Mastitis and Mammary Abscess Management Audit (MAMMA) in the UK and Ireland.

BACKGROUND: The aim of this multicentre prospective audit was to describe the current practice in the management of mastitis and breast abscesses in the UK and Ireland, with a specific focus on rates of surgical intervention. METHODS: This audit was conducted in two phases from August 2020 to August 2021; a phase 1 practice survey and a phase 2 prospective audit. Primary outcome measurements for phase 2 included patient management pathway characteristics and treatment type (medical/radiological/surgical). RESULTS: A total of 69 hospitals participated in phase 2 (1312 patients). The key findings were a high overall rate of incision and drainage (21.0 per cent) and a lower than anticipated proportion of ultrasound-guided aspiration of breast abscesses (61.0 per cent). Significant variations were observed regarding the rate of incision and drainage (range 0-100 per cent; P < 0.001) and the rate of needle aspiration (range 12.5-100 per cent; P < 0.001) between individual units. Overall, 22.5 per cent of patients were admitted for inpatient treatment, out of whom which 72.9 per cent were commenced on intravenous antibiotics. The odds of undergoing incision and drainage for a breast abscess or being admitted for inpatient treatment were significantly higher if patients presented at the weekend compared with a weekday (P ≤ 0.023). Breast specialists reviewed 40.9 per cent of all patients directly, despite the majority of patients (74.2 per cent) presenting within working hours on weekdays. CONCLUSIONS: Variation in practice exists in the management of mastitis and breast abscesses, with high rates of incision and drainage in certain regions of the UK. There is an urgent need for a national best-practice toolbox to minimize practice variation and standardize patient care.

Mastitis and breast abscess is a painful infection of the breast. It is an extremely common breast problem. One in three women can get this condition at some stage in their life. To treat a breast abscess, the pus inside should be drained out of the body. This can be done either by cutting into the breast using surgery or by inserting a fine needle using an ultrasonography scan (which uses ultrasound). Fine-needle drainage has the benefit that it does not require admission to hospital. Surgery can cause the breast to look misshapen. It is unknown which method is used more often in the UK and Ireland. The aim of this study was to describe how mastitis and breast abscesses are treated in the UK and Ireland. This study involved a survey of practice (phase 1) and collection of data, which are routinely recorded for these patients (phase 2). This study involved 69 hospitals and 1312 patient records. One in five women had an operation for a breast abscess. This was higher than expected. Six in 10 women had a pus drainage using a fine needle. The chance of having an operation depended on the hospital. Women that came to hospital at the weekend were almost twice as likely to have an operation. One in five women were admitted to hospital. The chances of that more than doubled if a woman came to hospital at the weekend. There are differences in treatment of mastitis and breast abscesses across the UK and Ireland. Changes need to be put in place to make access to treatment more equal.

Microbial-driven preterm labour involves crosstalk between the innate and adaptive immune response.

There has been a surge in studies implicating a role of vaginal microbiota in spontaneous preterm birth (sPTB), but most are associative without mechanistic insight. Here we show a comprehensive approach to understand the causative factors of preterm birth, based on the integration of longitudinal vaginal microbiota and cervicovaginal fluid (CVF) immunophenotype data collected from 133 women at high-risk of sPTB. We show that vaginal depletion of Lactobacillus species and high bacterial diversity leads to increased mannose binding lectin (MBL), IgM, IgG, C3b, C5, IL-8, IL-6 and IL-1ß and to increased risk of sPTB. Cervical shortening, which often precedes preterm birth, is associated with Lactobacillus iners and elevated levels of IgM, C3b, C5, C5a and IL-6. These data demonstrate a role for the complement system in microbial-driven sPTB and provide a scientific rationale for the development of live biotherapeutics and complement therapeutics to prevent sPTB.

Direct on-swab metabolic profiling of vaginal microbiome host interactions during pregnancy and preterm birth.

The pregnancy vaginal microbiome contributes to risk of preterm birth, the primary cause of death in children under 5 years of age. Here we describe direct on-swab metabolic profiling by Desorption Electrospray Ionization Mass Spectrometry (DESI-MS) for sample preparation-free characterisation of the cervicovaginal metabolome in two independent pregnancy cohorts (VMET, n = 160; 455 swabs; VMET II, n = 205; 573 swabs). By integrating metataxonomics and immune profiling data from matched samples, we show that specific metabolome signatures can be used to robustly predict simultaneously both the composition of the vaginal microbiome and host inflammatory status. In these patients, vaginal microbiota instability and innate immune activation, as predicted using DESI-MS, associated with preterm birth, including in women receiving cervical cerclage for preterm birth prevention. These findings highlight direct on-swab metabolic profiling by DESI-MS as an innovative approach for preterm birth risk stratification through rapid assessment of vaginal microbiota-host dynamics.

