Patterns, predictors and outcomes of asthma control and exacerbations during pregnancy: a prospective cohort study

There exists a paucity of data for socially disadvantaged populations describing patterns and predictors of asthma control status and exacerbations during pregnancy, and their relationship to adverse perinatal outcomes. Asthmatic women (n=189) were followed prospectively during pregnancy, with visits at 12, 20, 28 and 36 weeks gestation. Data on loss of control, recurrent uncontrolled asthma and moderate/severe exacerbations were collected at each visit and their relationship to perinatal outcomes examined following stratification for fetal sex. 50% of asthmatic women experienced a loss of control or moderate/severe exacerbation during pregnancy, with 22% of women experiencing a moderate/severe exacerbation. Factors associated with an increased risk of women experiencing recurrent uncontrolled asthma during pregnancy included smoking (relative risk 2.92, 95% CI 1.53-5.58), inhaled corticosteroid use at the beginning of pregnancy (relative risk 2.40, 95% CI 1.25-4.60) and increasing maternal age (relative risk 1.06, 95% CI 1.01-1.11). No factors were associated with moderate/severe exacerbations. Asthma control rather than exacerbations during pregnancy appeared to be most strongly correlated with perinatal outcomes. Following stratification by fetal sex, the presence of recurrent uncontrolled asthma was associated with an increased risk of being small for gestational age in women pregnant with females (33.3% versus 9.5%; p=0.018). In contrast, there was a nonsignificant increased risk of preterm birth in women with recurrent uncontrolled asthma that were pregnant with males (25.0% versus 11.8%; p=0.201) These results suggest that the key to improving perinatal outcomes lies in improving asthma control as early as possible in pregnancy and monitoring throughout pregnancy, rather than focusing on preventing exacerbations alone.Luke E. Grzeskowiak, Brian Smith, Anil Roy, Gustaaf A. Dekker and Vicki L. Clifto

Prenatal antidepressant exposure and child behavioural outcomes at 7 years of age: a study within the Danish National Birth Cohort

Objective: To investigate the impact of prenatal antidepressant exposure on behavioural problems in children at 7 years of age. Design: Nationwide population-based study. Setting: Danish National Birth Cohort. Population: A cohort of 49 178 pregnant women recruited between 1996 and 2002. Methods: Data obtained from computer-assisted telephone interviews twice during pregnancy were used to identify children born to: (i) depressed women who took antidepressants during pregnancy (n = 210); (ii) depressed women who did not take any antidepressants during pregnancy (n = 231); and (iii) healthy women who were not depressed (n = 48 737). Childhood behavioural problems at 7 years of age were examined using the validated Danish parent-report version of the Strengths and Difficulties Questionnaire (SDQ). Main outcome measures: SDQ scores. Results: No associations were observed between prenatal antidepressant exposure and abnormal SDQ scores for overall problem behaviour (adjusted relative risk, aRR 1.00; 95% confidence interval, 95% CI 0.49–2.05), hyperactivity/inattention (aRR 0.99; 95% CI 0.56–1.75), or peer problems (aRR 1.04; 95% CI 0.57–1.91). Although prenatal antidepressant exposure appeared to be associated with abnormal SDQ scores on the subscales of emotional symptoms (aRR 1.68; 95% CI 1.18–2.38) and conduct problems (aRR 1.58; 95% CI 1.03–2.42), these associations were significantly attenuated following adjustment for antenatal mood status (aRR 1.20; 95% CI 0.85–1.70 and aRR 1.19; 95% CI 0.77 1.83, respectively). Untreated prenatal depression was associated with an increased risk of all behavioural outcomes evaluated, compared with unexposed children, with significant attenuation following adjustment for antenatal mood status. Conclusions: The results of this study suggest that independent of maternal illness, prenatal antidepressant exposure is not associated with an increased risk of behavioural problems in children at 7 years of age.LE Grzeskowiak, JL Morrison, TB Henrikse, BH Bech, C Obel, J Olsen, LH Pederse

Trajectories of anxiety and health related quality of life during pregnancy

Published: July 24, 2017Anxiety and health related Quality of Life (HRQoL) have emerged as important mental health measures in obstetric care. Few studies have systematically examined the longitudinal trajectories of anxiety and HRQoL in pregnancy. Using a linear growth modeling strategy, we analyzed the course of State-Trait Anxiety Inventory (STAI)- and Short Form (36) Health Survey (SF-36) scores between the 12th and the 36th week of gestation, in a sample of 355 women. We additionally analyzed the impact of depressive symptoms and a chronic medical condition (asthma), on STAI and SF-36 trajectory curves. STAI scores remained stable throughout pregnancy. A previous history of anxiety increased the overall STAI scores. Asthma and depressive symptoms scores had no impact on the STAI trajectory. Physical SF-36 scores decreased over the course of pregnancy, whereas mental SF-36 trended towards improvement. Asthma reduced physical SF-36 overall. While high depressive symptoms decreased the overall mental SF-36, they were also significantly associated with mental SF-36 improvements over time. Anxiety symptoms are stable during pregnancy and are not modulated by depressive symptoms or asthma. Physical HRQoL declines in pregnancy. In contrast, mental HRQoL appears to improve, particularly in women with high initial levels of depressive symptoms.K. Oliver Schubert, Tracy Air, Scott R. Clark, Luke E. Grzeskowiak, Edward Miller, Gustaaf A. Dekker, Bernhard T. Baune, Vicki L. Clifto

