Links between psychotic and neurotic symptoms in the general population: an analysis of longitudinal British National Survey data using Directed Acyclic Graphs.

BACKGROUND: Non-psychotic affective symptoms are important components of psychotic syndromes. They are frequent and are now thought to influence the emergence of paranoia and hallucinations. Evidence supporting this model of psychosis comes from recent cross-fertilising epidemiological and intervention studies. Epidemiological studies identify plausible targets for intervention but must be interpreted cautiously. Nevertheless, causal inference can be strengthened substantially using modern statistical methods. METHODS: Directed Acyclic Graphs were used in a dynamic Bayesian network approach to learn the overall dependence structure of chosen variables. DAG-based inference identifies the most likely directional links between multiple variables, thereby locating them in a putative causal cascade. We used initial and 18-month follow-up data from the 2000 British National Psychiatric Morbidity survey (N = 8580 and N = 2406). RESULTS: We analysed persecutory ideation, hallucinations, a range of affective symptoms and the effects of cannabis and problematic alcohol use. Worry was central to the links between symptoms, with plausible direct effects on insomnia, depressed mood and generalised anxiety, and recent cannabis use. Worry linked the other affective phenomena with paranoia. Hallucinations were connected only to worry and persecutory ideation. General anxiety, worry, sleep problems, and persecutory ideation were strongly self-predicting. Worry and persecutory ideation were connected over the 18-month interval in an apparent feedback loop. CONCLUSIONS: These results have implications for understanding dynamic processes in psychosis and for targeting psychological interventions. The reciprocal influence of worry and paranoia implies that treating either symptom is likely to ameliorate the other.

Virtual reality in the assessment, understanding, and treatment of mental health disorders.

Mental health problems are inseparable from the environment. With virtual reality (VR), computer-generated interactive environments, individuals can repeatedly experience their problematic situations and be taught, via evidence-based psychological treatments, how to overcome difficulties. VR is moving out of specialist laboratories. Our central aim was to describe the potential of VR in mental health, including a consideration of the first 20 years of applications. A systematic review of empirical studies was conducted. In all, 285 studies were identified, with 86 concerning assessment, 45 theory development, and 154 treatment. The main disorders researched were anxiety (n = 192), schizophrenia (n = 44), substance-related disorders (n = 22) and eating disorders (n = 18). There are pioneering early studies, but the methodological quality of studies was generally low. The gaps in meaningful applications to mental health are extensive. The most established finding is that VR exposure-based treatments can reduce anxiety disorders, but there are numerous research and treatment avenues of promise. VR was found to be a much-misused term, often applied to non-interactive and non-immersive technologies. We conclude that VR has the potential to transform the assessment, understanding and treatment of mental health problems. The treatment possibilities will only be realized if - with the user experience at the heart of design - the best immersive VR technology is combined with targeted translational interventions. The capability of VR to simulate reality could greatly increase access to psychological therapies, while treatment outcomes could be enhanced by the technology's ability to create new realities. VR may merit the level of attention given to neuroimaging.

Understanding jumping to conclusions in patients with persecutory delusions: working memory and intolerance of uncertainty.

BACKGROUND: Persecutory delusions are a key psychotic experience. A reasoning style known as 'jumping to conclusions' (JTC) - limited information gathering before reaching certainty in decision making - has been identified as a contributory factor in the occurrence of delusions. The cognitive processes that underpin JTC need to be determined in order to develop effective interventions for delusions. In the current study two alternative perspectives were tested: that JTC partially results from impairment in information-processing capabilities and that JTC is a motivated strategy to avoid uncertainty. METHOD: A group of 123 patients with persistent persecutory delusions completed assessments of JTC (the 60:40 beads task), IQ, working memory, intolerance of uncertainty, and psychiatric symptoms. Patients showing JTC were compared with patients not showing JTC. RESULTS: A total of 30 (24%) patients with delusions showed JTC. There were no differences between patients who did and did not jump to conclusions in overall psychopathology. Patients who jumped to conclusions had poorer working memory performance, lower IQ, lower intolerance of uncertainty and lower levels of worry. Working memory and worry independently predicted the presence of JTC. CONCLUSIONS: Hasty decision making in patients with delusions may partly arise from difficulties in keeping information in mind. Interventions for JTC are likely to benefit from addressing working memory performance, while in vivo techniques for patients with delusions will benefit from limiting the demands on working memory. The study provides little evidence for a contribution to JTC from top-down motivational beliefs about uncertainty.

