Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Risk Factors for Wheezing in Primary School Children in Bursa, Turkey No effect of probiotics on respiratory allergies: a seven-year follow-up of a randomized controlled trial in infancy. Randomized, Double-Blind, Placebo-Controlled Trial of Probiotics for Primary Prevention: No Clinical Effects of Lactobacillus GG Supplementation Infant sleeping environment and asthma at 7 years: a prospective cohort study. Maternal intake of vitamin D during pregnancy and risk of recurrent wheeze in children at 3 y of age. Differences between infants and adults in the social aetiology of wheeze. The ALSPAC Study Team. Avon Longitudinal Study of Pregnancy and Childhood. Incidence and prognosis of asthma and wheezing illness from early childhood to age 33 in a national British cohort Vitamin D supplementation in pregnancy, prenatal 25(OH)D levels, race, and subsequent asthma or recurrent wheeze in offspring: Secondary analyses from the Vitamin D Antenatal Asthma Reduction Trial Maternal fish consumption during pregnancy and risks of wheezing and eczema in childhood: The Generation R Study Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. Prenatal origins of bronchiolitis: protective effect of optimised asthma management during pregnancy Maternal smoking in pregnancy and asthma in preschool children: a pooled analysis of eight birth cohorts. Asthma symptoms in early childhood--what happens then? Maternal vitamin D intake during pregnancy and early childhood wheezing. Allergen exposure in infancy and the development of sensitization, wheeze, and asthma at 4 years. The natural course of atopic dermatitis from birth to age 7 years and the association with asthma. Maternal smoking during pregnancy, prematurity and recurrent wheezing in early childhood. Probiotics prevent IgE-associated allergy until age 5 years in cesarean-delivered children but not in the total cohort. Predictors of asthma three years after hospital admission for wheezing in infancy. Maternal B vitamin intake during pregnancy and wheeze and eczema in Japanese infants aged 16-24 months: the Osaka Maternal and Child Health Study. Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial. The impact of early nutrition on incidence of allergic manifestations and common respiratory illnesses in children.
RATIONALE Virus-induced wheezing episodes in infancy often precede the development of asthma . Whether infections with specific viral pathogens confer differential future asthma risk is incompletely understood . OBJECTIVES To define the relationship between specific viral illnesses and early childhood asthma development . METHODS A total of 259 children were followed prospect ively from birth to 6 years of age . The etiology and timing of specific viral wheezing respiratory illnesses during early childhood were assessed using  nasal lavage , culture , and multiplex reverse transcriptase-polymerase chain reaction . The relationships of these virus-specific wheezing illnesses and other risk factors to the development of asthma were analyzed . MEASUREMENTS AND MAIN RESULTS Viral etiologies were identified in 90 % of wheezing illnesses . From birth to age 3 years , wheezing with respiratory syncytial virus ( RSV ) ( odds ratio [ OR ] , 2.6 ) , rhinovirus ( RV ) ( OR , 9.8 ) , or both RV and RSV ( OR , 10 ) was associated with increased asthma risk at age 6 years . In Year 1 , both RV wheezing ( OR , 2.8 ) and aeroallergen sensitization ( OR , 3.6 ) independently increased asthma risk at age 6 years . By age 3 years , wheezing with RV ( OR , 25.6 ) was more strongly associated with asthma at age 6 years than aeroallergen sensitization ( OR , 3.4 ) . Nearly 90 % ( 26 of 30 ) of children who wheezed with RV in Year 3 had asthma at 6 years of age . CONCLUSIONS Among outpatient viral wheezing illnesses in infancy and early childhood , those caused by RV infections are the most significant predictors of the subsequent development of  asthma  at age 6 years in a high-risk birth cohort Background Wheezing is the most common symptom of childhood respiratory tract illnesses . It is important not only for its associated acute morbidity , but also for the fact that early childhood wheezing confers a high risk for asthma . Epidemiological studies from various countries show