Adverse neonatal outcomes in pregnant women with asthma: An updated systematic review and meta-analysis.

BACKGROUND: A systematic review and meta-analysis from 2013 reported increased risks of congenital malformations, neonatal death and neonatal hospitalization amongst infants born to women with asthma compared to infants born to mothers without asthma. OBJECTIVE: Our objective was to update the evidence on the associations between maternal asthma and adverse neonatal outcomes. SEARCH STRATEGY: We performed an English-language MEDLINE, Embase, CINAHL, and COCHRANE search with the terms (asthma or wheeze) and (pregnan* or perinat* or obstet*). SELECTION CRITERIA: Studies published from March 2012 until September 2023 reporting at least one outcome of interest (congenital malformations, stillbirth, neonatal death, perinatal mortality, neonatal hospitalization, transient tachypnea of the newborn, respiratory distress syndrome and neonatal sepsis) in a population of women with and without asthma. DATA COLLECTION AND ANALYSIS: The study was reported following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) guidelines. Quality of individual studies was assessed by two reviewers independently using the Newcastle-Ottawa Scale. Random effects models (≥3 studies) or fixed effect models (≤2 studies) were used with restricted maximum likelihood to calculate relative risk (RR) from prevalence data and the inverse generic variance method where adjusted odds ratios (aORs) from individual studies were combined. MAIN RESULTS: A total of 18 new studies were included, along with the 22 studies from the 2013 review. Previously observed increased risks remained for perinatal mortality (relative risk [RR] 1.14, 95% confidence interval [CI]: 1.05, 1.23 n = 16 studies; aOR 1.07, 95% CI: 0.98-1.17 n = 6), congenital malformations (RR 1.36, 95% CI: 1.32-1.40 n = 17; aOR 1.42, 95% CI: 1.38-1.47 n = 6), and neonatal hospitalization (RR 1.27, 95% CI: 1.25-1.30 n = 12; aOR 1.1, 95% CI: 1.07-1.16 n = 3) amongst infants born to mothers with asthma, while the risk for neonatal death was no longer significant (RR 1.33, 95% CI: 0.95-1.84 n = 8). Previously reported non-significant risks for major congenital malformations (RR1.18, 95% CI: 1.15-1.21; aOR 1.20, 95% CI: 1.15-1.26 n = 3) and respiratory distress syndrome (RR 1.25, 95% CI: 1.17-1.34 n = 4; aOR 1.09, 95% CI: 1.01-1.18 n = 2) reached statistical significance. CONCLUSIONS: Healthcare professionals should remain aware of the increased risks to neonates being born to mothers with asthma.

Comparative effect of varenicline and nicotine patches on preventing repeat cardiovascular events.

OBJECTIVE: To determine the comparative effectiveness of postdischarge use of varenicline versus prescription nicotine replacement therapy (NRT) patches for the prevention of recurrent cardiovascular events and mortality and whether this association differs by sex. METHODS: Our cohort study used routinely collected hospital, pharmaceutical dispensing and mortality data for residents of New South Wales, Australia. We included patients hospitalised for a major cardiovascular event or procedure 2011-2017, who were dispensed varenicline or prescription NRT patches within 90day postdischarge. Exposure was defined using an approach analogous to intention to treat. Using inverse probability of treatment weighting with propensity scores to account for confounding, we estimated adjusted HRs for major cardiovascular events (MACEs), overall and by sex. We fitted an additional model with a sex-treatment interaction term to determine if treatment effects differed between males and females. RESULTS: Our cohort of 844 varenicline users (72% male, 75% <65 years) and 2446 prescription NRT patch users (67% male, 65% <65 years) were followed for a median of 2.93 years and 2.34 years, respectively. After weighting, there was no difference in risk of MACE for varenicline relative to prescription NRT patches (aHR 0.99, 95% CI 0.82 to 1.19). We found no difference (interaction p=0.098) between males (aHR 0.92, 95% CI 0.73 to 1.16) and females (aHR 1.30, 95% CI 0.92 to 1.84), although the effect among females deviated from the null. CONCLUSION: We found no difference between varenicline and prescription NRT patches in the risk of recurrent MACE. These results should be considered when determining the most appropriate choice of smoking cessation pharmacotherapy.