The past and future of delusions research: from the inexplicable to the treatable.

BACKGROUND: Problems with the diagnosis and treatment of schizophrenia have led for a call to change strategy and focus on individual psychotic experiences. In recent years, research on delusions has led the way. AIMS: To update our 1999 review of almost 40 studies on delusions. METHOD: A systematic literature search was conducted of reasoning and affective processes related to delusions. RESULTS: Over 200 studies were identified. The presence of 'jumping to conclusions' in individuals with delusions has been substantiated, the theory of mind account has not stood up to subsequent testing, and there is a promising new focus on the ways that affective processes contribute to delusional experience. CONCLUSIONS: Theoretical work rendering delusions understandable can be translated into treatment; future clinical trials should focus on individual psychotic experiences as outcomes.

Patients' beliefs about the causes, persistence and control of psychotic experiences predict take-up of effective cognitive behaviour therapy for psychosis.

BACKGROUND: There is evidence that patients with schizophrenia benefit from standard cognitive behaviour therapy (CBT) only if active techniques are used ('full therapy'). By contrast, attending sessions but not proceeding beyond engagement and assessment strategies ('partial therapy'), or simply not attending sessions ('no therapy'), is not associated with better outcomes. The factors leading to full therapy are unknown. We hypothesized that patients' initial ideas about the nature and extent of their problems would predict use of CBT. A match between patients' views of their problems and the principles underlying treatment would lead to better outcomes. METHOD: Ninety-two patients with a recent relapse of psychosis completed the Illness Perception Questionnaire (IPQ) before receiving CBT. We examined whether their illness perceptions predicted the take-up of therapy. RESULTS: Patients who did not attend sessions believed their problems would not last as long as those who attended them. Those who attended sessions but did not proceed to full therapy had a lower sense of control over their problems and a more biological view of their causes. Patients who took up full therapy were more likely to attribute the cause of their problems to their personality and state of mind. The take-up of therapy was predicted neither by levels of psychiatric symptoms nor by insight. CONCLUSIONS: People with psychosis who have psychologically orientated views of their problems, including the potential to gain control over them, may be more likely to engage fully and do well with standard CBT for psychosis, irrespective of the severity of their problems.

Paranoia and post-traumatic stress disorder in the months after a physical assault: a longitudinal study examining shared and differential predictors.

BACKGROUND: Being physically assaulted is known to increase the risk of the occurrence of post-traumatic stress disorder (PTSD) symptoms but it may also skew judgements about the intentions of other people. The objectives of the study were to assess paranoia and PTSD after an assault and to test whether theory-derived cognitive factors predicted the persistence of these problems. METHOD: At 4 weeks after hospital attendance due to an assault, 106 people were assessed on multiple symptom measures (including virtual reality) and cognitive factors from models of paranoia and PTSD. The symptom measures were repeated 3 and 6 months later. RESULTS: Factor analysis indicated that paranoia and PTSD were distinct experiences, though positively correlated. At 4 weeks, 33% of participants met diagnostic criteria for PTSD, falling to 16% at follow-up. Of the group at the first assessment, 80% reported that since the assault they were excessively fearful of other people, which over time fell to 66%. Almost all the cognitive factors (including information-processing style during the trauma, mental defeat, qualities of unwanted memories, self-blame, negative thoughts about self, worry, safety behaviours, anomalous internal experiences and cognitive inflexibility) predicted later paranoia and PTSD, but there was little evidence of differential prediction. CONCLUSIONS: Paranoia after an assault may be common and distinguishable from PTSD but predicted by a strikingly similar range of factors.

Consanguineous mating, specialization, and the environment: how multiple variable interactions affect the evolution of dioecy.

