Caesarean birth in women with infertility: population-based cohort study.

OBJECTIVE: Caesarean section (CS) is more common following infertility treatment (IT) but the reasons why remain unclear and confounded. The Robson 10-Group Classification System (TGCS) may further explain variation in CS rates. We assessed the association between mode of conception and CS across Robson groups. DESIGN: Population-based cohort study. SETTING: Ontario, Canada, in a public healthcare system. POPULATION: 921 023 births, 2006-2014. METHODS: Modified Poisson regression produced relative risks (RR) and 95% confidence intervals, comparing the risk of CS among women with (1) subfertility without IT, (2) non-invasive IT (OI, IUI) or (3) invasive IT (IVF)-each relative to (4) spontaneous conception (SC). MAIN OUTCOME MEASURES: CS rate according to one of four modes of conception, overall and stratified by each of the TGCS groups. RESULTS: Relative to SC (26.9%), the risk of CS increased in those with subfertility without IT (RR 1.17, 95% CI 1.16-1.18), non-invasive IT (RR 1.21, 95% CI 1.18-1.24) and invasive IT (RR 1.39, 95% CI 1.36-1.42). Within each Robson group, similar patterns of RRs were seen, but with markedly differing rates. For example, in Group 1 (nulliparous, singleton, cephalic at ≥37 weeks, with spontaneous labour), the respective rates were 15.0, 19.4, 18.7 and 21.9%; in Group 2 (nulliparous, singleton, cephalic at ≥37 weeks, without spontaneous labour), the rates were 35.9, 44.4, 43.2 and 54.1%; and in Group 8 (multiple pregnancy), they were 55.9, 67.5, 65.0 and 69.3%, respectively. CONCLUSIONS: CS is relatively more common in women with subfertility and those receiving IT, an effect that persists across Robson groups. TWEETABLE ABSTRACT: Caesarean delivery is more common in women with infertility independent of demographics and prenatal conditions.

Hippocampal volume and vasculature before and after exercise in treatment-resistant schizophrenia.

BACKGROUND: Schizophrenia is associated with poor cognitive function and elevated cardiometabolic disease risk. These health concerns may exacerbate neurocognitive dysfunction associated with hippocampal abnormalities, particularly hippocampal volume reductions. Regular exercise is thought to improve symptom severity, reduce depression, and improve cognition in schizophrenia, and may trigger exercise-mediated hippocampal growth. The potential for the benefits of exercise for treatment-resistant schizophrenia patients has not been clearly assessed. This study aims to assess the effect of exercise on hippocampal plasticity and clinical outcomes in chronic schizophrenia. METHODS: Seventeen DSM-IV criteria schizophrenia or schizoaffective disorder patients completed a customized moderate intensity 12-week aerobic or weight-bearing exercise program. Adherence rates were 83% ±â€¯9.4%) with 70% of participants completing the entire exercise program. Concomitant neuroimaging, clinical and cognitive assessments were obtained at baseline and 12-weeks. RESULTS: At follow-up, symptom severity scores (t(16) = -16.8, p. ≤ 0.0001) and social functioning (t(16) = 4.4, p. = 0.0004) improved. A trend for improved depression scores (t(16) = -2.0, p. = 0.06) with no change in anxiety, or extrapyramidal symptoms were seen. Hippocampal volume increased (t(16) = -2.54, p. = 0.02), specifically in the left CA-1 field (F(16) = -2.33, p. = 0.03). Hippocampal vascular volume was unchanged. Change in hippocampal volume and vascular volume was not significantly correlated with change in symptom severity or affect scores. CONCLUSIONS: Adjunct exercise may accelerate symptom improvement in treatment-resistant psychosis patients. While the underlying mechanism remains unclear, these results indicate that chronic schizophrenia patients experience hippocampal plasticity in response to exercise. STUDY REGISTRATION: Clinical Trials.govNCT01392885.