Beliefs about medicines and adherence to asthma medications during pregnancy.

OBJECTIVE: Discontinuation of, and non-adherence to, inhaled corticosteroids (ICS) for asthma treatment is a significant issue in pregnancy. This study characterized beliefs about medicines in pregnant women with asthma and investigated associations with ICS adherence. METHODS: Pregnant women with relatively mild asthma (n = 302) were grouped according to ICS use and self-reported adherence (≥80% doses taken). They completed questions about dislike of asthma medications and the validated Beliefs about Medicines Questionnaire (BMQ), which consists of ten questions about asthma medicines ("necessity" questions about maintaining health, or "concern" questions about adverse effects), and eight general medicine questions, scored on five-point Likert scales. The Necessity Concerns differential (N-C) was calculated, with positive scores indicating that the patient perceives the benefits of medicines to outweigh the risks. RESULTS: ICS was used by 87 (29%) women, with 49 (56%) self-reporting adherence. Of the 22% who disliked taking asthma medications during pregnancy, 20% had the belief that the medication was unsafe. ICS users had a significantly higher BMQ necessity score and higher necessity-concern differential score than nonusers; when adjusted for covariates, ICS non-adherence was associated with a lower necessity score (p = 0.015). Women adherent to ICS were more likely to agree to "my health at present depends on my asthma medication" compared to non-adherent ICS users. CONCLUSIONS: ICS non-adherence was not associated with having relatively more concerns about asthma medicines; however, ICS users were more likely to perceive that the benefits of medication use outweighed any risks. Interventions to improve asthma medication adherence in pregnancy are needed.

Uptake of prescription smoking cessation pharmacotherapies after hospitalization for major cardiovascular disease.

AIMS: We determined the prevalence of prescription smoking cessation pharmacotherapy (SCP) use after hospitalization for major cardiovascular disease (MCD) among people who smoke and whether this varies by sex. METHODS AND RESULTS: We conducted a population-based cohort study including all people hospitalized in New South Wales, Australia, between July 2013 and December 2018 (2017 for private hospitals) with an MCD diagnosis. For patients who also had a diagnosis of current tobacco use, we used linked pharmaceutical dispensing records to identify prescription SCP dispensings within 90 days post-discharge. We determined the proportion who were dispensed an SCP within 90 days, overall and by type of SCP. We used logistic regression to estimate the odds of females being dispensed an SCP relative to males. Of the 150 758 patients hospitalized for an MCD, 20 162 (13.4%) had a current tobacco use diagnosis, 31% of whom were female. Of these, 11.3% (12.4% of females, 10.9% of males) received prescription SCP within 90 days post-discharge; 3.0% were dispensed varenicline, and 8.3% were dispensed nicotine replacement therapy patches. Females were more likely than males to be dispensed a prescription SCP [odds ratio (OR) 1.16, 95% confidence interval (CI) 1.06-1.27)]; however, this was not maintained after adjusting for potential confounders (adjusted OR 1.04, 95% CI 0.94-1.15). CONCLUSION: Very few females and males who smoke use prescription SCPs after hospitalization for an MCD. The use of varenicline, the SCP with the highest efficacy, was particularly low. This represents a missed opportunity to increase smoking cessation in this high-risk population, thereby reducing their risk of recurrent cardiovascular events.

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.

Risk factors for asthma exacerbation during pregnancy: protocol for a systematic review and meta-analysis.