Pregnancy and neonatal outcomes in COVID-19: study protocol for a global registry of women with suspected or confirmed SARS-CoV-2 infection in pregnancy and their neonates, understanding natural history to guide treatment and prevention.

INTRODUCTION: Previous novel COVID-19 pandemics, SARS and middle east respiratory syndrome observed an association of infection in pregnancy with preterm delivery, stillbirth and increased maternal mortality. COVID-19, caused by SARS-CoV-2 infection, is the largest pandemic in living memory.Rapid accrual of robust case data on women in pregnancy and their babies affected by suspected COVID-19 or confirmed SARS-CoV-2 infection will inform clinical management and preventative strategies in the current pandemic and future outbreaks. METHODS AND ANALYSIS: The pregnancy and neonatal outcomes in COVID-19 (PAN-COVID) registry are an observational study collecting focused data on outcomes of pregnant mothers who have had suspected COVID-19 in pregnancy or confirmed SARS-CoV-2 infection and their neonates via a web-portal. Among the women recruited to the PAN-COVID registry, the study will evaluate the incidence of: (1) miscarriage and pregnancy loss, (2) fetal growth restriction and stillbirth, (3) preterm delivery, (4) vertical transmission (suspected or confirmed) and early onset neonatal SARS-CoV-2 infection.Data will be centre based and collected on individual women and their babies. Verbal consent will be obtained, to reduce face-to-face contact in the pandemic while allowing identifiable data collection for linkage. Statistical analysis of the data will be carried out on a pseudonymised data set by the study statistician. Regular reports will be distributed to collaborators on the study research questions. ETHICS AND DISSEMINATION: This study has received research ethics approval in the UK. For international centres, evidence of appropriate local approval will be required to participate, prior to entry of data to the database. The reports will be published regularly. The outputs of the study will be regularly disseminated to participants and collaborators on the study website (https://pan-covid.org) and social media channels as well as dissemination to scientific meetings and journals. STUDY REGISTRATION NUMBER: ISRCTN68026880.

Rapid quality improvement in a preterm birth clinic care pathway during the COVID-19 pandemic.

BACKGROUND: Preterm birth (PTB) occurs in 8% of births in the UK. At Imperial College Healthcare NHS Trust, our PTB prevention clinic manages the care of approximately 1000 women/year. Women referred to the clinic are seen from 12 weeks of pregnancy with subsequent appointments every 2-4 weeks to measure cervical length (CL) using transvaginal ultrasound (TVUS). Women with a history of cervical weakness or short cervix on TVUS are offered a cervical cerclage. LOCAL PROBLEM: During the COVID-19 outbreak, pregnant women were strongly advised to avoid social mixing and public transport. The National Health Service had to rapidly adopt remote consultation and redesign clinical pathways in order to reduce transmission, exposure and spread among women at high risk of PTB. METHODS: We focused on Specific, Measurable, Achievable, Realistic and Timebound aims and used a driver diagram to visualise our changes. We used a series of Plan Do Study Act cycles to evaluate and adapt change ideas through the UK's national lockdown during the COVID-19 pandemic between 23 March and 29 May 2020. RESULTS: We reduced the number of face-to-face appointments by 54%. This was achieved by increasing remote telephone consultations from 0% to 64%, and by reducing the intensity of surveillance. The rate of regional anaesthetic was increased from 53% to 95% for cerclage placement in order to minimise the number of aerosol-generating procedures. Patient and staff satisfaction responses to these changes were used to tailor practices. No women tested positive for COVID-19 during the study period. CONCLUSIONS: By using quality improvement methodology, we were able to safely and rapidly implement a new care pathway for women at high risk of PTB which was acceptable to patients and staff, and effective in reducing exposure of COVID-19.

The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk.

