Risk Of Childhood Asthma Research Articles

Revisiting the Hispanic Health Paradox: The Relative Contributions of Nativity, Country of Origin, and Race/Ethnicity to Childhood Asthma

This study examined the relationship between race and Hispanic ethnicity, maternal and child nativity, country of origin and asthma among 2,558 non-Hispanic white and Hispanic children across 65 Los Angeles neighborhoods. A series of two-level multilevel models were estimated to examine the independent effects of race, ethnicity, and country of origin on childhood asthma. Lifetime asthma prevalence was reported among 9% of children, with no significant differences between Hispanics and non-Hispanic whites overall. However, in fully adjusted models, Hispanic children of non-Mexican origin reported higher odds of asthma compared to non-Hispanic white children. A protective nativity effect was also observed among children of foreign born mothers compared to US born mothers. Our study provides evidence in support of the heterogeneity of childhood asthma by Hispanic ethnicity and maternal nativity. These findings suggest moving beyond solely considering racial/ethnic classifications which could mask subgroups at increased risk of childhood asthma.

Maternal folate exposure in pregnancy and childhood asthma and allergy: a systematic review

Adequate folate status in early pregnancy is critical to prevent congenital malformations, yet little is known about whether exposure to folate, specifically folic acid supplementation beyond the recommended dose, influences chronic health outcomes. The link between maternal folate levels and risk of childhood asthma and allergic disease has been investigated in 10 large prospective cohort studies that reported conflicting results. While the majority of studies reported no association, those supporting a positive relationship found a small increase in risk that was generally transient in nature, confined to early childhood, and associated with folic acid supplementation in late pregnancy. This systematic review presents background information on maternal folate exposure and childhood asthma, synthesizes the current epidemiologic evidence in the context of the methodological differences among studies and their potential limitations, and offers direction for future research.

Fish and fish oil intake in relation to risk of asthma: a systematic review and meta-analysis.

Although laboratory studies suggest that long-chain n-3 polyunsaturated fatty acids (LCn3PUFAs) may reduce risk of asthma, epidemiological data remain controversial and inconclusive. We quantitatively reviewed the epidemiological studies published through December 2012 in PubMed and EMBASE by using a fixed-effects or random-effects model. Eleven studies, comprised of 99,093 individuals (3,226 cases), were included in the final dataset. Of them, 7 studies examined associations between intake of fish or LCn3PUFA and risk of asthma: 4 studies in children (996 cases from 12,481 children) and 3 in adults (1,311 cases from 82,553 individuals). Two studies (69 cases from 276 infants) investigated LCn3PUFA levels in mothers’ milk, and two studies assessed maternal fish consumption (786 cases from 2,832 individuals) during lactation and/or plasma LCn3PUFA levels during pregnancy (64 cases from 951 infants) in relation to offspring’s asthma. The pooled relative risk of child asthma were 0.76 (95% CI, 0.61–0.94) for fish consumption and 0.71 (95% CI, 0.52–0.96) for LCn3PUFA intake. No statistically significant association was found in studies among adults. Epidemiological data to date indicate that fish or LCn3PUFA intake may be beneficial to prevent asthma in children. Further studies are needed to establish causal inference and to elucidate the potential mechanisms.

Serum vitamin E concentrations at 1 year and risk of atopy, atopic dermatitis, wheezing, and asthma in childhood: the PASTURE study

Prospective studies investigating the role of serum vitamin E concentrations during early life in the development of childhood allergies and asthma are limited. To study the associations between serum vitamin E concentrations at first year of life and longitudinal development of atopy, atopic dermatitis, wheeze, and asthma up to 6 years of age. The setting was the PASTURE study, a multicenter prospective birth cohort study in five European rural settings. Children of 1133 mothers recruited during pregnancy were followed from birth with measurement of serum vitamin E levels at year 1 and repeated assessments of serum immunoglobulin E antibodies (year 1, 4.5, 6), atopic dermatitis, wheezing symptoms, and asthma (year 1, 1.5, 2, 3, 4, 5, 6). At 6 years of age, 66% and 82% of the original 1133 subjects underwent blood test for IgE and answered the questionnaire, respectively. We did not observe any statistically significant associations between serum vitamin E concentrations at year 1 and the endpoints, but borderline inverse associations between alpha tocopherol and wheezing without cold (OR 0.45, 95% CI 0.19-1.09) and any wheezing symptom (OR 0.52, 95% CI 0.27-1.02). Serum vitamin E concentrations at year 1 were not associated with allergies or asthma by 6 years of age. While further prospective studies with repeated assessments of vitamin E during early life may clarify its putative role in the development of the diseases, it is also possible that the antioxidant hypothesis in the development of allergies and asthma does not hold.

