectant management, active management (in the setting of a maternity hospital) was associated with the following reduced risks: maternal blood loss (weighted mean difference -79.33 millilitres, 95% confidence interval -94.29 to -64. 37); post partum haemorrhage of more than 500 millilitres (odds ratio 0.34, 95% confidence interval 0.28 to 0.41); prolonged third stage of labour (weighted mean difference -3.40 minutes, 95% confidence interval -4.66 to -2.13). Active management was associated with an increased risk of maternal nausea (odds ratio 1. 95, 95% confidence interval 1.58 to 2.42), vomiting and raised blood pressure (probably due to the use of ergometrine). No advantages or disadvantages were apparent for the baby. REVIEWER'S CONCLUSIONS: Routine 'active management' is superior to 'expectant management' in terms of blood loss, post partum haemorrhage and other serious complications of the third stage of labour. Active managment is, however, associated with an increased risk of unpleasant side effects (eg nausea and vomiting), and hypertension, where ergometrine is used. Active management should be the routine management of choice for women expecting a single baby by vaginal delivery in a maternity hospital. The implications are less clear for other settings including domiciliary practice (in developing and industrialised countries).

OBJECTIVE: Intestinal pathology, i.e., ileocolonic lymphoid nodular hyperplasia (LNH) and mucosal inflammation, has been described in children with developmental disorders. This study describes some of the endoscopic and pathological characteristics in a group of children with developmental disorders (affected children) that are associated with behavioral regression and bowel symptoms, and compares them with pediatric controls. METHODS: Ileocolonoscopy and biopsy were performed on 60 affected children (median age 6 yr, range 3-16; 53 male). Developmental diagnoses were autism (50 patients), Asperger's syndrome (five), disintegrative disorder (two), attention deficit hyperactivity disorder (ADHD) (one), schizophrenia (one), and dyslexia (one). Severity of ileal LNH was graded (0-3) in both affected children and 37 developmentally normal controls (median age 11 yr, range 2-13 yr) who were investigated for possible inflammatory bowel disease (IBD). Tissue sections were reviewed by three pathologists and scored on a standard proforma. Data were compared with ileocolonic biopsies from 22 histologically normal children (controls) and 20 children with ulcerative colitis (UC), scored in an identical manner. Gut pathogens were sought routinely. RESULTS: Ileal LNH was present in 54 of 58 (93%) affected children and in five of 35 (14.3%) controls (p < 0.001). Colonic LNH was present in 18 of 60 (30%) affected children and in two of 37 (5.4%) controls (p < 0.01). Histologically, reactive follicular hyperplasia was present in 46 of 52 (88.5%) ileal biopsies from affected children and in four of 14 (29%) with UC, but not in non-IBD controls (p < 0.01). Active ileitis was present in four of 51 (8%) affected children but not in controls. Chronic colitis was identified in 53 of 60 (88%) affected children compared with one of 22 (4.5%) controls and in 20 of 20 (100%) with UC. Scores of frequency and severity of inflammation were significantly greater in both affected children and those with UC, compared with controls (p < 0.001). CONCLUSIONS: A new variant of inflammatory bowel disease is present in this group of children with developmental disorders.