that 10–15 % of children < 1 year of age and 25 % of children < 5 years of age have wheezing-associated respiratory tract illness , and one-third of these children develop asthma later in life . Methods In this retrospective study , we evaluated the association between a history of wheezing and prenatal , postnatal , familial , and environmental risk factors in 858 7-year-old children , r and omly selected from seven primary schools in Bursa , Turkey , by means of an easy-to-underst and question naire form . Among these children , 12.4 % had a history of early transient wheezing , 7.1 % had persistent wheezing , and 7.7 % had late onset wheezing ; 72.8 % had no wheezing symptoms and 33.3 % of children who experienced wheezing during the first 3 years of life had physician-diagnosed asthma . Results Notable risk factors associated with wheezing were as follows : male gender , lower socioeconomic status , premature birth , maternal smoking during pregnancy , bottle-feeding before 2 months of age , dampness and mold at home , hospitalization due to any respiratory illness in infancy , history of croup between 6 months and 5 years of age , frequent upper respiratory infections during the first 3 years of life , allergic eczema in the child , and any allergic disease in the mother or siblings . Conclusion This study shows that the high rates of reported wheezing in the 858 primary school children in Bursa are clearly attributable to important risk factors that have long been recognized and discussed by research ers worldwide , and this suggests that all efforts at primary prevention may be insufficient BACKGROUND Supplementation with the probiotic Lactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy . This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age . OBJECTIVE To evaluate whether perinatal and infant supplementation with L. reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects . METHODS A r and omized , placebo-controlled trial with oral supplementation with L. reuteri ATCC 55730 ( 1 × 10(8 ) CFU ) during the last month of gestation and through the first year of life comprising 232 families with allergic disease , of whom 184 completed a 7-yr follow-up . The primary outcomes at 7 yr of age were allergic disease and skin prick test reactivity ( Clinical Trials.gov ID NCT01285830 ) . RESULTS The prevalence of asthma ( 15 % in the probiotic vs. 16 % in placebo group ) , allergic rhinoconjunctivitis ( 27 % vs. 20 % ) , eczema ( 21 % vs. 19 % ) and skin prick test reactivity ( 29 % vs. 26 % ) was similar in the probiotic and placebo group . Growth indices and gastrointestinal symptoms were similar in the two groups . No severe adverse events were reported . CONCLUSION The effect of L. reuteri on sensitization and IgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age . Thus , the effect of L. reuteri on the immune system seems to be transient . Administration of L. reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects BACKGROUND . The value of probiotics for primary prevention is controversial . Published trials vary considerably in study design and the applied probiotics , thereby limiting comparability of the results . OBJECTIVE . The purpose of this trial was to study the preventive effect of the probiotic Lactobacillus GG on the development of atopic dermatitis . METHODS . In a double-blind , placebo-controlled prospect i ve trial , 105 pregnant women from families with ≥1 member ( mother , father , or child ) with an atopic disease were r and omly assigned to receive either the probiotic Lactobacillus GG ( American Type Culture Collection 53103 ; 5 × 109 colony-forming units of Lactobacillus GG twice daily ) or placebo .  