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BACKGROUND: Clinical and preclinical evidence indicate that in utero maternal asthma exposure increases progeny asthma risk. Whether maternal asthma also increases the risks of progeny allergy is unclear. OBJECTIVES: To synthesise the available evidence on the relationship between in utero exposure to maternal asthma and postnatal asthma, wheezing and allergic diseases (Prospero: CRD42020201538). SEARCH STRATEGY: We systematically searched MEDLINE [PubMed], Embase [Ovid], Web of Science, Informit Health, the Cochrane Library, CINAHL [EBSCOhost], MedNar [Deep Web Technologies], ProQuest Theses and Dissertations, Scopus [Elsevier] and Trove, to the end of 2023. SELECTION CRITERIA: Studies reporting asthma, wheeze and/or allergic disease in progeny of women with and without asthma or with asthma classified by control, exacerbation or severity. DATA COLLECTION AND ANALYSIS: Double screening, selection, data extraction and quality assessment were performed, using Joanna Briggs Institute (JBI) scoring. MAIN RESULTS: Of 134 non-overlapping studies, 127 were included in ≥1 meta-analysis. Maternal asthma ever was associated with greater risks of asthma (65 studies, risk ratio [95% confidence interval] 1.76 [1.57-1.96]), wheeze (35 studies, 1.59 [1.52-1.66]), food allergy (5 studies, 1.32 [1.23-1.40]), allergic rhinitis (7 studies, 1.18 [1.06-1.31]) and allergic dermatitis (14 studies, 1.17 [1.11-1.23]) ever in progeny. Asthma during the pregnancy, more severe, and uncontrolled maternal asthma were each associated with greater risks of progeny asthma. CONCLUSIONS: Children of mothers with asthma are at increased risk for the development of allergic diseases. Whether improved maternal asthma control reduces risks of child allergy as well as asthma requires further investigation.
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OBJECTIVES: To compare fetal pulmonary artery Doppler parameters between pregnant women with asthma and healthy pregnant women. METHODS: This prospective, cross-sectional study was conducted on 50 pregnant women diagnosed with asthma and 61 healthy pregnant women. Fetal pulmonary artery Doppler parameters and the fetal main pulmonary artery acceleration time/ejection time (PATET) ratio were compared between the study and control groups. Thereafter, the study group was divided into two subgroups as non-severe and severe asthma. PATET ratio was compared between the subgroups. RESULTS: The fetal main pulmonary artery acceleration time was 25â¯ms in pregnant women with asthma and 33â¯ms in the healthy group, indicating a statistically significant difference (p=0.001). The acceleration time/ejection time ratio was statistically lower in the asthma group (0.185 vs. 0.240, p<0.001). The acceleration time/ejection time ratio was 0.172 in patients with severe asthma and 0.195â¯ms in the non-severe study group (p=0.156). In the maternal asthma group, the PATET ratio of those who went to the NICU due to respiratory distress was also 0.188, and the PATET ratio of those who went to the NICU for other reasons was 0.269 (p=0.053). CONCLUSIONS: Fetal pulmonary artery acceleration time and PATET decreased statistically in pregnant women with severe or non-severe asthma. Maternal asthma is associated with changes in pulmonary Doppler parameters in the fetus.
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Asma , Arteria Pulmonar , Ultrasonografía Prenatal , Humanos , Femenino , Embarazo , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/fisiopatología , Asma/fisiopatología , Asma/diagnóstico por imagen , Asma/complicaciones , Estudios de Casos y Controles , Ultrasonografía Prenatal/métodos , Adulto , Estudios Transversales , Estudios Prospectivos , Complicaciones del Embarazo/fisiopatología , Complicaciones del Embarazo/diagnóstico por imagen , Ultrasonografía Doppler/métodosRESUMEN
Asthma is a highly heterogeneous inflammatory disease that can have a significant effect on both the respiratory system and central nervous system. Population based studies and animal models have found asthma to be comorbid with a number of neurological conditions, including depression, anxiety, and neurodevelopmental disorders. In addition, maternal asthma during pregnancy has been associated with neurodevelopmental disorders in the offspring, such as autism spectrum disorders and attention deficit hyperactivity disorder. In this article, we review the most current epidemiological studies of asthma that identify links to neurological conditions, both as it relates to individuals that suffer from asthma and the impacts asthma during pregnancy may have on offspring neurodevelopment. We also discuss the relevant animal models investigating these links, address the gaps in knowledge, and explore the potential future directions in this field.