Please cite this paper as: Lutomski J, Byrne B, Devane D, Greene R. Increasing trends in atonic postpartum haemorrhage in Ireland: an 11‐year population‐based cohort study. BJOG 2011; DOI: 10.1111/j.1471‐0528.2011.03198.x Objective To derive nationally representative incidence rates of postpartum haemorrhage (PPH), and to investigate trends associated with method of delivery, blood transfusion and morbidly adherent placenta (accreta, percreta and increta). Design Population‐based retrospective cohort study. Setting Republic of Ireland. Population Childbirth hospitalisations during the period 1999–2009. Methods International Classification of Diseases (ICD)‐9‐CM and ICD‐10‐AM diagnostic codes from hospital discharge records were used to identify cases of PPH. Significant temporal trends in PPH incidence were determined using Cochrane–Armitage tests for trend. Log‐binomial regression was conducted to assess annual changes in the risk of PPH diagnosis, with adjustment for potential confounding factors. Main outcome measures PPH, uterine atony, blood transfusion and morbidly adherent placenta. Results A total of 649 019 childbirth hospitalisations were recorded; 2.6% ( n = 16 909) included a diagnosis of PPH. The overall PPH rate increased from 1.5% in 1999 to 4.1% in 2009; atonic PPH rose from 1.0% in 1999 to 3.4% in 2009. Significant increasing trends in atonic PPH rates were observed across vaginal, instrumental, and emergency and elective caesarean deliveries ( P &lt; 0.001). The rate of atonic PPH co‐diagnosed with blood transfusion also significantly increased ( P &lt; 0.001). Relative to 1999, the risk of atonic PPH in 2009 was three‐fold increased (adjusted RR 3.03; 95% CI 2.76–3.34). Women diagnosed with a morbidly adherent placenta had a markedly higher risk of total PPH (unadjusted RR 13.14; 95% CI 11.43–15.11). Conclusions Increasing rates of atonic PPH highlight the pressing need for research and for clinical audit focusing on aetiological factors, preventative measures and quality of care, to guide current clinical practice.

AIM: To analyse and compare expression patterns of three potential biomarkers-p16(INK4A), CDC6, and MCM5-and evaluate their use as predictive biomarkers in squamous and glandular cervical preinvasive neoplasia. METHODS: Immunocytochemical analysis of p16(INK4A), MCM5, and CDC6 expression was performed on 20 normal, 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, 10 squamous cell carcinoma, 19 cervical glandular intraepithelial neoplasia (cGIN), and 10 adenocarcinoma samples. Staining intensity was assessed using a 0-3 scoring system. p16(INK4A), MCM5, and CDC6 expression was also examined in ThinPrep slides exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) was detected using a modified SYBR green assay. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: All three markers showed a linear correlation between expression and grade of dysplasia. p16(INK4A) and MCM5 protein expression was upregulated in all grades of squamous and glandular dysplasia. CDC6 protein was preferentially expressed in high grade lesions and in invasive squamous cell carcinoma. CONCLUSION: p16(INK4A) expression was closely associated with high risk HPV infection-all grades of squamous and glandular cervical lesions were immunohistochemically positive. MCM5 staining intensity was independent of high risk HPV infection, highlighting its potential as a biomarker in both HPV dependent and independent cervical dysplasia. CDC6 may be a biomarker of high grade and invasive lesions of the cervix, with limited use in low grade dysplasia. p16(INK4A) was the most reliable marker of cervical dysplasia. Combinations of dysplastic biomarkers may be useful in difficult diagnostic cases.

Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical specimens dated 2001-2008. The pooled prevalence of individual HPV types was estimated using meta-analytic methods. A total of 3,103 women were diagnosed with HG-CIN and a total of 3,162 with ICC (median ages: 34 and 49 years, respectively), of which 98.5 and 91.8% were HPV-positive, respectively. The most common HPV types in women with HG-CIN were HPV16/33/31 (59.9/10.5/9.0%) and in ICC were HPV16/18/45 (63.3/15.2/5.3%). In squamous cell carcinomas, HPV16/18/33 were most frequent (66.2/10.8/5.3%), and in adenocarcinomas, HPV16/18/45 (54.2/40.4/8.3%). The prevalence of HPV16/18/45 was 1.1/3.5/2.5 times higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both HG-CIN and ICC, whereas HPV18/45 are associated with a low median age of ICC. HPV18/45 are more frequent in ICC than HG-CIN and associated with a high median age of HG-CIN, with a narrow age interval between HG-CIN and ICC detection. These findings support the need for primary prevention of HPV16/18/45-related cervical lesions.