BACKGROUND: Preterm birth is the primary cause of infant death worldwide. A short cervix in the second trimester of pregnancy is a risk factor for preterm birth. In specific patient cohorts, vaginal progesterone reduces this risk. Using 16S rRNA gene sequencing, we undertook a prospective study in women at risk of preterm birth (n = 161) to assess (1) the relationship between vaginal microbiota and cervical length in the second trimester and preterm birth risk and (2) the impact of vaginal progesterone on vaginal bacterial communities in women with a short cervix. RESULTS: Lactobacillus iners dominance at 16 weeks of gestation was significantly associated with both a short cervix <25 mm (n = 15, P < 0.05) and preterm birth <34+0 weeks (n = 18; P < 0.01; 69% PPV). In contrast, Lactobacillus crispatus dominance was highly predictive of term birth (n = 127, 98% PPV). Cervical shortening and preterm birth were not associated with vaginal dysbiosis. A longitudinal characterization of vaginal microbiota (<18, 22, 28, and 34 weeks) was then undertaken in women receiving vaginal progesterone (400 mg/OD, n = 25) versus controls (n = 42). Progesterone did not alter vaginal bacterial community structure nor reduce L. iners-associated preterm birth (<34 weeks). CONCLUSIONS: L. iners dominance of the vaginal microbiota at 16 weeks of gestation is a risk factor for preterm birth, whereas L. crispatus dominance is protective against preterm birth. Vaginal progesterone does not appear to impact the pregnancy vaginal microbiota. Patients and clinicians who may be concerned about "infection risk" associated with the use of a vaginal pessary during high-risk pregnancy can be reassured.

Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage.

Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004-2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth.

Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage.

Preterm birth, the leading cause of death in children under 5 years, may be caused by inflammation triggered by ascending vaginal infection. About 2 million cervical cerclages are performed annually to prevent preterm birth. The procedure is thought to provide structural support and maintain the endocervical mucus plug as a barrier to ascending infection. Two types of suture material are used for cerclage: monofilament or multifilament braided. Braided sutures are most frequently used, although no evidence exists to favor them over monofilament sutures. We assessed birth outcomes in a retrospective cohort of 678 women receiving cervical cerclage in five UK university hospitals and showed that braided cerclage was associated with increased intrauterine death (15% versus 5%; P = 0.0001) and preterm birth (28% versus 17%; P = 0.0006) compared to monofilament suture. To understand the potential underlying mechanism, we performed a prospective, longitudinal study of the vaginal microbiome in women at risk of preterm birth because of short cervical length (≤25 mm) who received braided (n = 25) or monofilament (n = 24) cerclage under comparable circumstances. Braided suture induced a persistent shift toward vaginal microbiome dysbiosis characterized by reduced Lactobacillus spp. and enrichment of pathobionts. Vaginal dysbiosis was associated with inflammatory cytokine and interstitial collagenase excretion into cervicovaginal fluid and premature cervical remodeling. Monofilament suture had comparatively minimal impact upon the vaginal microbiome and its interactions with the host. These data provide in vivo evidence that a dynamic shift of the human vaginal microbiome toward dysbiosis correlates with preterm birth.

The effect of gestational age and cervical length measurements in the prediction of spontaneous preterm birth in twin pregnancies: an individual patient level meta-analysis.

OBJECTIVE: To assess the effect of gestational age (GA) and cervical length (CL) measurements at transvaginal ultrasound (TVUS) in the prediction of preterm birth in twin pregnancy. DESIGN: Individual patient data (IPD) meta-analysis. SETTING: International multicentre study. POPULATION: Asymptomatic twin pregnancy. METHODS: MEDLINE and EMBASE searches were performed and IPD obtained from authors of relevant studies. Multinomial logistic regression analysis determined probabilities for birth at ≤28(+0) , 28(+1) to 32(+0) , 32(+1) to 36(+0) , and ≥36(+1) weeks as a function of GA at screening and CL measurements. MAIN OUTCOME MEASURES: Predicted probabilities for preterm birth at ≤28(+0) , 28(+1) to 32(+0) , and 32(+1) to 36(+0) . RESULTS: A total of 6188 CL measurements were performed on 4409 twin pregnancies in 12 studies. Both GA at screening and CL had a significant and non-linear effect on GA at birth. The best prediction of birth at ≤28(+0) weeks was provided by screening at ≤18(+0) weeks (P < 0.001), whereas the best prediction of birth between 28(+1) and 36(+0) weeks was provided by screening at ≥24(+0) weeks (P < 0.001). Negative prediction value of 100% for birth at ≤28(+0) weeks is achieved at CL 65 mm and 43 mm at ultrasound GA at ≤18(+0) weeks and at 22(+1) to 24(+0) weeks, respectively. CONCLUSION: In twin pregnancies, prediction of preterm birth depends on both CL and the GA at screening. When CL is <30 mm, screening at ≤18(+0) weeks is most predictive for birth at ≤28(+0) weeks. Later screening at >22(+0) weeks is most predictive of delivery at 28(+1) to 36(+0) weeks. In twins, we recommend CL screening in twins to commence from ≤18(+0) weeks. TWEETABLE ABSTRACT: An individual patient meta-analysis assessing gestation and CL in the prediction of preterm birth in twins.

