Risk Of Childhood Asthma Research Articles

Air Pollution and Family Related Determinants of Asthma Onset and Persistent Wheezing in Children: Nationwide Case-Control Study

To identify risk factors (air pollution and family related) for the onset of asthma and persistent wheezing in children.All Danish children born from 1997 to 2014 who were managed for asthma onset and persistent wheezing from the age of 1 year to 15 years by using a national registry based, matched case-control design.Children were managed in the Danish National Patient Register for the classification of asthma or persistent wheezing after hospital discharge, or with a minimum of 2 prescriptions for asthma medications. Information regarding concentration of air pollutants (several gases, aerosols, particular matter <2.5µm [PM2.5] and particular matter <10µm), parental asthma diagnoses and asthma medication prescriptions, maternal smoking habits, highest completed parental education, and parental income levels were collected and analyzed for hazard ratios (HRs).From 1997–2014, 3 192 785 children were included in the study, and 122 842 (3.84%) children developed asthma and/or persistent wheezing, with a mean age of development of 1.9 years. Maternal asthma had a higher risk than paternal asthma (adjusted HR): 1.72 (95% CI: 1.72 to 1.77) vs 1.51 (95% CI: 1.48 to 1.53)], but having 2 parents with asthma was associated with a 2.40-fold (2.34-fold to 2.47-fold) risk of childhood asthma. Maternal smoking during pregnancy (adjusted HR: 1.23 [1.18 to 1.28]) or quitting during pregnancy (HR: 1.20 [1.18 to 1.22]) increased the risk of childhood asthma. Exposures to PM2.5, particular matter <10µm, and nitrogen dioxide were also associated with development of asthma, with PM2.5 exposure being the most consistent. Higher parental income levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.85 [95% CI: 0.81 to 0.89) for the highest parental income level, compared with 1.04 (95% CI: 1.00 to 1.08) for the lowest parental income level]. Higher parental education levels, together and independently, had a reduced risk for childhood asthma (adjusted HR: 0.72 [95% CI: 0.69 to 0.75]) for the highest parental education level, compared with 0.98 [95% CI: 0.95 to 1.00] for the lowest parental education level).Parental history of asthma, higher levels of exposure to PM2.5, and maternal smoking during pregnancy all increase a child’s risk of developing asthma and persistent wheezing. High levels of parental educational attainment and income are associated with a lower risk of developing asthma and persistent wheezing in children.Strengths of this study include the use of a large database that covered 18 years. In this study, researchers did not analyze atopy, lung function, or inflammatory markers. A family history of asthma, tobacco exposure and environmental pollutants were confirmed as risk factors for asthma development. Smoking cessation campaigns and environmental strategies to decrease particulate matter exposure may reduce the number of children who develop asthma.

Delivery Mode and Gut Microbial Changes Correlate With an Increased Risk of Childhood Asthma

Children born via cesarean delivery have higher rates of childhood asthma. In this study, researchers examined associations between mode of delivery and the gut microbiome and tested for relationships between these changes and asthma risk.In this study, 700 children enrolled in the Copenhagen Prospective Studies on Asthma in Childhood 2010 birth cohort were included. Of these children, 151 were born via cesarean delivery, and 549 were born by vaginal delivery.In this study, researchers used a nested case-control design. All children had at least 1 fecal sample collected before 1 year of age (1 week, 1 month, and/or 1 year), analyzed by using 16S rRNA sequencing. A sparse partial least squares model was used to identify correlations between cesarean delivery and gut microbial composition at each time point. A “cesarean microbial score” was calculated for each time point, and a Kaplan-Meyer estimate was used to identify the cumulative asthma risk on the basis of delivery method and cesarean microbial score.Cesarean delivery was associated with significant increases in asthma prevalence at age 6 (odds ratio: 2.45). Cesarean delivery was also associated with marked differences in gut microbiota at 1 week and 1 month of age that became less significant by 1 year. The relationship between cesarean delivery and asthma depended on the microbiome composition at the age of 1 year. Of the children delivered by cesarean, only those who still had a significant cesarian microbiota signature at 1 year of age had higher rates of asthma at age 6 (odds ratio: 1.37).Cesarean delivery was associated with increased asthma risk but only in children who still had a cesarean gut microbial signature at 1 year of age.There is increasing evidence that early-life microbial exposures drive immune maturation and the risk of allergic diseases and asthma. With this study, the authors help to explain how delivery method influences asthma risk. In the results, it is indicated that cesarean delivery prevents the transfer of bacteria that produce short chain fatty acids in the gut to promote immune system regulation. With this observation, it is suggested that replacing these “missing bacteria” or their metabolites could reduce the risk for allergies and asthma in children born by cesarean delivery.

