Effect of fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy versus usual care on infant development, temperament, sensory function and autism signs.

Asthma during pregnancy is associated with a range of adverse perinatal outcomes. It is also linked to increased rates of neurodevelopmental conditions in the offspring. We aimed to assess whether fractional exhaled nitric oxide (FENO)-based asthma management during pregnancy improves child developmental and behavioural outcomes compared to usual care. The Breathing for Life Trial was a randomised controlled trial that compared FENO-based asthma management during pregnancy to usual care. Participants were invited to the developmental follow-up, the Breathing for Life Trial - Infant Development study, which followed up infants at 6 weeks, 6 months and 12 months. The primary outcomes were measured in infants at 12 months using the Bayley-III: Cognitive, Language and Motor composite scores. Secondary outcomes included Bayley-III social-emotional and adaptive behaviour scores, autism likelihood and sensory and temperament outcomes. The exposure of interest was the randomised intervention group. Two hundred and twenty-two infants and their 217 participating mothers were recruited to the follow-up; 107 mothers were in the intervention group and 113 were in the control group. There was no evidence of an intervention effect for the primary outcomes: Bayley-III cognitive (mean = 108.9 control, 108.5 intervention, p = 0.93), language (mean = 95.9 control, 95.6 intervention, p = 0.87) and motor composite scores (mean = 97.2 control, 97.9 intervention, p = 0.25). Mean scores for secondary outcomes were also similar among infants born to control and FENO group mothers, with few results reaching p < 0.05. CONCLUSION:  In this sample, FENO-guided asthma treatment during pregnancy did not improve infant developmental outcomes in the first year of life. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ACTRN12613000202763. WHAT IS KNOWN: • Maternal asthma during pregnancy has been associated with increased rates of neurodevelopmental conditions in offspring, including intellectual disability and autism. WHAT IS NEW: • This is the first study to examine how managing asthma during pregnancy via a FENO-guided algorithm or usual care affects infant developmental and behavioural outcomes. While the results of the study showed no impact of the intervention, and therefore do not support the integration of FENO-based management of asthma in antenatal settings for optimal infant development, they do send a positive message about the implications of active asthma management during pregnancy on infant developmental outcomes.

Parenting stress in mothers with asthma during the postpartum period.

OBJECTIVE: Maternal asthma often complicates pregnancy and is linked with poorer quality of life. Additionally, individuals with asthma are at an increased risk of depression and anxiety. We examined whether asthma during pregnancy is related to parenting stress in the first year postpartum and if this relationship varies with level of asthma control. METHODS: This cohort survey-based study included mothers with (n = 157) and without (n = 79) asthma. Mothers with asthma participated in this study following participation in a randomized controlled trial of a novel asthma management strategy during pregnancy. Mothers completed the Parenting Stress Index - Short Form during the first 12 months postpartum. Mothers with asthma also completed the Asthma Control Questionnaire. RESULTS: Parenting stress did not differ between mothers with and without asthma. Additionally, for mothers with asthma, there were no differences in levels of parenting stress based on asthma control. CONCLUSIONS: This study suggests that mothers with asthma are not at an increased risk for excessive parenting stress. However, due to response and sampling bias, levels of parenting stress in asthmatic mothers may be underreported in our sample.

Observational study of mental health in asthmatic women during the prenatal and postnatal periods.

Objective: We aimed to examine the prevalence and severity of psychological distress of women with asthma in both the prenatal and postnatal periods, and to determine whether asthmatic women with and without mental health problems differ in self-management, medications knowledge, and asthma symptoms.Methods: We assessed spirometry performance and asthma symptoms in 120 women (mean age 29.8 years) before 23 weeks gestation, as part of the Breathing for Life Trial (Trial ID: ACTRN12613000202763). Prenatal depression data was obtained from medical records. At 6 weeks postpartum, we assessed general health, self-reported asthma control, depression symptoms (with the Edinburgh Postnatal Depression Scale) and adaptive functioning (with the Achenbach System of Empirically Based Assessment scales).Results: Twenty percent of our sample reported having a current mental health diagnosis, 14% reported currently receiving mental health care, while 47% reported having received mental health care in the past (and may/may not have received a diagnosis). The sample scored high on the Aggressive Behavior, Avoidant Personality, and Attention Deficit/Hyperactivity scales. Poorer self-reported postnatal asthma control was strongly correlated with elevated somatic complaints, externalizing problems, antisocial personality problems, and greater withdrawal. Prenatal spirometry or asthma severity and control were largely not associated with measures of psychopathology.Conclusions: These findings indicate that pregnant women with asthma frequently report issues with psychopathology during the prenatal and postnatal periods, and that the subjective perception of asthma control may be more related to psychopathology than objective asthma measures. However, due to sample bias, these findings are likely to be understated.