Management of hypertriglyceridaemia-induced acute pancreatitis in pregnancy.

INTRODUCTION: Acute pancreatitis is a recognised rare complication in pregnancy. The reported incidence varies between 3 and 7 in 10 000 pregnancies and is higher in the third trimester. The commonest causes in pregnancy include gallstones, alcohol and hypertriglyceridaemia. Non-gallstone pancreatitis is associated with more complications and poorer outcome with hypertriglyceridaemia-induced acute pancreatitis having mortality rates ranging from 7.5 to 9.0% and 10.0 to 17.5% for mother and foetus, respectively. CASE HISTORY: A 40-year-old para 4 woman, who presented at 15(+4) weeks' gestation, was diagnosed with acute pancreatitis. Past medical history included Graves' disease and hypertriglyceridaemia. Fenofibrate was discontinued immediately after discovery of the pregnancy. Initial investigations showed elevated amylase (475.0 µ/L) and triglycerides (46.6 mmol/L). Imaging revealed an inflamed pancreas without evidence of biliary obstruction/gallstones hence confirming the diagnosis of hypertriglyceridaemia-induced acute pancreatitis. Laboratory tests gradually improved (triglyceride 5.2 mmol/L on day 17). On day 18, ultrasound confirmed foetal demise (18(+1) weeks) and a hysterotomy was performed as she had had four previous caesarean sections. CONCLUSION: Management of acute pancreatitis in pregnancy requires a multi-disciplinary approach. Hypertriglyceridaemia-induced acute pancreatitis has poor outcomes when diagnosed in early pregnancy. Identifying those at risk pre-pregnancy and antenatally can allow close monitoring through pregnancy to optimise care.

Time interval from elective removal of cervical cerclage to onset of spontaneous labour.

OBJECTIVE: To determine the time interval between elective removal of a cervical cerclage to the onset of spontaneous labour in women who had either a history- or ultrasound-indicated cervical cerclage. STUDY DESIGN: A retrospective cohort study of women with a singleton pregnancy that had either a modified Shirodkar or McDonald cervical cerclage inserted were evaluated for the time interval between elective cerclage removal and onset of spontaneous labour and also spontaneous labour with 72 h of cervical cerclage removal. RESULTS: Two hundred and sixty-nine singleton pregnancies with either a modified Shirodkar or McDonald cervical cerclage were analysed. The mean gestational age at cerclage removal was 36.7 ± 1.10 weeks and gestational age at spontaneous labour was 39.0 ± 1.94 weeks (mean ± SD). The median interval between cerclage removal and spontaneous labour was 14 days. Only 18% of women laboured spontaneously within 72 h. Women with ultrasound-indicated cerclage were more likely to deliver within 72 h, compared with women with a history-indicated cervical cerclage (odds ratio, 3.68; 95% confidence interval, 1.31-10.85, p=0.01). CONCLUSION: Independent of the indication or technique used for cervical cerclage, the rate of early spontaneous labour following elective removal of cervical cerclage is sufficiently low to justify outpatient management.

Nuclear factor kappa B activation occurs in the amnion prior to labour onset and modulates the expression of numerous labour associated genes.