Intrapartum antibiotics and childhood asthma and allergic rhinitis: a retrospective cohort study.

This study aimed to evaluate the association between intrapartum antibiotics (IABX) and asthma and allergic rhinitis among children by ages 6, 8 and 10 years. Retrospective cohort. Data were collected though Kaiser Permanente Northern California's (KPNC) integrated healthcare system. Children were eligible if they were born in a KPNC hospital between 1997 and 2012 and stayed enrolled through age 6. Modified Poisson regressions with robust error variances were used to estimate risk ratios for IABX and each outcome at each follow-up age during two separate time periods: 1997-2004 (n = 91 739) and 2005-2012 (n = 108 314). Asthma and allergic rhinitis by ages 6, 8 and 10. The proportion of women receiving IABX increased drastically over the study period (from 4% in 1997 to 49% in 2011), while the incidence of asthma (8%) and allergic rhinitis (6%) stayed relatively stable. In adjusted models, risk ratios for the association between IABX and asthma and allergic rhinitis were largely compatible with the null, with some slightly elevated risk ratios observed. For births from 1997 to 2004, risk ratios for asthma were 1.08 (95% CI 1.00-1.17) at age 6, 1.05 (95% CI 0.97-1.15) at age 8, and 1.08 (95% CI 0.99-1.18) at age 10. For births from 2005 to 2012, risk ratios were 1.00 (95% CI 0.95-1.04) at age 6, 1.07 (95% CI 1.01-1.12) at age 8, and 1.11 (95% CI 1.03-1.20) at age 10. Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk. Exposure to intrapartum antibiotics is not a strong predictor of childhood asthma or allergic rhinitis risk.

Association of infant antibiotic exposure and risk of childhood asthma: A meta-analysis

BackgroundInfant antibiotic exposure may be associated with childhood asthma development. ObjectiveTo examine and detail this association considering potential confounders. Study designPubMed, EMBASE, Web of Science, and the Cochrane Library were searched for publications from January 2011 to March 2021. Eligible studies were independently reviewed to extract data and assess quality. Random effect model was used to pool odds ratio (OR) and corresponding 95% confidence intervals (CIs). ResultsA total of 52 studies were included. The association of infant antibiotic exposure and childhood asthma was statistically significant for overall analysis (OR, 1.37; 95% CI, 1.29–1.45) and for studies that addressed reverse causation (RC) and confounding by indication (CbI) (1.19; 95% CI, 1.11–1.28). Significance remained after stratification by adjustment for maternal antibiotic exposure, medical consultation, sex, smoke exposure, parental allergy, birth weight, and delivery mode. In detailed analyses, macrolides (OR, 1.56; 95% CI, 1.31–1.86), antibiotic course≥5 (OR, 1.79; 95% CI, 1.36–2.36), exposure within 1 week of birth (OR, 1.82; 95% CI, 1.34–2.47), asthma developed among 1–3 years (OR, 1.84; 95% CI, 1.63–2.08), short time lag between exposure and asthma onset (OR, 2.05; 95% CI, 1.91–2.20), persistent asthma (OR, 2.61; 95% CI, 1.49–4.59), and atopic asthma (OR, 2.14; 95% CI, 1.58–2.90) showed higher pooled estimates. ConclusionInfant antibiotic exposure is associated with increased risk of childhood asthma considering confounding, and the association varied with different settings of exposure and outcomes. This highlights the need for prevention of asthma after early antibiotic exposure. Heterogeneity among studies called for caution when interpretation.

Machine Learning for Predicting the Risk for Childhood Asthma Using Prenatal, Perinatal, Postnatal and Environmental Factors.

The prevalence rate for childhood asthma and its associated risk factors vary significantly across countries and regions. In the case of Morocco, the scarcity of available medical data makes scientific research on diseases such as asthma very challenging. In this paper, we build machine learning models to predict the occurrence of childhood asthma using data from a prospective study of 202 children with and without asthma. The association between different factors and asthma diagnosis is first assessed using a Chi-squared test. Then, predictive models such as logistic regression analysis, decision trees, random forest and support vector machine are used to explore the relationship between childhood asthma and the various risk factors. First, data were pre-processed using a Chi-squared feature selection, 19 out of the 36 factors were found to be significantly associated (p-value < 0.05) with childhood asthma; these include: history of atopic diseases in the family, presence of mites, cold air, strong odors and mold in the child’s environment, mode of birth, breastfeeding and early life habits and exposures. For asthma prediction, random forest yielded the best predictive performance (accuracy = 84.9%), followed by logistic regression (accuracy = 82.57%), support vector machine (accuracy = 82.5%) and decision trees (accuracy = 75.19%). The decision tree model has the advantage of being easily interpreted. This study identified important maternal and prenatal risk factors for childhood asthma, the majority of which are avoidable. Appropriate steps are needed to raise awareness about the prenatal risk factors.

