Socio-economic disadvantage and utilisation of labour epidural analgesia in Scotland: a population-based study†.

Socio-economic deprivation is associated with adverse maternal and childhood outcomes. Epidural analgesia, the gold standard for labour analgesia, may improve maternal well-being. We assessed the association of socio-economic status with utilisation of epidural analgesia and whether this differed when epidural analgesia was advisable for maternal safety. This was a population-based study of NHS data for all women in labour in Scotland between 1 January 2007 and 23 October 2020, excluding elective caesarean sections. Socio-economic status deciles were defined using the Scottish Index of Multiple Deprivation. Medical conditions for which epidural analgesia is advisable for maternal safety (medical indications) and contraindications were defined according to national guidelines. Of 593,230 patients in labour, 131,521 (22.2%) received epidural analgesia. Those from the most deprived areas were 16% less likely to receive epidural analgesia than the most affluent (relative risk 0.84 [95%CI 0.82-0.85]), with the inter-decile mean change in receiving epidural analgesia estimated at -2% ([95%CI -2.2% to -1.7%]). Among the 21,219 deliveries with a documented medical indication for epidural analgesia, the socio-economic gradient persisted (relative risk 0.79 [95%CI 0.75-0.84], inter-decile mean change in receiving epidural analgesia -2.5% [95%CI -3.1% to -2.0%]). Women in the most deprived areas with a medical indication for epidural analgesia were still less likely (absolute risk 0.23 [95%CI 0.22-0.24]) to receive epidural analgesia than women from the most advantaged decile without a medical indication (absolute risk 0.25 [95%CI 0.24-0.25]). Socio-economic deprivation is associated with lower utilisation of epidural analgesia, even when epidural analgesia is advisable for maternal safety. Ensuring equitable access to an intervention that alleviates pain and potentially reduces adverse outcomes is crucial.

Comparison of ultra-low, low and high concentration local anaesthetic for labour epidural analgesia: a systematic review and network meta-analysis.

Lumbar epidural is the gold standard for labour analgesia. Low concentrations of local anaesthetic are recommended. This network meta-analysis investigated whether further reducing the concentration of local anaesthetic can improve maternal and neonatal outcomes without compromising analgesia. We conducted a systematic search of relevant databases for randomised controlled trials comparing high (>0.1%), low (>0.08% to ≤0.1%) or ultra-low (≤0.08%) concentration local anaesthetic (bupivacaine or equivalent) for labour epidural. Outcomes included mode of delivery, duration of labour and maternal/neonatal outcomes. Bayesian network meta-analysis with random-effects modelling was used to calculate odds ratios or weighted mean differences and 95% credible intervals. A total of 32 studies met inclusion criteria (3665 women). The total dose of local anaesthetic received increased as the concentration increased; ultra-low compared with low (weighted mean difference -14.96 mg, 95% credible interval [-28.38 to -1.00]) and low compared with high groups (weighted mean difference -14.99 [-28.79 to -2.04]), though there was no difference in the number of rescue top-ups administered between the groups. Compared with high concentration, ultra-low concentration local anaesthetic was associated with increased likelihood of spontaneous vaginal delivery (OR 1.46 [1.18 to 1.86]), reduced motor block (Bromage score >0; OR 0.32 [0.18 to 0.54]) and reduced duration of second stage of labour (weighted mean difference -13.02 min [-21.54 to -4.77]). Compared with low, ultra-low concentration local anaesthetic had similar estimates for duration of second stage of labour (weighted mean difference -1.92 min [-14.35 to 10.20]); spontaneous vaginal delivery (OR 1.07 [0.75 to 1.56]; assisted vaginal delivery (OR 1.35 [0.75 to 2.26]); caesarean section (OR 0.76 [0.49 to 1.22]); pain (scale 1-100, weighted mean difference -5.44 [-16.75 to 5.93]); and maternal satisfaction. Although a lower risk of an Apgar score < 7 at 1 min (OR 0.43 [0.15 to 0.79]) was reported for ultra-low compared with low concentration, this was not sustained at 5 min (OR 0.12 [0.00 to 2.10]). Ultra-low concentration local anaesthetic for labour epidural achieves similar or better maternal and neonatal outcomes as low and high concentration, but with reduced local anaesthetic consumption.