PREMISE: The evolution of dioecy in plants is usually modeled as a consequence of self-fertilization. While increased seed and pollen production and dispersal patterns of specialized unisexuals have been examined, mating among relatives and interaction effects have been largely ignored. Here, we examine multiple variables simultaneously providing a more ecologically realistic set of conditions favoring the evolution of dioecy. • METHODS: We developed two complementary models to explore the evolution of dioecious plants. In both models, we examined the effects of inbreeding, compensation, and specialization on unisexual invasibility and were able to directly measure the influence of related matings on such a system. • KEY RESULTS: Our results support previous studies indicating dispersal specialization, consanguineous mating, and inbreeding depression facilitate the evolution of dioecy. However, our results suggest that it is the interaction effect of multiple forces acting simultaneously that allows for unisexual invasion at thresholds and frequencies witnessed in nature. Additionally, our results suggest that subdioecious populations often result, and depending on population conditions, dioecy evolves at different rates, lending importance to the ecological and life history conditions of the species. • CONCLUSION: Mating among relatives significantly enhances the invasibility of a unisexual mutant into a hermaphroditic population and lowers the levels of inbreeding depression required for invasion than previously reported conditions for unisexual invasion especially, if we consider multiple pressures simultaneously.

Micro-techniques for analysis of human adipose tissue fatty acid composition in dietary studies.

BACKGROUND AND AIMS: Adipose tissue (AT) fatty acid (FA) composition is considered to be the gold standard long-term biomarker of dietary fatty acid intake. Typically this measurement is made directly from samples collected via large-needle-biopsy or incision. However, with growing interest in the role of AT in relation to health, ideally the fatty acid composition would be analysed along with other measurements, such as gene expression or histology, on a single AT sample. Here we assess alternative ways of obtaining AT for measuring FA composition, in some cases in conjunction with other measurements. METHODS AND RESULTS: The FA composition of tissue obtained via different methods was compared to that of tissue collected via large-needle or surgical biopsy. Fatty acid composition was not significantly different in AT collected by small-needle mini-biopsy (n = 10), from an RNA 'lipid layer' (obtained during RNA extraction, 2 sites, n = 6 for each), or from cryosectioned tissue prepared for histology (n = 10). We also assessed the usefulness of the composition of plasma NEFA as a surrogate marker of subcutaneous AT (n = 58-80). Most FAs in plasma NEFA correlated strongly with those in AT (P < 0.05). CONCLUSION: It is feasible to measure the FA composition of AT on very small amounts of tissue. Additionally, it is possible to measure FA composition on the lipid rich 'by-product' of AT samples undergoing RNA extraction for gene expression. Samples sectioned for histology are also suitable. This provides further opportunities for multidisciplinary collaborations that may lead to a better application of dietary biomarkers.

Cytology at the time of cervical colposcopy.

OBJECTIVE: The efforts of the authors are to evaluate the role of performing a Papanicolaou (Pap) smear at the time of colposcopy. MATERIALS AND METHODS: This retrospective chart review included patients from 2004 to 2009 who underwent cold knife cone (CKC) biopsy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia types 2 and 3 (CIN 2 and 3) or patients with discrepancy between Pap and colposcopic results. All patients presented to the gynecology clinics in a tertiary care hospital. Results were compared which included: the abnormal Pap smear which led to referral for colposcopy, the Pap smear performed at the time of colposcopy, the colposcopic biopsy, and the excisional biopsy. Interpretation of results was calculated with Cohen's K Statistics. RESULTS: One hundred forty-seven patients qualified for the study. One hundred five patients had excisional biopsy proven high-grade squamous intraepithelial lesion (HSIL). Eighty-two of these high-grade excisional pathology results were preceded by high-grade Pap cytology at the time of colposcopy; however 23 Pap cytology results indicated either low-grade squamous intraepithelial lesion (LSIL) or negative (20 and 3 respectively), but were followed by an excisional procedure revealing high-grade pathology. Eighty-one colposcopic biopsies confirmed high-grade excisional biopsy pathology. However, 24 colposcopic biopsies were low-grade or negative (13 and 11 respectively), but followed by a high-grade excisional biopsy. CONCLUSION: The addition of a Pap smear at the time of colposcopy has the potential role of recognizing high-grade cervical dysplasia.

Increase in mortality rate of liver transplant candidates residing in specific geographic areas: analysis of UNOS data.