The effects of maternal asthma during pregnancy on child cognitive and behavioral development: A systematic review.

OBJECTIVE: Maternal asthma during pregnancy is associated with a higher risk of negative perinatal outcomes. However, little is known about the direct effects of maternal asthma on infant cognitive development. We examined the evidence for an impact of maternal asthma during pregnancy on cognitive and behavioral development of the child. DATA SOURCES: We conducted a MEDLINE, PsychINFO, and manual search of the databases for all available studies until January 9th, 2018. STUDY SELECTIONS: Studies were deemed relevant if they included child cognitive and behavioral development as the outcome, with maternal asthma as the determinant of interest. RESULTS: Ten articles matched selection criteria. Some studies report that maternal asthma is associated with increased risk for autism and intellectual disability in children. However, these effects are small and are often eliminated when controlling for confounding variables. Other studies have found no association. The only prospective study found that well-managed asthma during pregnancy was not associated with negative developmental outcomes in children. CONCLUSIONS: The evidence suggests that the relationship between maternal asthma during pregnancy and poor developmental and behavioral outcomes of children is weak. Children of mothers with well-managed asthma during pregnancy have similar developmental trajectories to those born to healthy mothers. Prospective, longitudinal studies are needed to confirm these conclusions. Optimal asthma management is important in pregnancy as it may have longer term benefits for the health of the offspring. As the rate of asthma increases in the population, the implications of maternal asthma on child development will be of greater importance.

Autism likelihood in infants born to mothers with asthma is associated with blood inflammatory gene biomarkers in pregnancy.

Mothers with asthma or atopy have a higher likelihood of having autistic children, with maternal immune activation in pregnancy implicated as a mechanism. This study aimed to determine, in a prospective cohort of mothers with asthma and their infants, whether inflammatory gene expression in pregnancy is associated with likelihood of future autism. Mothers with asthma were recruited to the Breathing for Life Trial. RNA was extracted from blood samples collected at mid-pregnancy. 300 ng total RNA was hybridized with the nCounter Human Inflammation gene expression panel (Nanostring Technologies, 249 inflammation-related genes). Parents completed the First Year Inventory (FYI) at 12-month follow-up, which assessed an infant's likelihood for autism across 2 behavioural domains: social communication and sensory regulation. A total score ≥19.2 indicated increased likelihood for future autism. Inflammatory gene expression was profiled from 24 mothers: four infants scored in the high autism likelihood range; 20 scored in the low autism likelihood range. Six inflammatory genes were differentially expressed and significantly up-regulated in the high autism likelihood group: CYSLTR2, NOX1, C1QA, CXCL10, C8A, IL23R. mRNA count significantly correlated with social communication FYI score for CYSLTR2 (Pearson r = 0.46, p = 0.024) and CXCL10 (r = 0.43, p = 0.036) and with sensory regulation score for ALOX5 (r = -0.43, p = 0.038) and MAFK (r = -0.46, p = 0.022). In this proof-of-concept study, inflammatory gene expression during pregnancy in mothers with asthma was associated with an infant's likelihood of future autism as well as scores relating to social communication and sensory regulation.

The relationship between pitch contours in infant-directed speech and early signs of autism in infancy.

PURPOSE: Mother-infant interactions during the first year of life are crucial to healthy infant development. The infant-directed speech (IDS), and specifically pitch contours, used by mothers during interactions are associated with infant language and social development. However, little research has examined pitch contours towards infants with socio-communication and language differences, such as those displaying early signs of autism spectrum disorder (autism). This study aimed to explore the association of infant autism signs and pitch contours used by mothers with their 12-month-old infants. METHOD: Mother-infant dyads (n = 109) were recruited from the University of Newcastle BabyLab. Parent-infant dyads completed a 15-min interaction, from which a total of 36,128 pitch contours were measured and correlated with infant autism signs. Infant autism signs were assessed via parent-report (First Year Inventory; Reznick et al., 2007). A subset of high-risk infants (admitted to a neonatal intensive care unit, n = 29) also received an observation-based assessment (Autism Detection in Early Childhood; Young & Nah, 2016). RESULTS: Mothers used fewer sinusoidal contours when they rated their infant as displaying more autism signs (rs = - .30, p = .004) and more autism-related sensory regulation issues (rs = - .31, p = .001). Mothers used fewer flat contours if their infant displayed more researcher-rated autism signs (r2 = - .39, p = .04). CONCLUSIONS: This study provides the early evidence that maternal pitch contours in IDS are related to early autism signs in infancy. If our findings are replicated in follow up studies where infants are followed to diagnosis, maternal IDS may be an important element of future early intervention protocols that focus on communication for infants with risk for autism.