BACKGROUND: Asthma is the most common medical condition to affect pregnancy. Asthma exacerbations occur in up to 45% of pregnant women and have been associated with adverse perinatal and infant outcomes. Conflicting literature exists regarding the risk factors for exacerbations, and no synthesis of the literature currently exists. Therefore, this systematic review and meta-analysis aims to determine risk factors for asthma exacerbations during pregnancy among pregnant women with asthma. METHODS: This protocol has been reported according to the Preferred Reporting Items for Systematic Review and Meta-Analysis protocols checklist. A systematic search will be conducted in the electronic MEDLINE, Embase, CINAHL and Cochrane Clinical Trials Register databases (from January 2000 onwards). Eligibility of each publication will be determined based on predefined selection criteria. Prospective cohort studies, retrospective cohort studies, case-control studies and randomised controlled trials (RCTs) will be included. Quality of included studies will be determined using the Newcastle Ottawa Scale and the Cochrane Risk of Bias tool. Pooled relative risk will be computed using random-effects meta-analyses. Heterogeneity will be assessed using the chi-squared test and the I2 parameter. Publication bias will be assessed by inspecting a funnel plot for asymmetry and with the Egger's test of analyses including ten studies or more. DISCUSSION: The results of this systematic review and meta-analysis will discuss the potential risk factors for asthma exacerbations during pregnancy. This may aid healthcare professionals in early identification of pregnant women with asthma at risk of poor outcomes, providing the opportunity to implement early interventions in order to avoid deterioration of asthma symptoms during pregnancy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020196190.

Risk factors for asthma exacerbations during pregnancy: a systematic review and meta-analysis.

BACKGROUND: Conflicting literature exists regarding the risk factors for exacerbations among pregnant women with asthma. This systematic review and meta-analysis aimed to determine risk factors for asthma exacerbations during pregnancy. METHODS: Electronic databases were searched for the following terms: (asthma or wheeze) and (pregnan* or perinat* or obstet*) and (exacerb* or flare up or morbidit* or attack*).All studies published between 2000 and 24 August 2021 were considered for inclusion if they reported at least one potential risk factor of asthma exacerbations in pregnant women with asthma. Of the 3337 references considered, 35 publications involving 429 583 pregnant women with asthma were included. Meta-analyses were conducted to determine mean difference in risk factor between exacerbation groups, or the relative risks of exacerbation with certain risk factors. Good study quality was found through the Newcastle-Ottawa Scale (median score 8, interquartile range 7-9). RESULTS: Increased maternal age (mean difference 0.62, 95% CI 0.11-1.13), obesity (relative risk 1.25, 95% CI 1.15-1.37), smoking (relative risk 1.35, 95% CI 1.04-1.75), black ethnicity (relative risk 1.62, 95% CI 1.52-1.73), multiparity (relative risk 1.31, 95% CI 1.01-1.68), depression/anxiety (relative risk 1.42, 95% CI 1.27-1.59), moderate-severe asthma (relative risk 3.44, 95% CI 2.03-5.83, versus mild) and severe asthma (relative risk 2.70, 95% CI 1.85-3.95, versus mild-moderate) were associated with an increased risk of asthma exacerbations during pregnancy. CONCLUSIONS: Future interventions aimed at reducing exacerbations in pregnancy could address the modifiable factors, such as smoking and depression/anxiety, and introduce more regular monitoring for those with nonmodifiable risk factors such as obesity and more severe asthma.

A cross-sectional survey of Australian healthcare professionals' confidence, evidence-based knowledge and guideline use for antenatal asthma management.

BACKGROUND: Asthma is one of the most common chronic health conditions experienced during pregnancy and is associated with numerous adverse maternal and perinatal outcomes. AIMS: To better understand the confidence, evidence-based knowledge and guideline use among healthcare professionals around Australia commonly involved in providing antenatal care for women with asthma. MATERIALS AND METHODS: An online, cross-sectional survey was developed and distributed to maternity carers (obstetricians and midwives), primary carers (general practitioners and general practice nurses) and respiratory specialists (respiratory physicians and respiratory nurses). Self-reported confidence and use of clinical guidelines were recorded. Evidence-based knowledge was assessed with 13 questions relating to four clinical scenarios that covered recommendations from national and international guidelines. RESULTS: Primary carers and respiratory specialists were more confident in providing antenatal asthma care, more likely to use clinical guidelines and scored significantly higher in evidence-based knowledge of antenatal asthma management than maternity carers (P < 0.01 and P < 0.001, respectively). There was no significant difference in evidence-based knowledge among healthcare professionals from metropolitan, regional and rural backgrounds. However, healthcare professionals who used clinical guidelines scored significantly higher than those who did not (P < 0.0001). CONCLUSION: Greater utilisation of clinical guidelines could improve the evidence-based knowledge of maternity carers. However, the absence of antenatal asthma management in obstetric- and maternity-specific guidelines poses a potential barrier that needs to be addressed. Furthermore, the development of multidisciplinary antenatal clinics, staffed by respiratory nurses and/or physicians, could improve outcomes for pregnant women with asthma who are not undertaking shared care.