BACKGROUND: Azathioprine (AZA) is used during pregnancy by women with inflammatory bowel disease (IBD), other autoimmune disorders, malignancy, and organ transplantation. Previous studies have demonstrated potential risks. METHODS: The Swedish Medical Birth Register was used to identify 476 women who reported the use of AZA in early pregnancy. The effect of AZA exposure on pregnancy outcomes was studied after adjustment for maternal characteristics that could act as confounders. RESULTS: The most common indication for AZA use was IBD. The rate of congenital malformations was 6.2% in the AZA group and 4.7% among all infants born (adjusted OR: 1.41, 95% CI: 0.98-2.04). An association between early pregnancy AZA exposure and ventricular/atrial septal defects was found (adjusted OR: 3.18, 95% CI: 1.45-6.04). Exposed infants were also more likely to be preterm, to weigh <2500 gm, and to be small for gestational age compared to all infants born. This effect remained for preterm birth and low birth weight when infants of women with IBD but without AZA exposure were used as a comparison group. A trend toward an increased risk of congenital malformations was found among infants of women with IBD using AZA compared to women with IBD not using AZA (adjusted OR: 1.42, 95% CI: 0.93-2.18). CONCLUSIONS: Infants exposed to AZA in early pregnancy may be at a moderately increased risk of congenital malformations, specifically ventricular/atrial septal defects. There is also an increased risk of growth restriction and preterm delivery. These associations may be confounded by the severity of maternal illness.

BACKGROUND: The admission cardiotocograph (CTG) is a commonly used screening test consisting of a short (usually 20 minutes) recording of the fetal heart rate (FHR) and uterine activity performed on the mother's admission to the labour ward. This is an update of a review published in 2012. OBJECTIVES: To compare the effects of admission cardiotocography with intermittent auscultation of the FHR on maternal and infant outcomes for pregnant women without risk factors on their admission to the labour ward. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register to 30 November 2016 and we planned to review the reference list of retrieved papers SELECTION CRITERIA: All randomised and quasi-randomised trials comparing admission CTG with intermittent auscultation of the FHR for pregnant women between 37 and 42 completed weeks of pregnancy and considered to be at low risk of intrapartum fetal hypoxia and of developing complications during labour. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility and quality, and extracted data. Data were checked for accuracy. MAIN RESULTS: We included no new trials in this update. We included four trials involving more than 13,000 women which were conducted in the UK and Ireland and included women in labour. Three trials were funded by the hospitals where the trials took place and one trial was funded by the Scottish government. No declarations of interest were made in two trials; the remaining two trials did not mention declarations of interest. Overall, the studies were assessed as low risk of bias. Results reported in the 2012 review remain unchanged.Although not statistically significant using a strict P < 0.05 criterion, data were consistent with women allocated to admission CTG having, on average, a higher probability of an increase in incidence of caesarean section than women allocated to intermittent auscultation (risk ratio (RR) 1.20, 95% confidence interval (CI) 1.00 to 1.44, 4 trials, 11,338 women, I² = 0%, moderate quality evidence). There was no clear difference in the average treatment effect across included trials between women allocated to admission CTG and women allocated to intermittent auscultation in instrumental vaginal birth (RR 1.10, 95% CI 0.95 to 1.27, 4 trials, 11,338 women, I² = 38%, low quality evidence) and perinatal mortality rate (RR 1.01, 95% CI 0.30 to 3.47, 4 trials, 11,339 infants, I² = 0%, moderate quality evidence).Women allocated to admission CTG had, on average, higher rates of continuous electronic fetal monitoring during labour (RR 1.30, 95% CI 1.14 to 1.48, 3 trials, 10,753 women, I² = 79%, low quality evidence) and fetal blood sampling (RR 1.28, 95% CI 1.13 to 1.45, 3 trials, 10,757 women, I² = 0%) than women allocated to intermittent auscultation. There were no differences between groups in other secondary outcome measures including incidence and severity of hypoxic ischaemic encephalopathy (incidence only reported) (RR 1.19, 95% CI 0.37 to 3.90; 2367 infants; 1 trial; very low quality evidence) and incidence of seizures in the neonatal period (RR 0.72, 95% CI 0.32 to 1.61; 8056 infants; 1 trial; low quality evidence). There were no data reported for severe neurodevelopmental disability assessed at greater than, or equal to, 12 months of age. AUTHORS' CONCLUSIONS: Contrary to continued use in some clinical areas, we found no evidence of benefit for the use of the admission CTG for low-risk women on admission in labour.Furthermore, the probability is that admission CTG increases the caesarean section rate by approximately 20%. The data lacked power to detect possible important differences in perinatal mortality. However, it is unlikely that any trial, or meta-analysis, will be adequately powered to detect such differences. The findings of this review support recommendations that the admission CTG not be used for women who are low risk on admission in labour. Women should be informed that admission CTG is likely associated with an increase in the incidence of caesarean section without evidence of benefit.Evidence quality ranged from moderate to very low, with downgrading decisions based on imprecision, inconsistency and a lack of blinding for participants and personnel. All four included trials were conducted in developed Western European countries. One additional study is ongoing.The usefulness of the findings of this review for developing countries will depend on FHR monitoring practices. However, an absence of benefit and likely harm associated with admission CTG will have relevance for countries where questions are being asked about the role of the admission CTG.Future studies evaluating the effects of the admission CTG should consider including women admitted with signs of labour and before a formal diagnosis of labour. This would include a cohort of women currently having admission CTGs and not included in current trials.