Ninety-four families ( 89.5 % ) completed the trial . The supplementation period started 4 to 6 weeks before expected delivery , followed by a postnatal period of 6 months . The primary end point was the occurrence of atopic dermatitis at the age of 2 years . Secondary outcomes were severity of atopic dermatitis , recurrent episodes of wheezing bronchitis , and allergic sensitization at the age of 2 years . RESULTS . Atopic dermatitis was diagnosed in 14 ( 28 % ) of 50 in the Lactobacillus GG group and in 12 ( 27.3 % ) of 44 in the placebo group . The risk of atopic dermatitis in children on probiotics relative to placebo was 0.96 ( confidence interval 0.38–2.33 ) . Severity of atopic dermatitis was comparable between the 2 groups . Notably , children with recurrent ( ≥5 ) episodes of wheezing bronchitis were more frequent in the Lactobacillus GG group ( 26 % ; n = 13 ) , as compared with the placebo group ( 9.1 % ; n = 4 ) . No difference was observed between both groups in total immunoglobulin E concentrations or numbers of specific sensitization to inhalant allergens . CONCLUSIONS . Supplementation with Lactobacillus GG during pregnancy and early infancy neither reduced the incidence of atopic dermatitis nor altered the severity of atopic dermatitis in affected children but was associated with an increased rate of recurrent episodes of wheezing bronchitis . Therefore , Lactobacillus GG can not be generally recommended for primary prevention OBJECTIVES We investigated the role of  infant bedding items , as part of a composite bedding environment , in the development of  childhood wheezing .  METHODS This prospect i ve cohort investigation involved 863 children who participated in an infant survey in 1988 and an asthma study in Tasmania , Australia , in 1995 . The derived 3 composite infant bedding categories corresponded to increasing numbers of house dust mite (HDM)-rich bedding items used . Outcomes measured included recent and frequent wheezing . RESULTS Composite infant bedding used was associated with recent wheezing . Effects increased at increasing levels of HDM-rich bedding items used . Effects were further enhanced by home environmental factors of bedroom heating , recent bedroom painting , and absence of bedroom carpeting . When any 2 or more of these environmental factors were present , a strong dose-response relationship was evident . CONCLUSIONS Our results show that bedding exposures in infancy are prospect ively associated with  childhood wheezing  and that home environmental conditions may modify this association BACKGROUND Vitamin D deficiency and asthma are common at higher latitudes . Although vitamin D has important immunologic effects , its relation with asthma is unknown . OBJECTIVE We hypothesized that a higher maternal intake of vitamin D during pregnancy is associated with a lower risk of  recurrent wheeze in children at 3 y of age . DESIGN The participants were 1194 mother-child pairs in Project Viva-a prospect i ve prebirth cohort study in Massachusetts . We assessed the maternal intake of vitamin D during pregnancy from a vali date d food-frequency question naire . The primary outcome was recurrent wheeze , ie , a positive asthma predictive index ( > or=2 wheezing attacks among children with a personal diagnosis of eczema or a parental history of asthma ) . RESULTS The mean ( + /-SD ) total vitamin D intake during pregnancy was 548 + /- 167 IU/d . By age 3 y , 186 children ( 16 % ) had recurrent wheeze . Compared with mothers in the lowest quartile of daily intake ( median : 356 IU ) , those in the highest quartile ( 724 IU ) had a lower risk of having a child with recurrent wheeze [ odds ratio ( OR ) : 0.39 ; 95 % CI : 0.25 , 0.62 ; P for trend < 0.001 ] . A 100-IU increase in vitamin D intake was associated with lower risk ( OR : 0.81 ; 95 % CI : 0.74 , 0.89 ) , regardless of whether vitamin D was from the diet ( OR : 0.81 ; 95 % CI : 0.69 , 0.96 ) or supplements ( OR : 0.82 ; 95 % CI : 0.73 , 0.92 ) . Adjustment for 12 potential confounders , including maternal intake of other dietary factors , did not change the results . CONCLUSION In the northeastern United States , a higher maternal intake of vitamin D during pregnancy may decrease the risk of recurrent wheeze in early childhood OBJECTIVES : To compare the relation between relative deprivation , its associated social risk factors and the prevalence of wheeze in infancy and in adulthood . DESIGN : A cross sectional population study . SETTING : The three District Health Authorities of Bristol . SUBJECTS : A r and om sample of 1954 women stratified by age and housing tenure to be representative of women with children < 1 in Great Britain and selected from the Avon Longitudinal Study of Pregnancy and Childhood ( ALSPAC ) . MAIN OUTCOME MEASURES : The prevalence of wheeze for infants at six months after birth and for their mothers and fathers at eight months postpartum . Potential