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.

Longitudinal Analysis of Lung Function in Pregnant Women with and without Asthma.

BACKGROUND: Spirometry is commonly used to assess and monitor lung function. It may also be a useful tool to monitor maternal health during pregnancy. However, large studies examining lung function across gestation are limited. Also, whether spirometry values follow the same pattern during pregnancy in women with and without asthma is unknown. OBJECTIVE: To investigate the effect of advancing gestation, and its interaction with asthma, on lung function in a large well-defined cohort of pregnant women. METHODS: Data were obtained from prospective cohorts involving women with (n = 770) and without (n = 259) asthma (2004-2017), recruited between 12 and 22 weeks' gestation. Lung function (forced vital capacity [FVC], FEV1, FEV1:FVC%) was assessed periodically during pregnancy using spirometry. Multilevel mixed-effect regression models were used to assess changes in lung function over gestation. RESULTS: Asthma had a significant effect on baseline lung function (FEV1%, -9%; FVC%, -3%; FEV1:FVC%, -4%). FVC% decreased with advancing gestation (-0.07%/wk; 95% CI, -0.10 to -0.04]), as did FEV1%, but only among those without asthma (women without asthma: -0.14%/wk, 95% CI, -0.22 to -0.06%; compared with women with asthma: 0.02%/wk, 95% CI, -0.01 to 0.06). FEV1:FVC% remained relatively stable for women without asthma (0.03%/wk; 95% CI, -0.08 to 0.02), but increased for women with asthma (0.06%/wk; 95% CI, 0.04 to 0.16). CONCLUSIONS: Data suggest that advancing gestation negatively affects FVC% and FEV1%. This is consistent with extrapulmonary restriction from advancing pregnancy. Yet, the presence of asthma altered the trajectories of FEV1% and FEV1:FVC%. Optimal asthma management during pregnancy might have opposed the negative effects of gestation on lung function.

Effect of maternal asthma exacerbations on perinatal outcomes: a population-based study.

BACKGROUND: Although there is a growing body of literature about the impact of asthma exacerbations during pregnancy on adverse perinatal outcomes, it is still unclear whether asthma exacerbations themselves or asthma severity are the driving factor for negative outcomes. This study aimed to estimate the associations between maternal asthma exacerbations and perinatal outcomes, and whether this differed by asthma treatment regime as a proxy for severity. METHODS: We included births of women with asthma in Sweden from July 2006 to November 2013 (n=33 829). Asthma exacerbations were defined as unplanned emergency visits/hospitalisations or a short course of oral corticosteroids. Adjusted odds ratios (aOR) were estimated for the associations between exacerbations during pregnancy and perinatal outcomes (small for gestational age (SGA), preterm birth, birthweight and mode of delivery), stratified by preconception treatment regime. RESULTS: Exacerbations occurred in 1430 (4.2%) pregnancies. Exacerbations were associated with reduced birthweight (aOR 1.45, 95% CI 1.24-1.70), and elective (aOR 1.50, 95% CI 1.25-1.79) and emergency caesarean section (aOR 1.35, 95% CI 1.13-1.61). Multiple exacerbations were associated with a 2.6-fold increased odds of SGA (95% CI 1.38-4.82). Amongst women treated prepregnancy with combination therapy (proxy for moderate-severe asthma), exacerbators were at increased odds of elective (aOR 1.69, 95% CI 1.30-2.2) and emergency (aOR 1.62, 95% CI 1.26-2.08) caesarean section, and SGA (aOR 1.74, 95% CI 1.18-2.57) versus non-exacerbators. CONCLUSION: Maternal asthma exacerbations increase the risk of SGA and caesarean sections, particularly in women with multiple exacerbations or moderate-severe asthma. Adequate antenatal asthma care is needed to reduce exacerbations and reduce risks of poor outcomes.