Prediction of premature ovarian insufficiency: foolish fallacy or feasible foresight?

Prediction of premature ovarian insufficiency (POI) would be of substantial individual benefit, but being a heterogeneous and fluctuating condition, with an extensive range of complex etiologies and arbitrary diagnostic criteria, might make this seem foolhardy. However, contemporary and complementary genetic strategies assessing consanguineous and large POI pedigrees and cohorts with age at natural menopause have shown strong enrichment in genes regulating DNA damage repair, homologous recombination, and meiosis, processes that are critical to oogenesis and folliculogenesis. Recognition of the molecular architecture of POI and its contribution to baseline genotypic risk may enable these estimates to be refined further by estimation of the residual ovarian reserve. Increasing data derived from spontaneous and gonadotoxic-induced POI cohorts demonstrate the utility of anti-Müllerian hormone (AMH) to predict POI. This review presents current understanding of how genetics in combination with AMH may facilitate the prediction of POI.

UK stillbirth trends in over 11 million births provide no evidence to support effectiveness of Growth Assessment Protocol program.

OBJECTIVE: Use of the Growth Assessment Protocol (GAP) has increased internationally under the assumption that it reduces the stillbirth rate. The evidence for this is limited and based largely on an ecological time-trend study. Discordance in the uptake of the GAP program between Scotland and England/Wales enabled us to assess the assertion that implementation of GAP leads to a reduced stillbirth rate. METHODS: We analyzed data from the National Records for Scotland and the Office for National Statistics on the number of singleton maternities and stillbirths in Scotland and in England and Wales, respectively, from 1 January 2000 to 31 December 2015. National uptake of the GAP program over time in each of the regions was recorded. Stillbirth rate per 1000 maternities was calculated, according to year of delivery, and compared between Scotland and England/Wales. RESULTS: During the study period, there were 870 632 singleton maternities in Scotland, of which 4243 were stillbirths, and there were 10 469 120 singleton maternities in England and Wales, of which 51 562 were stillbirths. There was a marked difference in uptake of the GAP program between the two regions, with substantially fewer maternity units in Scotland implementing the program. Stillbirth rates were static up to 2010, with a decline thereafter in both regions, to 3.75 (95% CI, 3.25-4.30) per 1000 maternities in Scotland and 4.30 (95% CI, 4.15-4.46) per 1000 maternities in England and Wales in 2015. From 2010 onwards, the decline in Scotland was faster, equating to 48 (95% CI, 47.9-48.1) fewer stillbirths per 100 000 maternities in Scotland than in England and Wales from 2010 to 2015 compared with 2000 to 2009. CONCLUSIONS: We observed a decline in stillbirth rate in England and Wales, which coincided with implementation of the GAP program. However, a concurrent decline in stillbirth rate was observed in Scotland in the absence of increased implementation of GAP. The secular rates of change in stillbirth rate in England and Wales cannot be used to infer efficacy of the GAP program. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Pharmacodynamics of ciprofloxacin against Pseudomonas aeruginosa planktonic and biofilm-derived cells.