Severe bronchiolitis profiles and risk of asthma development in Finnish children

Recent studies support the existence of several entities under the clinical diagnosis of bronchiolitis. Among infants with severe bronchiolitis, distinct profiles have been differentially associated with development of recurrent wheezing by age 3 years. However, their associations with actual asthma remain unclear. Our aim was to study the association between severe bronchiolitis profiles identified by using a clustering approach and childhood asthma. Among 408 children (aged <2 years) hospitalized with bronchiolitis in Finland (in 2008-2010), latent class analysis identified 3 bronchiolitis profiles: profile A(47%), characterized by history of wheezing and/or eczema, wheezing during acute illness, and rhinovirus infection; profile BC (38%), characterized by severe illness and respiratory syncytial virus infection; and profile D (15%), characterized by the least severely ill children, including mostly children without wheezing and with rhinovirus infection. The children were followed by questionnaire 4 years later (86% [n= 348]) and through a nationwide social insurance database 7 years later (99% [n= 403]). Current asthma at the 4- and 7-year follow-ups was defined by regular use (according to parental report and medical records) or purchase (according to the social insurance database) of asthma control medication. Compared with risk of current asthma associated with profile BC, we observed increased risk of current asthma associated with profile Aboth at the 4-year follow-up (age- and sex-adjusted odds ratio= 2.42 [95% CI= 1.23-4.75]) and at the 7-year follow-up (age- and sex-adjusted odds ratio= 3.14 [95% CI= 1.33-7.42]). No significant difference in asthma risk was observed between profile D and profile BC. These longitudinal results provide further support for an association between a distinct severe bronchiolitis profile (characterized by a history of wheezing and/or eczema and rhinovirus infection) and risk of development childhood asthma.

Interaction of maternal asthma history and plasma folate levels on child asthma risk in the Boston Birth Cohort.

Previous studies on maternal folate status during pregnancy and child asthma risk yielded mixed results, and few considered maternal asthma history, a known risk factor of childhood asthma. This study examined whether the role of maternal folate in childhood asthma differs by maternal asthma history and whether there is an interaction between the two factors. This study included 1948 mother-child dyads from the Boston Birth Cohort. Childhood asthma was defined based on physician diagnosis documented in electronic medical records, and maternal asthma was based on standard questionnaire interview. Maternal plasma folate level within a few days of delivery was measured by chemiluminescent immunoassay. Logistic regression models were applied to examine individual and joint associations of maternal asthma history and plasma folate level with childhood asthma, adjusting for other covariables. When stratified by maternal asthma history, an L-shaped relationship between maternal folate level and child asthma was observed in children born to mothers with asthma history (pinteraction = 0.03). The highest risk was found in children having maternal asthma history and low maternal folate level (odds ratio = 5.93; 95% confidence interval: 2.86-12.3) compared with children without maternal asthma history and with sufficient maternal folate levels. Sensitivity analyses using different definitions of asthma and stratified by major covariables yielded similar findings. In this US prospective high-risk birth cohort, maternal asthma history and low folate level interactively increased the risk of child asthma. If further confirmed, optimizing maternal folate levels during pregnancy may mitigate child asthma risk in the setting of maternal asthma history.

Association between vesicoureteral reflux, urinary tract infection and antibiotics exposure in infancy and risk of childhood asthma.