Maternal intake of vitamins A, E and K in pregnancy and child allergic disease: a longitudinal study from the Danish National Birth Cohort

Fat-soluble vitamins A, E and K have been shown to play roles in immunity and inflammation, but studies on child allergic disease have been few and inconsistent. The aim of the present study was to examine the relationship between maternal intake of vitamins A, E and K in mid-pregnancy and child asthma and allergic rhinitis. We used data on 44594 mother-child pairs from the Danish National Birth Cohort. Maternal intake of fat-soluble vitamins was calculated based on the information from a validated FFQ completed in mid-pregnancy. At 18 months, interviews with the mothers were conducted to evaluate doctor-diagnosed child asthma. At age 7 years, we assessed child asthma and allergic rhinitis using questions from the International Study of Asthma and Allergies in Childhood questionnaire and by national registries on hospital contacts and medication use. Current asthma was defined as asthma diagnosis and wheeze in the past 12 months by maternal report. We calculated multivariable risk ratios and 95% CI by comparing the highest v. lowest quintile (Q) of maternal vitamin A, E and K intake in relation to child allergic disease outcomes. Maternal total vitamin K intake was directly associated with ever admitted asthma (Q5 v. Q1: 1·23, 95% CI 1·01, 1·50) and current asthma at 7 years (Q5 v. Q1: 1·30, 95% CI 0·99, 1·70). Weak inverse associations were present for maternal vitamin A and E intake during pregnancy with child allergic rhinitis. Maternal vitamin K intake during pregnancy may increase the risk of child asthma, and should be explored further on a mechanistic level. Conversely, maternal vitamin A and E intake may protect against child allergic rhinitis.

Investigation of childhood asthma morbidity rate and risk factors in Wuhan area

Objective To investigate the relative risk factors of childhood asthma. Methods An investigation was carried out by random sampling in Wuhan city. The investigation included questionnaire and clinic examination. The studied atients were the infants and children aged from 0 to 14 years old, and the sample size was of 4132 cases. The relative analysis between childhood asthma and other allergic diseases was carried out, and high risk factors were screened by multiple Logistic regression analysis with SPSS 17.0 software. Results There were 173 children with asthma, and the accumulation incidence rate was 4.2%, during which the rate of male children were higher than that of female children (4.8% vs 3.6%). Four years old was a key point, because the incidence rates of allergic rhinitis, eczema, drug allergy and food allergy were obviously increased after this point. The relative analysis results showed that allergic rhinitis was the first factor related to asthma (r=0.30, P<0.01), the second factor was eczema(r=0.24, P<0.01). The multiple Logistic regression analysis results showed that the risk factors of asthma were listed by risk degree as allergic rhinitis (OR=5.61, 95%CI: 3.88-8.13), repeated respiratory infection (OR=3.99, 95%CI: 2.78-5.74), eczema (OR=3.38, 95%CI: 2.35-4.87), drug allergy (OR=2.20, 95%CI: 1.44-3.36), asthma history of the first degree relative (OR=3.14, 95%CI: 1.60-6.13) and asthma history of the second degree relative (OR=1.92, 95%CI: 1.13-3.28). Conclusions Allergic rhinitis and repeated respiratory infection are the first and the second important risk factors of asthma. It is necessary to enhance the health management of the related children to prevent them from developing asthma. Key words: Asthma; Risk factor; Allergic rhinitis; Respiratory tract infection; Asthma history; Child