mediators of the relation between  relative deprivation  and wheeze measured were overcrowded living conditions , number of other siblings in the household , damp or mouldy housing conditions , maternal and paternal smoking behaviour , and infant feeding practice . RESULTS : 63.4 % ( 1239 ) of the sample lived in owner occupied/mortgaged accommodation ( relatively affluent ) and 36.6 % ( 715 ) lived in council house/rented accommodation ( relatively deprived ) . Wheeze was significantly more likely for infants living in council house/rented accommodation ( chi 2 = 15.93 , df = 1 , p < 0.0001 ) , their mothers ( chi 2 = 9.28 , df = 1 , p < 0.001 ) and their fathers ( chi 2 = 7.41 , df = 1 , p < 0.01 ) . For those living in council house/rented accommodation backward stepwise logistic regression analyses showed that infants with other siblings in the household were significantly more likely to wheeze ( OR = 1.83 , 95 % CI = 1.27 , 2.65 ) , as were infants whose mothers smoked ( OR = 1.82 , 95 % CI = 1.30 , 2.55 ) and those who were breast fed for less than three months ( OR = 0.66 , 95 % CI = 0.44 , 0.98 ) . Mothers with a partner who smoked were significantly more likely to report wheeze ( OR = 1.73 , 95 % CI = 1.05 , 2.85 ) . There was no independent association between the social factors included in the analysis and the likelihood of wheeze for fathers . CONCLUSIONS : This study identified differences in the social factors associated with a higher prevalence of wheeze in infancy and in adulthood ; results suggested that this symptom was commonly linked to infection in infancy , but not in adulthood . While environmental tobacco smoke was associated with a higher prevalence of wheeze in infancy and in adulthood , this does not necessarily indicate a common underlying mechanism ; possible explanations are discussed Abstract Objective : To describe the incidence and prognosis of wheezing illness from birth to age 33 and the relation of incidence to perinatal , medical , social , environmental , and lifestyle factors . Design : Prospect i ve longitudinal study . Setting : Engl and , Scotl and , and Wales . Subjects : 18 559 people born on 3 - 9 March 1958 . 5801 ( 31 % ) contributed information at ages 7 , 11 , 16 , 23 , and 33 years . Attrition bias was evaluated using information on 14 571 ( 79 % ) subjects . Main outcome measure : History of asthma , wheezy bronchitis , or wheezing obtained from interview with subjects ' parents at ages 7 , 11 , and 16 and reported at interview by subjects at ages 23 and 33 . Results : The cumulative incidence of wheezing illness was 18 % by age 7 , 24 % by age 16 , and 43 % by age 33 . Incidence during childhood was strongly and independently associated with pneumonia , hay fever , and eczema . There were weaker independent associations with male sex , third trimester antepartum haemorrhage , whooping cough , recurrent abdominal pain , and migraine . Incidence from age 17 to 33 was associated strongly with active cigarette smoking and a history of hay fever . There were weaker independent associations with female sex , maternal albuminuria during pregnancy , and histories of eczema and migraine . Maternal smoking during pregnancy was weakly and inconsistently related to childhood wheezing but was a stronger and significant independent predictor of incidence after age 16 . Among 880 subjects who developed asthma or wheezy bronchitis  from birth to age 7 , 50 % had attacks in the previous year at age 7 ; 18 % at 11 , 10 % at 16 , 10 % at 23 , and 27 % at 33 . Relapse at 33 after prolonged remission of childhood wheezing was more common among current smokers and atopic subjects . Conclusion : Atopy and active cigarette smoking are major influences on the incidence and recurrence of wheezing during adulthood . Key messages Incidence of wheezing illness at all ages was strongly and consistently related to a history of hay fever or eczema ( atopy ) . Associations with maternal smoking during pregnancy , abdominal pain , and migraine were largely confined to those without atopy Active smoking was a powerful and potentially avoidable risk factor for wheeze starting in adult life among both atopic and non-atopic subjects A quarter of the children with a history of asthma or wheezy bronchitis by age 7 reported wheeze in the past