The use of antibiotics for treating infection in childhood and their association with increased risk of asthma remain controversial. Infants diagnosed with vesicoureteral reflux (VUR) belong to a unique population who are administered antibiotics for a long time and are susceptible to recurrent UTI. It is interesting to study the risk of asthma in these infants with or without VUR. Taiwanese children born between 2000 and 2007 were enrolled in population-based birth cohort study. Participants diagnosed with VUR and UTI within first year were classified into four groups (VUR, UTI, VUR and UTI, and control). We calculated follow-up person-years for each participant from the index date until the asthma diagnosis, their withdrawal from the insurance system (because of death or loss to follow-up), or till the end of 2008. The risk of asthma was compared between the 4 cohorts by using Cox proportional hazards model analysis, adjusted hazard ratio (aHR), and 95% confidence interval (95% CI). Children diagnosed with VUR (n = 350), UTI (n = 15542), VUR and UTI (n = 1696), and randomly selected controls (n = 17588) were enrolled. The overall rate of incidence of asthma was found to be 1.64-fold, 1.45-fold, and 1.17-fold higher in the UTI, VUR/UTI, and VUR cohorts than in the controls (5.60, 5.07, and 4.10 vs. 3.17 per 100 person-years), respectively. After adjusting the potential factors, the overall risk of asthma remained the highest in UTI (aHR: 1.74, 95% CI : 1.65 to 1.80) followed by VUR/UTI (aHR: 1.56, 95% CI : 1.40 to 1.75) and VUR cohorts (aHR: 1.25, 95% CI: 0.96 to 1.62). The incidence of asthma was higher in boys than in girls. The nationwide retrospective cohort study demonstrated that short-term therapeutic dose of antibiotics for UTI in infants with or without VUR has a positive correlation with the prevalence of childhood asthma. Significant risk of childhood asthma was not observed when VUR cohort was exposed to long-term low-dose of prophylactic antibiotics.

Self-Reported Physical Activity and Asthma Risk in Children

Increased physical activity (PA) may protect against asthma but PA can trigger asthma symptoms. To investigate relationships between moderate-to-vigorous PA (MVPA) assessed during routine care visits and incident asthma. For this retrospective cohort, 542,486 children between 2 and 17 years from 2010 to 2017 were included who had an MVPA assessment (exercise vital sign) during routine care visits. The association of MVPA and asthma was analyzed using Cox proportional hazards regression models as a function of age, with MVPA and body mass index (BMI) being time-varying factors, adjusted for race and ethnicity, socioeconomic status, and air pollution. The mean MVPA was 5.4 (standard deviation: 4.4) hours/week. Crude asthma incidence density rate (IDR) was highest in children with <1 hour/week of MVPA (IDR: 9.07, 95% confidence interval [CI]: 8.79, 9.36) and lowest in children engaging in 4 to 7 hours/week of MVPA (IDR: 6.55, 95% CI: 6.33, 6.77). In adjusted models, an increase in MVPA wasassociated with lower asthma risk in children reporting 0 hour/week of MVPA (hazard ratio: 0.981, 95% CI: 0.973, 0.990). In children with ≥8 hours/week of MVPA, an increase in MVPA was associated with higher asthma risk (1.005, 95% CI: 1.002, 1.009). There was no significant BMI by MVPA interaction. Increasing MVPA in children with low activity levels is associated with lower asthma risk; children reporting high levels of activity may experience greater asthma risk as their activity levels increase further. Understanding the role of PA in the development of asthma and assessing MVPA during routine care visits in children may help to develop targeted interventions and guide asthma management.

Consumption of differently processed milk products and the risk of asthma in children.

Consumption of unprocessed cow's milk has been associated with a lower risk of childhood asthma and/or atopy. Not much is known about differently processed milk products. We aimed to study the association between the consumption of differently processed milk products and asthma risk in a Finnish birth cohort. We included 3053 children from the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study. Asthma and its subtypes were assessed at the age of 5years, and food consumption by food records, at the age of 3 and 6months and 1, 2, 3, 4, and 5years. We used conventional and processing (heat treatment and homogenization)-based classifications for milk products. The data were analyzed using a joint model for longitudinal and time-to-event data. At the age of 5years, 184 (6.0%) children had asthma, of whom 101 (54.9%) were atopic, 75 (40.8%) were nonatopic, and eight (4.3%) could not be categorized. Consumption of infant formulas [adjusted hazard ratio (95% confidence intervals) 1.15 (1.07, 1.23), p<.001] and strongly heat-treated milk products [1.06 (1.01, 1.10), p=.01] was associated with the risk of all asthma. Consumption of all cow's milk products [1.09 (1.03, 1.15), p=.003], nonfermented milk products [1.08 (1.02, 1.14), p=.008], infant formulas [1.23 (1.13, 1.34), p<.001], and strongly heat-treated milk products [1.08 (1.02, 1.15), p=.006] was associated with nonatopic asthma risk. All these associations remained statistically significant after multiple testing correction. High consumption of infant formula and other strongly heat-treated milk products may be associated with the development of asthma.