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Asma , Trastorno del Espectro Autista , Trastornos del Neurodesarrollo , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Animales , Humanos , Enfermedades Neuroinflamatorias , Trastorno del Espectro Autista/epidemiología , Comorbilidad , Asma/epidemiología , Trastornos del Neurodesarrollo/epidemiología , Modelos Animales de EnfermedadRESUMEN
Background: We aimed to assess whether exposure to risk factors in early life from conception to puberty continue to contribute to lung function decline later in life by using a pooled cohort comprising approx. 11,000 adults followed for more than 20 years and with up to three lung function measurements. Methods: Participants (20-68 years) in the ECRHS and NFBC1966 cohort studies followed in the periods 1991-2013 and 1997-2013, respectively, were included. Mean annual decline in maximum forced expired volume in 1 s (FEV1) and forced vital capacity (FVC) were main outcomes. Associations between early life risk factors and change in lung function were estimated using mixed effects linear models adjusted for sex, age, FEV1, FVC and height at baseline, accounting for personal smoking. Findings: Decline in lung function was accelerated in participants with mothers that smoked during pregnancy (FEV1 2.3 ml/year; 95% CI: 0.7, 3.8) (FVC 2.2 ml/year; 0.2, 4.2), with asthmatic mothers (FEV1 2.6 ml/year; 0.9, 4.4) (FEV1/FVC 0.04 per year; 0.04, 0.7) and asthmatic fathers (FVC 2.7 ml/year; 0.5, 5.0), and in women with early menarche (FVC 2.4 ml/year; 0.4, 4.4). Personal smoking of 10 pack-years contributed to a decline of 2.1 ml/year for FEV1 (1.8, 2.4) and 1.7 ml/year for FVC (1.3, 2.1). Severe respiratory infections in early childhood were associated with accelerated decline among ever-smokers. No effect-modification by personal smoking, asthma symptoms, sex or cohort was found. Interpretation: Mothers' smoking during pregnancy, parental asthma and early menarche may contribute to a decline of FEV1 and FVC later in life comparable to smoking 10 pack-years. Funding: European Union's Horizon 2020; Research Council of Norway; Academy of Finland; University Hospital Oulu; European Regional Development Fund; Spanish Ministry of Science and Innovation; Generalitat de Catalunya.
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Inflammation during pregnancy is associated with an increased risk for neurodevelopmental disorders (NDD). Increased gestational inflammation can be a result of an immune condition/disease, exposure to infection, and/or environmental factors. Epidemiology studies suggest that cases of NDD are on the rise. Similarly, rates of asthma are increasing, and the presence of maternal asthma during pregnancy increases the likelihood of a child being later diagnosed with NDD such as autism spectrum disorders (ASD). Particulate matter (PM), via air pollution, is an environmental factor known to worsen the symptoms of asthma, but also, PM has been associated with increased risk of neuropsychiatric disorders. Despite the links between asthma and PM with neuropsychiatric disorders, there is a lack of laboratory models investigating combined prenatal exposure to asthma and PM on offspring neurodevelopment. Thus, we developed a novel mouse model that combines exposure to maternal allergic asthma (MAA) and ultrafine iron-soot (UIS), a common component of PM. In the current study, female BALB/c mice were sensitized for allergic asthma with ovalbumin (OVA) prior to pregnancy. Following mating and beginning on gestational day 2 (GD2), dams were exposed to either aerosolized OVA to induce allergic asthma or phosphate buffered saline (PBS) for 1 h. Following the 1-h exposure, pregnant females were then exposed to UIS with a size distribution of 55 to 169 nm at an average concentration of 176 ± 45 µg/m3) (SD), or clean air for 4 h, over 8 exposure sessions. Offspring brains were collected at postnatal days (P)15 and (P)35. Cortices and hippocampal regions were then isolated and assessed for changes in cytokines using a Luminex bead-based multiplex assay. Analyses identified changes in many cytokines across treatment groups at both timepoints in the cortex, including interleukin-1 beta (IL-1ß), and IL-17, which remained elevated from P15 to P35 in all treatment conditions compared to controls. There was a suppressive effect of the combined MAA plus UIS on the anti-inflammatory cytokine IL-10. Potentially shifting the cytokine balance towards more neuroinflammation. In the hippocampus at P15, elevations in cytokines were also identified across the treatment groups, namely IL-7. The combination of MAA and UIS exposure (MAA-UIS) during pregnancy resulted in an increase in microglia density in the hippocampus of offspring, as identified by IBA-1 staining. Together, these data indicate that exposure to MAA, UIS, and MAA-UIS result in changes in the neuroimmune environment of offspring that persist into adulthood.