year at age 33 Recurrence of wheezing after prolonged remis- sion during late adolescence was strongly associ- ated with atopy and cigarette smoking Background Nutrient trials differ from drug trials because participants have varying circulating levels at entry into the trial . Objective We sought to study the effect of a vitamin D intervention in pregnancy between subjects of different races and the association between 25‐hydroxyvitamin D3 ( 25[OH]D ) levels in pregnancy and the risk of asthma/recurrent wheeze in offspring . Methods The Vitamin D Antenatal Asthma Reduction Trial is a r and omized trial of pregnant women at risk of having children with asthma r and omized to 4400 international units/d vitamin D or placebo plus 400 international units/d vitamin D. Asthma and  recurrent wheezing until age 3 years were recorded . Results African American ( AA ) women ( n = 312 ) had lower initial levels of 25(OH)D ( mean [ SD ] , 17.6 ng/mL [ 8.3 ng/mL ] ) compared with non‐AA women ( n = 400 ; 27.1 ng/mL [ 9.7 ng/mL ] , P < .001 ) . No racial difference was found from vitamin D supplementation in pregnancy on asthma/recurrent wheezing in offspring ( P for interaction = .77 ) . Having an initial level of greater than 30 ng/mL and being r and omized to the intervention group was associated with the lowest risk for asthma/recurrent wheeze by age 3 years compared with having an initial level of less than 20 ng/mL and receiving placebo ( adjusted odds ratio , 0.42 ; 95 % CI , 0.19‐0.91 ) . Conclusions We did not find differences between AA and non‐AA mothers in the effect of maternal vitamin D supplementation and asthma/recurrent wheeze in offspring at 3 years . Maternal supplementation of vitamin D , particularly in mothers with initial 25(OH)D levels of greater than 30 ng/mL , reduced asthma/recurrent wheeze in the offspring through age 3 years , suggesting that higher vitamin D status beginning in early pregnancy is necessary for asthma/recurrent wheeze prevention in early life . Graphical abstract Figure . No Caption available Background / Objectives : Maternal fish consumption during pregnancy might influence the fetal immune system through anti-inflammatory effects of omega-3 fatty acids , and might affect the risks of childhood asthma and atopy . In Generation R , a prospect i ve cohort study in the Netherl and s , we examined the associations of first trimester fish consumption with childhood wheezing and eczema in the first 4 years of life . Methods : In total , 2976 mothers completed a 293-item semiquantitative food frequency question naire covering dietary intake in the first trimester . The occurrence of wheezing and eczema was yearly assessed by question naires . Results : Median weekly fish consumption was 83 ( 95 % range 0–316 ) grams per week . We observed no consistent associations of maternal total- , lean- or fatty-fish consumption during pregnancy with the risks of childhood wheezing . Maternal shellfish consumption of 1–13 g per week was associated with overall increased risks of childhood wheezing and eczema ( OR 1.20 ( 1.04 , 1.40 ) and OR 1.18 ( 1.01 , 1.37 ) , respectively ) . Maternal fatty fish consumption of 35–69 g per week was associated with increased overall risks of childhood eczema ( OR 1.17 ( 1.00 , 1.38 ) ) , but maternal total- or lean-fish consumption was not . Conclusions : During pregnancy , shellfish consumption was associated with increased risks of wheezing and eczema , while fatty fish consumption was associated with a higher risk of eczema only . Maternal total fish or lean fish consumption were not associated with wheezing or eczema . Further studies are needed to replicate these findings and to explore underlying mechanisms IMPORTANCE Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring , but the preventive effect of vitamin D supplementation to pregnant women is unknown . OBJECTIVE To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring . DESIGN , SETTING , AND PARTICIPANTS A double-blind , single-center , r and omized clinical trial conducted within the Copenhagen Prospect i ve Studies on Asthma in Childhood 2010 cohort . Enrollment began March 2009 with a goal of 708 participants , but due to delayed ethical approval , only 623 women were recruited at 24 weeks of pregnancy . Follow-up of the children ( N = 581 ) was completed when the youngest child reached age 3 years in March 2014 . INTERVENTIONS Vitamin D3 ( 2400 IU/d ; n = 315 ) or matching placebo tablets ( n = 308 ) from pregnancy week 24 to 1 week postpartum . All women received 400 IU/d of vitamin D3 as part of usual pregnancy care . MAIN OUTCOMES AND MEASURES Age at onset of persistent wheeze in the first 3 years of life . Secondary outcomes included number of episodes of troublesome lung symptoms , asthma , respiratory tract infections , and neonatal airway immunology . Adverse events were assessed . RESULTS Of the 581 children ,  persistent wheeze  was diagnosed during the first 3 years of life in 47 children ( 16 % ) in the  vitamin D3 group and 57 children ( 20 % ) in the  control group .  Vitamin D3 supplementation was not associated with the risk of persistent wheeze , but the number of episodes of troublesome lung symptoms was reduced , and the airway immune profile was up-regulated ( principal component analysis , P = .04 ) . There was no effect on additional end points . Intrauterine death was observed in 1 fetus ( < 1 % ) in the vitamin D3 group vs 3 fetuses ( 1 % ) in the control group and congenital malformations in 17 neonates ( 5 % ) in the vitamin D3 group vs 23 neonates ( 8 % ) in the control group . [ table : see text ] . CONCLUSIONS AND RELEVANCE The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years . However , interpretation of the study is limited by a wide CI that includes a clinical ly important protective effect . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00856947 Objective Maternal asthma is the most common chronic disease complicating pregnancy and is a risk factor for bronchiolitis in infancy . Recurrent episodes of bronchiolitis are strongly associated with the development of childhood asthma . Methods We conducted a follow-up study of infants born to women with asthma who completed a double-blind r and omised controlled trial during pregnancy . In this trial , pregnant women with asthma were assigned to treatment adjustment by an algorithm using clinical symptoms ( clinical group ) or the fraction of exhaled nitric oxide ( FeNO group ) and we showed that the FeNO group had significantly lower asthma exacerbation rates in pregnancy . Results 146 infants attended the 12-month follow-up visit . Infants born to mothers from the FeNO group were significantly less likely to have recurrent episodes of bronchiolitis in the first year of life ( OR 0.08 , 95 % CI 0.01 to 0.62 ; p=0.016 ) as compared with the clinical group . Conclusions Optimised management of asthma during pregnancy may reduce recurrent episodes of bronchiolitis in infancy , which could potentially modulate the risk to develop or the severity of emerging childhood asthma RATIONALE Although epidemiological studies suggest that exposure to maternal smoking during fetal and early life increases the risk of  childhood wheezing and asthma  , previous studies were not able to differentiate the effects of prenatal from postnatal exposure . OBJECTIVES To assess the effect of exposure to maternal smoking only during pregnancy on  wheeze and asthma among preschool-age children . METHODS A pooled analysis was performed based on individual participant data from eight European birth cohorts . Cohort-specific effects of maternal smoking during pregnancy , but not during the first year , on wheeze and asthma at 4 to 6 years of age were estimated using logistic regression and then combined using a r and om effects model . Adjustments were made for sex , parental education , parental asthma , birth weight , and siblings . MEASUREMENTS AND MAIN RESULTS Among the 21,600 children included in the analysis , 735 children ( 3.4 % ) were exposed to maternal smoking exclusively during pregnancy but not in the first year after birth . In the pooled analysis , maternal smoking only during pregnancy was associated with wheeze and asthma at 4 to 6 years of age , with adjusted odds ratios of 1.39 ( 95 % confidence interval , 1.08 - 1.77 ) and 1.65 ( 95 % confidence interval , 1.18 - 2.31 ) , respectively . The likelihood to develop wheeze and asthma increased statistically significantly in a linear dose-dependent manner in relation to maternal daily cigarette consumption during the first trimester of pregnancy . CONCLUSIONS