Personal strategies to reduce the effects of landscape fire smoke on asthma-related outcomes: a protocol for systematic review and meta-analysis.

INTRODUCTION: Landscape fire smoke (LFS) contains several hazardous air pollutants that are known to be detrimental to human health. People with asthma are more vulnerable to the health impact of LFS than general populations. The aim of this review is to investigate the effectiveness of personal strategies to reduce the effect of LFS on asthma-related outcomes. METHODS AND ANALYSIS: We will electronically search databases such as Medline, Embase, CINAHL and Cochrane Clinical Trials Register to identify eligible articles for the review. Screening of search results and data extraction from included studies will be completed by two independent reviewers. The risk of bias (RoB 2) will be assessed using the Risk of Bias Assessment Tool for Non-Randomised Studies for observational studies, the Cochrane Collaboration tool for assessing the RoB 2 for randomised controlled trials (RCTs) and the Risk Of Bias In Nonrandomized Studies of Interventions tool for non-RCTs. A random-effect meta-analysis will be performed to determine the pooled summary of findings of the included studies. If meta-analysis is not possible, we will conduct a narrative synthesis. Findings will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. ETHICS AND DISSEMINATION: This study will synthesise the available evidence obtained from published studies and as such, no ethical approval is required. The review will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42022341120.

Parent-infant interaction quality is related to preterm status and sensory processing.

BACKGROUND: Parent-infant interactions provide the foundation for the development of infant socioemotional wellbeing. Preterm birth can have a substantial, and often detrimental, impact on the quality of early parent-infant interactions. Sensory processing difficulties, common in preterm infants, are further associated with poorer interaction quality. There is a paucity of research, however, examining the links between the quality of parent-infant interaction, preterm birth, and sensory processing difficulties. This study aimed to characterise the quality of interactions of parent-infant dyads involving preterm infants who may display sensory processing differences and examine the associations between parent-infant interaction quality, preterm status and infant sensory processing. METHOD: 67 parent-infant dyads (12-months infant age, 22 preterm, 45 full-term) participated in a recorded, semi-structured 15-minute play interaction. Parents also filled out questionnaires on demographics, and infant sensory processing (Infant and Toddler Sensory Profile-2; ITSP-2). Interaction quality was rated using the Parenting Interactions with Children: Checklist of Observations Linked to Outcomes (PICCOLO). RESULTS: Preterm and full-term infants differed in sensory processing and parent-infant interaction. Infant prematurity was associated with the sensory domains of; visual (r = - 0.37, p = .005), touch (r = - 0.39, p = .002), and movement (rs = - .32, p = .01), as well as the interaction domains of; responsivity (rs;= - .43, p = .001), teaching (rs = - .31, p = .02), and interaction total score (r = - 0.34, p = .01). Interaction quality was related to sensory registration (rs = - .38, p = .008), auditory (rs = - .34, p = .02), seeking (rs = .29, p = .05) and sensory behavioural scores (rs = - .52, p < .001). Overall, interaction quality was best predicted by infant prematurity and auditory scores, R2 = .15, F(1, 47) = 4.01, p = .02. DISCUSSION: Preterm infants differed from their full-term peers in both their sensory processing and in their dyadic interactions with parents. Preterm status was associated with less responsivity and teaching and was found to predict overall interaction quality. Poorer infant sensory processing was associated with less parental teaching, affection and responsivity during interactions. Our results suggest that preterm birth is related to sensory processing difficulties, and that prematurity and sensory processing are differentially associated with aspects of interaction quality. These findings support the further examination of the interplay between preterm birth, sensory processing, and parent-infant interaction quality.

Maternal asthma and gestational diabetes mellitus: Exploration of potential associations.

Asthma and gestational diabetes mellitus are prevalent during pregnancy and associated with adverse perinatal outcomes. The risk of gestational diabetes mellitus is increased with asthma, and more severe asthma; yet, the underlying mechanisms are unknown. This review examines existing literature to explore possible links. Asthma and gestational diabetes mellitus are associated with obesity, excess gestational weight gain, altered adipokine levels and low vitamin D levels; yet, it's unclear if these underpin the gestational diabetes mellitus-asthma association. Active antenatal asthma management reportedly mitigates asthma-associated gestational diabetes mellitus risk. However, mechanistic studies are lacking. Existing research suggests asthma management during pregnancy influences gestational diabetes mellitus risk; this may have important implications for future antenatal strategies to improve maternal-fetal outcomes by addressing both conditions. Addressing shared risk factors, as part of antenatal care, may also improve outcomes. Finally, mechanistic studies, to establish the underlying pathophysiology linking asthma and gestational diabetes mellitus, could uncover new treatment approaches to optimise maternal and child health outcomes.