The influence of growth phase and state on the survival and recovery of Pseudomonas aeruginosa exposed to ciprofloxacin was investigated using batch culture grown planktonic cells and disaggregated biofilm populations. Biofilms were either nonantibiotic exposed or previously exposed to ciprofloxacin before disaggregation and subsequent challenge with ciprofloxacin. Viable counts showed that late stationary phase cells were tolerant to ciprofloxacin over 24 h exposure, while all other populations presented a biphasic killing pattern. In contrast, the metabolic activity of planktonic and biofilm-derived cells remained similar to controls during the initial 6 h of ciprofloxacin exposure, despite a significant reduction in viable cell numbers. A similar effect was observed when assessing the postantibiotic effect of 1 h ciprofloxacin exposure. Thus, although cell reduction occurred, the metabolic status of the cells remained unchanged. The recovery of disaggregated biofilm cells previously exposed to ciprofloxacin was significantly quicker than naïve biofilm cells, and this latter population's recovery was significantly slower than all planktonic populations. Results from this work have implications for our understanding of biofilm-related infections and their resilience to antimicrobial treatment. SIGNIFICANCE AND IMPACT OF THE STUDY: Removal of biofilms from surfaces and infection sites via disaggregation and induction of dispersion may reverse their antibiotic tolerant state. However, little is known of the recovery of the cells upon disaggregation from biofilms. Driven by this gap in knowledge we quantified the effect of ciprofloxacin on disaggregated biofilms of Pseudomonas aeruginosa, including those previously exposed to ciprofloxacin. Our results provide further insight into bacterial resilience, regrowth, and antimicrobial efficacy, as reduction in cell viability does not directly correlate with the metabolic activity of bacteria at the time of the exposure to antimicrobials. Thus, despite a perceived reduction in viability, the potential for cell persistence and regrowth remains and recovery is quicker upon subsequent exposure to antimicrobial, supporting the increase in resilience and recurrence of infections.

An in vitro biofilm model of Staphylococcus aureus infection of bone.

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an in vitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24 h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72 h biofilms with gentamicin and daptomycin for 24 h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100 mg l-1 gentamicin and 1000 mg l-1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7 days resulted in ≥3 log reductions in cell numbers by 48 h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7 days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. SIGNIFICANCE AND IMPACT OF THE STUDY: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an in vitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis.

Association of Thyroid Function Test Abnormalities and Thyroid Autoimmunity With Preterm Birth: A Systematic Review and Meta-analysis.

Importance: Maternal hypothyroidism and hyperthyroidism are risk factors for preterm birth. Milder thyroid function test abnormalities and thyroid autoimmunity are more prevalent, but it remains controversial if these are associated with preterm birth. Objective: To study if maternal thyroid function test abnormalities and thyroid autoimmunity are risk factors for preterm birth. Data Sources and Study Selection: Studies were identified through a search of the Ovid MEDLINE, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and Google Scholar databases from inception to March 18, 2018, and by publishing open invitations in relevant journals. Data sets from published and unpublished prospective cohort studies with data on thyroid function tests (thyrotropin [often referred to as thyroid-stimulating hormone or TSH] and free thyroxine [FT4] concentrations) or thyroid peroxidase (TPO) antibody measurements and gestational age at birth were screened for eligibility by 2 independent reviewers. Studies in which participants received treatment based on abnormal thyroid function tests were excluded. Data Extraction and Synthesis: The primary authors provided individual participant data that were analyzed using mixed-effects models. Main Outcomes and Measures: The primary outcome was preterm birth (<37 weeks' gestational age). Results: From 2526 published reports, 35 cohorts were invited to participate. After the addition of 5 unpublished data sets, a total of 19 cohorts were included. The study population included 47 045 pregnant women (mean age, 29 years; median gestational age at blood sampling, 12.9 weeks), of whom 1234 (3.1%) had subclinical hypothyroidism (increased thyrotropin concentration with normal FT4 concentration), 904 (2.2%) had isolated hypothyroxinemia (decreased FT4 concentration with normal thyrotropin concentration), and 3043 (7.5%) were TPO antibody positive; 2357 (5.0%) had a preterm birth. The risk of preterm birth was higher for women with subclinical hypothyroidism than euthyroid women (6.1% vs 5.0%, respectively; absolute risk difference, 1.4% [95% CI, 0%-3.2%]; odds ratio [OR], 1.29 [95% CI, 1.01-1.64]). Among women with isolated hypothyroxinemia, the risk of preterm birth was 7.1% vs 5.0% in euthyroid women (absolute risk difference, 2.3% [95% CI, 0.6%-4.5%]; OR, 1.46 [95% CI, 1.12-1.90]). In continuous analyses, each 1-SD higher maternal thyrotropin concentration was associated with a higher risk of preterm birth (absolute risk difference, 0.2% [95% CI, 0%-0.4%] per 1 SD; OR, 1.04 [95% CI, 1.00-1.09] per 1 SD). Thyroid peroxidase antibody-positive women had a higher risk of preterm birth vs TPO antibody-negative women (6.6% vs 4.9%, respectively; absolute risk difference, 1.6% [95% CI, 0.7%-2.8%]; OR, 1.33 [95% CI, 1.15-1.56]). Conclusions and Relevance: Among pregnant women without overt thyroid disease, subclinical hypothyroidism, isolated hypothyroxinemia, and TPO antibody positivity were significantly associated with higher risk of preterm birth. These results provide insights toward optimizing clinical decision-making strategies that should consider the potential harms and benefits of screening programs and levothyroxine treatment during pregnancy.