How Maternal BMI Modifies the Impact of Personalized Asthma Management in Pregnancy.

BACKGROUND: Maternal asthma is associated with perinatal complications and respiratory illness in offspring. Obesity increases asthma exacerbation risk in pregnancy and risk of wheeze in offspring. OBJECTIVES: In this secondary analysis of a randomized controlled trial, we investigated the influence of maternal body mass index, gestational weight gain (GWG), and fractional exhaled nitric oxide (FENO)-based management on asthma exacerbations in pregnancy and offspring wheeze. METHODS: A total of 220 women were randomized to asthma treatment adjustment according to symptoms (control group), or FENO and symptoms (FENO group). Exacerbations were recorded prospectively. Height and weight were measured at baseline, and in late pregnancy. GWG was categorized according to Institute of Medicine guidelines. A validated parent-completed questionnaire assessed infant wheeze-related outcomes. RESULTS: FENO-based management was associated with a significantly lower incidence rate ratio for maternal exacerbations in nonobese mothers (0.52, 95% confidence interval [CI], 0.31-0.88, P = .015, n = 129), and women with GWG within recommendations (0.35, 95% CI, 0.12-0.96, P = .042, n = 43), but not for obese mothers (0.59, 95% CI, 0.32-1.08, P = .089, n = 88), or women with excess GWG (0.58, 95% CI, 0.32-1.04, P = .07, n = 104). Recurrent bronchiolitis occurred in 5.3% (n = 1) of infants born to non-overweight mothers, 16.7% (n = 3) of infants of overweight mothers, and 21.7% (n = 5) of infants of obese mothers in the control group. In the FENO group, 2 infants of obese mothers had recurrent bronchiolitis (7.1%, P = .031). CONCLUSIONS: The benefits of FENO-based management are attenuated among obese mothers and those with excess GWG, indicating the importance of weight management in contributing to improved asthma management in pregnancy.

Biomarker-guided management reduces exacerbations in non-eosinophilic asthma in pregnancy: A secondary analysis of a randomized controlled trial.

BACKGROUND AND OBJECTIVE: The aim of this secondary analysis of a randomized controlled trial (RCT) of asthma management in pregnancy was to determine the treatment decision differences between a symptom control algorithm and a fractional exhaled nitric oxide (FENO)-guided algorithm, and whether the approach was effective in non-eosinophilic asthma (NEA). METHODS: In this double-blind parallel group RCT, women with asthma were randomized prior to 22 weeks gestation to treatment adjustment according to a symptom control algorithm (control group), or a FENO-guided algorithm (inhaled corticosteroid (ICS) dose adjusted according to FENO with long-acting beta-agonist (LABA) added for uncontrolled symptoms). NEA was classified as baseline blood eosinophils <0.26 × 109 /L and FENO ≤29 ppb. Exacerbations requiring medical intervention were recorded. RESULTS: Among 220 non-smokers (n = 109 control, n = 111 FENO), 1006 treatment decisions were made, with significant group differences after the first and second algorithm applications. 53% of women had NEA. Treatment was better targeted to phenotype in the FENO group: ICS use increased in eosinophilic asthma (EA, 48-86%), while ICS/LABA increased in NEA (11-30%). Fewer women in the FENO group had exacerbations during pregnancy in NEA only (18.9% FENO vs 44% control, P = 0.006). CONCLUSION: The FENO algorithm was more effective in treating NEA, resulting in reduced exacerbations, compared to a symptom control algorithm. This was not the result of ICS overtreatment, since the benefits occurred at a lower median daily ICS dose. Two applications of the FENO-guided algorithm, one month apart, were sufficient to achieve beneficial effects in terms of asthma exacerbations, among pregnant women with asthma.

Inhaled corticosteroid use during pregnancy among women with asthma: A systematic review and meta-analysis.