Prenatal folic acid and risk of asthma in children: a systematic review and meta-analysis

Childhood asthma has become a critical public health problem because of its high morbidity and increasing prevalence. The impact of nutrition and other exposures during pregnancy on long-term health and development of children has been of increasing interest. We performed a systematic review and meta-analysis of the association of folate and folic acid intake during pregnancy and risk of asthma and other allergic outcomes in children. We performed a systematic search of 8 electronic databases for articles that examined the association between prenatal folate or folic acid exposure and risk of asthma and other allergic outcomes (eg, allergy, eczema, and atopic dermatitis) in childhood. We performed a meta-analysis by using a random-effects model to derive a summary risk estimate of studies with similar exposure timing, exposure assessment, and outcomes. Our meta-analysis provided no evidence of an association between maternal folic acid supplement use (compared with no use) in the prepregnancy period through the first trimester and asthma in childhood (summary risk estimate: 1.01; 95% CI: 0.78, 1.30). Because of substantial heterogeneity in exposures and outcomes, it was not possible to generate summary measures for other folate indicators (eg, blood folate concentrations) and asthma or allergy-related outcomes; however, the preponderance of primary risk estimates was not elevated. Our findings do not support an association between periconceptional folic acid supplementation and increased risk of asthma in children. However, because of the limited number and types of studies in the literature, additional research is needed.

Neonatal Bilirubin Levels and Childhood Asthma in the US Collaborative Perinatal Project, 1959–1965

Evidence shows that asthma originates in early life. Studies have found that phototherapy and/or neonatal jaundice may be associated with asthma. We investigated the association between neonatal bilirubin levels and childhood asthma without phototherapy intervention in the Collaborative Perinatal Project, a multicenter prospective cohort study conducted in the United States from 1959 to 1965. A total of 54,795 livebirths were included, and 40,063 children were followed up until 7 years of age or older. Total serum bilirubin (TSB) levels were examined at 48 hours postpartum in newborns with birthweights of 2,250 g or more. Information on asthma and other diseases through age 7 years was summarized and confirmed by a group of pediatricians and child neurologists. Among 28,807 term infants, the overall prevalence of asthma was 5.26%. Risks of asthma increased with both maximum TSB levels and TSB levels at 48 hours postpartum (P for trend < 0.01). Neonatal maximum TSB levels greater than 15 mg/dL were associated with a 61% increase in the risk of childhood asthma (odds ratio = 1.61, 95% confidence interval: 1.04, 2.08) after adjustment for confounders. In this prospective cohort study of infants born at a time when phototherapy was unavailable, neonatal hyperbilirubinemia was associated with an increased risk of childhood asthma.

17q21 locus and ORMDL3: an increased risk for childhood asthma

Genetic variations in the 17q21 locus are strongly associated with childhood nonallergic asthma. Expression of the 17q21 genes, orosomucoid like 3 (ORMDL3) and gasdermin B (GSMDB), is affected by these disease-associated variants. However, until recently, no functional connection of the protein products coded by these genes with asthma was known. Lately, it has been identified that ORMDL3 function has been related to various cellular processes that could be relevant for the pathogenesis of asthma. This includes dysregulation of the unfolded protein response (UPR) associated with airway remodeling and also an effect of ORMDL3-dysregulated sphingolipid synthesis on bronchial hyperreactivity. These findings are crucial for a better understanding of the mechanism of childhood asthma and may lead to asthma therapeutics that target pathways previously not thought to be related to this common pediatric respiratory disease. Furthermore, this may validate the unbiased genome-wide association study (GWAS) approach for complex diseases such as asthma, to better define pathomechanisms and drug targets.