We sought to evaluate survival of liver transplant candidates living in geographic areas with limited access to specialized transplant centers (TxC). We analyzed survival outcome among candidates listed for liver transplant in United Network of Organ Sharing (UNOS) Region 4 from 2004 to 2010. Candidates were stratified into three groups according to the distance from the patient's residence to the closest hospital with a liver transplant program: Group 1 (Gr 1) <30 miles (m), Group 2 (Gr 2) 30-60 m and Group 3 (Gr 3) >60 m. Of the 5673 patients included in the study, 49% resided >30 m from a TxC. Eight percent of the cohort experienced death or dropped out of the list due to medical condition deterioration, with worse outcomes for Gr 2 and Gr 3 (8.5% and 9.9%, respectively, vs. 6.5% for Gr 1 [p < 0.001]). Among patients with a MELD score <20, mortality was higher in Gr 2 and Gr 3 compared to Gr 1 (p < 0.001). We conclude that for Region 4, the mortality risk in patients living >30 m from a TxC is higher. We suggest that the variable "distance from a TxC" should be used to improve the estimate of the mortality risk for patients on the waiting list.

Effective elements of cognitive behaviour therapy for psychosis: results of a novel type of subgroup analysis based on principal stratification.

BACKGROUND: Meta-analyses show that cognitive behaviour therapy for psychosis (CBT-P) improves distressing positive symptoms. However, it is a complex intervention involving a range of techniques. No previous study has assessed the delivery of the different elements of treatment and their effect on outcome. Our aim was to assess the differential effect of type of treatment delivered on the effectiveness of CBT-P, using novel statistical methodology. METHOD: The Psychological Prevention of Relapse in Psychosis (PRP) trial was a multi-centre randomized controlled trial (RCT) that compared CBT-P with treatment as usual (TAU). Therapy was manualized, and detailed evaluations of therapy delivery and client engagement were made. Follow-up assessments were made at 12 and 24 months. In a planned analysis, we applied principal stratification (involving structural equation modelling with finite mixtures) to estimate intention-to-treat (ITT) effects for subgroups of participants, defined by qualitative and quantitative differences in receipt of therapy, while maintaining the constraints of randomization. RESULTS: Consistent delivery of full therapy, including specific cognitive and behavioural techniques, was associated with clinically and statistically significant increases in months in remission, and decreases in psychotic and affective symptoms. Delivery of partial therapy involving engagement and assessment was not effective. CONCLUSIONS: Our analyses suggest that CBT-P is of significant benefit on multiple outcomes to patients able to engage in the full range of therapy procedures. The novel statistical methods illustrated in this report have general application to the evaluation of heterogeneity in the effects of treatment.

Endothelial FOS expression and pre-eclampsia.

OBJECTIVE: To study gene expression profiles in human endothelial cells incubated with plasma from women who developed pre-eclampsia and women with normotensive pregnancies. DESIGN: A case-control study. SETTING: A longitudinal nested case-control study within three maternity units. POPULATION: A mixed obstetric population attending maternity hospitals in Glasgow. METHODS: Plasma was obtained at both 16 and 28 weeks of gestation from 12 women: six women subsequently developed pre-eclampsia (cases) and six women, matched for age, body mass index (BMI) and parity, remained normotensive (controls). Human umbilical vein endothelial cells (HUVECs) were incubated with plasma for 24 hour before RNA isolation. MAIN OUTCOME MEASURES: Gene expression profiles were compared between the two gestational time points using Illumina(®) HumanHT-12 v4 Expression BeadChips. Differential mRNA expression observed in microarray experiments were validated using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), and gene networks were analysed using Ingenuity(®) pathway analysis. RESULTS: There was a significant difference in the expression of 25 genes following incubation with plasma from controls, and an increase in the expression of 11 genes following incubation with plasma from cases, with no overlap between the two groups (false discovery rate, FDR < 0.05). There was a 3.74-fold (FDR < 0.001) increase in the expression of the c-Fos gene (FOS) when HUVECs were incubated with control plasma from 16 and 28 weeks of gestation, with no significant difference between the two time points with plasma from cases. Similar findings for FOS were obtained by qRT-PCR. CONCLUSIONS: Plasma from women who subsequently develop pre-eclampsia appears to contain factors that lead to the dysregulation of FOS in endothelial cells during pregnancy. Reduced expression of c-Fos may lead to impaired vasculogenesis, and thereby contribute to the development of pre-eclampsia.