Maternal pre-gravid cardiometabolic health and infant birthweight: A prospective pre-conception cohort study.

BACKGROUND AND AIMS: Both low birthweight and high birthweight have been associated with the development of cardiometabolic disease in adulthood, possibly reflecting the effect of intrauterine fetal programming. As developmental programming can begin before conception, pre-gravid factors that predict birthweight may be relevant in this context. However, little is known about such factors. Thus, we established a pre-conception cohort to identify maternal pre-gravid cardiometabolic determinants of infant birthweight. METHODS AND RESULTS: In this prospective observational cohort study, 1484 newly-married women in Liuyang, China, underwent baseline (pre-gravid) evaluation and then were followed across a subsequent pregnancy. Pre-gravid cardiometabolic characterization consisted of clinical (anthropometry, blood pressure) and biochemical evaluation (total/LDL/HDL cholesterol, triglycerides, glucose) at median 20 weeks before a singleton pregnancy. Mean birthweight was 3294 ± 444 g, with 173 neonates large-for-gestational-age (LGA) and 110 small-for-gestational-age (SGA). On multiple linear regression analysis, positive determinants of birthweight were maternal age, pre-gravid body mass index (BMI), weight gain in pregnancy, length of gestation, and male infant (all p ≤ 0.0003). On logistic regression analysis, independent predictors of an LGA delivery were maternal age (OR = 1.10 per year, 95%CI 1.03-1.18), pre-gravid BMI (OR = 1.21 per kg/m2, 1.07-1.37), and gestational weight gain (OR = 1.10 per kg, 1.06-1.14). The only independent predictor of SGA was gestational weight gain (OR = 0.93 per kg, 0.89-0.97). CONCLUSION: Maternal weight before and during pregnancy is the predominant cardiometabolic determinant of infant birthweight, rather than pre-gravid blood pressure, glucose or lipid profile.

Adsorption of Small Cationic Nanoparticles onto Large Anionic Particles from Aqueous Solution: A Model System for Understanding Pigment Dispersion and the Problem of Effective Particle Density.

The present study focuses on the use of copolymer nanoparticles as a dispersant for a model pigment (silica). Reversible addition-fragmentation chain transfer (RAFT) alcoholic dispersion polymerization was used to synthesize sterically stabilized diblock copolymer nanoparticles. The steric stabilizer block was poly(2-(dimethylamino)ethyl methacrylate) (PDMA) and the core-forming block was poly(benzyl methacrylate) (PBzMA). The mean degrees of polymerization for the PDMA and PBzMA blocks were 71 and 100, respectively. Transmission electron microscopy (TEM) studies confirmed a near-monodisperse spherical morphology, while dynamic light scattering (DLS) studies indicated an intensity-average diameter of 30 nm. Small-angle X-ray scattering (SAXS) reported a volume-average diameter of 29 ± 0.5 nm and a mean aggregation number of 154. Aqueous electrophoresis measurements confirmed that these PDMA71-PBzMA100 nanoparticles acquired cationic character when transferred from ethanol to water as a result of protonation of the weakly basic PDMA chains. Electrostatic adsorption of these nanoparticles from aqueous solution onto 470 nm silica particles led to either flocculation at submonolayer coverage or steric stabilization at or above monolayer coverage, as judged by DLS. This technique indicated that saturation coverage was achieved on addition of approximately 465 copolymer nanoparticles per silica particle, which corresponds to a fractional surface coverage of around 0.42. These adsorption data were corroborated using thermogravimetry, UV spectroscopy and X-ray photoelectron spectroscopy. TEM studies indicated that the cationic nanoparticles remained intact on the silica surface after electrostatic adsorption, while aqueous electrophoresis confirmed that surface charge reversal occurred below pH 7. The relatively thick layer of adsorbed nanoparticles led to a significant reduction in the effective particle density of the silica particles from 1.99 g cm-3 to approximately 1.74 g cm-3, as judged by disk centrifuge photosedimentometry (DCP). Combining the DCP and SAXS data suggests that essentially no deformation of the PBzMA cores occurs during nanoparticle adsorption onto the silica particles.

