Effect of asthma management with exhaled nitric oxide versus usual care on perinatal outcomes.

INTRODUCTION: Asthma exacerbations in pregnancy are associated with adverse perinatal outcomes. We aimed to determine whether fractional exhaled nitric oxide (F ENO)-based asthma management improves perinatal outcomes compared to usual care. METHODS: The Breathing for Life Trial was a multicentre, parallel-group, randomised controlled trial conducted in six hospital antenatal clinics, which compared asthma management guided by F ENO (adjustment of asthma treatment according to exhaled nitric oxide and symptoms each 6-12 weeks) to usual care (no treatment adjustment as part of the trial). The primary outcome was a composite of adverse perinatal events (preterm birth, small for gestational age (SGA), perinatal mortality or neonatal hospitalisation) assessed using hospital records. Secondary outcomes included maternal asthma exacerbations. Concealed random allocation, stratified by study site and self-reported smoking status was used, with blinded outcome assessment and statistical analysis (intention to treat). RESULTS: Pregnant women with current asthma were recruited; 599 to the control group (608 infants) and 601 to the intervention (615 infants). There were no significant group differences for the primary composite perinatal outcome (152 (25.6%) out of 594 control, 177 (29.4%) out of 603 intervention; OR 1.21, 95% CI 0.94-1.56; p=0.15), preterm birth (OR 1.14, 95% CI 0.78-1.68), SGA (OR 1.06, 95% CI 0.78-1.68), perinatal mortality (OR 3.62, 95% CI 0.80-16.5), neonatal hospitalisation (OR 1.24, 95% CI 0.89-1.72) or maternal asthma exacerbations requiring hospital admission or emergency department presentation (OR 1.19, 95% CI 0.69-2.05). CONCLUSION: F ENO-guided asthma pharmacotherapy delivered by a nurse or midwife in the antenatal clinic setting did not improve perinatal outcomes.

Factors Associated with Asthma Exacerbations During Pregnancy.

BACKGROUND: Asthma exacerbations during pregnancy are associated with adverse pregnancy outcomes. OBJECTIVE: The aim of this study was to establish factors associated with asthma exacerbations during pregnancy. METHODS: We obtained data from three cohorts of pregnant women with asthma recruited in eastern Australia (2004-2019; n = 1461). Severe exacerbations were defined as episodes of asthma requiring hospitalization, an emergency department visit, or prescription of oral corticosteroids after enrollment. Baseline information on potential risk factors included demographic characteristics, asthma characteristics (eg, lung function, asthma triggers, asthma control, medication use), pregnancy factors (eg, fetal sex, parity, antenatal care type), and other maternal factors (body mass index, smoking status, mental health). Backward stepwise logistic regression and Akaike information criterion were used to determine the best-fitting model. RESULTS: A total of 135 participants experienced a severe exacerbation during pregnancy (9.2%). Medium to high ICS dose was most strongly associated with severe asthma exacerbations (adjusted odds ratio = 3.20; 95% confidence interval, 1.85-5.53). Worse asthma control, possession of a written action plan, and a history of asthma exacerbations in the year preceding pregnancy were associated with an increased rate of exacerbations. CONCLUSIONS: Asthma exacerbations before pregnancy and more severe asthma at the beginning of pregnancy were associated with an increased rate of exacerbations during pregnancy. Despite Global Initiative for Asthma step 3 and 4 treatment and optimal management including a written asthma action plan, there is still a significant asthma burden in a group of women at high risk for severe exacerbations in pregnancy.

Factors Associated with Nonadherence to Inhaled Corticosteroids for Asthma During Pregnancy.

BACKGROUND: Nonadherence is common among pregnant women prescribed inhaled corticosteroids (ICS) for asthma and may have serious consequences for mother and baby. Factors associated with ICS nonadherence have not been determined in this population. OBJECTIVES: To determine factors associated with {1} nonadherence to ICS in early-mid pregnancy (cross-sectional) and {2} persistent nonadherence to ICS during pregnancy (longitudinal). METHODS: Data used come from 3 prospective studies (2004-2019) involving women with asthma recruited by 23 weeks' gestation (N = 1614). Demographics, asthma history, and current symptoms were assessed, and spirometry was performed at baseline and throughout pregnancy. Women self-reported current medication use and number of ICS doses missed in the past week. Nonadherence was defined as ≥20% of prescribed dosages missed in the past week (baseline) and on at least 2 occasions during follow-up (persistent). Factors associated with ICS nonadherence were examined using backward stepwise logistic regression. RESULTS: Of 610 (38%) women prescribed ICS at baseline, 236 (39%) were classified as nonadherent. Of 612 (38%) women prescribed ICS during at least 2 follow-up visits, 149 (24%) were classified as persistent nonadherent. Factors associated with nonadherence at baseline were current or ex-smoking, non-Caucasian/non-Indigenous ethnicity, adult diagnosis of asthma, and lower lung function. Factors associated with persistent nonadherence to ICS were lower maternal age, higher parity, and no prescribed ICS at baseline. CONCLUSION: Young multiparous non-Caucasian/non-Indigenous mothers are at increased risk of being nonadherent to ICS during pregnancy. Strategies to improve ICS nonadherence should address maternal smoking and target women who (re-)initiate ICS use in pregnancy.