Accuracy of physician and nurse practitioner colposcopy to effect improved surveillance of cervical cancer.

PURPOSE: To compare physician and nurse practitioner accuracy in recognizing cervical dysplasia during colposcopy. MATERIALS AND METHODS: A retrospective review was performed of cervical excisional biopsies from 2007 to 2009 performed by gynecologists and nurse practitioners in the same patient population. Cervical cone biopsy and loop electrosurgical excision procedure (LEEP) pathology were used as a gold standard compared to the previous colposcopy biopsies. RESULTS: Four hundred fifty-five patients qualified for the study. Patients were stratified according to age: under 30 years, 30-39, and 40 and above. For physicians, 77% of high-grade colposcopy biopsy results agreed with high-grade pathology on cone biopsy or LEEP. This was statistically similar to nurse practitioner results (p = 0.12). Likewise, there was no significant difference between physician and nurse practitioner accuracy within the various patient age strata. CONCLUSION: Colposcopy biopsy results compared to cone biopsy or LEEP results were statistically similar between gynecologists and nurse practitioners.

Concomitants of paranoia in the general population.

BACKGROUND: Paranoia is an unregarded but pervasive attribute of human populations. In this study we carried out the most comprehensive investigation so far of the demographic, economic, social and clinical correlates of self-reported paranoia in the general population. METHOD: Data weighted to be nationally representative were analysed from the Adult Psychiatric Morbidity Survey in England (APMS 2007; n=7281). RESULTS: The prevalence of paranoid thinking in the previous year ranged from 18.6% reporting that people were against them, to 1.8% reporting potential plots to cause them serious harm. At all levels, paranoia was associated with youth, lower intellectual functioning, being single, poverty, poor physical health, poor social functioning, less perceived social support, stress at work, less social cohesion, less calmness, less happiness, suicidal ideation, a great range of other psychiatric symptoms (including anxiety, worry, phobias, post-traumatic stress and insomnia), cannabis use, problem drinking and increased use of treatment and services. CONCLUSIONS: Overall, the results indicate that paranoia has the widest of implications for health, emotional well-being, social functioning and social inclusion. Some of these concomitants may contribute to the emergence of paranoid thinking, while others may result from it.

Total knee arthroplasty patients using the in-home X10 machine fully recovered. No additional therapy required.

Following total knee arthroplasties patients using the X10 increased their quadriceps strength 120% at 30 days post-surgery compared to their pre-surgical baseline. This contrasts sharply with contrast studies outpatient physical therapy that show patients suffer a 50-60% quadriceps strength deficit at 30 days post-surgery. For X10 patients, the average range of motion at 30 days was 124° and at discharge it was 128° (mean 43 days). The trial involved a single surgeon and two groups. Group one (21 patients) used only the X10 for pre-habilitation and rehabilitation, while group two (20 patients) used X10 alone for pre-habilitation and then utilized the X10 plus home care plus outpatient physical therapy for rehabilitation. Adding home care and outpatient physical therapy did not improve outcomes compared to patients who utilized X10 alone. Our results show no significant difference between the two groups. Indicating that the X10 by itself is adequate to completely rehabilitation patients from total knee arthroplasties. Finally, we compared our results to those of Calatayud et al.1 who monitored two groups of patients, one group had only physical therapy for rehabilitation while the other group used physical therapy for both prehabilitation and rehabilitation. Our results were superior to Calatayud et al.1 for extension, flexion, and quadriceps strength; for each of these measures the X10 treatment groups improved over time, while the Calatayud et al.1 groups showed losses.

Nitrogen oxidation consortia dynamics influence the performance of full-scale rotating biological contactors.