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Asma , Efectos Tardíos de la Exposición Prenatal , Humanos , Animales , Embarazo , Ratones , Niño , Femenino , Material Particulado/toxicidad , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Asma/inducido químicamente , Citocinas , InflamaciónRESUMEN
Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. DNA methylation is one form of epigenetic modification that regulates gene expression and is both inherited and modified by environmental exposures throughout life. Prenatal development is a particularly vulnerable time period during which exposure to maternal asthma increases asthma risk in offspring. How maternal asthma affects DNA methylation in offspring and what the consequences of differential methylation are in subsequent generations are not fully known. In this study, we tested the effects of grandmaternal house dust mite (HDM) allergen sensitization during pregnancy on airway physiology and inflammation in HDM-sensitized and challenged second-generation mice. We also tested the effects of grandmaternal HDM sensitization on tissue-specific DNA methylation in allergen-naïve and -sensitized second-generation mice. Descendants of both allergen- and vehicle-exposed grandmaternal founders exhibited airway hyperreactivity after HDM sensitization. However, grandmaternal allergen sensitization significantly potentiated airway hyperreactivity and altered the epigenomic trajectory in second-generation offspring after HDM sensitization compared with HDM-sensitized offspring from vehicle-exposed founders. As a result, biological processes and signaling pathways associated with epigenetic modifications were distinct between lineages. A targeted analysis of pathway-associated gene expression found that Smad3 was significantly dysregulated as a result of grandmaternal allergen sensitization. These data show that grandmaternal allergen exposure during pregnancy establishes a unique epigenetic trajectory that reprograms allergen responses in second-generation offspring and may contribute to asthma risk.NEW & NOTEWORTHY Asthma susceptibility is influenced by environmental, genetic, and epigenetic factors. This study shows that maternal allergen exposure during pregnancy promotes unique epigenetic trajectories in second-generation offspring at baseline and in response to allergen sensitization, which is associated with the potentiation of airway hyperreactivity. These effects are one mechanism by which maternal asthma may influence the inheritance of asthma risk.
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Asma , Efectos Tardíos de la Exposición Prenatal , Embarazo , Humanos , Femenino , Ratones , Animales , Alérgenos , Epigenómica , Efectos Tardíos de la Exposición Prenatal/genética , Asma/genética , Susceptibilidad a Enfermedades , Epigénesis Genética , PyroglyphidaeRESUMEN
OBJECTIVE: Asthma occurs in â¼17% of Australian pregnancies and is associated with adverse perinatal outcomes, which worsen with poor asthma control. Consequently, the South Australian 'Asthma in Pregnancy' perinatal guidelines were revised in 2012 to address management according to severity. This study investigated if these revised guidelines reduced the impact of maternal asthma on risks of adverse perinatal outcomes before (Epoch 1, 2006-2011) and after the revision (Epoch 2, 2013-2018). METHODS: Routinely collected perinatal and neonatal datasets from the Women's and Children's Hospital (Adelaide, Australia) were linked. Maternal asthma (prevalence:7.5%) was defined as asthma medication use or symptoms described to midwives. In imputation (n = 59131) and complete case datasets (n = 49594), analyses were conducted by inverse proportional weighting and multivariate logistic regression, accounting for confounders. RESULTS: Overall, maternal asthma was associated with increased risks of any antenatal corticosteroid treatment for threatened preterm birth (aOR 1.319, 95% CI 1.078-1.614), any Cesarean section (aOR 1.196, 95% CI 1.059-1.351), Cesarean section without labor (aOR 1.241, 95% CI 1.067-1.444), intrauterine growth restriction (IUGR, aOR 1.285, 95% CI 1.026-1.61), and small for gestational age (aOR 1.324, 95% CI 1.136-1.542). After guideline revision, asthma-associated risks of any Cesarean section (p < 0.001), any antenatal corticosteroids (p = 0.041), and small for gestational age (p = 0.050), but not IUGR and Cesarean section without labor, were reduced. CONCLUSIONS: Clinical practice guidelines based on the latest evidence do not guarantee clinical efficacy. Since adverse perinatal outcomes did not all improve, this work highlights the need to evaluate the ongoing impact of guidelines on clinical outcomes.