BACKGROUND: Correlates and predictors of mood disturbances at 3 days and 6 weeks postpartum were assessed in Irish mothers and their partners. METHOD: The Edinburgh Postnatal Depression Scale (EPDS) and the Highs Scale were used to assess 370 mothers and their partners. Socio-demographic, clinical and obstetric data were collected at patients' first antenatal visit. Factors associated with EPDS scores of > or = 13 and Highs score of > or = 8 were examined. RESULTS: On the EPDS 11.4% of mothers scored > or = 13 at 3 days postpartum and 11% at 6 weeks, while 18.3% of mothers scored > or = 8 on the Highs Scale at 3 days and 9% at 6 weeks. Scores on the EPDS and Highs Scale were interrelated. Factors associated with EPDS scores of > or = 13 at 6 weeks were single status, unemployment, unplanned pregnancy, public status and bottlefeeding. The best predictors of EPDS > or = 13 at 6 weeks were mothers' scores on the EPDS and the Highs Scale at 3 days. Three per cent of partners scored > or = 13 on the EPDS at 3 days postpartum and 1.2% at 6 weeks. CONCLUSIONS: Factors associated with mothers' mood disturbance were readily identifiable and collected routinely at antenatal intake. Mothers' mood within 3 days of delivery was the best predictor of later postnatal depression. Paternal mood disturbance was rare. Certain women may be at increased risk for postnatal mood disturbance and may be amenable to early identification and intervention.

OBJECTIVES: Patent ductus arteriosus (PDA) remains a challenging issue in very low birth weight (VLBW) infants, and its management varies widely. Our aim in this study was to document the natural course of ductus arteriosus in a cohort of VLBW infants who underwent conservative PDA management with no medical or surgical intervention. METHODS: A retrospective cohort study conducted in 2 European level-3 neonatal units. RESULTS: A total of 368 VLBW infants were born within the study period. Two hundred and ninety-seven infants were free of congenital malformations or heart defects and survived to hospital discharge. Out of those, 280 infants received truly conservative PDA management. In 237 (85%) of nontreated infants, the PDA closed before hospital discharge. The Kaplan-Meier model was used to document the incidence proportion of PDA closure over time for different gestational age groups. The median time to ductal closure was 71, 13, 8, and 6 days in <26+0, 26+0 to 27+6, 28+0 to 29+6, and ≥30 weeks, respectively. For different birth weight groups, the median was 48, 22, 9, and 8 days in infants weighing <750, 750 to 999, 1000 to 1249, and 1250 to 1500 g, respectively. No statistically significant relationship was found between PDA closure before hospital discharge and neonatal morbidities. CONCLUSIONS: The likelihood of PDA spontaneous closure in VLBW infants is extremely high. We provide in our findings a platform for future placebo-controlled trials focused on the smallest and youngest infants.