Diffusion Tensor Imaging of White Matter in Children Born from Preeclamptic Gestations.

BACKGROUND AND PURPOSE: Individuals born from pregnancies complicated by preeclampsia have an elevated risk for cognitive impairment. Deviations in maternal plasma angiokines occur for prolonged intervals before clinical signs of preeclampsia. We hypothesized that fetal brain vascular and nervous tissue development become deviated during maternal progression toward preeclampsia and that such deviations would be detectable by MR imaging. MATERIALS AND METHODS: In this pilot study, 10 matched (gestational and current ages) pairs (5 boys/5 girls, 7-10 years of age) from preeclampsia or control pregnancies were examined by using diffusion tensor MR imaging. An unbiased voxel-based analysis was conducted on fractional anisotropy and mean diffusivity parametric maps. Six brain ROIs were identified for subsequent analysis by tractography (middle occipital gyrus, caudate nucleus and precuneus, cerebellum, superior longitudinal fasciculus, and cingulate gyrus). RESULTS: Statistical differences were present between groups for fractional anisotropy in the caudate nucleus (offspring from preeclamptic gestation > controls), volume of the tract for the superior longitudinal fasciculus (offspring from preeclamptic gestation > controls) and the caudate nucleus (offspring from preeclamptic gestation > controls), and for parallel diffusivity of the cingulate gyrus (offspring from preeclamptic gestation > controls). CONCLUSIONS: These novel preliminary results along with previous results from the same children that identified altered cerebral vessel calibers and increased regional brain volumes justify fully powered MR imaging studies to address the impact of preeclampsia on human fetal brain development.

Brain Structural and Vascular Anatomy Is Altered in Offspring of Pre-Eclamptic Pregnancies: A Pilot Study.

BACKGROUND AND PURPOSE: Pre-eclampsia is a serious clinical gestational disorder occurring in 3%-5% of all human pregnancies and characterized by endothelial dysfunction and vascular complications. Offspring born of pre-eclamptic pregnancies are reported to exhibit deficits in cognitive function, higher incidence of depression, and increased susceptibility to stroke. However, no brain imaging reports exist on these offspring. We aimed to assess brain structural and vascular anatomy in 7- to 10-year-old offspring of pre-eclamptic pregnancies compared with matched controls. MATERIALS AND METHODS: Offspring of pre-eclamptic pregnancies and matched controls (n = 10 per group) were recruited from an established longitudinal cohort examining the effects of pre-eclampsia. Children underwent MR imaging to identify brain structural and vascular anatomic differences. Maternal plasma samples collected at birth were assayed for angiogenic factors by enzyme-linked immunosorbent assay. RESULTS: Offspring of pre-eclamptic pregnancies exhibited enlarged brain regional volumes of the cerebellum, temporal lobe, brain stem, and right and left amygdalae. These offspring displayed reduced cerebral vessel radii in the occipital and parietal lobes. Enzyme-linked immunosorbent assay analysis revealed underexpression of the placental growth factor among the maternal plasma samples from women who experienced pre-eclampsia. CONCLUSIONS: This study is the first to report brain structural and vascular anatomic alterations in the population of offspring of pre-eclamptic pregnancies. Brain structural alterations shared similarities with those seen in autism. Vascular alterations may have preceded these structural alterations. This pilot study requires further validation with a larger population to provide stronger estimates of brain structural and vascular outcomes among the offspring of pre-eclamptic pregnancies.

Cortical morphology and early adverse birth events in men with first-episode psychosis.