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Asma , Complicaciones del Embarazo , Nacimiento Prematuro , Niño , Embarazo , Femenino , Recién Nacido , Humanos , Resultado del Embarazo/epidemiología , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/epidemiología , Cesárea , Estudios Retrospectivos , Nacimiento Prematuro/epidemiología , Asma/tratamiento farmacológico , Asma/epidemiología , Asma/complicaciones , AustraliaRESUMEN
LAY ABSTRACT: Autism spectrum disorder is heterogeneous and often accompanied by co-occurring conditions. Previous studies have shown that maternal health conditions during pregnancy including obesity, diabetes, preeclampsia, and asthma were associated with increased likelihood of autism. However, little has been done examining the likelihood associated with autism with co-occurring conditions. This study assessed these maternal health conditions in relationship to autism and gastrointestinal disturbances, a common co-occurring condition in children diagnosed with autism. Data included 308,536 mother-child pairs from one integrated health care system with comprehensive electronic medical records. Among the study cohort, 5,131 (1.7%) children had a diagnosis of autism by age 5. Gastrointestinal disturbances were present in 35.4% of children diagnosed with autism and 25.1% of children without autism diagnoses. Our results showed that each of the four maternal health conditions during pregnancy was associated with increased likelihood of gastrointestinal disturbances, autism without gastrointestinal disturbances, and autism with gastrointestinal disturbances. For all four maternal health conditions, the association was greatest for likelihood of autism with gastrointestinal disturbances. Given that children diagnosed with autism are more likely to have gastrointestinal disturbances and over 80% of gastrointestinal disturbances in this cohort were diagnosed prior to autism diagnosis, this study suggests that there may be common biological pathways between autism and gastrointestinal disturbances impacted by these maternal exposures. Future studies are warranted to assess associations between different exposures and autism with other co-occurring conditions to increase our understanding of autism heterogeneity.
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Trastorno del Espectro Autista , Enfermedades Gastrointestinales , Complicaciones del Embarazo , Adulto , Preescolar , Femenino , Humanos , Lactante , Masculino , Embarazo , Asma/epidemiología , Trastorno del Espectro Autista/complicaciones , Trastorno del Espectro Autista/epidemiología , Enfermedades Gastrointestinales/complicaciones , Enfermedades Gastrointestinales/epidemiología , Obesidad Materna/epidemiología , Preeclampsia/epidemiología , Complicaciones del Embarazo/epidemiología , Embarazo en Diabéticas/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Maternal asthma affects up to 17% of pregnancies and is associated with adverse infant, childhood, and adult respiratory outcomes, including increased risks of neonatal respiratory distress syndrome, childhood wheeze and asthma. In addition to genetics, these poor outcomes are likely due to the mediating influence of maternal asthma on the in-utero environment, altering fetal lung and immune development and predisposing the offspring to later lung disease. Maternal asthma may impair glucocorticoid signalling in the fetus, a process critical for lung maturation, and increase fetal exposure to proinflammatory cytokines. Therefore, interventions to control maternal asthma, increase glucocorticoid signalling in the fetal lung, or Vitamin A, C, and D supplementation to improve alveologenesis and surfactant production may be beneficial for later lung function. This review highlights potential mechanisms underlying maternal asthma and offspring respiratory morbidities and describes how pregnancy interventions can promote optimal fetal lung development in babies of asthmatic mothers.
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Maternal asthma (MA) is among the most consistent risk factors for asthma in children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 nonasthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene coexpression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA and MA cases, respectively, compared with controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five comethylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared with NMA cases (P = 7.1 × 10−3), a finding that replicated in nasal epithelial cells from an independent cohort (P = 0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum immunoglobulin E, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that MA alters diverse epigenetically mediated pathways that lead to distinct subtypes of severe asthma in adults, including hard-to-treat T2-low asthma.