AIM: To examine the potential of p16(INK4A) as a biomarker for dysplastic squamous and glandular cells of the cervix in tissue sections and ThinPrep smears. METHODS: Immunocytochemical analysis of p16(INK4A) expression was performed on 22 normal cervical tissue samples, five cervical glandular intraepithelial neoplasia (cGIN), 38 cervical intraepithelial neoplasia 1 (CIN1), 33 CIN2, 46 CIN3, and 10 invasive cancer cases (eight squamous and two adenocarcinomas). All samples were formalin fixed and paraffin wax embedded, and immunohistochemical analysis was carried out using a mouse monoclonal anti-p16(INK4A) antibody after antigen unmasking. The staining intensity was assessed using a 0 to 3 scoring system. In addition, the expression status of p16(INK4A) was examined in 12 normal ThinPrep smears, one smear exhibiting cGIN, and a total of 20 smears exhibiting mild, moderate, and severe dyskaryosis. Human papillomavirus (HPV) detection was carried out using a modified SYBR green assay system. Fluorogenic polymerase chain reaction (PCR) and solution phase PCR were used for specific HPV typing. RESULTS: p16(INK4A) immunoreactivity was absent in all normal cervical tissues examined. Dysplastic squamous and glandular cells were positive for p16(INK4A) expression in all cases included in this study, except for one CIN3 case. p16(INK4A) expression was mainly nuclear in CIN1 cases, and both nuclear and cytoplasmic in CIN2, CIN3, cGIN, and invasive cases. All cases positive for HPV expressed the p16(INK4A) protein, although not all cases found positive for p16(INK4A) were HPV positive. In general, the p16(INK4A) staining intensity was lower in cases negative for HPV or those containing a low risk HPV type. CONCLUSION: This pattern of overexpression demonstrates the potential use of p16(INK4A) as a diagnostic marker for cervical squamous and also glandular neoplastic lesions. In addition, the technique can be used to identify individual dyskaryotic cells in ThinPrep smears. Thus, p16(INK4A) is a useful marker of cervical dyskaryosis.

OBJECTIVES: To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section. DESIGN: Randomised trial, conducted from May 2004 to August 2006. SETTING: Four maternity units in south west England, and Scotland. PARTICIPANTS: 742 pregnant women with one previous lower segment caesarean section and delivery expected at >or=37 weeks. Non-English speakers were excluded. INTERVENTIONS: Usual care: standard care given by obstetric and midwifery staff. Information programme: women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth, elective caesarean section, and emergency caesarean section. Decision analysis: mode of delivery was recommended based on utility assessments performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree. Both interventions were delivered via a laptop computer after brief instructions from a researcher. MAIN OUTCOME MEASURES: Total score on decisional conflict scale, and mode of delivery. RESULTS: Women in the information programme (adjusted difference -6.2, 95% confidence interval -8.7 to -3.7) and the decision analysis (-4.0, -6.5 to -1.5) groups had reduced decisional conflict compared with women in the usual care group. The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group (37% v 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were similar in the information programme and usual care groups. CONCLUSIONS: Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy. The decision analysis approach might substantially affect national rates of caesarean section. Trial Registration Current Controlled Trials ISRCTN84367722.