Impact of inter-pregnancy BMI change on perinatal outcomes: a retrospective cohort study

Abstract not availableRosemary D. McBain, Gustaaf A. Dekker, Vicki L. Clifton, Ben W. Mol, Luke E. Grzeskowia

Use of intravenous iron polymaltose in the management of iron deficiency in pregnancy: a retrospective cohort study

Background: Intravenous iron polymaltose (IPM) is commonly utilised in pregnancy when oral treatment is not tolerated or where rapid replenishment of iron stores is required, but data on use in pregnancy is scarce. Aim: To examine the use, safety and efficacy of intravenous IPM in pregnancy. Methods: Retrospective cohort study of pregnant women administered intravenous IPM between January 2014 and January 2016 at a Tertiary teaching hospital in Adelaide, Australia. Data on maternal characteristics, intravenous iron infusion details, and haematological parameters were collected from case notes and electronic records. Main outcome measures included indication for intravenous iron infusion, prevalence of infusion reactions, change in haemoglobin and correction of anaemia prior to delivery. Results: Intravenous IPM was administered in 213 pregnancies, 62.0% of women with iron deficiency anaemia (IDA) and the remainder (38.0%) with non-anaemic iron deficiency. Adverse drug reactions (ADRs) occurred in 24% of women, of which 32% required infusion cessation. Anaemia was still present at delivery among 7%, and 17% of women with mild, and moderate/severe anaemia respectively. Approximately one in five anaemic women received an intravenous IPM dose below that recommended by the local guideline, particularly in women with a body mass index ≥ 25 kg/m² compared with <25 kg/m² (30.9% vs 6.3%; P < 0.001). Doses ‘at recommended’ resulted in a greater increase in haemoglobin from treatment until delivery than doses ‘below recommended’ (adjusted beta coefficient 8.4 g/L; 95% CI 2.7–14.1 g/L). Conclusion: Intravenous IPM is effective in treating IDA in pregnancy but is associated with a high prevalence of ADRs and treatment cessation.Alaa Qassim, Rosina G. Gergis, Bill Jeffries, Rosalie M. Grivell and Luke E. Grzeskowia

Adverse events associated with peanut oral immunotherapy in children – a systematic review and meta-analysis

While peanut oral immunotherapy (POIT) represents a promising treatment for peanut allergies in children, safety concerns remain a common barrier to widespread adoption. We aimed to systematically assess available evidence to determine the risk and frequency of adverse events occurring during POIT, and examine study-level characteristics associated with their occurrence and severity. A systematic search of MEDLINE, EMBASE, and Web of Science was conducted through April 2019. Controlled and non-controlled studies evaluating POIT were eligible. Twenty-seven studies, involving 1488 subjects, were included. Adverse events to POIT were common and led to treatment discontinuation in 6.6% of children (95% CI 4.4–9.0; 27 studies, I² = 48.7%). Adverse events requiring treatment with epinephrine occurred among 7.6% (4.5–11.4; 26 studies, I² = 75.5%) of participants, at a rate of 2.0 per 10,000 doses (0.8–3.7; 15 studies, I² = 64.4). Use of a rush treatment phase and targeting a higher maintenance dose were associated with a higher risk and frequency of epinephrine use, while using co-treatments in addition to POIT was associated with a lower risk of treatment discontinuation due to adverse events. While adverse events to POIT are common, this study provides promising explorative evidence that certain modifications to existing treatment protocols could significantly improve treatment outcomes.Luke E. Grzeskowiak, Billy Tao, Emma Knight, Sarah Cohen-Woods, Timothy Chatawa

A randomized controlled trial to assess the clinical and cost effectiveness of a nurse-led Antenatal Asthma Management Service in South Australia (AAMS study)