Prenatal low-dose antibiotic exposure and children allergic diseases at 4 years of age: A prospective birth cohort study

BackgroundBased on a medical record or questionnaire survey approach, previous epidemiological studies have investigated associations between maternal antibiotic exposure during pregnancy and childhood allergic diseases. However, biomonitoring studies on the prenatal low-dose antibiotic exposure, mainly from the environment and contaminated food, and in relation to children allergic diseases, are missing. ObjectivesThis research aimed to examine the associations between prenatal low-dose antibiotic exposure measured at multiple time points and children current allergic diseases at 4 years of age. MethodsThe current study including 2453 mother-child pairs was based on the Ma’anshan Birth Cohort study. Selected 41 antibiotics and their two metabolites, which including human antibiotics (HAs), preferred as human antibiotics (PHAs), veterinary antibiotics (VAs) and preferred as veterinary antibiotics (PVAs), in urine samples from 2453 pregnant women were biomonitored through liquid chromatography-triple quadrupole tandem mass spectrometry. Information on children current allergic diseases were collected via validated questionnaires. Generalized estimating equation were used to explore the associations between the repeated measurements of maternal urinary antibiotic over three trimesters and current allergic diseases in children. ResultsThe detection rates of nine individual antibiotics in the three trimester during pregnancy are greater than 10%, and the 90th percentile concentration of the detected antibiotics ranges from 0.07 to 22.34 µg/g, and the 95th percentile concentration ranges from 0.17 to 59.57 µg/g. Among the participants, each one-unit concentration increment of sulfamethazine (adjusted OR=1.28, 95% CI: 1.10, 1.49, P-FDR=0.014) in the first trimester and ciprofloxacin (adjusted OR=1.17, 95% CI: 1.07, 1.28, P-FDR=0.008) in the second trimester were associated with an increased risk of current eczema in children. In the third trimester, each one-unit concentration increment of oxytetracycline (adjusted OR=1.90, 95% CI: 1.30, 2.78, P-FDR=0.014) was associated with an increased risk of current asthma in children. Gender-stratified analyses demonstrated that no gender differences were observed in the associations between prenatal antibiotic exposure and current allergic diseases in children. ConclusionsMaternal exposure to certain specific VAs or PVAs (sulfamethazine, ciprofloxacin and oxytetracycline) in different trimesters was associated with an increased risk of current asthma and current eczema in 4-year-old children. No gender differences were found in these associations. Further studies are warranted to confirm our findings and explore the potential mechanisms.

Breastfeeding and risk of childhood asthma: a systematic review and meta-analysis.

ObjectiveTo investigate the relationship between breastfeeding and the development of paediatric asthma.MethodsA systematic review and meta-analysis was conducted with MEDLINE, Embase, CINAHL and ProQuest Nursing and Allied Health source databases. Retrospective/prospective cohorts in children aged <18 years with breastfeeding exposure reported were included. The primary outcome was a diagnosis of asthma by a physician or using a guideline-based criterion. A secondary outcome was asthma severity.Results42 studies met inclusion criteria. 37 studies reported the primary outcome of physician-/guideline-diagnosed asthma, and five studies reported effects on asthma severity. Children with longer duration/more breastfeeding compared to shorter duration/less breastfeeding have a lower risk of asthma (OR 0.84, 95% CI 0.75–0.93; I2 = 62.4%). Similarly, a lower risk of asthma was found in children who had more exclusive breastfeeding versus less exclusive breastfeeding (OR 0.81, 95% CI 0.72–0.91; I2=44%). Further stratified analysis of different age groups demonstrated a lower risk of asthma in the 0–2-years age group (OR 0.73, 95% CI 0.63–0.83) and the 3–6-years age group (OR 0.69, 95% CI 0.55–0.87); there was no statistically significant effect on the ≥7-years age group.ConclusionThe findings suggest that the duration and exclusivity of breastfeeding are associated with a lower risk of asthma in children aged <7 years.

Association of blood trihalomethane concentrations with asthma among U.S. Children: NHANES 2005-2012