BACKGROUND: Reduced cortical gray-matter volume is commonly observed in patients with psychosis. Cortical volume is a composite measure that includes surface area, thickness and gyrification. These three indices show distinct maturational patterns and may be differentially affected by early adverse events. The study goal was to determine the impact of two distinct obstetrical complications (OCs) on cortical morphology. METHOD: A detailed birth history and MRI scans were obtained for 36 patients with first-episode psychosis and 16 healthy volunteers. RESULTS: Perinatal hypoxia and slow fetal growth were associated with cortical volume (Cohen's d = 0.76 and d = 0.89, respectively) in patients. However, the pattern of associations differed across the three components of cortical volume. Both hypoxia and fetal growth were associated with cortical surface area (d = 0.88 and d = 0.72, respectively), neither of these two OCs was related to cortical thickness, and hypoxia but not fetal growth was associated with gyrification (d = 0.85). No significant associations were found within the control sample. CONCLUSIONS: Cortical dysmorphology was associated with OCs. The use of a global measure of cortical morphology or a global measure of OCs obscured important relationships between these measures. Gyrification is complete before 2 years and its strong relationship with hypoxia suggests an early disruption to brain development. Cortical thickness matures later and, consistent with previous research, we found no association between thickness and OCs. Finally, cortical surface area is largely complete by puberty and the present results suggest that events during childhood do not fully compensate for the effects of early disruptive events.

Is thrombophilia associated with placenta-mediated pregnancy complications? A prospective cohort study.

BACKGROUND: Case control studies suggest that genetic thrombophilias increase the risk of placenta-mediated pregnancy complications (pregnancy loss, small for gestational age (SGA), preeclampsia and/or placental abruption). Cohort studies have not supported this association but were underpowered to detect small effects. OBJECTIVE: To determine if factor V Leiden (FVL) or the prothrombin gene mutation (PGM) were associated with placenta-mediated pregnancy complications. PATIENTS/METHODS: A prospective cohort of unselected, consenting pregnant women at three Canadian tertiary care hospitals had blood drawn in the early second trimester and were genotyped for FVL and PGM after delivery. The main outcome measure was a composite of pregnancy loss, SGA < 10th percentile, preeclampsia or placental abruption. RESULTS: Complete primary outcome and genetic data were available for 7343 women. Most were Caucasian (77.7%, n = 5707), mean age was 30.4 (± 5.1) years, and half were nulliparous. There were 507 (6.9%) women with FVL and/or PGM; 11.64% had a placenta-mediated pregnancy complication. Of the remaining 6836 women, 11.23% experienced a complication. FVL and/or PGM was associated with a relative risk of 1.04 (95% CI, 0.81-1.33) for the composite outcome, with similar results after adjustment for important covariates. CONCLUSIONS: Carriers of FVL or PGM are not at significantly increased risk of these pregnancy complications.

The effect of physical exercise strategies on weight loss in postpartum women: a systematic review and meta-analysis.

For women of reproductive age, excessive gestational weight gain and/or postpartum weight retention can increase the risk of obesity. This systematic review evaluates the effectiveness of lifestyle modification control trials that utilize exercise interventions, with or without dietary intervention, on weight loss among postpartum women. A search of randomized clinical trials (RCT) was performed using the follow databases and the bibliography of candidate studies: MEDLINE, Web of Science, EMBASE, CENTRAL/Cochrane and Physiotherapy Evidence Database. English language RCT papers published up to 31 October 2012, which present changes on maternal body weight from baseline to the end of exercise intervention were included. The primary meta-analysis examined the effects of exercise interventions, with or without complementary dietary intervention, on weight loss during the postpartum period compared with usual standard of care. Five subgroup analyses were performed to examine differences in study interventions and exercise modalities: duration of intervention, quality of study methodology, supervision of exercise intervention, exercise intervention goals used and the type of dietary intervention. In total 11 studies met eligibility criteria with 769 participants, 409 under intervention and 360 in the control group. The primary meta-analysis included all 11 studies and found a mean difference (MD) on weight loss of -2.57 kg (95% CI -3.66 to -1.47). The subgroup analysis demonstrated that the most effective interventions in reducing weight in postpartum women were exercise programs with objectively defined goals, such as the use of heart rate monitors or pedometer (MD of -4.09 kg-95% CI -4.94 to -3.25, I(2)=0%) and exercise combined with intensive dietary intervention (MD of -4.34 kg-95% CI -5.15 to -3.52, I(2)=0%). Thus, there is benefit from overall lifestyle interventions on weight loss in postpartum women and exercise plus intensive diet and objective targets are the most effective intervention strategies.