BACKGROUND: Prior to the onset of human labour there is an increase in the synthesis of prostaglandins, cytokines and chemokines in the fetal membranes, particular the amnion. This is associated with activation of the transcription factor nuclear factor kappa B (NFκB). In this study we characterised the level of NFκB activity in amnion epithelial cells as a measure of amnion activation in samples collected from women undergoing caesarean section at 39 weeks gestation prior to the onset of labour. METHODOLOGY/PRINCIPAL FINDINGS: We found that a proportion of women exhibit low or moderate NFκB activity while other women exhibit high levels of NFκB activity (n = 12). This activation process does not appear to involve classical pathways of NFκB activation but rather is correlated with an increase in nuclear p65-Rel-B dimers. To identify the full range of genes upregulated in association with amnion activation, microarray analysis was performed on carefully characterised non-activated amnion (n = 3) samples and compared to activated samples (n = 3). A total of 919 genes were upregulated in response to amnion activation including numerous inflammatory genes such cyclooxygenase-2 (COX-2, 44-fold), interleukin 8 (IL-8, 6-fold), IL-1 receptor accessory protein (IL-1RAP, 4.5-fold), thrombospondin 1 (TSP-1, 3-fold) and, unexpectedly, oxytocin receptor (OTR, 24-fold). Ingenuity Pathway Analysis of the microarray data reveal the two main gene networks activated concurrently with amnion activation are i) cell death, cancer and morphology and ii) cell cycle, embryonic development and tissue development. CONCLUSIONS/SIGNIFICANCE: Our results indicate that assessment of amnion NFκB activation is critical for accurate sample classification and subsequent interpretation of data. Collectively, our data suggest amnion activation is largely an inflammatory event that occurs in the amnion epithelial layer as a prelude to the onset of labour.

Management of maternal obesity prior to and during pregnancy.

The prevalence of obesity is high and rising worldwide. The greatest prevalence of obesity is found in the western world and in urban developing countries. There is an increased maternal mortality associated with maternal obesity. There are increased risks of most maternal complications in pregnancy including pre-eclampsia, gestational and pre-existing type 2 diabetes mellitus and thromboembolic disorders. There is an increased perinatal mortality associated with maternal obesity; there are increased risks of congenital malformation, fetal macrosomia and indeed risks for the fetus as a child and adult in the years to come. There are increased risks of complications of pregnancy including caesarean section, traumatic delivery and a reduced chance of breastfeeding. Maternal obesity in pregnancy predicts long-term risks for that mother. The management includes increased surveillance for these risks and lifestyle modulation during pregnancy. This includes dietary measures and encouraging modest increase in exercise. Ideally, the mother should achieve closer to an ideal body mass index prior to pregnancy using lifestyle intervention but possibly with pharmacological therapy or bariatric surgery. The ideal weight gain for an obese mother is less than the ideal weight gain for a lean mother.

A randomized controlled trial of cervical scanning vs history to determine cerclage in women at high risk of preterm birth (CIRCLE trial).

OBJECTIVE: We sought to compare history-indicated placement of cervical cerclage based on history- vs ultrasound-indicated placement in women at risk of preterm birth. STUDY DESIGN: We conducted a randomized controlled trial of history-indicated cervical cerclage suture based on history (clinician preference) vs ultrasound (< 20 mm cervical length) indicated in women at increased risk. RESULTS: The incidence of the primary outcome, preterm delivery between 24(+0) and 33(+6) weeks, was similar: 19/125 (15%) in the history-indicated group vs 18/122 (15%) in the ultrasound-indicated group (relative risk [RR], 0.97; 95% confidence interval [CI], 0.54-1.76). Those women randomized to the ultrasound-indicated arm were significantly more likely to receive a cerclage (32% vs 19%; RR, 1.66; 95% CI, 1.07-2.47) and progesterone (39% vs 25%; RR, 1.55; 95% CI, 1.06-2.25). CONCLUSION: Screening women at high risk with cervical ultrasound to determine cerclage placement results in more intervention but similar outcome compared with history-indicated placement.

Vitamin D deficiency and supplementation during pregnancy.