Polymorphism of the rs1800896 IL10 promoter gene protects children from post-bronchiolitis asthma

Viral bronchiolitis is a major cause of hospitalization in infancy, with increased asthma risk in later childhood. However, the principal mechanisms behind post-bronchiolitic asthma have remained unclear. Previously, different cytokine polymorphisms have been associated with asthma occurrence, but no previous follow-up study has investigated cytokine polymorphisms in relation to post-bronchiolitic asthma. We hypothesized that former bronchiolitis patients with cytokine gene variants associating with Th2 cell up-regulation are at asthma risk at preschool age. Our emphasis was in IL10 rs1800896, since IL-10 has an important role in immune tolerance, and lower production of IL-10 has been associated with Th2-type immunology, and accordingly, with increased asthma risk. IL10 rs1800896, IFNG rs2430561, and IL18 rs1872387 polymorphims and their associations with asthma and allergy were studied in 135 preschool-aged children hospitalized for bronchiolitis at age 0-6 months. Parents were interviewed to record asthma and allergy from infancy to present. At age 6.4 years (mean), asthma was present in 17(12.6%), atopic eczema in 47(34.8%) and allergic rhinitis in 36(26.7%) children. IL10 rs1800896 SNP associated significantly with asthma; only 1/32 (3.1%) of those with G/G genotype had asthma (P = 0.04). In logistic regression adjusted for gender, age and atopy, the carriage of allele A (rs1800896) was a significant risk factor for preschool asthma. IFNG rs2430561 or IL18 rs1872387 SNP's had no associations with asthma or allergy. In conclusion, IL10 rs1800896 SNP was significantly associated with preschool asthma after severe lower respiratory tract infection in early infancy.

GSTP1is a hub gene for gene-air pollution interactions on childhood asthma

There is growing evidence that multiple genes and air pollutants are associated with asthma. By identifying the effect of air pollution on the general population, the effects of air pollution on childhood asthma can be better understood. We conducted the Taiwan Children Health Study (TCHS) to investigate the influence of gene-air pollution interactions on childhood asthma. Complete monitoring data for the ambient air pollutants were collected from Taiwan Environmental Protection Agency air monitoring stations. Our results show a significant two-way gene-air pollution interaction between glutathione S-transferase P (GSTP1) and PM10 on the risk of childhood asthma. Interactions between GSTP1 and different types of air pollutants have a higher information gain than other gene-air pollutant combinations. Our study suggests that interaction between GSTP1 and PM10 is the most influential gene-air pollution interaction model on childhood asthma. The different types of air pollution combined with the GSTP1 gene may alter the susceptibility to childhood asthma. It implies that GSTP1 is an important hub gene in the anti-oxidative pathway that buffers the harmful effects of air pollution.

Predictors of exclusive breastfeeding at least 8 weeks among Asian and Native Hawaiian or other Pacific Islander race subgroups in Hawaii, 2004-2008.

Breastfeeding is nurturing, cost-effective, and beneficial for the health of mother and child. Babies receiving formula are sick more often and are at higher risk for childhood obesity, diabetes, asthma, and other conditions compared with breastfed children. National and international organizations recommend exclusive breastfeeding for 6 months. Exclusive breastfeeding in Asian and Native Hawaiian or Other Pacific Islander (NHOPI) subgroups is not well characterized. Data from the 2004-2008 Hawaii Pregnancy Risk Assessment Monitoring System, a population-based surveillance system on maternal behaviors and experiences before, during, and after pregnancy, were analyzed for 8,508 mothers with a recent live birth. We examined exclusive breastfeeding status for at least 8 weeks. We calculated prevalence risk ratios across maternal race groups accounting for maternal and socio-demographic characteristics. The overall estimate of exclusive breastfeeding for at least 8 weeks was 36.3%. After adjusting for maternal age, pre-pregnancy weight, cesarean delivery, return to work/school, and self-reported postpartum depressive symptoms, the racial differences in prevalence ratios for exclusive breastfeeding for each ethnic group compared to Whites were: Samoan (aPR = 0.54; 95% CI 0.43-0.69), Filipino (aPR = 0.58; 95% CI 0.53-0.63), Japanese (aPR = 0.58; 95% CI 0.52-0.65), Chinese (aPR = 0.64; 95% CI 0.58-0.70), Native Hawaiian (aPR = 0.67; 95% CI 0.61-0.72), Korean (aPR = 0.72; 95% CI 0.64-0.82), and Black (aPR = 0.79; 95% CI 0.65-0.96) compared to white mothers. Providers and community groups should be aware that just over one-third of mothers breastfeed exclusively at least 8 weeks with lower rates among Asian, NHOPI, and Black mothers. Culturally appropriate efforts to promote exclusive breastfeeding are recommended particularly among Asian subgroups that have high breastfeeding initiation rates that do not translate into high exclusivity rates.