White matter tract abnormalities in first-episode psychosis.

Fibers connecting fronto-temporal and fronto-medial structures that pass through the anterior limb of the internal capsule (ALIC) subserve executive and psychomotor functioning. Both of these functions are adversely affected in schizophrenia, and may be abnormal at illness onset. In a study of first-episode psychosis, we used diffusion tensor imaging (DTI) and cognitive testing to examine ALIC integrity. Fourteen early psychosis patients and 29 healthy volunteers were included. Symptoms were assessed with the Positive and Negative Syndromes Scale (PANSS). All structural and diffusion scans were acquired on a GE Signa 1.5T scanner. A T1-weighted 3D FSPGR Inversion Recovery imaging series was acquired for manual seeding in structural space. Diffusion tensor imaging (DTI) was performed, and all DTI images were co-registered to structural space. Seeds were manually drawn bilaterally on the coronal plane at a specified location. Diffusion images were post-processed for subsequent Tract-based Spatial Statistics (TBSS) analysis. First-episode psychosis patients had significantly smaller fronto-medial and fronto-temporal AIC tract volumes compared to healthy volunteers on the left and the right (p-values<0.04). No differences in mean fractional anisotropy (FA) were seen within either left or right tracts (p-values>0.05), nor did TBSS reveal any other differences in FA values between groups in other regions. Relationships between tract volumes and symptom severity were not observed in this study.

Preeclampsia and gestational diabetes mellitus: pre-conception origins?

Preeclampsia (PE) and gestational diabetes mellitus (GDM) are two of the most common medical complications of pregnancy, with risks for both mother and child. Like many other antepartum complications, PE and GDM occur only in pregnancy. However, it is not clear if pregnancy itself is the cause of these complications or it these conditions are caused by factors that existed prior to gestation. In this paper, we hypothesize that although the clinical findings of PE and GDM are first noted during pregnancy, the origins of both conditions may actually precede pregnancy. We further hypothesize that pathophysiologic changes underlying PE and GDM are present prior to pregnancy, but remain undetected in the non-gravid state either because pregnancy is the trigger that makes these pathologies become clinically detectable or because there has been limited prospective longitudinal data comparing the pre-gravid and antepartum status of women that go on to develop these conditions. Rigorous prospective cohort studies in which women undergo serial systematic evaluation in the pre-conception period, throughout pregnancy and into the postpartum are ideally needed to test this hypothesis of pre-conception origins of PE and GDM. In this context, we are creating a pre-conception cohort, involving about 5000 couples who plan to have a baby within six months in Liuyang county in the Chinese province of Hunan. Results from this pre-conception cohort program should be able to provide definitive answer to the question of whether the underpinnings of PE and GDM originate prior to pregnancy. Ultimately, the significance of addressing this hypothesis is underscored by its potential implications for targeted interventions that could be designed to (i) prevent the deleterious effects of PE/GDM and (ii) thereby interrupt the vicious cycle of disease that links affected women and their offspring.

PIERS proteinuria: relationship with adverse maternal and perinatal outcome.