OBJECTIVE: To determine the incidence of maternal bacteraemia during pregnancy and for 6 weeks postpartum, describe the gestation/stage at which sepsis occurs, the causative microorganisms, antibiotic resistance and review maternal, fetal and neonatal outcome. DESIGN: Prospective review. SETTING: Two tertiary referral, maternity hospitals in Dublin, Ireland. POPULATION: During 2005-2012 inclusive, 150 043 pregnant women attended and 24.4% of infants born in Ireland were delivered at the hospitals. METHODS: Demographic, clinical, microbiological and outcome data was collected from women with sepsis and compared with controls. MAIN OUTCOME MEASURES: Incidence, bacterial aetiology, gestation/stage at delivery, mode of delivery, antibiotic resistance, admission to augmented care, maternal, fetal and neonatal outcome. RESULTS: The sepsis rate was 1.81 per 1000 pregnant women. Escherichia coli was the predominant pathogen, followed by Group B Streptococcus. Sepsis was more frequent among nulliparous women (odds ratio [OR] 1.39; 95% confidence interval [CI] 1.07-1.79) and multiple births (OR 2.04; 95% CI 0.98-4.08). Seventeen percent of sepsis episodes occurred antenatally, 36% intrapartum and 47% postpartum. The source of infection was the genital tract in 61% (95% CI 55.1-66.6) of patients and the urinary tract in 25% (95% CI 20.2-30.5). Sepsis was associated with preterm delivery (OR 2.81; 95% CI 1.99-3.96) and a high perinatal mortality rate (OR =5.78; 95% CI 2.89-11.21). Almost 14% of women required admission to augmented care. The most virulent organisms were Group A Streptococcus linked to postpartum sepsis at term and preterm Escherichia coli sepsis. CONCLUSIONS: Maternal sepsis is associated with preterm birth, a high perinatal mortality rate and nulliparous women.

Viral pathogens are the most common cause of gastroenteritis in developed countries. Human rotavirus and adenovirus infections are major causes of acute outbreaks and sporadic cases of gastroenteritis, occurring primarily among children less than 2 years of age. Patient hospitalization is often required, with enormous infection control implications. This work describes the development of real-time PCR assays for the detection of group F adenovirus, rotavirus A, and rotavirus C from stool specimens. Two hundred twenty stool samples from pediatric patients exhibiting symptoms of diarrhea and/or vomiting were examined. PCR results were compared with those of virus detection by electron microscopy and latex agglutination antigen detection. The incorporation of an internal-control RNA that was spiked into individual stool extracts functioned as an internal validation for the reporting of PCR-negative results. Rotavirus C was not detected by real-time PCR in the patient stool samples examined. Real-time reverse transcription-PCR resulted in 175% and 111% increases in the rates of detection of adenovirus F and rotavirus A, respectively, compared with latex agglutination testing. Molecular detection increased the number of stool specimens in which causative agents of gastroenteritis were identified by 155% compared to electron microscopy. Genotyping of a proportion of the rotavirus and adenovirus strains identified only genotype G1 rotavirus and both adenovirus genotypes 40 and 41 in circulation within the patient cohort examined. The results highlight the significance of rapid molecular methods for the routine screening of stool samples in hospital laboratories to provide rapid definitive diagnoses.

AIM: To determine if there is a relationship between maternal methadone dose in pregnancy and the diagnosis or medical treatment of neonatal abstinence syndrome (NAS). METHODS: PubMed, EMBASE, the Cochrane Library and PsychINFO were searched for studies reporting on methadone use in pregnancy and NAS (1966-2009). The relative risk (RR) of NAS was compared for methadone doses above versus below a range of cut-off points. Summary RRs and 95% confidence intervals (CI) were estimated using random effects meta-analysis. Sensitivity analyses explored the impact of limiting meta-analyses to prospective studies or studies using an objective scoring system to diagnose NAS. RESULTS: A total of 67 studies met inclusion criteria for the systematic review; 29 were included in the meta-analysis. Any differences in the incidence of NAS in infants of women on higher compared with lower doses were statistically non-significant in analyses restricted to prospective studies or to those using an objective scoring system to diagnose NAS. CONCLUSIONS: Severity of the neonatal abstinence syndrome does not appear to differ according to whether mothers are on high- or low-dose methadone maintenance therapy.