BACKGROUND AND AIM: Population studies show that use of swimming pools is associated with risk of asthma and allergic diseases among children. However, few studies have examined exposure to disinfection by-products (DBP) from water chlorination with risk of asthma. To explore the associations between blood trihalomethane (THM) concentrations (a biomarker of DBP) and asthma among U.S. children and assess to what extent the association is modified by tobacco smoke exposure. METHODS: We included 2,359 children aged 12-19 years with measured blood concentrations of four THMs at baseline: chloroform (TCM), bromodichloromethane (BDCM), dibromochloromethane (DBCM), and bromoform (TBM) from the National Health and Nutrition Examination Surveys 2005-2012. Logistic regression models were fitted to assess the odds ratios (ORs) and 95% confidence intervals (CIs) for the association of THM concentrations (three or four categories) with the risk of self-reported lifetime and curent asthma. RESULTS:After adjusting for potential confounders, blood DBCM concentration was associated with a greater risk of ever asthma among all children (OR=1.54; 95% CI: 1.07, 2.21, comparing the extreme exposure categories). The relation was stronger among children exposed to tobacco smoke (OR=3.96; 95% CI: 1.89, 8.30, comparing the extreme exposure categories). We also found positive relationships between Br-THMs and risk of ever asthma (OR=3.28; 95% CI: 1.43, 7.53, comparing the extreme quartiles of exposure) and between DBCM and Br-THMs and risk of current asthma among children with tobacco smoke exposure (OR=3.72; 95% CI: 1.40, 9.89 and 3.79; 95% CI: 1.22, 11.79, resperctively, comparing the extreme exposure categories). CONCLUSIONS:Our findings provide novel evidence that exposure to disinfection by-products is associated with a greater risk of asthma in children, particularly among those exposed to tobacco smoke. KEYWORDS: Biomarkers of exposure, Water quality, Respiratory outcomes, Asthma, Environmental epidemiology

DEHP in house dust in relation to housing characteristics in the CHILD Cohort Study

BACKGROUND AND AIM: Di-(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, is ubiquitous in indoor environments. DEHP was the most prevalent phthalate measured in house dust in the CHILD Cohort, and was found to be associated with increased risk of childhood asthma in our recent case-cohort sub-analysis. Our aim was to identify possible sources of DEHP in dust in this cohort. METHODS: CHILD is a multi-center Canadian birth cohort study. DEHP levels were measured in house dust samples collected at age 3-4 months. Housing characteristics were assessed by Research Assistants at the time of dust collection and families completed an environment-related questionnaire. Using dust data from 726 homes involved in the case-cohort study, factors such as vinyl flooring, vinyl furniture and mattress coverings were investigated as potential indicators of DEHP sources. Mass-based DEHP concentrations were log-transformed and multivariable linear regression models were used to assess the associations, controlling for possible confounders such as household income and age of home. RESULTS:The quantity of vinyl/plastic furniture in homes was significantly associated with DEHP concentration. Higher DEHP concentrations were observed in homes with older flooring ( 3 years) in the mother’s bedroom. Homes with vinyl flooring in both the kitchen and bathroom showed higher levels of DEHP on average than those without vinyl flooring but the effect decreased after adjusting for the age of home as a proxy for unmeasured related confounders. The presence of mold, suggestive of dampness, was also associated with higher DEHP concentrations. No significant difference in DEHP concentrations in dust was observed between homes with and without mattress covering on children’s beds. CONCLUSIONS:DEHP in house dust is associated with specific housing characteristics. These findings could provide guidance to the public on the choice of building materials and furnishings, as well as in the development of policies, aimed at improving the indoor environment. KEYWORDS: phthalates, children’s environmental health, endocrine disrupting chemicals, chemical exposures, built environment

Evidence for causal associations between prenatal and postnatal antibiotic exposure and asthma in children, England.

Higher risks of asthma have been observed in children with prenatal exposure to antibiotics and during early life compared with those who have not. However, the causality of such associations is unclear. To assess whether exposure to antibiotics in early life had a causal effect in increasing the risk of asthma in children diagnosed at 5-8years of life, and the impact in the target population. Data were from electronic health records and questionnaires for children and their mothers in the Born in Bradford birth cohort. Exposure variables were prescriptions of systemic antibiotics to the mother during pregnancy (prenatal) and to the children at 0-24months of life (postnatal). We assessed the association in 12,476 children with several approaches to deal with different sources of bias (triangulation): the interactions with mother's ethnicity, mode of delivery, and between prenatal and postnatal exposures; dose-response; and estimated the population attributable risk. There was an association between prenatal exposure at 7-27days before the child's birth and asthma (adjusted OR=1.40; 1.05, 1.87), but no association with the negative control exposure (before pregnancy) (adjusted OR=0.99 (0.88, 1.12)). For postnatal exposure, the adjusted OR was 2.00 (1.71, 2.34), and for sibling analysis, it was 1.99 (1.00, 3.93). For postnatal exposure, the risk of asthma increased with the number of prescriptions. The observed effect of both exposures was lower among children with mothers of Pakistani ethnicity, but inconclusive (p>.25). The interaction between prenatal and postnatal exposures was also inconclusive (p=.287). The population attributable risk of postnatal exposure for asthma was 4.6% (0.1% for prenatal). We conclude that the associations between both late-pregnancy prenatal exposure to antibiotics and postnatal exposure to antibiotics and an increased risk of asthma are plausible and consistent with a causal effect.