OBJECTIVE: To examine the ability of three different proteinuria assessment methods (urinary dipstick, spot urine protein:creatinine ratio [Pr/Cr], and 24-hour urine collection) to predict adverse pregnancy outcomes. METHODS: We performed a prospective multicentre cohort study, PIERS (Preeclampsia Integrated Estimate of RiSk), in seven academic tertiary maternity centres practising expectant management of preeclampsia remote from term in Canada, New Zealand, and Australia. Eligible women were those admitted with preeclampsia who had at least one antenatal proteinuria assessment by urinary dipstick, spot urine Pr/Cr ratio, and/or 24-hour urine collection. Proteinuria assessment was done either visually at the bedside (by dipstick) or by hospital clinical laboratories for spot urine Pr/Cr and 24-hour urine collection. We calculated receiver operating characteristic area under the curve (95% CI) for each proteinuria method and each of the combined adverse maternal outcomes (within 48 hours) or adverse perinatal outcomes (at any time). Models with AUC ≥ 0.70 were considered of interest. Analyses were run for all women who had each type of proteinuria assessment and for a cohort of women ("ALL measures") who had all three proteinuria assessments. RESULTS: More women were proteinuric by urinary dipstick (≥ 2+, 61.4%) than by spot urine Pr/Cr (≥ 30 g/mol, 50.4%) or 24-hour urine collection (≥ 0.3g/d, 34.7%). Each proteinuria measure evaluated had some discriminative power, and dipstick proteinuria (categorical) performed as well as other methods. No single method was predictive of adverse perinatal outcome. CONCLUSION: The measured amount of proteinuria should not be used in isolation for decision-making in women with preeclampsia. Dipstick proteinuria performs as well as other methods of assessing proteinuria for prediction of adverse events.

Circulating CD56+ cells of diabetic women show deviated homing potential for specific tissues during and following pregnancy.

BACKGROUND: Human uterine natural killer (uNK) cells, the dominant lymphocytes in early pregnancy decidua, are important for spiral arterial remodelling. uNK cells are thought to arise from circulating CD56(bright) NK cells that egress into decidualizing endometrium. Both incomplete spiral arterial modification and aberrant NK cell function have been linked with pre-eclampsia, a syndrome that is more prevalent in diabetic women. Since previous in vitro studies have shown that changes in decidual endothelium induced by type 1 diabetes (T1D) reduce its interactions with circulating leucocytes, we hypothesized that diabetes additionally has direct effects on circulating CD56(+) NK cells that impair their decidual homing potential. METHODS: Serial blood samples were collected from control, T1D and T2D pregnant women throughout and after pregnancy. In vitro adhesion under shear forces was used to assay the functional capacity of circulating leucocytes and of CD56(+) cells to adhere to endothelium in cryostat sections of gestation day (gd) 7 normal mouse decidua, pancreas and lymph node. RESULTS: Fewer CD56(+) cells from diabetic compared with control women adhered to normal decidual endothelium. The CD56(+) cell/total cell adhesion ratio was also lower in diabetics. More diabetic CD56(+) cells adhered to pancreatic endothelium and their proportion was greater than for controls. Neither absolute nor proportional adhesion of CD56(+) cells to lymph node endothelium differed between diabetics and controls. CONCLUSIONS: The CD56(+) cell adhesion patterns of T1D and T2D women differ from those of non-diabetic women and support the hypothesis that diabetes impairs mechanisms that could be used by CD56(+) cells for egress into decidua.

Characterisation and performance of a Terfenol-D coated femtosecond laser inscribed optical fibre Bragg sensor with a laser ablated microslot for the detection of static magnetic fields.

We present a novel device for the characterisation of static magnetic fields through monitoring wavelength shifts of femtosecond inscribed fibre Bragg grating and micromachined slot, coated with Terfenol-D. The device was sensitive to static magnetic fields and can be used as a vectoral sensor for the detection of magnetic fields as low as 0.046 mT with a resolution of ± 0.3mT in transmission and ± 0.7mT in reflection. The use of a femtosecond laser to both inscribe the FBGs and micromachine the slot in a single stage prior to coating the device significantly simplifies the fabrication.

Anterior internal capsule volumes increase in patients with schizophrenia switched from typical antipsychotics to olanzapine.