BACKGROUND: Studies demonstrate the prescription rate for inhaled corticosteroids (ICS) decreases in early pregnancy, possibly increasing exacerbation risk. This could be related to non-adherence to prescribed asthma medication or medication cessation by the patient or doctor. ICS use during pregnancy has not previously been summarized in a systematic review. OBJECTIVE: The aim of this systematic review and meta-analysis was to evaluate the use of ICS during pregnancy among asthmatic women, specifically: (1) the prevalence of use, (2) changes of use during pregnancy compared with pre-pregnancy and (3) medication adherence among ICS users. METHODS: We systematically searched literature in Embase, MEDLINE, CINAL and Cochrane, using terms related to asthma, pregnancy and medication use. All English articles reporting ICS among pregnant women with asthma were included. Prevalence, changes in ICS use during pregnancy and ICS adherence were pooled using STATA (version 15.0, StataCorp USA). RESULTS: A total of 4237 references were retrieved in the initial search. Screening and review led to the inclusion of 52 articles for one or more aims (Aim 1: N = 45; Aim 2, N = 13; and Aim 3, N = 5). The pooled prevalence of ICS use during pregnancy was 41% (95%CI 36%-45%); 49% (95%CI 44%-55%) in Europe, 39% (95%CI 32%-47%) in Australia and 34% (95%CI 27%-41%) in North America. In eight prescription databases, ICS prescription rates lowered in the first trimester of pregnancy, compared with pre-pregnancy, increased in the second trimester and decreased in the third trimester. Five studies reported ICS adherence among pregnant women, using four measures of self-reported non-adherence. In two comparable studies, pooled ICS non-adherence was 40% (95%CI 36%-44%). CONCLUSIONS: The prevalence of ICS use among pregnant women with asthma is 41% and varies widely between countries and continents, and prescription rates for ICS change throughout pregnancy. More studies are needed to investigate ICS adherence during pregnancy in women with asthma.

Trends in asthma self-management skills and inhaled corticosteroid use during pregnancy and postpartum from 2004 to 2017.

OBJECTIVE: Asthma exacerbations and medication non-adherence are significant clinical problems during pregnancy. While asthma self-management education is effective, the number of education sessions required to maximise asthma management knowledge and inhaler technique and whether improvements persist postpartum, are unknown. This paper describes how asthma knowledge, skills, and inhaled corticosteroid (ICS) use have changed over time. METHODS: Data were obtained from 3 cohorts of pregnant women with asthma recruited in Newcastle, Australia between 2004 and 2017 (N = 895). Medication use, adherence, knowledge, and inhaler technique were compared between cohorts. Changes in self-management knowledge/skills and women's perception of medication risk to the fetus were assessed in 685 women with 5 assessments during pregnancy, and 95 women who had a postpartum assessment. RESULTS: At study entry, 41%, 29%, and 38% of participants used ICS in the 2004, 2007, and 2013 cohorts, respectively (p = 0.017), with 40% non-adherence in each cohort. Self-management skills of pregnant women with asthma did not improve between 2004 and 2017 and possession of a written action plan remained low. Maximum improvements were reached by 3 sessions for medications knowledge and one session for inhaler technique, and were maintained postpartum. ICS adherence was maximally improved after one session, but not maintained postpartum. Perceived risk of asthma medications on the fetus was highest for corticosteroid-containing medication; and was significantly reduced following education. CONCLUSIONS: There was a high prevalence of non-adherence and poor self-management skills in all cohorts. More awareness of the importance of optimal asthma management during pregnancy is warranted, since no improvements were observed over the past decade.

Recent developments in asthma in pregnancy.

PURPOSE OF REVIEW: Asthma affects up to 13% of pregnancies worldwide and has a varying and unpredictable clinical course during pregnancy. Pharmacological asthma treatment is recommended; however, studies show that some pregnant women with asthma cease their medication in early pregnancy. There is likely a large unmet disease burden arising from asthma in pregnancy. RECENT FINDINGS: Antenatal and asthma guidelines lack sufficient information on asthma management in pregnant women, and implementation of the current guidelines seems inadequate. Prescription databases provide evidence of cessation of asthma medication during pregnancy on a population level. Population-based databases also provide evidence of rare adverse perinatal outcomes. The risk of childhood asthma in the offspring of women with asthma is reduced by adequate control of maternal asthma during pregnancy. Vitamin D sufficiency during pregnancy could also reduce the risk of childhood asthma. SUMMARY: The findings of this review demonstrate the need for improved asthma and antenatal guidelines regarding asthma management during pregnancy, and the need of adequate implementation of these guidelines. Furthermore, adequate asthma control during pregnancy is needed to reduce the risk of childhood asthma. To maintain asthma control, prepregnancy medication should be continued throughout pregnancy and adjusted according to the current treatment steps if required.