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Asma , Metilación de ADN , Regulación de la Expresión Génica , Adulto , Femenino , Humanos , Hijos Adultos , Asma/genética , Asma/metabolismo , Islas de CpG , Epigénesis Genética , Madres , Gravedad del Paciente , Factores de RiesgoRESUMEN
Asthma is a heterogeneous inflammatory airway disease that develops in response to a combination of genetic predisposition and environmental exposures. Patients with asthma are grouped into phenotypes with shared clinical features and biomarker profiles to help tailor specific therapies. However, factors driving development of specific phenotypes are poorly understood. Prenatal exposure to maternal asthma is a unique risk factor for childhood asthma. Here we tested whether maternal asthma skews asthma phenotypes in offspring. We compared airway hyperreactivity and inflammatory and neurotrophin lung signatures before and after allergen challenge in offspring born to mice exposed to house dust mite (HDM) or vehicle during pregnancy. Maternal HDM exposure potentiated offspring responses to HDM allergen, significantly increasing both airway hyperreactivity and airway eosinophilia compared with control mice. Maternal HDM exposure broadly skewed the offspring cytokine response from a classic allergen-induced T-helper cell type 2 (Th2)-predominant signature in HDM-treated offspring of vehicle-exposed mothers, toward a mixed Th17/Th1 phenotype in HDM-treated offspring of HDM-exposed mothers. Morphologic analysis determined that maternal HDM exposure also increased airway epithelial sensory nerve density and induced distinct neurotrophin signatures to support airway hyperinnervation. Our results demonstrate that maternal allergen exposure alters fetal lung development and promotes a unique inflammatory phenotype at baseline and in response to allergen that persists into adulthood.
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Asma , Pyroglyphidae , Alérgenos , Animales , Asma/genética , Modelos Animales de Enfermedad , Femenino , Pulmón , Ratones , Factores de Crecimiento Nervioso/genética , Fenotipo , EmbarazoRESUMEN
PURPOSE: To evaluate the relationships among history of asthma, asthma severity, and spontaneous abortion (SAB). METHODS: Pregnancy Study Online is a preconception cohort study of North American couples. During the preconception period, female participants reported their history of physician-diagnosed asthma, age at first diagnosis, and use of asthma medications in the previous 4 weeks. Asthma severity was classified by medication use proximal to conception, from level 0 to 3 in increasing severity. Pregnancy and SAB were identified using data from follow-up questionnaires. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: Among 6325 participants who conceived, 19% experienced SAB and 17% reported a history of asthma. There was no appreciable association between asthma history and SAB incidence (HR = 0.98; 95% CI: 0.84, 1.14). HRs comparing severity levels 0, 1, and 2-3 with no asthma were 0.82 (95% CI: 0.67, 1.01), 1.20 (95% CI: 0.91, 1.60), and 1.31 (95% CI: 0.97, 1.78), respectively. Among women who conceived without the use of fertility treatment, level 2-3 severity was associated with SAB (HR = 1.39; 95% CI: 1.02, 1.89). CONCLUSIONS: While history of asthma diagnosis was not materially associated with SAB, having severe asthma (based on medication use) was associated with greater SAB risk.
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Aborto Espontáneo , Asma , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Asma/complicaciones , Asma/epidemiología , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Embarazo , Estudios ProspectivosRESUMEN
STUDY OBJECTIVE: To assess whether asthma medication use during pregnancy differs in women newly diagnosed with asthma early in pregnancy (first 19 weeks of pregnancy) compared to those newly diagnosed up to 2 years pre-pregnancy. DESIGN: A retrospective population-based cohort study. DATA SOURCE: To conduct this study, we used the Quebec Asthma and Pregnancy Database (QAPD) constructed by linking two administrative health databases from the province of Quebec (Canada): the Régie de l'Assurance Maladie du Québec and Maintenance et Exploitation des Données pour l'Étude de la Clientèle Hospitalière databases. PATIENTS: A cohort comprising pregnant women newly diagnosed with asthma at any time in the 2 years prior to pregnancy or during the first 19 weeks of pregnancy was selected from the QAPD. MEASUREMENTS AND MAIN RESULTS: We assessed the number of filled prescriptions of inhaled corticosteroids (ICS), ICS/long-acting ß2 agonists (LABA), and short-acting ß2 agonists (SABA), as well as the number of days' supply of oral corticosteroid (OCS) from the 20th week of pregnancy until delivery. Poisson regression was used to compare the rates of asthma medication use in women diagnosed pre-pregnancy versus early in pregnancy. The cohort included 1731 women newly diagnosed with asthma pre-pregnancy and 359 women newly diagnosed with asthma early in pregnancy. Women diagnosed early in pregnancy were more likely to use ICS (adjusted rate ratio: 1.9, 95% confidence interval (CI): 1.6-2.3) and SABA (adjusted rate ratio: 2.0, 95% CI: 1.7-2.4) from the 20th week of pregnancy until delivery than those newly diagnosed pre-pregnancy. No significant differences were observed in the use of ICS/LABA [adjusted rate ratio: 0.9, 95% CI: 0.7-1.3] and OCS [adjusted rate ratio: 0.8, 95% CI: 0.6-1.2]. CONCLUSION: The higher use of ICS and SABA observed in women newly diagnosed with asthma early in pregnancy may suggest a more persistent asthma phenotype caused by pregnancy-triggered hormonal changes.