AIMS: A new form of inflammatory bowel disease (ileocolonic lymphonodular hyperplasia) has been described in a cohort of children with developmental disorder. This study investigates the presence of persistent measles virus in the intestinal tissue of these patients (new variant inflammatory bowel disease) and a series of controls by molecular analysis. METHODS: Formalin fixed, paraffin wax embedded and fresh frozen biopsies from the terminal ileum were examined from affected children and histological normal controls. The measles virus Fusion (F) and Haemagglutinin (H) genes were detected by TaqMan reverse transcription polymerase chain reaction (RT-PCR) and the Nucleocapsid (N) gene by RT in situ PCR. Localisation of the mRNA signal was performed using a specific follicular dendritic cell antibody. RESULTS: Seventy five of 91 patients with a histologically confirmed diagnosis of ileal lymphonodular hyperplasia and enterocolitis were positive for measles virus in their intestinal tissue compared with five of 70 control patients. Measles virus was identified within the follicular dendritic cells and some lymphocytes in foci of reactive follicular hyperplasia. The copy number of measles virus ranged from one to 300,00 copies/ng total RNA. CONCLUSIONS: The data confirm an association between the presence of measles virus and gut pathology in children with developmental disorder.

OBJECTIVE: To compare the maternal and neonatal outcomes of operative vaginal delivery in relation to the use of episiotomy. DESIGN: Pilot randomised controlled trial (RCT). SETTING: Two urban maternity units in Scotland and England. SAMPLE: Nulliparous women anticipating a singleton cephalic vaginal delivery were recruited in the antenatal period. METHODS: If an operative vaginal delivery was required in the second stage of labour, women were randomised to either routine (in all cases) or restrictive (only if tearing apparent) use of episiotomy. MAIN OUTCOME MEASURES: The primary outcome was anal sphincter tearing (third or fourth degree). Secondary outcomes included postpartum haemorrhage (PPH), neonatal trauma and pelvic floor symptoms up until 10 days postpartum. RESULTS: In a group of 317 women requiring operative vaginal delivery, 200 were randomised: 99 to routine use of episiotomy and 101 to restrictive use. There were small differences in the rates of anal sphincter tears (8.1% routine versus 10.9% restrictive, OR 0.72, 95% CI 0.28-1.87) and primary PPH (36.4% routine versus 26.7% restrictive, OR 1.57, 95% CI 0.86-2.86). Neonatal trauma was similar between the two groups (45.5% routine versus 43.6% restrictive, OR 1.08, 95% CI 0.62-1.89), as was prolonged catheterisation, urinary incontinence, faecal incontinence, perineal infection and prolonged hospital admission. CONCLUSIONS: This pilot study does not provide conclusive evidence that a policy of routine episiotomy is better or worse than a restrictive policy. A definitive RCT is feasible but will require a large sample size to inform clinical practice.

The current paper presents the first part of Chapter 6 of the second edition of the European Guidelines for Quality Assurance in Cervical Cancer Screening. It provides guidance on how to manage women with abnormal cervical cytology. Throughout this article the Bethesda system is used for cervical cytology terminology, as the European guidelines have recommended that all systems should at least be translated into that terminology while cervical intraepithelial neoplasia (CIN) is used for histological biopsies (Cytopathology 2007; 18:213-9). A woman with a high-grade cytological lesion, a repeated low-grade lesion or with an equivocal cytology result and a positive human papillomavirus (HPV) test should be referred for colposcopy. The role of the colposcopist is to identify the source of the abnormal cells and to make an informed decision as to whether or not any treatment is required. If a patient requires treatment the colposcopist will decide which is the most appropriate method of treatment for each individual woman. The colposcopist should also organize appropriate follow-up for each woman seen. Reflex testing for high-risk HPV types of women with atypical squamous cells (ASC) of undetermined significance with referral for colposcopy of women who test positive is a first option. Repeat cytology is a second possibility. Direct referral to a gynaecologist should be restricted to special circumstances. Follow-up of low-grade squamous intraepithelial lesion is more difficult because currently there is no evidence to support any method of management as being optimal; repeat cytology and colposcopy are options, but HPV testing is not sufficiently selective, unless for older women. Women with high-grade squamous intraepithelial lesion (HSIL) or atypical squamous cells, cannot exclude HSIL (ASC-H) should be referred without triage. Women with glandular lesions require particular attention. In a subsequent issue of Cytopathology, the second part of Chapter 6 will be presented, with recommendations for management and treatment of histologically confirmed intraepithelial neoplasia and guidance for follow-up of special cases such as women who are pregnant, postmenopausal or immunocompromised.