The Impact of Birth Mode of Delivery on Childhood Asthma and Allergic Diseases—a Sibling Study

C Almqvist, S Cnattingius, P Lichtenstein, C Lundholm. Clin Exp Allergy. 2012;42(9):1369–1376 To investigate if cesarean delivery (CD) increases the risk of asthma in childhood and adolescence. The study population consisted of a cohort of 87 555 Swedish siblings (175 110 children). This register-based cohort study linked the study population to the Swedish Prescribed Drug Register and the National Patient Data Register. These databases contain prescriptions and inpatient and outpatient visit diagnoses for the majority of the study period. Asthma outcome variables, including medication and asthma diagnosis, were collected at the 10th or 13th year of life (age 10 for children born June 1996 through …

Use of Antibiotics During Pregnancy Increases the Risk of Asthma in Early Childhood

To investigate whether maternal use of antibiotics during pregnancy influences the development of asthma and eczema early in life.The Copenhagen Prospective Study on Asthma in Childhood (COPSAC), a birth cohort of 411 infants born between 1998 and 2001 to mothers with a history of asthma. The COPSAC data were supplemented by data from the Danish National Birth Cohort (DNBC) consisting of 101 042 pregnant women and their children recruited between 1997 and 2003. Both cohorts were followed prospectively for 5 years.History of maternal exposure to antibiotics in the third trimester was obtained during the first COPSAC enrollment visit. Asthma exacerbations were defined as need for oral prednisolone, high-dose inhaled corticosteroids (ICS), or asthma hospitalization. In the DNBC data, investigators defined maternal antibiotic use as at least 1 filled antibiotic prescription during pregnancy. Asthma was defined as either an asthma hospitalization or an ICS prescription filled at least once.In the COPSAC birth cohort, children of mothers who used antibiotics during the third trimester were at a significantly increased risk of developing early asthma exacerbation (hazard ratio [HR]: 1.98). Maternal use of antibiotics in the third trimester did not influence the child’s risk of eczema. An increased risk of asthma after maternal antibiotic exposure was confirmed via DNBC analysis: children of mothers exposed to antibiotics during pregnancy were at a higher risk of asthma hospitalization (HR: 1.17) and ICS use (HR: 1.18). For each additional antibiotic prescription filled during pregnancy, a progressively increased risk of asthma was demonstrated (adjusted P = .01).An increased risk of asthma was found in a prospectively followed cohort of children whose mothers received antibiotics during the third trimester of pregnancy. This finding was confirmed in an unselected national birth cohort of mothers. No increased risk of eczema was detected in either cohort.Perturbing the native microbiome in the lungs has been increasingly shown to affect both asthma development and clinical control. This study adds to the mounting evidence suggesting that changing the balance between beneficial and pathogenic bacteria may play a role in the development of asthma. In a prospective analysis, these investigators implicate in utero exposure to maternal antibiotics as a significant risk factor in early asthma pathogenesis.

Persistent Pollen Exposure During Infancy Is Associated With Increased Risk of Subsequent Childhood Asthma and Hayfever

B Erbas, AJ Lowe, CJ Lodge. Clin Exp Allergy. 2013;43(3):337–343 To determine if exposure to higher concentrations of pollen within the first 3 to 6 months of life increases the risk of eczema, sensitization to food or aeroallergens at 2 years old, and asthma or hayfever at 6 to 7 years old. The study used the Melbourne Atopy Cohort Study, a longitudinal birth cohort study, comprising 620 participants who were enrolled before birth. Children were born between 1990 and 1994 and had a family history of …

Predicting risk for childhood asthma by prenatal, perinatal, and postnatal factors