Vitamin D status in pregnant women with asthma and its association with adverse respiratory outcomes during infancy.

BACKGROUND: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. METHODS: Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother-infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D ≥ 75 nmol/L (at one or both time-points). RESULTS: In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26-110) nmol/L at 16 weeks, and 65 (range 32-116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points; 21 (40%) had 25(OH)D ≥ 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with "wheeze ever" at 12 months, compared with 25(OH)D ≥ 75 nmol/L (71 versus 43%, p = .04). Infant acute-care presentations (45 versus 13%, p = .02) and oral corticosteroid use (26 versus 4%, p = .03) due to "asthma/wheezing" were higher in the maternal group with 25(OH)D < 75 nmol/L, versus ≥75 nmol/L. CONCLUSIONS: Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.

The risk of congenital malformations, perinatal mortality and neonatal hospitalisation among pregnant women with asthma: a systematic review and meta-analysis.

BACKGROUND: There is conflicting literature on the effect of maternal asthma on congenital malformations and neonatal outcomes. OBJECTIVES: This review and meta-analysis sought to determine if maternal asthma is associated with an increased risk of adverse neonatal outcomes. SEARCH STRATEGY: We searched electronic databases for: (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Cohort studies published between 1975 and March 2012 reporting at least one perinatal outcome of interest (congenital malformations, neonatal complications, perinatal mortality). DATA COLLECTION AND ANALYSIS: In all, 21 studies met inclusion criteria in pregnant women with and without asthma. Further analysis was conducted on 16 studies where asthmatic women were stratified by exacerbation history, corticosteroid use, bronchodilator use or asthma severity. MAIN RESULTS: Maternal asthma was associated with a significantly increased risk of congenital malformations (relative risk [RR] 1.11, 95% confidence interval [95% CI] 1.02-1.21, I(2)  = 59.5%), cleft lip with or without cleft palate (RR 1.30, 95% CI 1.01-1.68, I(2)  = 65.6%), neonatal death (RR 1.49, 95% CI 1.11-2.00, I(2)  = 0%), and neonatal hospitalisation (RR 1.50, 95% CI 1.03-2.20, I(2)  = 64.5%). There was no significant effect of asthma on major malformations (RR 1.31, 95% CI 0.57-3.02, I(2)  = 70.9%) or stillbirth (RR 1.06, 95% CI 0.9-1.25, I(2)  = 35%). Exacerbations and use of bronchodilators and inhaled corticosteroids were not associated with congenital malformation risk. AUTHORS' CONCLUSIONS: Despite limitations related to the observational nature of the primary studies, this review demonstrates a small increased risk of neonatal complications among pregnant women with asthma. Further investigations into mechanisms and potential preventive interventions to improve infant outcomes are required.

A meta-analysis of adverse perinatal outcomes in women with asthma.

BACKGROUND: Asthma is a common condition during pregnancy and may be associated with adverse perinatal outcomes. OBJECTIVE: This meta-analysis sought to establish if maternal asthma is associated with an increased risk of adverse perinatal outcomes, and to determine the size of these effects. SEARCH STRATEGY: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Cohort studies published between 1975 and March 2009 were considered for inclusion. Studies were included if they reported at least one perinatal outcome in pregnant women with and without asthma. DATA COLLECTION AND ANALYSIS: A total of 103 articles were identified, and of these 40 publications involving 1,637,180 subjects were included. Meta-analysis was conducted with subgroup analyses by study design and active asthma management. MAIN RESULTS: Maternal asthma was associated with an increased risk of low birthweight (RR 1.46, 95% CI 1.22-1.75), small for gestational age (RR 1.22, 95% CI 1.14-1.31), preterm delivery (RR 1.41, 95% CI 1.22-1.61) and pre-eclampsia (RR 1.54, 95% CI 1.32-1.81). The relative risk of preterm delivery and preterm labour were reduced to non-significant levels by active asthma management (RR 1.07, 95% CI 0.91-1.26 for preterm delivery; RR 0.96, 95% CI 0.73-1.26 for preterm labour). AUTHOR'S CONCLUSIONS: Pregnant women with asthma are at increased risk of perinatal complications, including pre-eclampsia and outcomes that affect the baby's size and timing of birth. Active asthma management with a view to reducing the exacerbation rate may be clinically useful in reducing the risk of perinatal complications, particularly preterm delivery.