P–724 The association between use of assisted reproductive techniques and childhood asthma: a Swedish nationwide register-based cohort study

Abstract Study question Are the previously reported greater risks of childhood asthma in children conceived by assisted reproductive techniques due to the intervention or unmeasured parental confounding? Summary answer After accounting for both measured and unmeasured parental factors we found no indication that the use of assisted reproductive techniques increases children’s risk of asthma. What is known already Several earlier studies have reported a higher risk of childhood asthma among children conceived by ART. However, only one previous study has attempted a sibling comparison to account for infertility as well as parental background factors, and their findings need to be replicated. Little is thus known on what underlies the higher risk of childhood asthma. Study design, size, duration In this nationwide register-based cohort, we identified all 1,671,532 live births between 1997 and 2013 in the Swedish Medical Birth Register (MBR) and followed them to the end of 2018. Participants/materials, setting, methods Infertility and ART use were ascertained from IVF clinic reporting, clinical diagnosis, and maternal self-report during the first antenatal visit. Childhood asthma was identified from diagnosis in hospitalization and outpatient specialist care records, and dispensations of asthma medication. Cox proportional hazard regression was used to estimate the association of ART and asthma in the population, in children of couples with known infertility, and in a sample of siblings conceived with and without ART (differentially exposed). Main results and the role of chance Of the 1,671,532 live births in the cohort, 11.7% were born to couples with known infertility, and 3.5% were conceived with ART. Compared with all other children, children conceived by ART had a small, elevated risk of asthma (adjusted hazard ratio (aHR)=1.14, 95% Confidence interval (CI) 1.11 to 1.16). When the comparison was restricted to children of couples with known infertility the difference in risk was even smaller (aHR=1.07, 95% CI 1.05 to 1.10), and in the comparison of siblings conceived with and without ART no difference in risk was seen (aHR=0.98, 95% CI 0.86 to 1.13). Among children conceived with ART, those in which intra-cytoplasmic sperm injection (ICSI) had been used had a slightly lower risk of asthma (aHR=0.93, 95% CI 0.90 to 0.97), and no difference in risk was seen between use of fresh and frozen-thawed embryo transfer. Limitations, reasons for caution Sibling comparison is sensitive to potential misclassification, unmeasured confounding and carryover effects, so should be interpreted with this in mind. Differences in treatment implementation across time and settings could affect the ability to extrapolate the conclusions to another clinical context (where e.g., single-embryo transfer policy is not implemented). Wider implications of the findings: This study found a modestly elevated risk of asthma in children conceived with ART to be largely explained by confounding from parental background factors. There were further no indications of adverse influence from increasingly utilized ART procedures such as ICSI or embryo-freezing, with respect to asthma in childhood. Trial registration number Not applicable

Association of the Risk of Childhood Asthma at Age 6 With Maternal Allergic or Immune-Mediated Inflammatory Diseases: A Nationwide Population-Based Study.

Objective: This study aimed to assess the associations of the risk of asthma diagnosed in children aged 6 years or younger and having maternal immune-mediated inflammatory diseases (IMIDs), including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), inflammatory myositis, rheumatoid arthritis (RA), Sjögren's syndrome (SS), ankylosing spondylitis (AS), and autoimmune thyroiditis.Methods: A total of 628,878 singleton newborns documented in 2006–2009 and followed up for at least 6 years were identified. Overall, 153,085 (24.3%) children developed asthma at the age of ≤ 6 years. Two groups of maternal ages, i.e., <35 and ≥35 years, were evaluated. The associations of the risk of asthma occurring in children who were 6 years old or younger and had maternal IMIDs were examined.Results: The risk of asthma increased in children whose mothers had SLE [odds ratio (OR), 1.13; 95% confidence intervals (CI), 1.00–1.27; p = 0.04), RA (OR, 1.21; 95% CI, 1.07–1.38; p = 0.003), inflammatory myositis (OR, 1.41; 95% CI, 1.12–1.74; p = 0.003), asthma (OR, 1.58; 95% CI, 1.52–1.63), allergic rhinitis (OR, 1.30; 95% CI, 1.28–1.32), or atopic dermatitis (OR, 1.07; 95% CI, 1.02–1.12). Conversely, this increased risk was not observed in children whose mothers had AS (OR, 1.02; 95% CI, 0.87–1.20), SS (OR, 0.96; 95% CI, 0.86–1.07), SSc (OR, 1.28; 95% CI, 0.77–2.14), or autoimmune thyroiditis (OR, 1.01; 95% CI, 0.95–1.07). Other risk factors of childhood asthma included high urbanization level, preterm birth, and low birth weight.Conclusion: The risk of childhood asthma at 6 years of age increased in children whose mothers suffered from SLE, RA, inflammatory myositis, asthma, allergic rhinitis, and atopic dermatitis.