Abnormalities in connectivity are thought to contribute to the symptoms of schizophrenia. Accumulating evidence suggests that antipsychotic medication affects both subcortical and cortical grey and white matter volumes. The goal of this study was to investigate the effects of antipsychotic medication on two white matter tracts: a subcortical-cortical tract, the anterior and posterior limbs of the internal capsule; and a cortical-cortical tract, the corpus callosum. Magnetic resonance imaging was conducted on 10 chronic schizophrenia patients treated with typical antipsychotics and 20 healthy controls at baseline. Patients were switched to olanzapine and both groups were rescanned after 1 year. At baseline, the volume of the anterior limb of the internal capsule was 24% smaller in typical-treated patients than controls (p = 0.009). Patients treated with greater amounts of chlorpromazine-equivalent daily dosage had smaller anterior internal capsule volumes at baseline (r = -0.65, p = 0.04). At follow-up, after being switched to olanzapine, there were no significant differences between patients and controls. Patients with schizophrenia had a significant 25% increase in anterior internal capsule volume from baseline to follow-up compared with controls (p = 0.04). These effects were most prominent in the anterior limb of the internal capsule, which consists of fronto-thalamic pathways, and were not statistically significant in the posterior limb of the internal capsule or corpus callosum. Olanzapine may be effective in normalizing fronto-thalamic structural connectivity in schizophrenia.

Current CHS and NHBPEP criteria for severe preeclampsia do not uniformly predict adverse maternal or perinatal outcomes.

OBJECTIVE: To determine the association between adverse maternal/perinatal outcomes and Canadian and U.S. preeclampsia severity criteria. METHODS: Using PIERS data (Preeclampsia Integrated Estimate of RiSk), an international continuous quality improvement project for women hospitalized with preeclampsia, we examined the association between preeclampsia severity criteria and adverse maternal and perinatal outcomes (univariable analysis, Fisher's exact test). Not evaluated were variables performed in <80% of pregnancies (e.g., 24-hour proteinuria). RESULTS: Few of the evaluated variables were associated with adverse maternal (chest pain/dyspnea, thrombocytopenia, 'elevated liver enzymes', HELLP syndrome, and creatinine >110 microM) or perinatal outcomes (dBP >110 mm Hg and suspected abruption) (at p < 0.01). CONCLUSIONS: In the PIERS cohort, most factors used in the Canadian or American classifications of severe preeclampsia do not predict adverse maternal and/or perinatal outcomes. Future classification systems should take this into account.

Pregnancy-induced hypertension and infant mortality in triplets.

OBJECTIVE: To assess the effects of pregnancy-induced hypertension on infant mortality in triplets stratified by gestational age at birth. METHODS: A retrospective cohort study was conducted using the linked 1995-2000 US birth/infant death database. Generalized estimating equations were used to evaluate the observed association. RESULTS: Pregnancy-induced hypertension was associated with lesser neonatal mortality (odds ration [OR]: 0.34, 95% CI: 0.21, 0.54), postneonatal mortality (OR: 0.54, 95% CI: 0.30, 0.99) and infant mortality (OR, 0.37, 95% CI: 0.25, 0.55) in triplets. It was also associated with a decreased risk of neonatal death (OR, 0.38; 95% CI, 0.21-0.67), postneonatal death (OR, 0.45; 95% CI, 0.21-0.97), and infant death (OR, 0.39; 95% CI, 0.24-0.64) in early preterm triplets, whereas the association was not significant in late preterm or in full-term triplets. CONCLUSION: Pregnancy-induced hypertension is associated with a decreased risk of infant mortality in triplets. This effect varies with gestational age at birth.

Lung transplant metalloproteinase levels are elevated prior to bronchiolitis obliterans syndrome.