Maternal depression and antidepressant use during pregnancy and the risk of autism spectrum disorder in offspring.

BACKGROUND: Results of some studies suggest that prenatal antidepressant exposure increases the risk of autism spectrum disorder (ASD) in offspring, while other studies suggest that depression independently increases the risk of having a child with ASD. Thus, confounding by indication is a concern. OBJECTIVE: The aim of this study was to estimate the risk of ASD in offspring of women who were exposed to antidepressants and/or had depression during pregnancy compared to unexposed women. MATERIALS AND METHODS: We conducted a cohort study with nested sibling case-control analysis. Using the UK Clinical Practice Research Datalink (CPRD), we identified mother- baby pairs where the mother had ≥12 months of history before the delivery date and the child had ≥3 years of follow-up. Exposures during pregnancy were classified as 1) depression treated with antidepressants, 2) untreated depression, 3) other indications for antidepressant use, and 4) 4:1 match of unexposed women with no history of depression or antidepressant use. We calculated the prevalence of ASD and relative risk (RR) with 95% CI. In the sibling analysis, we compared exposure among ASD cases to that of non-ASD siblings born to the same mother. We calculated ORs and 95% CIs for women with treated and untreated depression, compared to unexposed. RESULTS: We identified 2,154 offspring with ASD among 194,494 mother-baby pairs. Compared to unexposed, the RR of ASD was 1.72 (95% CI 1.54-1.93) for treated depression and 1.50 (95% CI 1.28-1.75) for untreated depression, while the RR was not elevated in women who received antidepressants for other indications (RR =0.73, 95% CI 0.41-1.29). Additional analyses to assess the effects of severity of depression suggest that the risk of ASD in offspring increases with increasing severity, not with the antidepressant treatment. The results of the sibling analysis were similar to the main analysis. CONCLUSION: Women with depression during pregnancy have an increased risk of having a child with ASD, regardless of antidepressant use.

Increased life expectancy as a result of non-hormonal targeted therapies for HER2 or hormone receptor positive metastatic breast cancer: A systematic review and meta-analysis.

This article aimed to assess the clinical effectiveness of non-hormonal targeted therapies (TTs) in terms of increase of median progression-free survival (PFS) and overall survival (OS) in receptor-positive metastatic breast cancer (MBC) patients by performing a systematic review and meta-analysis. We systematically searched relevant randomized controlled trials and extracted data about number of patients on targeted and comparator therapy, receptor status, line of treatment, median PFS and OS, p values, hazard ratios (HRs) and 95% confidence intervals (CI). Inverse variance was used to estimate pooled HRs, chi-square test for heterogeneity and Jadad scale for quality were applied. Thirty-eight studies (n=17,192 patients) were eligible for inclusion. TTs added 3.3months to the median PFS [0.7-9.6; HRs 0.74, 95% CI 0.71-0.77] of receptor-positive MBC patients and prolonged their median OS with 3.5months [0-4.7; HRs 0.90, 95% CI 0.82-0.98]. The highest increase in median PFS of 3.6months was found in HER2-/hormone receptor(HR)+ patients, while the highest increase in median OS of 7.2months was observed in HER2+/HRmixed status patients. First-line TTs were most effective in increasing the median PFS in the HR+/HER2- group with 2.0months, and in the HER2+/HRmixed group by adding 4.7months to the median OS. Second-line TTs were most effective for HER2-/HR+ patients by adding 2.6months to their PFS, and for HER2+/HRmixed patients by adding 3.1months to their median OS. Albeit small, the gain in months of median PFS and median OS was significant. Importantly, the results reported show large variation, and thus routinely applying a personalized approach seems warranted.