Research Progress on Association between Early-Life Exposure to Phthalates and Childhood Asthma

Phthalates (Phthalic acid esters, PAEs) as a common industrial products, a growing body of scientific evidences indicate that exposure to PAEs in early life has a potential harmful effect on the growth and development of organisms in later life, among these hazards, exposure to PAEs widely may increase the risk of asthma in children, which has attracted more and more attention. This article introduced the reasons and effects of PAEs exposure in early life, the relationships between early-life PAEs exposure and childhood asthma from the perspectives of epidemiological and animal studies and the underlying mechanisms of action.

Prenatal tobacco exposure and risk of asthma and allergy outcomes in childhood.

Harmful effects of prenatal tobacco exposure and possible interaction with 17q12-21 genetic variants have been shown for some asthma outcomes in childhood, whereas findings related to allergy outcomes are more inconsistent. This study aimed to examine the effect of prenatal tobacco exposure and relation to 17q12-21 genotype on a wide array of asthma and allergy-related outcomes in early childhood. Prenatal tobacco exposure was determined by maternal smoking during the third trimester (yes/no) in 411 children from the phenotyped Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) birth cohort with clinical follow-up to age 7 years. The rs7216389 single nucleotide polymorphism was used as main representative of the 17q12-21 locus. Asthma end-points included asthma diagnosis, exacerbations, episodes with troublesome lung symptoms and lower respiratory tract infections, spirometry, plethysmography, bronchial responsiveness to methacholine, exercise and cold dry air. Allergy-related endpoints included aeroallergen sensitisation, allergic rhinitis, fractional exhaled nitric oxide, blood eosinophil count and urine eosinophil protein X levels. Statistical analyses were done using Cox regression, linear regression, logistic regression and quasi-Poisson regression. Prenatal tobacco exposure increased the risk of asthma (adjusted hazard ratio (aHR) 2.05, 95% CI 1.13-3.73; p=0.02), exacerbations (aHR 3.76, 95% CI 2.05-6.91; p<0.001), number of LRTIs (adjusted incidence rate ratio 1.87, 95% CI 1.34-2.55; p<0.001), and was associated with decreased spirometry indices (forced expiratory volume in 1 s (FEV1) adjusted mean difference (aMD) -0.07 L, 95% CI -0.13- -0.005 L, p=0.03; maximal mid-expiratory flow aMD -0.19 L·s-1, -0.34- -0.04 L·s-1, p=0.01) and increased bronchial responsiveness to methacholine (provocative dose of methacholine causing a 20% drop in FEV1 adjusted geometric mean ratio 0.55, 95% CI 0.31-0.96; p=0.04). In contrast, there was no association with any allergy-related end-points. The effect on asthma depended on 17q12-21 genotype with an increased risk only among children without risk alleles. Prenatal tobacco exposure was associated with asthma dependent on 17q12-21 genotype and with exacerbations, lung function and bronchial responsiveness, but not with any allergy-related outcomes. This suggests that tobacco exposure in utero leads to adverse lung developmental/structural effects rather than susceptibility to develop allergy and type 2 inflammation.

Postnatal probiotics administration does not prevent asthma in children, but using prebiotics or synbiotics may be the effective potential strategies to decrease the frequency of asthma in high-risk children - a meta-analysis of clinical trials.

The role of probiotics, prebiotics, and synbiotics in preventing asthma and other allergic diseases has been widely explored via many randomized controlled trials. However, the results on the effect of their supplementation during infancy to the incidence of allergic rhinitis or asthma, are conflicting.The study was designed to bring to light the potential effects of pro-, pre-, and synbiotics supplementation in early childhood with regard to the future occurrence of allergic diseases. The results of randomized controlled trials were searched for in several medical data bases. The study protocol was prepared in accordance with PRISMA guidelines and applied a Revised Cochrane risk-of-bias tool for randomized trials. Two writers were designed to perform studies selection. Eleven randomized controlled trials, among 1659 children (525 in the probiotic group, 342 in prebiotic group, 128 in synbiotic group and 833 in control groups) were analyzed. There was no difference in asthma risk development between the groups that received probiotics or placebo. We observed lower risk of asthma in children receiving prebiotic and synbiotic than in control groups. The current study indicates that probiotics supplementation in the first months after birth does not decrease the risk of asthma development in the first years of life in high-risk children, although prebiotics and synbiotics may be the potential preventive factors that reduce the incidence of asthma in children.