Metabolism of synthetic steroids by the human placenta.

Pregnant women with asthma are frequently exposed to synthetic glucocorticoids and glucocorticoids are known to reduce fetal growth. The fetus is normally protected from the harmful effects of maternally derived glucocorticoids by the placental enzyme 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Whether 11beta-HSD2 inactivates the synthetic glucocorticoids used for asthma treatment during pregnancy (budesonide, beclomethasone dipropionate and fluticasone propionate) remains unknown. To investigate the relationship between steroid use during pregnancy and fetal growth and development, pregnant women with (n=119) and without asthma (n=84) were followed throughout pregnancy. Data on asthma medication use, neonatal size at birth, placental weight and cord blood cortisol and estriol were collected. Placental tissue samples were collected from non-asthmatic women (n=8) for metabolism studies. Placental 11beta-HSD2 activity was determined using beclomethasone dipropionate, budesonide, fluticasone propionate, prednisolone, dexamethasone and betamethasone as steroid substrates. Steroids and their oxidised metabolites were examined using thin layer chromatography and densitometry. Placental 11beta-HSD2 metabolised beclomethasone, prednisolone, dexamethasone and betamethasone, but not budesonide or fluticasone. No association between the use of inhaled steroids for asthma treatment during pregnancy and alterations in neonatal size, placental weight, gestational age at delivery, or umbilical vein estriol concentrations was demonstrated compared to non-asthmatic women. In conclusion, the use of inhaled steroids for asthma treatment does not affect fetal growth, despite differences in placental metabolism by 11beta-HSD2.

Asthma exacerbations during pregnancy: incidence and association with adverse pregnancy outcomes.

Exacerbations of asthma during pregnancy represent a significant clinical problem and may be related to poor pregnancy outcomes. A systematic review of the literature was conducted for publications related to exacerbations during pregnancy. Four studies with a control group (no asthma) and two groups of women with asthma (exacerbation, no exacerbation) were included in meta-analyses using fixed effects models. During pregnancy, exacerbations of asthma which require medical intervention occur in about 20% of women, with approximately 6% of women being admitted to hospital. Exacerbations during pregnancy occur primarily in the late second trimester; the major triggers are viral infection and non-adherence to inhaled corticosteroid medication. Women who have a severe exacerbation during pregnancy are at a significantly increased risk of having a low birth weight baby compared with women without asthma. No significant associations between exacerbations during pregnancy and preterm delivery or pre-eclampsia were identified. Inhaled corticosteroid use may reduce the risk of exacerbations during pregnancy. Pregnant women may be less likely to receive oral steroids for the emergency management of asthma. The effective management and prevention of asthma exacerbations during pregnancy is important for the health of both the mother and fetus.

Asthma self-management skills and the use of asthma education during pregnancy.

During pregnancy, patients with asthma are at risk of poor outcomes, particularly when asthma is poorly controlled. The aim of this study was to determine the level of asthma self-management skills and knowledge among pregnant subjects and describe the implementation of an asthma education programme delivered in an antenatal clinic setting. Pregnant subjects with asthma were assessed by an asthma educator at 20 (n = 211) and 33 weeks gestation (n = 149). Lung function, symptoms, medication use, adherence, knowledge and inhaler technique were assessed. They were asked whether they had a written asthma action plan, or performed peak flow monitoring. Asthma was classified as mild, moderate or severe. At the first visit with the asthma educator, 40% of females reported nonadherence to inhaled corticosteroids, inhaler technique was assessed as inadequate in 16% and 42% had inadequate medication knowledge. Peak flow monitoring was performed by 3% and 15% had a written action plan. There were significant improvements in all aspects of asthma self-management following education. In females with severe asthma, night symptoms and reliever medication use significantly decreased after education. In conclusion, during pregnancy, patients with asthma have poor asthma knowledge and skills, and may benefit from self-management education as part of their obstetric care.