OBJECTIVE: Vitamin D is essential for skeletal health and prolonged deficiency results in infantile rickets and adult osteomalacia. The aim of this study is to determine the vitamin D status in pregnancy and to evaluate the effects of daily and of single-dose vitamin D supplementation. DESIGN: A prospective randomized study at St Mary's Hospital London. PATIENTS: A total of 180 women (Indian Asian, Middle Eastern, Black and Caucasian) were recruited at 27 weeks gestation and randomized into three treatment groups: a single oral dose of 200,000 IU vitamin D, a daily supplement of 800 IU vitamin D from 27 weeks until delivery and a no treatment group. MEASUREMENTS: Vitamin D (25-hydroxyvitamin D), PTH and corrected calcium levels in mothers at 27 weeks and at delivery and cord 25-hydroxyvitamin D and corrected calcium levels. RESULTS: The final maternal 25-hydroxyvitamin D levels were significantly higher in the supplemented group [daily dose (median) 42 (IQR 31-76) nmol/l, stat dose (median) 34 (IQR 30-46) nmol/l vs. median 27 (IQR 27-39) nmol/l in the no treatment; P < 0.0001] and significantly fewer women with secondary hyperparathyroidism in the supplemented group (10% in daily dose vs. 12% in stat dose vs. 27% in the no treatment; P < 0.05). Cord 25-hydroxyvitamin D levels were significantly higher with supplementation [daily dose median 26 (IQR 17-45) nmol/l, stat dose median 25 (IQR 18-34) nmol/l vs. median 17 (IQR 14-22) nmol/l in no treatment; P = 0.001]. CONCLUSION: Single or daily dose improved 25-hydroxyvitamin D levels significantly. However, even with supplementation, only a small percentage of women and babies were vitamin D sufficient. Further research is required to determine the optimal timing and dosing of vitamin D in pregnancy.

A cost-effectiveness analysis of delayed sphincteroplasty for anal sphincter injury.

OBJECTIVE: Anal-sphincter injury may result in faecal incontinence. Sphincteroplasty is usually performed as a primary (immediate) procedure. Delayed sphincteroplasty (DS) can be performed if there is significant trauma or soiling, if the primary procedure has failed, and if the injury was not recognized initially. This study aimed to determine the cost to patient and health service in the event a DS is performed. METHOD: Patients with anal-sphincter-injury who underwent primary sphincteroplasty (PS)/DS were identified from the published literature (primary, n = 103; delayed, n = 777) using Medline, Embase, Ovid and Cochrane databases for studies published between 1976 and 2006. Studies included described at least one of the measured outcomes--probability of functional success/failure and quality of life (QOL). An economic model was constructed and decision analysis performed using a decision tree based on a Markov process. Main outcomes were quality-adjusted-life-years (QALYs) gained from each strategy, costs incurred and incremental cost-effectiveness ratio (ICER) over a 10- and 15-year time horizon. RESULTS: Over 10 years, primary sphincteroplasty (PS) produced a gain of 5.72 QALYs for an estimated 2750 pounds, giving an ICER of 487 pounds per QALY. DS produced a gain of 3.73 QALYs for a cost of 2667 pounds, giving an ICER of 719 pounds per QALY. Both procedures fell below the 10,000 pounds per QALY willingness-to-pay threshold, but PS produced the highest QALYs. Both procedures performed poorly beyond the 10-year mark. CONCLUSION: If DS has to be performed, the resultant cost is greater with concurrently lower QALYs gained. Successful PS substantially improves QOL and reduces overall cost-of-treatment.

A meta-analysis on the influence of inflammatory bowel disease on pregnancy.

BACKGROUND: Inflammatory bowel disease (IBD) has a typical onset during the peak reproductive years. Evidence of the risk of adverse pregnancy outcomes in IBD is important for the management of pregnancy to assist in its management. AIM: To provide a clear assessment of risk of adverse outcomes during pregnancy in women with IBD. DESIGN: The Medline literature was searched to identify studies reporting outcomes of pregnancy in patients with IBD. Random-effect meta-analysis was used to compare outcomes between women with IBD and normal controls. PATIENTS AND SETTING: A total of 3907 patients with IBD (Crohn's disease 1952 (63%), ulcerative colitis 1113 (36%)) and 320 531 controls were reported in 12 studies that satisfied the inclusion criteria. RESULTS: For women with IBD, there was a 1.87-fold increase in incidence of prematurity (<37 weeks gestation; 95% CI 1.52 to 2.31; p<0.001) compared with controls. The incidence of low birth weight (<2500 g) was over twice that of normal controls (95% CI 1.38 to 3.19; p<0.001). Women with IBD were 1.5 times more likely to undergo caesarean section (95% CI 1.26 to 1.79; p<0.001), and the risk of congenital abnormalities was found to be 2.37-fold increased (95% CI 1.47 to 3.82; p<0.001). CONCLUSION: The study has shown a higher incidence of adverse pregnancy outcomes in patients with IBD. Further studies are required to clarify which women are at higher risk, as this was not determined in the present study. This has an effect on the management of patients with IBD during pregnancy, who should be treated as a potentially high-risk group.