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Antiasmáticos , Asma , Antiasmáticos/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Femenino , Humanos , Embarazo , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND: Severity of human metapneumovirus (hMPV) lower respiratory illness (LRTI) is considered similar to that observed for respiratory syncytial virus (RSV). However, differences in severity between these pathogens have been noted, suggesting the degree of illness may vary in different populations. Moreover, a potential association between hMPV and asthma also suggests that hMPV may preferentially affect asthmatic subjects. METHODS: In a population-based surveillance study in children aged <2 years admitted for severe LRTI in Argentina, nasopharyngeal aspirates were tested by RT-PCR for hMPV, RSV, influenza A, and human rhinovirus. RESULTS: Of 3947 children, 383 (10%) were infected with hMPV. The hospitalization rate for hMPV LRTI was 2.26 per 1000 children (95% confidence interval [CI], 2.04-2.49). Thirty-nine (10.2%) patients infected with hMPV experienced life-threatening disease (LTD; 0.23 per 1000 children; 95% CI, .16-.31/1000), and 2 died (mortality rate 0.024 per 1000; 95% CI, .003-.086). In hMPV-infected children birth to an asthmatic mother was an increased risk for LTD (odds ratio, 4.72; 95% CI, 1.39-16.01). We observed a specific interaction between maternal asthma and hMPV infection affecting risk for LTD. CONCLUSIONS: Maternal asthma increases the risk for LTD in children <2 years old hospitalized for severe hMPV LRTI.
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Asma , Infecciones por Paramyxoviridae , Infecciones del Sistema Respiratorio , Argentina/epidemiología , Asma/epidemiología , Preescolar , Susceptibilidad a Enfermedades , Humanos , Lactante , Pulmón , Metapneumovirus , Infecciones por Paramyxoviridae/complicaciones , Infecciones por Paramyxoviridae/epidemiología , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/epidemiologíaRESUMEN
BACKGROUND: Childhood asthma developmental programming is complex. Maternal asthma is a strong risk factor for childhood asthma, whereas vitamin D (VD) has emerged as a modifiable prenatal exposure. OBJECTIVE: Our aim was to examine the combined effect of early and late prenatal VD status in during pregnancies in women with and without asthma on childhood asthma or recurrent wheeze development. METHODS: We conducted a cohort study using prospectively collected data from the Vitamin D Antenatal Asthma Reduction Trial, a randomized, double-blinded, placebo-controlled VD supplementation trial in pregnant women at high risk of offspring asthma (N = 806 mother-offspring pairs). 25-Hydroxyvitamin-D (25(OH)D) level was measured in early and late pregnancy. Our main exposure was an ordered variable representing early and late prenatal VD sufficiency (25(OH)D level ≥ 30 ng/mL) status during pregnancy in women with and without asthma. The primary outcome was offspring with asthma or recurrent wheeze by age 3 years. We also examined the effect of prenatal VD level on early life asthma or recurrent wheeze progression to active asthma at age 6 years. RESULTS: Among mothers with asthma versus among mothers with early and late prenatal VD insufficiency, those with early or late VD sufficiency (adjusted odds ratio = 0.56; 95% CI = 0.31-1.00) or early and late VD sufficiency (adjusted odds ratio = 0.36; 95% CI = 0.15-0.81) had a lower risk of offspring with asthma or recurrent wheeze by age 3 years (Pfor trend = .008). This protective trend was reiterated in asthma or recurrent wheeze progression to active asthma from age 3 to 6 years (Pfor trend = .04). CONCLUSION: This study implies a protective role for VD sufficiency throughout pregnancy, particularly in attenuating the risk conferred by maternal asthma on childhood asthma or recurrent wheeze development.