Distinct Stages of Moment-to-Moment Processing in the Cinguloopercular and Frontoparietal Networks.

Control of goal-directed tasks is putatively carried out via the cinguloopercular (CO) and frontoparietal (FP) systems. However, it remains unclear whether these systems show dissociable moment-to-moment processing during distinct stages of a trial. Here, we characterize dynamics in the CO and FP networks in a meta-analysis of 5 decision-making tasks using fMRI, with a specialized "slow reveal" paradigm which allows us to measure the temporal characteristics of trial responses. We find that activations in left FP, right FP, and CO systems form separate clusters, pointing to distinct roles in decision-making. Left FP shows early "accumulator-like" responses, suggesting a role in pre-decision processing. CO has a late onset and transient response linked to the decision event, suggesting a role in performance reporting. The majority of right FP regions show late onsets with prolonged responses, suggesting a role in post-recognition processing. These findings expand upon past models, arguing that the CO and FP systems relate to distinct stages of processing within a trial. Furthermore, the findings provide evidence for a heterogeneous profile in the FP network, with left and right FP taking on specialized roles. This evidence informs our understanding of how distinct control networks may coordinate moment-to-moment components of complex actions.

Infant adiposity following a randomised controlled trial of a behavioural intervention in obese pregnancy.

OBJECTIVES: Randomised controlled trials are required to address causality in the reported associations between maternal influences and offspring adiposity. The aim of this study was to determine whether an antenatal lifestyle intervention, associated with improvements in maternal diet and reduced gestational weight gain (GWG) in obese pregnant women leads to a reduction in infant adiposity and sustained improvements in maternal lifestyle behaviours at 6 months postpartum. SUBJECTS AND METHODS: We conducted a planned postnatal follow-up of a randomised controlled trial (UK Pregnancies Better Eating and Activity Trial (UPBEAT)) of a complex behavioural intervention targeting maternal diet (glycaemic load (GL) and saturated fat intake) and physical activity in 1555 obese pregnant women. The main outcome measure was infant adiposity, assessed by subscapular and triceps skinfold thicknesses. Maternal diet and physical activity, indices of the familial lifestyle environment, were assessed by questionnaire. RESULTS: A total of 698 (45.9%) infants (342 intervention and 356 standard antenatal care) were followed up at a mean age of 5.92 months. There was no difference in triceps skinfold thickness z-scores between the intervention vs standard care arms (difference -0.14 s.d., 95% confidence interval -0.38 to 0.10, P=0.246), but subscapular skinfold thickness z-score was 0.26 s.d. (-0.49 to -0.02; P=0.03) lower in the intervention arm. Maternal dietary GL (-35.34; -48.0 to -22.67; P<0.001) and saturated fat intake (-1.93% energy; -2.64 to -1.22; P<0.001) were reduced in the intervention arm at 6 months postpartum. Causal mediation analysis suggested that lower infant subscapular skinfold thickness was partially mediated by changes in antenatal maternal diet and GWG rather than postnatal diet. CONCLUSIONS: This study provides evidence from follow-up of a randomised controlled trial that a maternal behavioural intervention in obese pregnant women has the potential to reduce infant adiposity and to produce a sustained improvement in maternal diet at 6 months postpartum.

Ovarian hyperstimulation syndrome: review and new classification criteria for reporting in clinical trials.