Obesity in pregnancy.

Overweight and obesity are common findings in women of reproductive age in the UK; as 32% of 35- to 64-year-old women are overweight and 21% obese. Obesity causes major changes in many features of maternal intermediary metabolism. Insulin resistance appears to be central to these changes and may also be involved in increased energy accumulation by the fetus. Maternal obesity is associated with many risks to the pregnancy, with increased risk of miscarriage (three-fold) and operative delivery (20.7 versus 33.8% in the obese and 47.4% in the morbidly obese group). Other risks to the mother include an increased risk of pre-eclampsia (3.9 versus 13.5% in the obese group) and thromboembolism (0.05 versus 0.12% in the obese group). There are risks to the fetus with increased perinatal mortality (1.4 per 1000 versus 5.7 per 1000 in the obese group) and macrosomia (>90th centile; 9 versus 17.5% in the obese group). Maternal obesity is associated with an increased risk of obesity in the long term. Obese woman should try to lose weight before pregnancy but probably not during pregnancy. There is no real evidence base for the management of maternal obesity but some practical suggestions are made.

Glucose production in the human placenta.

Glucose transfer from mother to fetus by placental facilitated diffusion is the dominant mechanism by which the fetus acquires glucose. In small for gestational age pregnancies, fetal glucose concentrations tend to be lower than normal and this persists following delivery. GLUT1 is the major glucose transporter in human placenta but there is no evidence of GLUT1 deficiency as a cause of the lower fetal glucose concentration in small for gestational age pregnancy. The physiological and pathological roles of the other glucose transporters (and there are 14 currently described) are unknown. In recent years, the possibility has been raised that the placenta is itself capable of supplying glucose for fetal needs. This hypothesis derived from glucose isotope studies in normal pregnancy, where dilution of glucose isotope was demonstrated in blood samples taken from the fetal circulation during intravenous infusion of glucose isotope in the mother. Although other gluconeogenic enzymes were known to be present, the placenta was previously considered incapable of glucose secretion because it lacked functional glucose-6-phosphatase. Recent studies, however, have suggested that specific glucose-6-phosphatase may be present in placenta but it may be the product of a different gene from conventional hepatic glucose-6-phosphatase. The presence of the specific transporters necessary for glucose-6-phosphatase activity is currently being investigated. The role of placental glucose secretion in normal and growth-restricted pregnancies is an area of current study.

Uterine artery Doppler in predicting pregnancy outcome in women with antiphospholipid syndrome.

OBJECTIVE: To assess midtrimester uterine artery Doppler in the prediction of preeclampsia and small for gestational age (SGA) infants in women with primary antiphospholipid syndrome. METHODS: One hundred seventy pregnant women with histories of recurrent miscarriage in association with antiphospholipid antibodies (32 lupus anticoagulant positive, 47 IgG anticardiolipin positive, 78 IgM anticardiolipin positive, and 13 lupus anticoagulant and anticardiolipin antibodies positive) treated with low-dose aspirin and heparin were recruited prospectively. Doppler assessment of the uterine arteries (presence or absence of notches and pulsatility index) were performed at 16-18 and 22-24 weeks. The main outcome measures were the delivery of a SGA infant and the development of preeclampsia. RESULTS: There were 164 live births and six midtrimester losses. The prevalence of preeclampsia and SGA was similar at 10%. In predicting preeclampsia or SGA, uterine artery pulsatility index at either interval was of no value, and the diagnostic accuracy of the Doppler was limited to bilateral uterine artery notches at 22-24 weeks in the subgroup of women with positive lupus anticoagulant. In this subgroup, bilateral uterine artery notches at 22-24 weeks in predicting preeclampsia generated a high likelihood ratio for positive test (12.8, 95% confidence interval 2.2, 75), sensitivity (75%), specificity (94%), positive (75%) and negative (94%) predictive value. In predicting SGA, the corresponding figures were respectively 13.6 (95% confidence interval 1.9, 96), 80%, 94%, 80%, 94%. Uterine artery Doppler was of limited value in pregnancies associated with anticardiolipin antibodies in isolation. CONCLUSION: In pregnancies associated with lupus anticoagulant, uterine artery Doppler at 22-24 weeks is a useful screening test in predicting preeclampsia and SGA infants.