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Asma/epidemiología , Efectos Tardíos de la Exposición Prenatal/epidemiología , Deficiencia de Vitamina D/epidemiología , Vitamina D/uso terapéutico , Adulto , Asma/dietoterapia , Niño , Preescolar , Estudios de Cohortes , Suplementos Dietéticos , Método Doble Ciego , Femenino , Humanos , Masculino , Exposición Materna , Efecto Placebo , Embarazo , Trimestres del Embarazo , Efectos Tardíos de la Exposición Prenatal/dietoterapia , Estudios Prospectivos , Recurrencia , Ruidos Respiratorios , Riesgo , Vitamina D/metabolismo , Deficiencia de Vitamina D/dietoterapia , Adulto JovenRESUMEN
BACKGROUND: Children with a history of rhinovirus (RV) positive bronchiolitis have a high risk of developing subsequent asthma. Maternal asthma might also increase this risk. The aim of this study was to investigate the combined effects of hospitalization for RV positive bronchiolitis in infancy and a history of maternal asthma on the development of asthma at preschool age. METHODS: This is a prospective cohort study of 139 preschool-aged children, with a history of hospital admission for bronchiolitis in infancy, followed-up to ascertain asthma and asthma-like symptoms, skin prick allergy test positivity, and lung function measured pre- and post-bronchodilator using impulse oscillometry. RESULTS: Children with a past hospitalization for RV positive bronchiolitis (42.4% of all) and a history of maternal asthma (36.7% of all) had the greatest prevalence and risk ratio (RR) for doctor-diagnosed asthma (prevalence 81.8% and RR 2.10, 95% confidence interval [CI] 1.37-3.19, p = .001), use of inhaled corticosteroids (68.2% and RR 2.17, 95% CI 1.19-3.99, p = .001) and short-acting ß-agonists in the last 12 months (95.2% and RR 1.49, 95% CI 1.17-1.89, p = .001), as compared to those with RV negative bronchiolitis and no maternal asthma history. More children in this group had an abnormal airway resistance (33.3% and adjusted risk ratio [aRR] 3.11, 95% CI 1.03-9.47, p = .045) and reactance (27.8% and aRR 2.11, 95% CI 1.06-4.26, p = .035) at 5 Hz, as compared to those with RV negative bronchiolitis and no maternal asthma history. CONCLUSION: Hospitalization for RV positive bronchiolitis in early life combined with a history of maternal asthma identifies a subgroup of children with a high asthma burden while participants with only one of the two risk factors had intermediate risk for asthma.
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Asma/epidemiología , Bronquiolitis/epidemiología , Infecciones por Picornaviridae/epidemiología , Rhinovirus , Asma/fisiopatología , Bronquiolitis/fisiopatología , Preescolar , Femenino , Hospitalización , Humanos , Lactante , Pulmón/fisiopatología , Masculino , Madres , Oportunidad Relativa , Infecciones por Picornaviridae/fisiopatología , Estudios Prospectivos , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
INTRODUCTION: Asthma is a highly prevalent co-morbidity during pregnancy that can worsen as gestation progresses and is associated with several adverse perinatal outcomes. These adverse outcomes often result from uncontrolled asthma during pregnancy and acute asthma exacerbations that are associated with alterations in placental function and fetal growth. AREAS COVERED: This paper will discuss how maternal asthma in pregnancy affects fetal growth and development which may alter future offspring health. Changes in placental function occur in a sex-specific manner in pregnancies complicated by asthma and result in differences in fetal growth and development which may influence child health. The follow up of children from mothers with asthma suggests they are at greater risk of developing asthma, have alterations in microvascular structure that may contribute to a future risk of cardiovascular disease and epigenetic modifications in immune cell function. The current evidence suggests that appropriately managed asthma during pregnancy results in normal fetal growth and development. EXPERT OPINION: Clinical management of asthma during pregnancy needs significant improvement to prevent adverse outcomes for the fetus. The key to improving maternal and fetal outcomes is through education of health professionals and parents about controlling asthma during pregnancy.