Rhinitis in pregnant women with asthma is associated with poorer asthma control and quality of life.

OBJECTIVE: To describe the pattern and severity of rhinitis in pregnancy and the impact rhinitis has on asthma control and quality of life (QoL) in pregnant women with asthma. METHODS: Two hundred and eighteen non-smoking pregnant women with asthma were participants in a randomised controlled trial of exhaled nitric oxide guided treatment adjustment. Rhinitis was assessed using a visual analogue scale (VAS) scored from 0 to 10 and classified as current (VAS > 2.5), moderate/severe versus mild (VAS > 6 vs <5), atopic versus non-atopic and pregnancy rhinitis. At baseline, women completed the 20-Item Sino-Nasal Outcome Test (SNOT20), asthma-specific (AQLQ-M) QoL questionnaires and the Six-Item Short-Form State Trait Anxiety Inventory (STAI-6). Asthma control was assessed using the asthma control questionnaire (ACQ). Perinatal outcomes were collected after delivery. RESULTS: Current rhinitis was present in 142 (65%) women including 45 (20%) women who developed pregnancy rhinitis. Women with current rhinitis had higher scores for ACQ (p = 0.004), SNOT20 (p < 0.0001) and AQLQ-M (p < 0.0001) compared to women with no rhinitis. Current rhinitis was associated with increased anxiety symptoms (p = 0.002), rhinitis severity was associated with higher ACQ score (p = 0.004) and atopic rhinitis was associated with poorer lung function (p = 0.037). Rhinitis symptom severity improved significantly during gestation (p < 0.0001). There was no impact on perinatal outcomes. Improved asthma control was associated with improvement in rhinitis. CONCLUSION: Rhinitis in pregnant women with asthma is common and associated with poorer asthma control, sino-nasal and asthma-specific QoL impairment and anxiety. In the context of active asthma management there was significant improvement in rhinitis symptoms and severity as pregnancy progressed.

Management of asthma in pregnancy guided by measurement of fraction of exhaled nitric oxide: a double-blind, randomised controlled trial.

BACKGROUND: Asthma exacerbations during pregnancy are common and can be associated with substantial maternal and fetal morbidity. Treatment decisions based on sputum eosinophil counts reduce exacerbations in non-pregnant women with asthma, but results with the fraction of exhaled nitric oxide (F(E)NO) to guide management are equivocal. We tested the hypothesis that a management algorithm for asthma in pregnancy based on F(E)NO and symptoms would reduce asthma exacerbations. METHODS: We undertook a double-blind, parallel-group, controlled trial in two antenatal clinics in Australia. 220 pregnant, non-smoking women with asthma were randomly assigned, by a computer-generated random number list, before 22 weeks' gestation to treatment adjustment at monthly visits by an algorithm using clinical symptoms (control group) or F(E)NO concentrations (active intervention group) used to uptitrate (F(E)NO >29 ppb) or downtitrate (F(E)NO <16 ppb) inhaled corticosteroid dose. Participants, caregivers, and outcome assessors were masked to group assignment. Longacting ß2 agonist and minimum dose inhaled corticosteroid were used to treat symptoms when F(E)NO was not increased. The primary outcome was total asthma exacerbations (moderate and severe). Analysis was by intention to treat. This study is registered with the Australian and New Zealand Clinical Trials Registry, number 12607000561482. FINDINGS: 111 women were randomly assigned to the F(E)NO group (100 completed) and 109 to the control group (103 completed). The exacerbation rate was lower in the F(E)NO group than in the control group (0·288 vs 0·615 exacerbations per pregnancy; incidence rate ratio 0·496, 95% CI 0·325-0·755; p=0·001). The number needed to treat was 6. In the F(E)NO group, quality of life was improved (score on short form 12 mental summary was 56·9 [95% CI 50·2-59·3] in F(E)NO group vs 54·2 [46·1-57·6] in control group; p=0·037) and neonatal hospitalisations were reduced (eight [8%] vs 18 [17%]; p=0·046). INTERPRETATION: Asthma exacerbations during pregnancy can be significantly reduced with a validated F(E)NO-based treatment algorithm. FUNDING: National Health and Medical Research Council of Australia.

Effect of maternal asthma, inhaled glucocorticoids and cigarette use during pregnancy on the newborn insulin-like growth factor axis.