STUDY QUESTION: What is an objective approach that employs measurable and reproducible physiologic changes as the basis for the classification of ovarian hyperstimulation syndrome (OHSS) in order to facilitate more accurate reporting of incidence rates within and across clinical trials? SUMMARY ANSWER: The OHSS flow diagram is an objective approach that will facilitate consistent capture, classification and reporting of OHSS within and across clinical trials. WHAT IS KNOWN ALREADY: OHSS is a potentially life-threatening iatrogenic complication of the early luteal phase and/or early pregnancy after ovulation induction (OI) or ovarian stimulation (OS). The clinical picture of OHSS (the constellation of symptoms associated with each stage of the disease) is highly variable, hampering its appropriate classification in clinical trials. Although some degree of ovarian hyperstimulation is normal after stimulation, the point at which symptoms transition from those anticipated to those of a disease state is nebulous. STUDY DESIGN, SIZE, DURATION: An OHSS working group, comprised of subject matter experts and clinical researchers who have significantly contributed to the field of fertility, was convened in April and November 2014. PARTICIPANTS/MATERIALS, SETTING, METHODS: The OHSS working group was tasked with reaching a consensus on the definition and the classification of OHSS for reporting in clinical trials. The group engaged in targeted discussion regarding the scientific background of OHSS, the criteria proposed for the definition and the rationale for universal adoption. An agreement was reached after discussion with all members. MAIN RESULTS AND THE ROLE OF CHANCE: One of the following conditions must be met prior to making the diagnosis of OHSS in the context of a clinical trial: (i) the subject has undergone OS (either controlled OS or OI) AND has received a trigger shot for final oocyte maturation (e.g. hCG, GnRH agonist [GnRHa] or kisspeptin) followed by either fresh transfer or segmentation (cryopreservation of embryos) or (ii) the subject has undergone OS or OI AND has a positive pregnancy test. All study patients who develop symptoms of OHSS should undergo a thorough examination. An OHSS flow diagram was designed to be implemented for all subjects with pelvic or abdominal complaints, such as lower abdominal discomfort or distention, nausea, vomiting and diarrhea, and/or for subjects suspected of having OHSS. The diagnosis of OHSS should be based on the flow diagram. LIMITATIONS, REASONS FOR CAUTION: This classification system is primarily intended to address the needs of the clinical investigator undertaking clinical trials in the field of OS and may not be applicable for the use in clinical practice or with OHSS occurring under natural circumstances. WIDER IMPLICATIONS OF THE FINDINGS: The proposed OHSS classification system will enable an accurate estimate of the incidence and severity of OHSS within and across clinical trials performed in women with infertility. STUDY FUNDING/COMPETING INTERESTS: Financial support for the advisory group meetings was provided by Merck & Co., Inc., Kenilworth, NJ, USA. P.H. reports unrestricted research grants from MSD, Merck and Ferring, and honoraria for lectures from MSD, Merck and IBSA. S.M.N. reports that he has received fees and grant support from the following companies (in alphabetic order): Beckman Coulter, Besins, EMD Serono, Ferring Pharmaceuticals, Finox, MSD and Roche Diagnostics over the previous 5 years. P.D., C.C.C., J.L.F., H.M.F., and P.L. report no relationships that present a potential conflict of interest. B.C.T. REPORTS: grants and honorarium from Merck Serono; unrestricted research grants, travel grants and honorarium, and participation in a company-sponsored speaker's bureau from Merck Sharp & Dohme; grants, travel grants, honoraria and advisory board membership from IBSA; travel grants from Ferring; and advisory board membership from Ovascience. L.B.S. reports current employment with Merck & Co, Inc., Kenilworth, NJ, USA, and owns stock in the company. K.G. and B.J.S. report prior employment with Merck & Co., Inc., Kenilworth, NJ, USA, and own stock in the company. All reported that competing interests are outside the submitted work. No other relationships or activities exist that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: Not applicable.

Prediction of gestational diabetes in obese pregnant women from the UK Pregnancies Better Eating and Activity (UPBEAT) pilot trial.