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Asma/fisiopatología , Desarrollo Fetal/fisiología , Complicaciones del Embarazo/fisiopatología , Asma/complicaciones , Niño , Desarrollo Infantil/fisiología , Femenino , Humanos , Recién Nacido , Masculino , Placenta/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores SexualesRESUMEN
BACKGROUND: Maternal asthma during pregnancy is considered an environmental risk factor for asthma development in children. Immunoglobulin G (IgG) antibodies that are transferred from the mother to the fetus are known to act in a pro- or anti-inflammatory manner depending on their glycosylation status. OBJECTIVE: Using a mouse model, we examined how maternal allergic airway inflammation during pregnancy influenced offspring experimental asthma severity, as well as maternal and offspring serum IgG antibody glycosylation patterns. Additionally, the effects of maternal and offspring exposure to the same or different allergens were investigated. METHODS: Female mice were either sham sensitized or sensitized to casein (CAS) or ovalbumin (OVA) before mating. Subsequently, allergic lung inflammation was induced in pregnant dams via aerosol allergen challenge (sham, CAS or OVA). After weaning, pups were subjected to an experimental asthma protocol using OVA. Asn-297 IgG glycosylation was analysed in maternal and offspring serum. RESULTS: When mothers and offspring were sensitized to the same allergen (OVA-OVA), offspring had more severe experimental asthma. This was evidenced by altered antibody concentrations, increased bronchoalveolar lavage inflammatory cell influx and decreased lung tissue and lung draining lymph node regulatory T cell percentages. When mothers and offspring were sensitized to different allergens (CAS-OVA), this phenotype was no longer observed. Additionally, maternal serum from allergic mothers had significantly higher levels of pro-inflammatory IgG1, shown by decreased galactosylation and sialylation at the Asn-297 glycosylation site. Similar glycosylation patterns were observed in the serum of adult allergic offspring from allergic mothers. CONCLUSIONS AND CLINICAL RELEVANCE: We observed a strong association between maternal experimental asthma during pregnancy, increased offspring airway inflammation and pro-inflammatory IgG glycosylation patterns in mothers and offspring. IgG glycosylation is not a standard measurement in the clinical setting, and we argue that it may be an important parameter to include in future clinical studies.
Asunto(s)
Asma/inmunología , Inmunoglobulina G/inmunología , Exposición Materna/efectos adversos , Complicaciones del Embarazo/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunología , Animales , Asma/patología , Femenino , Glicosilación , Ratones , Ratones Endogámicos BALB C , Embarazo , Complicaciones del Embarazo/patología , Efectos Tardíos de la Exposición Prenatal/patologíaRESUMEN
OBJECTIVE: To examine maternal preexisting type 2 diabetes (T2D) and gestational diabetes mellitus (GDM) on risk of childhood asthma. STUDY DESIGN: This retrospective birth cohort study included 97â554 singletons born in 2007-2011 within hospitals from a single integrated healthcare system. Children were prospectively followed from age 5 until December 31, 2017, using electronic medical records. Relative risks of childhood asthma associated with maternal diabetes in utero were estimated by hazard ratios using Cox regression adjusting for potential confounders. RESULTS: There were 3119 children (3.2%) who were exposed to preexisting T2D and 9836 (10.1%) to GDM. Among mothers with GDM, 3380 (34.4%) were dispensed antidiabetic medication during pregnancy. During a median of 7.6 years (IQR, 6.3-9.0 years) after birth, 15â125 children (15.5%) were diagnosed with asthma after age 5. Maternal diabetes interacted with maternal asthma history to affect child's asthma risk (P = .05). Among children without maternal asthma (n = 89â487), the adjusted hazard ratios for childhood asthma were 1.21 (95% CI, 1.08-1.36; P < .001) for exposure to T2D, 1.12 (95% CI, 1.01-1.25; P = .04) for GDM requiring antidiabetic medications, and 1.01 (95% CI, 0.93-1.10; P = .82) for GDM not requiring medications compared with no diabetes during pregnancy. The corresponding hazard ratios were 1.53 (95% CI, 1.19-1.96; P < .001), 1.11 (95% CI, 0.65-1.46; P = .44), and 0.84 (95% CI, 0.66-1.08; P = .17) among children without maternal asthma (n = 8067). Gestational age at GDM diagnosis was not associated with childhood asthma (P = .27). CONCLUSIONS: The risk of childhood asthma was predominately observed for exposure to preexisting T2D, small for GDM requiring medication, and not increased for GDM not requiring medication during pregnancy, compared with no diabetes during pregnancy.
Asunto(s)
Asma/epidemiología , Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Niño , Preescolar , Estudios de Cohortes , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Gestacional/tratamiento farmacológico , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Embarazo , Estudios Retrospectivos , Factores de RiesgoRESUMEN
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.