Patterns of sensory modulation by age and sex in young people on the autism spectrum.

Sensory modulation symptoms form a diagnostic criterion for autism spectrum disorder and are associated with significant daily functional limitations. Utilizing caregiver report on Short Sensory Profile-2 (SSP-2) for 919 autistic children (3-14.11 years), we examined the expression of sensory modulation symptoms by age and sex and investigated the existence of specific sensory modulation subtypes. Sensory modulation symptoms appeared to peak in frequency during middle childhood, particularly in sensory sensitivity and avoidance. Symptoms associated with sensory hypo-reactivity and seeking tended not differ between age cohorts. Males and females demonstrated similar overall sensory modulation profiles, however, females showed elevated symptoms relating to sensory sensitivity. Model-based cluster analysis revealed five interpretable sensory modulation subtypes which related to symptom severity (low, mid-range, high). Subtypes demonstrating mid-range symptom severity differed in focus on sensory hyper-reactivity or seeking symptoms. The findings of this study report for the first time that age-related differences in sensory modulation symptoms may be associated with sensory hyper-reactivity only. The subtyping results also suggest that sensory modulation symptom severity is a reliable means of classifying variance within autistic children, however, consideration of differences in the behavioral strategies employed by individuals to manage sensory modulation symptoms may inform tailored supportive strategies. LAY SUMMARY: We studied sensory symptoms such as over-responding, under-responding and sensation seeking behaviors in 919 autistic children and adolescents. We found that 6-12-year-olds and females displayed the most sensory over-responding symptoms. Autistic children could be grouped into mild, moderate, and severe levels of sensory symptoms, however, children differed in the type of strategies used to cope with their sensory symptoms meaning that they may require different intervention approaches.

TACTICS - Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship: evaluating the effectiveness of an 'implementation intervention' in providing better patient access to reperfusion therapies: protocol for a non-randomised controlled stepped wedge cluster trial in acute stroke.

INTRODUCTION: Stroke reperfusion therapies, comprising intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT), are best practice treatments for eligible acute ischemic stroke patients. In Australia, EVT is provided at few, mainly metropolitan, comprehensive stroke centres (CSC). There are significant challenges for Australia's rural and remote populations in accessing EVT, but improved access can be facilitated by a 'drip and ship' approach. TACTICS (Trial of Advanced CT Imaging and Combined Education Support for Drip and Ship) aims to test whether a multicomponent, multidisciplinary implementation intervention can increase the proportion of stroke patients receiving EVT. METHODS AND ANALYSIS: This is a non-randomised controlled, stepped wedge trial involving six clusters across three Australian states. Each cluster comprises one CSC hub and a minimum of three primary stroke centre (PSC) spokes. Hospitals will work in a hub and spoke model of care with access to a multislice CT scanner and CT perfusion image processing software (MIStar, Apollo Medical Imaging). The intervention, underpinned by behavioural theory and technical assistance, will be allocated sequentially, and clusters will move from the preintervention (control) period to the postintervention period. PRIMARY OUTCOME: Proportion of all stroke patients receiving EVT, accounting for clustering. SECONDARY OUTCOMES: Proportion of patients receiving IVT at PSCs, proportion of treated patients (IVT and/or EVT) with good (modified Rankin Scale (mRS) score 0-2) or poor (mRS score 5-6) functional outcomes and European Quality of Life Scale scores 3 months postintervention, proportion of EVT-treated patients with symptomatic haemorrhage, and proportion of reperfusion therapy-treated patients with good versus poor outcome who presented with large vessel occlusion at spokes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Hunter New England Human Research Ethics Committee (18/09/19/4.13, HREC/18/HNE/241, 2019/ETH01238). Trial results will be disseminated widely through published manuscripts, conference presentations and at national and international platforms regardless of whether the trial was positive or neutral. TRIAL REGISTRATION NUMBER: ACTRN12619000750189; UTNU1111-1230-4161.

Breastfeeding and wheeze-related outcomes in high-risk infants: A systematic review and meta-analysis.