BACKGROUND: Fetal growth varies in a sex-specific manner in response to maternal asthma during pregnancy, but the mechanisms are unclear. OBJECTIVE: We examined the influence of maternal asthma severity and associated exposures, inhaled glucocorticoid treatment, maternal cigarette use, and fetal sex on fetal growth and placental function during pregnancy and on the newborn insulin-like growth factor (IGF) axis. STUDY SUBJECTS AND DESIGN: Fetal growth was assessed in a prospective cohort of asthmatic and non-asthmatic women (n=145). At delivery, umbilical vein plasma was collected from male (n=61, controls n=16 and asthmatic n=45) or female (n=84, controls n=22 and asthmatic n=62) fetuses. Cord plasma insulin-like growth factor (IGF) binding protein (BP)-1, IGFBP-3, IGF-1 and IGF-2 were measured by radioimmunoassay and ELISA. RESULTS: Cord plasma IGF-1 was the main component of the neonatal IGF axis altered by asthma and cigarette use. IGF-1 was increased in the presence of mild asthma and a male fetus and decreased in the presence of a female fetus and maternal asthma with cigarette use. IGFBP-3 was also decreased in the female fetuses of pregnancies complicated by asthma and cigarette use. Inhaled glucocorticoid use for the treatment of asthma did not affect the IGF axis. The strongest overall predictor of female birth weight after accounting for asthma severity, inhaled glucocorticoid treatment and cigarette use was IGF-1. For males, the strongest predictor of birth weight was IGFBP-3. CONCLUSION: The data suggest male and female fetuses institute different strategies in response to adverse pregnancy conditions such as asthma and cigarette use.

Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor.

CONTEXT: Clinical prediction of preterm delivery is largely ineffective, and the mechanism mediating progesterone (P) withdrawal and estrogen activation at the onset of human labor is unclear. OBJECTIVES: Our objectives were to determine associations of rates of change of circulating maternal CRH in midpregnancy with preterm delivery, CRH with estriol (E3) concentrations in late pregnancy, and predelivery changes in the ratios of E3, estradiol (E2), and P. DESIGN AND SETTING: A cohort of 500 pregnant women was followed from first antenatal visits to delivery during the period 2000-2004 at John Hunter Hospital, New South Wales, Australia, a tertiary care obstetric hospital. PATIENTS: Unselected subjects were recruited (including women with multiple gestations) and serial blood samples obtained. MAIN OUTCOME MEASURES: CRH daily percentage change in term and preterm singletons at 26 wk, ratios E3/E2, P/E3, and P/E2 and the association between E3 and CRH concentrations in the last month of pregnancy (with spontaneous labor onset) were assessed. RESULTS: CRH percentage daily change was significantly higher in preterm than term singletons at 26 wk (medians 3.09 and 2.73; P = 0.003). In late pregnancy, CRH and E3 concentrations were significantly positively associated (P = 0.003). E3/E2 increased, P/E3 decreased, and P/E2 was unchanged in the month before delivery (medians: E3/E2, 7.04 and 10.59, P < 0.001; P/E3, 1.55 and 0.98, P < 0.001; P/E2, 11.78 and 10.79, P = 0.07). CONCLUSIONS: The very rapid rise of CRH in late pregnancy is associated with an E3 surge and critically altered P/E3 and E3/E2 ratios that create an estrogenic environment at the onset of labor. Our evidence provides a rationale for the use of CRH in predicting preterm birth and informs approaches to delaying labor using P supplementation.

Institution of universal screening for Group B streptococcus (GBS) from a risk management protocol results in reduction of early-onset GBS disease in a tertiary obstetric unit.

AIM: To determine the effect of institution of a universal screening protocol as per CDC 2002 guidelines had on the incidence of early-onset Group B streptococcal (GBS) and non-GBS disease in a tertiary obstetric unit. METHODS: A prospective study with historical control data reporting the incidence of early-onset GBS and non-GBS disease following institution of a universal screening strategy at John Hunter Hospital, Newcastle, Australia. We compared the incidence of early-onset GBS and non-GBS disease during prescreening (1994-2002) with screening period (2004 to June 2006). The outcome measure was the incidence of early-onset GBS disease. We specifically reported the number of women needed to treat (NNT) with antibiotics and the number of women needed to screen. RESULTS: The incidence of early-onset GBS and non-GBS during the prescreening period was 0.84/1000 and 0.94/1000 live births, respectively. After institution of universal screening, the incidence was 0.00/1000 and 0.72/1000 live births, respectively. This is a statistically significant reduction in early-onset GBS disease by 84% (chi(2) = 5.75; P = 0.016). There was no difference in non-GBS disease (chi2 = 0.14; P = 0.71). The NNT is 1191 and we needed to screen 5704 women to prevent one case of early-onset GBS disease. CONCLUSION: Screening for GBS rather than by assessing risk factors has significantly reduced the incidence of early-onset GBS disease in our unit. Despite low incidence of early-onset GBS prior to screening period, we still found a significant decrease in early-onset GBS disease after institution of universal screening protocol. These results support the screening-based approach at 34-37 weeks gestation.