Background: Symptoms of asthma start early in human life, important life and environmental factors cannot be studied in detail if the participants are preschool children or older. Aims: To investigate the early risk factors for childhood asthma and to develop a predictive model for the development of asthma by birth cohort study. Methods: A representative sample of mother-newborn pairs was obtained by multistage, stratified systematic sampling from the Taiwan national birth register in 2005. Home interviews at 6 months and 5 years of age were conducted to inquire potential risk factors and children's health status, respectively. Multivariate regression analysis was used to determine the risk factors for children asthma in predictive models. Area-under-curve (AUC) statistic from receiver-operating characteristic curve analysis was used to compare the ability of models to discriminate between children with and without asthma. Results: A total of 19,192 mother-newborn pairs completed the study satisfactorily. The prevalence of physician-diagnose asthma was 7.6% in boys and 5.5% in girls, respectively. Prenatal (parental atopy and socioeconomic status), perinatal (resident area and painting wall during pregnancy), and postnatal factors (mother with postpartum stress and children with atopic dermatitis (AD) before 6 months old) were chosen in predictive models by backward stepwise analysis. The highest predicted probability of asthma was 68.1% in boys and 76.1% in girls with above factors. The lowest probability was 7.7%, among boys and girls with none of above factors, respectively. Compared with AUCs of prenatal factor model and the model adding perinatal factors, model more adding postnatal factors provided significantly higher ability to discriminate between children with and without asthma. Conclusions: This investigation provides technique for predicting risk of childhood asthma by prenatal, perinatal, and postnatal factors that can be used for developing preventive strategy against asthma, especially among those children with AD and family history of atopy.

Use of acid-suppressive drugs in pregnancy and the risk of childhood asthma: bidirectional crossover study using the general practice research database.

BackgroundRecent studies have reported an association between maternal use of gastric acid-suppressive drugs during pregnancy and asthma in the offspring, but the association could have been confounded by unmeasured risk factors.ObjectiveWe assessed the association between the use of acid-suppressive drugs during pregnancy and the risk of developing childhood asthma using a bidirectional crossover design.MethodsMother–infant matched sets in the UK General Practitioners Research Database were used to identify children with a drug-treated asthma diagnosis during the years 2006–2010 who were matched to a sibling without asthma as controls. Primary exposure was use of any anti-suppressive drug during pregnancy, and subgroup analyses were conducted according to drug class (e.g. proton pump inhibitors or histamine 2 receptor antagonists) and trimester. Conditional logistic regression was used to estimate odds ratios (OR) with their corresponding 95 % confidence intervals (CIs).ResultsA total of 1,874 children with asthma and 1,874 control siblings were included in the analysis. The exposure rate among case and control pregnancies was 22 and 20 %, respectively. After adjustments for gender, birth order, mother’s age and general practice visits, the exposure to any gastric-acid suppressive drug during pregnancy slightly increased the risk for developing asthma (OR 1.23, 95 % CI 1.01–1.51; p = 0.042). A trend towards increased risks was observed for those who used proton pump inhibitors and/or histamine 2 receptor antagonists (adjusted OR 1.72, 95 % CI 1.00–2.98; p = 0.048).ConclusionsThese findings lend support to the emerging evidence that exposure to acid-suppressive drugs during pregnancy is associated with childhood asthma. More basic research is now warranted to investigate the mechanisms.Electronic supplementary materialThe online version of this article (doi:10.1007/s40264-013-0093-z) contains supplementary material, which is available to authorized users.

Prediction of Childhood Asthma Using Conditional Probability and Discrete Event Simulation

Asthma prevalence in children and adolescents in Spain is 10-17%. It is the most common chronic illness during childhood. Prevalence has been increasing over the last 40 years and there is considerable evidence that, among other factors, continued exposure to cigarette smoke results in asthma in children. No statistical or simulation model exist to forecast the evolution of childhood asthma in Europe. Such a model needs to incorporate the main risk factors that can be managed by medical authorities, such as tobacco (OR = 1.44), to establish how they affect the present generation of children. A simulation model using conditional probability and discrete event simulation for childhood asthma was developed and validated by simulating realistic scenario. The parameters used for the model (input data) were those found in the bibliography, especially those related to the incidence of smoking in Spain. We also used data from a panel of experts from the Hospital del Mar (Barcelona) related to actual evolution and asthma phenotypes. The results obtained from the simulation established a threshold of a 15-20% smoking population for a reduction in the prevalence of asthma. This is still far from the current level in Spain, where 24% of people smoke. We conclude that more effort must be made to combat smoking and other childhood asthma risk factors, in order to significantly reduce the number of cases. Once completed, this simulation methodology can realistically be used to forecast the evolution of childhood asthma as a function of variation in different risk factors.