Parenchymal disease in the allograft lung is associated with interstitial remodeling believed to be mediated by matrix metalloproteinases (MMPs). Recent studies suggest high levels of MMP-9 are associated with bronchiolitis obliterans syndrome (BOS) in lung transplant recipients. Since BOS occurs late in the posttransplant period and may be preceded by episodes of acute rejection or infection, which are associated with interstitial remodeling, we examined MMP profiles in allograft bronchoalveolar lavage (BAL) fluid in the early posttransplant period (preceding BOS). Gelatin zymography, protein array analysis and specific ELISA on BAL fluids from transplanted lungs indicated that MMP-8, MMP-9 and TIMP-1 were strongly expressed in allograft BAL fluid from stable patients, or those with infection or rejection compared to BAL fluid from normal volunteers. Elevated expression of MMP-8, MMP-9 and TIMP-1 occurred early, and was sustained for the 3.2 years covered in this study. Elevations of MMP-8, MMP-9 and TIMP-1 in the first 2 years posttransplant appear to be associated with lung transplantation itself, and not infection or rejection. These data suggest that ongoing and clinically silent MMP activity could perpetuate progressive disease in the allograft lung.

The incidence of schizophrenia in European immigrants to Canada.

OBJECTIVE: The risk for schizophrenia in immigrants to Europe is approximately three times that of native-born populations. Discrimination and marginalization may influence the risk for schizophrenia within migrant populations. The primary objective of the present study was to determine whether the risk associated with migration was also evident 100 years ago. A second objective was to determine whether changing social stresses are associated with changes to the incidence of schizophrenia. METHOD: During the first two decades of the twentieth century, the Provincial Mental Hospital was the sole provider of psychiatric services in British Columbia, Canada. Detailed clinical records have been preserved for 99.5% of 2477 patients who had a psychiatric admission between 1902 and 1913. Diagnoses were made after a detailed file review and 807 patients met DSM-IV criteria for first-episode schizophrenia, schizophreniform disorder, schizoaffective disorder, or psychosis not otherwise specified. Diagnoses had high inter-rater reliability. The incidence of schizophrenia in migrants from Britain or Continental Europe was compared with that in the Canadian-born population using indirect standardization and Poisson models. RESULTS: Migration from Britain or Continental Europe to Canada in the early twentieth century was associated with an increased rate of schizophrenia; IRR=1.54, (95% CI=1.33-1.78). Incidence increased over time in immigrants but not in the native-born population and this increase occurred during a period of economic recession. CONCLUSIONS: Migration was a risk factor for schizophrenia a century ago as it is today. This risk occurred in white migrants from Europe and increased during a period of increased social stress.

Reduced anterior internal capsule and thalamic volumes in first-episode psychosis.

BACKGROUND: The thalamus is the gateway for sensory and motor information en route to the cortex. Information is processed via thalamocortical and corticothalamic pathways coursing through the internal capsules. In this study, we investigated the relationship between the anterior limb of the internal capsule, posterior limb of the internal capsule, and thalamus in first-episode psychosis (FEP). METHODS: Twenty-nine FEP subjects (26 DSM-IV schizophrenia, 2 schizoaffective disorder, 1 psychosis not otherwise specified) and 22 healthy volunteers participated in this study. Anterior limb of the internal capsule (AIC), posterior limb of the internal capsule (PIC), and the thalamus volumes were manually determined from MRI scans. RESULTS: FEP subjects had reduced AIC volumes (F(1,45)=6.18, p=0.017) and thalamic volumes (F(1,45)=8.00, p=0.007) compared to healthy volunteers. PIC volumes did not differ. Significant correlations between AIC volumes and thalamic volumes were observed in subjects with FEP, but not in healthy volunteers. Negative relationships between thalamic volumes and symptom severity were also observed. CONCLUSIONS: The AIC and thalamic volumes were reduced in subjects with FEP compared to healthy volunteers. Abnormalities in thalamocortical and orticothalamic pathways may contribute to functional disruption of neural circuits in psychosis.