AIM: To examine the prediction of gestational diabetes in obese women using routine clinical measures and measurement of biomarkers related to insulin resistance in the early second trimester. METHODS: A total of 117 obese pregnant women participating in a pilot trial of a complex intervention of dietary advice and physical activity were studied. Blood samples were obtained at recruitment (15⁺°-17⁺6 weeks' gestation) and demographic, clinical history and anthropometric measures recorded. The biomarkers analysed were plasma lipids (HDL cholesterol, LDL cholesterol, triglycerides), high-sensitivity C-reactive protein, alanine transaminase, aspartate transaminase, ferritin, fructosamine, insulin, adiponectin, tissue plasminogen activator, interleukin-6, visfatin and leptin. Univariate and logistic regression analyses were performed to determine independent predictors and area under the receiver-operating curve was calculated for the model. RESULTS: Of the 106 participants included in the analysis, 29 (27.4%) developed gestational diabetes. Participants with gestational diabetes were older (P = 0.002), more often of parity ≥ 2, had higher systolic (P = 0.02) and diastolic blood pressure (P = 0.02) and were more likely to be black (P = 0.009). Amongst the blood biomarkers measured, plasma adiponectin alone remained independently associated with gestational diabetes in adjusted models (P = 0.002). The area under the receiver-operating curve for clinical factors alone (0.760) increased significantly (area under the curve 0.834, chi-square statistic (1) = 4.00, P = 0.046) with the addition of adiponectin. CONCLUSIONS: A combination of routinely measured clinical factors and adiponectin measured in the early second trimester in obese women may provide a useful approach to the prediction of gestational diabetes. Validation in a large prospective study is required to determine the usefulness of this algorithm in clinical practice.

Data-driven assessment of the human ovarian reserve.

Human ovarian physiology is still poorly understood, with the factors and mechanisms that control initiation of follicular recruitment and loss remaining particularly unclear. Conventional hypothesis-led studies provide new data, results and insights, but datasets from individual studies are often small, allowing only limited interpretation. Great power is afforded by the aggregation of data from multiple studies into single datasets. In this paper, we describe how modern computational analysis of these datasets provides important new insights into ovarian function and has generated hypotheses that are testable in the laboratory. Specifically, we can hypothesize that age is the most important factor for variations in individual ovarian non-growing follicle (NGF) populations, that anti-Müllerian hormone (AMH) levels generally rise and fall in childhood years before peaking in the mid-twenties, and that there are strong correlations between AMH levels and both NGF populations and rates of recruitment towards maturation, for age ranges before and after peak AMH levels.

The journey from the old to the new AMH assay: how to avoid getting lost in the values.

Anti-Müllerian hormone (AMH) is set to dominate reproductive endocrinology because of its unique relationship with the ovarian reserve. To date half of the published articles have used the Diagnostic Systems Lab (DSL) assay and the other half the Immunotech (IOT) assay. Unfortunately, these assays utilize two different primary antibodies against AMH and different standards, and consequently the crude values reported can differ substantially, with the IOT assay giving values for AMH that are higher than those obtained with the DSL assay. With the recent consolidation of these two companies by Beckman Coulter, and their sole ownership of the patent to measure mammalian AMH, there is finally a single commercially available assay - the AMH Gen II assay, which will fully replace the DSL and IOT assays. The aim of this article is to briefly focus on the different assays for AMH evaluation in order to give readers hopefully helpful suggestions for a correct interpretation of the AMH measurement. A brief overview on the development and performance characteristics of the new assay, how it relates to previous values and previously developed nomograms and where the future lies for AMH is also provided.

Anti-Müllerian hormone-based prediction model for a live birth in assisted reproduction.

Prediction of assisted reproduction treatment outcome has been the focus of clinical research for many years, with a variety of prognostic models describing the probability of an ongoing pregnancy or a live birth. This study assessed whether serum anti-Müllerian hormone (AMH) concentrations may be incorporated into a model to enhance the prediction of a live birth in women undergoing their first IVF cycle, by analysing a database containing clinical and laboratory information on IVF cycles carried out between 2005 and 2008 at the Mother-Infant Department of University Hospital, Modena. Logistic regression was used to examine the association of live birth with baseline patient characteristics. Only AMH and age were demonstrated in regression analysis to predict live birth, so a model solely based on these two criteria was generated. The model permitted the identification of live birth with a sensitivity of 79.2% and a specificity of only 44.2%. In the prediction of a live birth following IVF, a distinction, however moderate, can be made between couples with a good and a poor prognosis. The success of IVF was found to mainly depend on maternal age and serum AMH concentrations, one of the most relevant and valuable markers of ovarian reserve.