Ammonia oxidising microorganisms (AOM) play an important role in ammonia removal in wastewater treatment works (WWTW) including rotating biological contactors (RBCs). Environmental factors within RBCs are known to impact the performance of key AOM, such that only some operational RBCs have shown ability for elevated ammonia removal. In this work, long-term treatment performance of seven full-scale RBC systems along with the structure and abundance of the ammonia oxidising bacteria (AOB) and archaea (AOA) communities within microbial biofilms were examined. Long term data showed the dominance of AOB in most RBCs, although two RBCs had demonstrable shift toward an AOA dominated AOM community. Next Generation Sequencing of the 16S rRNA gene revealed diverse evolutionary ancestry of AOB from RBC biofilms while nitrite-oxidising bacteria (NOBs) were similar to reference databases. AOA were more abundant in the biofilms subject to lower organic loading and higher oxygen concentration found at the distal end of RBC systems. Modelling revealed a distinct nitrogen cycling community present within high performing RBCs, linked to efficient control of RBC process variables (retention time, organic loading and oxygen concentration). We present a novel template for enhancing the resilience of RBC systems through microbial community analysis which can guide future strategies for more effective ammonia removal. To best of the author's knowledge, this is the first comparative study reporting the use of next generation sequencing data on microbial biofilms from RBCs to inform effluent quality of small WWTW.

Intervention strategies for microbial therapeutics in cancer immunotherapy.

Immunotherapies have drastically improved clinical outcomes in a wide range of malignancies. Nevertheless, patient responses remain highly variable, and reliable biomarkers that predict responses accurately are not yet fully understood. Compelling evidence from preclinical studies and observational data from clinical cohorts have shown that commensal microorganisms that reside in the human gastrointestinal tract, collectively termed the 'microbiome', can actively modify responses to chemotherapeutic agents and immunotherapies by influencing host immunosurveillance. Notably, microbial correlates are largely context specific, and response signatures may vary by patient population, geographic location and type of anticancer treatment. Therefore, the incongruence of beneficial microbiome signatures across studies, along with an emerging understanding of the mechanisms underlying the interactions between the microbiome, metabolome and host immune system, highlight a critical need for additional comprehensive and standardized multi-omics studies. Future research should consider key host factors, such as diet and use of medication, in both preclinical animal models and large-scale, multicenter clinical trials. In addition, there is a strong rationale to evaluate the microbiome as a tumor-extrinsic biomarker of clinical outcomes and to test the therapeutic potential of derived microbial products (e.g. defined microbial consortia), with the eventual goal of improving the efficacy of existing anticancer treatments. This review discusses the importance of the microbiome from the perspective of cancer immunotherapies, and outlines future steps that may contribute to wide-ranging clinical and translational benefits that may improve the health and quality of life of patients with cancer.

Are elevated circulating intercellular adhesion molecule 1 levels more strongly predictive of diabetes than vascular risk? Outcome of a prospective study in the elderly.

AIMS/HYPOTHESIS: The aim of this prospective study was to determine whether circulating intercellular adhesion molecule (ICAM) 1, as a potential surrogate of 'endothelial activation', is more strongly associated with risk of vascular events than with incident diabetes. METHODS: We related baseline ICAM-1 levels to vascular events (866 CHD and stroke events in 5,685 participants) and incident diabetes (292 in 4,945 without baseline diabetes) in the elderly over 3.2 years of follow-up. RESULTS: ICAM-1 levels correlated positively with triacylglycerol but negatively with LDL- and HDL-cholesterol. ICAM-1 levels were higher in those who developed diabetes (388.6 +/- 1.42 vs 369.4 +/- 1.39 ng/ml [mean+/-SD], p = 0.011) and remained independently associated with new-onset diabetes (HR 1.84, 95% CI 1.26-2.69, p = 0.0015 per unit increase in log[ICAM-1] after adjusting for classical risk factors and C-reactive protein). By contrast, ICAM-1 levels were not significantly (p = 0.40) elevated in those who had an incident vascular event compared with those who remained event-free, and corresponding adjusted risk associations were null (HR 0.98, 95% CI 0.80-1.22, p = 0.89) in analyses adjusted for other risk factors. CONCLUSIONS/INTERPRETATION: We show that elevated ICAM-1 levels are associated with risk of incident diabetes in the elderly at risk, despite no association with incident cardiovascular disease risk. We suggest that perturbations in circulating ICAM-1 levels are aligned more towards diabetes risk.

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.