Asthma during pregnancy: mechanisms and treatment implications.

Asthma is becoming increasingly prevalent worldwide. Numerous historical and prospective cohort studies have investigated the effects of maternal asthma on pregnancy outcome; however, the data has been conflicting and many studies have not used standard classifications for asthma severity. Overall, the literature suggests that asthmatic females are more at risk of low birth weight neonates, pre-term delivery and complications such as pre-eclampsia, especially in the absence of actively managed asthma treated with inhaled corticosteroids. Pregnancy with a female foetus may particularly increase the risk of these outcomes. In addition, pregnancy has an effect on the course of asthma. The risk of an exacerbation requiring medical intervention may be as high as 50% in females with severe asthma and this may further increase the risk of poor outcomes, particularly low birth weight and pre-term delivery. The mechanisms responsible for changes in asthma with pregnancy, or alterations in pregnancy outcomes due to asthma have not been thoroughly explored. Maternal inflammatory pathways may contribute to reduced foetal growth through alterations in placental function. Asthma treatment, by reducing maternal inflammation and preventing exacerbations, is safe for use in pregnant females and contributes to improved outcomes for both mother and foetus.

Maternal asthma as a model for examining fetal sex-specific effects on maternal physiology and placental mechanisms that regulate human fetal growth.

Studying the effect of maternal asthma during pregnancy on placental function and fetal development has highlighted that there is a strong interaction between mother, placenta and fetus and these interactions appear to be sex-specific. This work has found that the female fetus alters maternal asthma during pregnancy by upregulating maternal inflammatory pathways. When asthma-associated inflammatory pathways are not treated with inhaled steroids during pregnancy, the female fetus has reduced growth and adrenal function due to alterations in placental glucocorticoid metabolism. When the mother uses inhaled steroid for the treatment of her asthma during pregnancy, female fetal growth and placental function are comparable to the control population. The growth of the male fetus appears to be unaffected by asthma or inhaled steroid use. These findings indicate there may be different mechanisms regulating placental glucocorticoid and immune mechanisms depending on fetal sex in both asthmatic and non-asthmatic pregnancies.

Alterations in human placental 11beta-hydroxysteroid dehydrogenase type 1 and 2 with gestational age and labour.

11beta-hydroxysteroid dehydrogenase type 1 and type 2 may be important in the process of human parturition and the regulation of fetal growth, by the modulation of cortisol concentrations in the fetal compartment. Changes in the expression and activity of these enzymes in late gestation have not been well described. This study has examined the gene expression of placental 11beta-HSD1 and 2, activity of 11beta-HSD2 and fetal cortisol concentrations during the final few weeks of human pregnancy and with the onset of labour. Placental 11beta-HSD2 activity decreased significantly between 38 and 40 weeks. There were no significant changes in mRNA abundance or protein expression with gestational age or labour. Placental 11beta-HSD1 mRNA abundance significantly increased with spontaneous labour. Fetal cortisol concentrations increased significantly with spontaneous labour. This study is the first to describe a decrease in 11beta-HSD2 activity in the last few weeks of human gestation. This decrease in type 2 activity, along with an increase in 11beta-HSD1 gene expression may be a mechanism by which cortisol concentrations rise at term to regulate fetal maturation and activate pathways associated with labour.

No association between 5HT-2A and bipolar disorder irrespective of genomic imprinting.

Recent evidence that 5HT-2A may be subjected to genomic imprinting prompted us to examine a collection of Irish family trios (an affected individual and both parents) for evidence of an association between 5HT-2A and bipolar disorder. Family trios offer an advantage over case control studies in regard to genomic imprinting since with family trios it is possible to trace the path of alleles from the parents to the offspring. Using haplotype-based haplotype relative risk (HHRR) and transmission/disequilibrium (TDT) analyses, no evidence was found for an association of 5HT-2A with bipolar affective disorder under the assumption of no imprinting and of imprinting.

Search for bipolar disorder susceptibility loci: the application of a modified genome scan concentrating on gene-rich regions.