Maternal smoking during pregnancy appears to increase the risk of wheeze and asthma among children who are not exposed to maternal smoking after birth AIM To study the outcome in early adulthood for children with early asthma symptoms  and to analyse the factors associated with current asthma . METHODS In a prospect i ve study , we have re-investigated 89/101 children who were hospitalized before the age of two years due to wheezing . The children were investigated using a question naire and allergy and bronchial hyper-responsiveness tests at the age of 17 - 20 years and compared with age-matched controls . RESULTS In the cohort , 43 % had had asthma symptoms in the preceding 12 months compared with 15 % in the control group . The strongest risk factors for asthma were current allergy , bronchial hyper-responsiveness and female gender . Female gender and passive smoking in infancy were independent infantile risk factors . In addition to female gender , two pathways led to current asthma : an allergic pathway from family atopy via the development of allergy and another pathway from early passive smoking via hyper-responsiveness and active smoking . CONCLUSION In children with early wheezing disorder , current allergy , bronchial hyper-responsiveness and female gender were the strongest risk factors for asthma in early adulthood , while female gender and passive smoking in infancy were independent infantile risk factors . The effects of early passive smoking persist longer than previously reported BACKGROUND Maternal intake of vitamin D in pregnancy is a potentially modifiable but understudied risk factor for the development of asthma in children . OBJECTIVE We investigated whether maternal vitamin D intake in pregnancy is associated with decreased risks of  wheezing symptoms in young children . DESIGN Subjects were from a birth cohort recruited in utero with the primary objective of identifying associations between maternal diet during pregnancy and asthma and allergies in children . A r and om sample of 2000 healthy pregnant women was recruited while attending antenatal clinics at the Aberdeen Maternity Hospital , Scotl and , at approximately 12 wk gestation . Maternal vitamin D intake was ascertained from a food-frequency question naire completed at 32 wk of gestation . The main outcome measures were wheezing symptoms , spirometry , bronchodilator response , atopic sensitization , and exhaled nitric oxide at 5 y. RESULTS Respiratory details through 5 y and maternal food-frequency- question naire data were available for 1212 children . In models adjusted for potential confounders , including the children 's vitamin D intake , a comparison of the highest and lowest quintiles of maternal total vitamin D intake conferred lower risks for ever wheeze [ odds ratio ( OR ) : 0.48 ; 95 % CI : 0.25 , 0.91 ] , wheeze in the previous year ( OR : 0.35 ; 95 % CI : 0.15 , 0.83 ) , and persistent wheeze ( OR : 0.33 ; 95 % CI : 0.11 , 0.98 ) in 5-y-old children . In addition , lower maternal total vitamin D intakes in pregnancy were also associated with decreased bronchodilator response ( P = 0.04 ) . No associations were observed between maternal  vitamin D intakes and spirometry or exhaled nitric oxide concentrations . CONCLUSION Increasing maternal vitamin D intakes during pregnancy may decrease the risk of wheeze symptoms in early childhood BACKGROUND The relationship between mite and pet allergen exposure in infancy and the subsequent development of sensitization and asthma is complex . OBJECTIVE We prospect ively investigated the effect of allergen exposure at 3 months of age on the development of sensitization , wheeze , and physician-diagnosed asthma in the first 4 years of life in a birth cohort of children with and without an atopic mother . METHODS Children participated in the Prevention and Incidence of Asthma and Mite Allergy study .  