Perinatal Tumor Necrosis Factor-α Production, Influenced by Maternal Pregnancy Weight Gain, Predicts Childhood Asthma

Innate immune responses marked by increases in tumor necrosis factor (TNF)-α have been associated with asthma but whether such alterations are evident before symptoms is not yet clear. To determine if prevalence of childhood asthma or asthma-related traits is predicted by perinatal innate immune status and if maternal factors related to pregnancy influence asthma prevalence and innate immune status. In the Tucson Infant Immune Study (a nonselected birth cohort), presence of eczema and wheezing in the child's first year and physician-diagnosed asthma through age 9 and asthma in the parents was obtained from parent-completed questionnaires. TNF-α, IL-6, IL-10, and IL-12 were measured in supernatants of LPS-stimulated peripheral blood mononuclear cells at birth and 3 months as was TNF-α in plasma. TNF-α single nucleotide polymorphisms were genotyped by Sequenom. Percent predicted FEV1/FVC was measured at age 9. Maternal weight gain during pregnancy and prepregnancy weight were ascertained from medical records. Infants with persistently elevated LPS-induced TNF-α at birth and 3 months were at increased risk for childhood asthma (odds ratio [OR], 4.1; confidence interval [CI], 1.9-8.8; n = 233; P = 0.0003) and had decreased FEV1/FVC ratios at age 9. Children with mothers in the top tertile for pregnancy weight gain had increased risk for asthma (OR, 3.4; CI, 1.7-6.9; n = 225; P = 0.001) and persistently elevated TNF-α in early life (OR, 2.9; CI, 1.4-8.2; n = 195; P = 0.013). These relations were independent of maternal asthma and rhinitis. Persistently elevated LPS-induced TNF-α production early in life acts as a predictive biomarker for childhood asthma, and excess pregnancy weight gain in the mother seems to contribute to both.

Prenatal alcohol exposure and childhood atopic disease: A Mendelian randomization approach

BackgroundAlcohol consumption in western pregnant women is not uncommon and could be a risk factor for childhood atopic disease. However, reported alcohol intake may be unreliable, and associations are likely to be confounded.ObjectiveWe aimed to study the relation between prenatal alcohol exposure and atopic phenotypes in a large population-based birth cohort with the use of a Mendelian randomization approach to minimize bias and confounding.MethodsIn white mothers and children in the Avon Longitudinal Study of Parents and Children (ALSPAC) we first analyzed associations between reported maternal alcohol consumption during pregnancy and atopic outcomes in the offspring measured at 7 years of age (asthma, wheezing, hay fever, eczema, atopy, and total IgE). We then analyzed the relation of maternal alcohol dehydrogenase (ADH)1B genotype (rs1229984) with these outcomes (the A allele is associated with faster metabolism and reduced alcohol consumption and, among drinkers, would be expected to reduce fetal exposure to ethanol).ResultsAfter controlling for confounders, reported maternal drinking in late pregnancy was negatively associated with childhood asthma and hay fever (adjusted odds ratio [OR] per category increase in intake: 0.91 [95% CI, 0.82-1.01] and 0.87 [95% CI, 0.78-0.98], respectively). However, maternal ADH1B genotype was not associated with asthma comparing carriers of A allele with persons homozygous for G allele (OR, 0.98 [95% CI, 0.66-1.47]) or hay fever (OR, 1.11 [95% CI, 0.71-1.72]), nor with any other atopic outcome.ConclusionWe have found no evidence to suggest that prenatal alcohol exposure increases the risk of asthma or atopy in childhood.