Conducting genome wide screens for evidence of genetic linkage has become a well-established method for identifying regions of the human genome harboring susceptibility loci for complex disorders. For bipolar disorder, a number of such studies have been performed, and several regions of the genome have potentially been implicated in the disorder. The classic design for a genome screen involves examining polymorphic genetic markers spaced at regular intervals throughout the genome, typically every 10 cM, for evidence of linkage. An alternative design, based on the observation that genes do not appear to be evenly distributed, was proposed, enabling the number of markers examined in a genome wide screen to be reduced. This article describes the application of such a modified screen to a collection of 48 Irish families with bipolar disorder, comprising a total of 82 affected sib-pairs. From the results obtained a number of regions are highlighted for further study. One of these regions (17q11.1-q12) coincides with the location of a candidate gene, the serotonin transporter, whereas others concur with the findings of published studies. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:728-732, 2000.

Localization and characterization of urocortin during human pregnancy.

Urocortin, a recently identified peptide of the corticotropin releasing hormone (CRH) peptide family, has potent vasodilatory effects in the human fetal placental circulation in vitro, promoting us to hypothesize that urocortin is produced locally to regulate uteroplacental vascular tone during pregnancy. In the present study, we examined the distribution of urocortin in the human placenta, fetal membranes and uterine tissue at term in the presence and absence of labour, using a urocortin antibody produced in our laboratory and the immunoperoxidase staining method. Immunoreactive (IR)-urocortin was observed in the vascular smooth muscle of the myometrium (n=5), decidual stromal cells, syncytiotrophoblast and amnion epithelium (n=10). No differences in staining intensity for urocortin were detected between tissues obtained in the absence (n=5) or presence (n=5) of labour. Staining intensity for IR-urocortin was greatest in the decidua suggesting this may be a site of urocortin production during pregnancy. Subsequently, we tested urocortin secretion from chorio-decidual cells in vitro, using an immunoblot technique. Positive staining for urocortin was observed in 40 per cent of chorio-decidual cells with 34 per cent of these cells secreting urocortin under basal conditions. Since urocortin was secreted by decidual cells we questioned whether urocortin was present in maternal plasma throughout gestation, using radioimmunoassay. Urocortin was detectable in maternal plasma from 7 weeks of gestation and concentrations did not change as gestation progressed. IR-urocortin in the maternal plasma eluted from a Sephadex G-50 column at the same site as synthetic urocortin and had a calculated retention coefficient (Kd) of 0.44. In summary, this study indicates that urocortin is produced by the decidua during human pregnancy and is detectable in maternal plasma. These data are consistent with the hypothesis that urocortin is produced locally by the decidua and may act to regulate uteroplacental blood flow.

Preliminary evidence of an association between bipolar disorder in females and the catechol-O-methyltransferase gene.

Catechol-O-methyltransferase (COMT) catalyses the methylation, and hence the inactivation, of catecholamines including the neurotransmitters dopamine and noradrenaline. There is evidence implicating COMT as a candidate gene for a number of neuropsychiatric conditions including bipolar disorder. A long recognized population variation in COMT activity exists and it has recently been established that variation in enzyme activity results from a polymorphic genetic variation within the COMT gene which can be readily assayed as a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP). A collection of 60 Irish bipolar I probands have been genotyped together with their parents. Tests comparing transmitted and non-transmitted alleles provide no evidence that the polymorphism contributes to a susceptibility to bipolar disorder within the sample as a whole. However, amongst female bipolar I probands (n = 30) there was a tendency for the low-activity allele of COMT to be preferentially transmitted. Furthermore, a re-examination of an Irish case-control sample resulted in a similar observation amongst female bipolar I sufferers and pooling the data sets strengthened the findings.

Lack of evidence for a major locus for bipolar disorder in the pericentromeric region of chromosome 18 in Irish pedigrees.

Seven families, multiply affected by bipolar mood disorder, have been collected from the Irish population and have been genotyped with microsatellite markers from the pericentromeric region of chromosome 18, a region that has been implicated as a site for a susceptibility gene for this relative common psychiatric disorder. The families significantly excluded linkage of bipolar disorder to this region under various models. Although the data provided no evidence of linkage heterogeneity among families, the number of families investigated may be too small to exclude completely the possibility of linkage in a small number of families.