Association of existing diabetes, gestational diabetes and glycosuria in pregnancy with macrosomia and offspring body mass index, waist and fat mass in later childhood: findings from a prospective pregnancy cohort.

AIMS/HYPOTHESIS: The aim of the study was to examine the association of existing diabetes (i.e. already diagnosed prior to pregnancy), gestational diabetes and glycosuria (both diagnosed and ascertained during pregnancy) with birthweight and future offspring BMI, waist circumference and fat mass (assessed by dual x-ray emission absorptiometry). METHODS: A prospective pregnancy/birth cohort study was performed using data from the Avon Longitudinal Study of Parents and Children. RESULTS: Among 10,591 mother-offspring pairs included in analyses with birth size, women with existing diabetes (n = 40), those diagnosed with gestational diabetes (n = 53) and those with at least two episodes of ++ glycosuria (n = 372) had greater mean birthweight and odds for macrosomia (birthweight > 4,000 g) than women with none of these. Adjusted odds ratios for macrosomia were 3.56 (95% CI 1.53-8.28), 5.50 (95% CI 1.18-10.30) and 1.58 (95% CI 1.18-2.12) for existing diabetes, gestational diabetes and glycosuria, respectively. Among 6,842 mother-offspring pairs with anthropometric measurements at age 9-11 years, maternal gestational diabetes and glycosuria (but not existing diabetes) were associated with increased offspring odds of general or central overweight/obesity. For gestational diabetes, these associations attenuated towards the null with adjustment for maternal prepregnancy BMI, but independent associations remained for glycosuria. The adjusted odds ratio for general overweight/obesity when comparing women with at least two episodes of ++ glycosuria with those with no evidence of diabetes or glycosuria was 1.35 (95% CI 1.00-1.82) and that for central obesity (top 10% waist circumference vs all others) was 1.31 (95% CI 1.00-1.72). CONCLUSIONS/INTERPRETATION: These results provide some evidence for a long-term effect of maternal glycaemia in pregnancy on offspring obesity risk.

A point prevalence study to determine the inpatient rate of carbapenemase-producing organisms at a large London NHS Trust.

BACKGROUND: There has been an increase in the number of carbapenemase-producing organisms documented across the UK over the past 10 years. From these, the 'big five' carbapenemases (KPC, OXA-48, IMP, VIM, and NDM) are the most common types reported in the order Enterobacterales, identified from a variety of reactive screening, outbreak, inpatient surveillance, and diagnostic samples. AIM: To perform a point prevalence study to determine the inpatient carriage rate of carbapenemase-producing organisms at Barts Health NHS Trust, which encompasses 2.5 million patients across four London boroughs: Tower Hamlets, Newham, Redbridge, and Waltham Forest. METHODS: Rectal swabs were collected from consenting inpatients, alongside details of the ward's medical specialty, patient's country of birth, history of foreign travel, length of hospitalization, and history of prior hospitalization. Swabs were enriched and subcultured on to mSuperCARBA selective medium. All Enterobacterales, Acinetobacter, and Pseudomonas species were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectroscopy and underwent antibiotic susceptibility testing by disc diffusion, according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines. All isolates were screened for the 'big five' carbapenemases using a modified version of a published reverse transcriptase-polymerase chain reaction assay. FINDINGS: Of the 977 inpatients tested, 35 CPOs were isolated from 30 patients. NDM was the most frequently detected carbapenemase, followed by OXA-48, with an overall prevalence of 3.1%. Organisms isolated included Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, and Escherichia coli. Renal and elderly care patients had the highest prevalences of CPOs, whereas the intensive care unit prevalence was low. Statistical analysis found that hospitalization abroad, any previous hospitalization, foreign travel and, specifically, travel to India, Pakistan, and Bangladesh were associated with increased risk of CPO carriage. CONCLUSION: The overall prevalence of CPOs at Barts Health Trust was 3.1%, comprising NDM and OXA-48-type carbapenemases, which is in line with other London-based studies. Renal patients and the elderly had the highest burden of CPOs, whereas previous hospitalization and foreign travel were associated with an increased risk of CPO carriage.