Background: Pregnancy presents a unique situation for the management of asthma as it can alter the course of asthma severity and its treatment, which in turn can affect pregnancy outcomes. Despite awareness of the substantial adverse effects associated with asthma during pregnancy, little has been done to improve its management and reduce associated perinatal morbidity and mortality. The aim of this randomized controlled trial is to evaluate the clinical and cost effectiveness of an Antenatal Asthma Management Service. Methods/design: Design: Multicentre, randomized controlled trial. Inclusion criteria: Women with physician diagnosed asthma, which is not currently in remission, who are less than 20 weeks gestation with a singleton pregnancy and do not have a chronic medical condition. Trial entry and randomization: Eligible women with asthma, stratified by treatment site, disease severity and parity, will be randomized into either the ‘Standard Care Group’ or the ‘Intervention Group’. Study groups: Both groups will be followed prospectively throughout pregnancy. Women in the ‘Standard Care Group’ will receive routine obstetric care reflecting current clinical practice in Australian hospitals. Women in the ‘Intervention Group’ will receive additional care through the nurse-led Antenatal Asthma Management Service, based in the antenatal outpatient clinic. Women will receive asthma education with a full assessment of their asthma at 18, 24, 30 and 36 weeks gestation. Each antenatal visit will include a 60 min session where asthma management skills are assessed including: medication adherence and knowledge, inhaler device technique, recognition of asthma deterioration and possession of a written asthma action plan. Furthermore, subjects will receive education about asthma control and management skills including trigger avoidance and smoking cessation counseling when appropriate. Primary study outcome: Asthma exacerbations during pregnancy. Sample size: A sample size of 378 women will be sufficient to show an absolute reduction in asthma exacerbations during pregnancy of 20% (alpha 0.05 two-tailed, 90% power, 5% loss to follow-up). Discussion: The integration of an asthma education program within the antenatal clinic setting has the significant potential to improve the participation of pregnant women in the self-management of their asthma, reduce asthma exacerbations and improve perinatal health outcomes.Luke E Grzeskowiak, Gustaaf Dekker, Karen Rivers, Kate Roberts-Thomson, Anil Roy, Brian Smith, Jeffery Bowden, Robert Bryce, Michael Davies, Justin Beilby, Anne Wilson, Philippa Middleton, Richard Ruffin, Jonathan Karnon, Vicki L Clifton and for the AAMS study grou

Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets

The clinical phenotype of human dilated cardiomyopathy (DCM) encompasses a broad spectrum of etiologically distinct disorders. As targeting of etiology-related pathogenic pathways may be more efficient than current standard heart failure treatment, we obtained the genomic expression profile of a DCM subtype characterized by cardiac inflammation to identify possible new therapeutic targets in humans. In this inflammatory cardiomyopathy (DCMi), a distinctive cardiac expression pattern not described in any previous study of cardiac disorders was observed. Two significantly altered gene networks of particular interest and possible interdependence centered around the cysteine-rich angiogenic inducer 61 (CYR61) and adiponectin (APN) gene. CYR61 overexpression, as in human DCMi hearts in situ, was similarly induced by inflammatory cytokines in vascular endothelial cells in vitro. APN was strongly downregulated in DCMi hearts and completely abolished cytokine-dependent CYR61 induction in vitro. Dysbalance between the CYR61 and APN networks may play a pathogenic role in DCMi and contain novel therapeutic targets. Multiple immune cell-associated genes were also deregulated (e.g., chemokine ligand 14, interleukin-17D, nuclear factors of activated T cells). In contrast to previous investigations in patients with advanced or end-stage DCM where etiology-related pathomechanisms are overwhelmed by unspecific processes, the deregulations detected in this study occurred at a far less severe and most probably fully reversible disease stage. ELECTRONIC SUPPLEMENTARY MATERIAL: Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s00109-006-0122-9 and is accessible for authorized users

Genetic diversity, linkage disequilibrium and power of a large grapevine (Vitis vinifera L) diversity panel newly designed for association studies

UMR-AGAP Equipe DAVV (Diversité, adaptation et amélioration de la vigne) ; équipe ID (Intégration de Données)International audienceAbstractBackgroundAs for many crops, new high-quality grapevine varieties requiring less pesticide and adapted to climate change are needed. In perennial species, breeding is a long process which can be speeded up by gaining knowledge about quantitative trait loci linked to agronomic traits variation. However, due to the long juvenile period of these species, establishing numerous highly recombinant populations for high resolution mapping is both costly and time-consuming. Genome wide association studies in germplasm panels is an alternative method of choice, since it allows identifying the main quantitative trait loci with high resolution by exploiting past recombination events between cultivars. Such studies require adequate panel design to represent most of the available genetic and phenotypic diversity. Assessing linkage disequilibrium extent and panel power is also needed to determine the marker density required for association studies.ResultsStarting from the largest grapevine collection worldwide maintained in Vassal (France), we designed a diversity panel of 279 cultivars with limited relatedness, reflecting the low structuration in three genetic pools resulting from different uses (table vs wine) and geographical origin (East vs West), and including the major founders of modern cultivars. With 20 simple sequence repeat markers and five quantitative traits, we showed that our panel adequately captured most of the genetic and phenotypic diversity existing within the entire Vassal collection. To assess linkage disequilibrium extent and panel power, we genotyped single nucleotide polymorphisms: 372 over four genomic regions and 129 distributed over the whole genome. Linkage disequilibrium, measured by correlation corrected for kinship, reached 0.2 for a physical distance between 9 and 458 Kb depending on genetic pool and genomic region, with varying size of linkage disequilibrium blocks. This panel achieved reasonable power to detect associations between traits with high broad-sense heritability (> 0.7) and causal loci with intermediate allelic frequency and strong effect (explaining > 10 % of total variance).ConclusionsOur association panel constitutes a new, highly valuable resource for genetic association studies in grapevine, and deserves dissemination to diverse field and greenhouse trials to gain more insight into the genetic control of many agronomic traits and their interaction with the environment