BACKGROUND: The risk of wheezing is high in infancy and is heightened in infants with a family history of asthma/atopy. The role of breastfeeding in influencing respiratory health for these high-risk infants is unclear. OBJECTIVES: To systematically appraise evidence for the association between breastfeeding and wheeze incidences and severity in high-risk infants. METHODS: Studies identified through electronic databases and reference lists were eligible if they assessed breastfeeding and respiratory outcomes in infants with a family history of asthma/atopy. The primary outcome was wheeze incidences in the first year of life. Secondary outcomes were wheeze incidences in the first 6 months of life, indicators of wheeze severity (recurrent wheeze, health-care utilization, and medication use), and other wheeze-related outcomes [bronchiolitis, pneumonia, croup, and incidence of lower respiratory tract infection (LRTI)] up to 12 months old. Meta-analyses were conducted where possible. RESULTS: Of 1843 articles screened, 15 observational studies met the inclusion criteria. Breastfeeding was associated with 32% reduced odds of wheezing during the first year of life (ever vs. never: OR, 0.68; 95% CI: 0.53, 0.88; n = 9 studies); this association was even stronger in the first 6 months (OR, 0.45; 95% CI: 0.27, 0.75; n = 5 studies). Breastfeeding for a "longer" versus "shorter" time (approximately longer vs. shorter than 3 months) was associated with 50% reduced odds of wheezing at the age of 6 months (OR, 0.50; 95% CI: 0.39, 0.64; n = 3 studies). CONCLUSIONS: Breastfeeding was associated with reduced odds of wheezing in high-risk infants, with the strongest protection in the first 6 months. More research is needed to understand the impact of breastfeeding intensity on wheezing and to examine additional respiratory outcomes, including wheeze severity. This review was registered at PROSPERO as CRD42019118631.

Early Sensory and Temperament Features in Infants Born to Mothers With Asthma: A Cross-Sectional Study.

Maternal asthma in pregnancy is associated with an increased risk of adverse perinatal outcomes. Adverse perinatal outcomes may result in poorer infant developmental outcomes, such as temperament and sensory difficulties. This study aimed to (1) assess differences in temperament and sensory features between infants born to mothers with and without asthma and (2) investigate differences in these infant behaviours as a function of maternal asthma severity and asthma control. Mothers completed the Carey Temperament Scales and the Sensory Profile 2 at either 6 weeks, 6 months, or 12 months postpartum. Overall, we observed no significant differences between infants born to mothers with and without asthma in their temperament or sensory features; scores in both domains fell within the normative range. More infants in the asthma group, however, were reported to be highly distractible. When compared with normative data, infants in both groups were reported to have poor predictability of biological functions and fewer infants engaged in low levels of sensory behaviours. Some infants were observed to experience difficulties with hyper-reactivity within several domains. Maternal asthma severity and control during pregnancy were not linked to significant differences between infant temperament and sensory features. The present findings indicate that infants born to mothers with asthma are not at an increased risk overall for temperament or sensory difficulties, compared to control infants. However, a subset of infants across both groups may be at risk for attention or sensory hyper-reactivity difficulties. Further research into the developmental outcomes of infants born to mothers with asthma is warranted.

The temperament features associated with autism spectrum disorder in childhood: A systematic review.

BACKGROUND: Temperament is an important construct that shapes child development. Temperament is suggested to present differently in different groups, such as children with neurodevelopmental disorders. However, it is not known whether there are specific temperament features associated with Autism Spectrum Disorder (ASD). AIM: This systematic review aimed to synthesise extant literature to determine whether there are temperament features associated with ASD in infancy, toddlerhood and childhood. METHODS AND PROCEDURES: Following the PRISMA guidelines for systematic reviews, we searched PsycINFO, CINAHL, Academic Search Ultimate and ProQuest for all available articles from database conception until January 2020. The Joanna Briggs Institute Critical Appraisal checklists were used to assess the methodological quality of included articles. OUTCOMES AND RESULTS: Twenty-six articles met the selection criteria: (1) reported on the temperament of children (0-12 years of age) diagnosed with ASD, (2) peer-reviewed; and (3) published in English. Articles varied in overall methodological quality. Infants later diagnosed with ASD were found to more frequently be described as having 'easy' temperament features in early infancy, compared to typically developing infants and infants with developmental concerns but not ASD. Once diagnosed, children with ASD were reported to, as a group, display more negative affect, less extraversion and less effortful control than typically developing children. CONCLUSIONS AND IMPLICATIONS: The literature suggests that more challenging temperament features are associated with ASD in childhood, but less is known about within group variability. Overall, this review highlights the need for further investigation into the variability of temperament in children with ASD.