Erythrocytosis in offspring of mothers with Type 1 diabetes--are factors other than insulin critical determinants?

AIM: Maternal diabetes is associated with polycythaemia and thrombocytopaenia in the offspring; however, the relationship with fetal hormones is unknown. We assessed the association of maternal glycaemic control, birthweight and fetal hormones with haematological indices in pregnancies complicated by maternal diabetes. METHODS: Prospective study using cord blood samples from 89 offspring of mothers with Type 1 diabetes (OT1DM) and 34 control offspring. Full blood count, insulin, leptin, adiponectin, cortisol, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3, intercellular adhesion molecule 1 and C-reactive protein were measured in the umbilical vein at birth. RESULTS: Haematocrit was higher in OT1DM (OT1DM 0.55 +/- 0.17%, control offspring 0.51 +/- 0.06%; P = 0.02). The difference in platelets count was not statistically significant [OT1DM 214 x 10(9)/l (173-259); control offspring 253 x 10(9)/l (180-310), P = 0.06]. Maternal glycated haemoglobin (HbA(1c)) showed a moderate positive correlation with fetal haematocrit (r = 0.30, P = 0.02). Cord platelet counts were negatively associated with birthweight in OT1DM (r = -0.27, P = 0.01). In multivariate models, cord insulin was not associated with haematocrit, but cord leptin was negatively associated with platelets in control offspring (P < 0.001) and OT1DM (P = 0.046), with additional contributions from male sex (P = 0.08) in OT1DM, and IGF-1 (P = 0.04) and insulin (P = 0.04) in control offspring. CONCLUSIONS: Fetal haematocrit is increased in response to diabetes in pregnancy and is related to maternal glycaemic control. Fetal hyperinsulinism, hyperleptinaemia or macrosomia, although readily demonstrable in this cohort, do not emerge as determinants of raised fetal haematocrit in OT1DM. Both increased birthweight and fetal leptin are negatively associated with platelet count.

Community prevalence of carbapenemase-producing organisms in East London.

BACKGROUND: Over the last decade there has been a rapid, worldwide increase in carbapenem resistance, which is of growing concern. The main protagonists, the carbapenemases Klebsiella pneumoniae carbapenemase (KPC), oxacillinase ß-lactamase 48 (OXA-48), imipenemase metallo-ß-lactamase (IMP), Verona integron-borne metallo-ß-lactamase (VIM), and New Delhi metallo-ß-lactamase (NDM) have also been reported across the UK. However, these reports are derived from a combination of reactive screening, outbreak control, inpatient surveillance, and diagnostic samples. Therefore, the true community prevalence is unknown. AIM: To determine the community prevalence of carbapenemase-producing organisms (CPOs) in the area served by Barts Health NHS Trust. METHODS: Active screening of 200 non-duplicate community stool samples was performed. Patient demographics and foreign travel history were extracted from the laboratory information management system to identify potential risk factors for carriage of CPOs. FINDINGS: Patients in this study were aged from one to 93 years and were evenly distributed between male and female. Foreign travel in the last year was listed for 46 out of 200 (23%) patients, with the most commonly visited countries including Bangladesh (4%), India (2.5%), Morocco (2%), and Turkey (1.5%). However, only one patient tested positive for a CPO, an NDM-producing Pseudomonas aeruginosa, and this patient had travelled to the Caribbean. CONCLUSION: To date, there have been no studies investigating the prevalence of CPOs in the UK community. Given the high-risk patient population served by Barts Health NHS Trust, it is reassuring that the prevalence observed here was low. However, it should be highlighted that travel to countries not previously categorized as high risk may also pose a threat.