Allergen exposure at 3 months of age was determined from mattress dust sample s. Specific IgE to inhalant allergens was measured at 4 years of age , and information about wheeze and physician-diagnosed asthma was collected with yearly question naires . RESULTS Mite and cat allergen exposure in infancy were associated with an increased risk of specific sensitization to house dust mite and cat , respectively , at 4 years of age . There were borderline significant associations between cat allergen exposure and persistent wheeze in the total study population and between dog allergen exposure and persistent wheeze in children with a nonatopic mother . In children with an atopic mother , there was some indication of a positive association between mite allergen exposure and physician-diagnosed asthma . CONCLUSION Early house dust mite and cat allergen exposure might lead to sensitization and , in case of cat allergen exposure , to persistent wheeze . Early mite and dog allergen exposure might lead to asthma and persistent wheeze , respectively , but only in subgroups defined by maternal atopy BACKGROUND Atopic dermatitis ( AD ) is considered to be one of the first manifestations in the atopic march . However , few prospect i ve studies on AD and its association with childhood asthma exist . OBJECTIVE The aim of this study was to prospect ively investigate the natural course of AD to determine factors influencing its prognosis and to analyze the relationship of AD with childhood asthma . METHODS The Multicenter Allergy Study , a German birth cohort , followed 1314 children from birth to age 7 years .  Physical examinations , parental interviews on atopic symptoms and diagnoses , and determination of specific IgE levels  were performed regularly . RESULTS The cumulative prevalence of AD in the first 2 years of life was 21.5 % . Of these children with early AD , 43.2 % were in complete remission by age 3 years , 38.3 % had an intermittent pattern of disease , and 18.7 % had symptoms of AD every year . Severity ( adjusted cumulative odds ratio , 5.86 ; 95 % CI , 3.04 - 11.29 ) and atopic sensitization ( adjusted cumulative odds ratio , 2.76 ; 95 % CI , 1.29 - 5.91 ) were major determinants of prognosis . Early wheeze and a specific sensitization pattern were significant predictors for wheezing at school age , irrespective of AD . Early AD without these cofactors constituted no increased risk of subsequent wheeze ( adjusted odds ratio , 1.11 ; 95 % CI , 0.56 - 2.20 ) or bronchial hyperreactivity . CONCLUSION AD is a common condition in infancy but disappears around age 3 years in a significant proportion of children . The prognosis is mostly determined by the severity and the presence of atopic sensitization . Early AD is associated with asthma at school age , but in many of these asthmatic children , wheezing manifests before or with the onset of AD . Children with AD and wheeze have a marked loss in lung function , suggesting a distinct phenotype rather than a progressive development from AD to asthma BACKGROUND Prenatal maternal smoking and prematurity independently affect  wheezing and asthma in childhood . OBJECTIVE We sought to evaluate the interactive effects of maternal smoking and prematurity upon the development of  early childhood wheezing . METHODS We evaluated 1,448 children with smoke exposure data from a prospect i ve urban birth cohort in Boston .  Maternal antenatal and postnatal exposure was determined from st and ardized question naires . Gestational age was assessed by the first day of the last menstrual period and early prenatal ultrasound ( preterm < 37 weeks gestation ) . Wheezing episodes were determined from medical record extraction of well and ill/unscheduled visits . The primary outcome was recurrent wheezing , defined as ≥ 4 episodes of physician documented wheezing . Logistic regression models and zero inflated negative binomial regression ( for number of episodes of wheeze ) assessed the independent and joint association of prematurity and maternal antenatal smoking on recurrent wheeze , controlling for relevant covariates . RESULTS In the cohort , 90 ( 6 % ) children had recurrent wheezing , 147 ( 10 % ) were exposed to in utero maternal smoke and 419 ( 29 % ) were premature . Prematurity ( odds ratio [ OR ] 2.0 ; 95 % confidence interval [ CI ] , 1.3 - 3.1 ) was associated with an increased risk of recurrent wheezing , but in utero maternal smoking was not ( OR 1.1 , 95 % CI 0.5 - 2.4 ) . Jointly , maternal smoke exposure and prematurity caused an increased risk of recurrent wheezing ( OR 3.8 , 95 % CI 1.8 - 8.0 ) . There was an interaction between prematurity and maternal smoking upon episodes of wheezing ( P = 0.049 ) . CONCLUSIONS We demonstrated an interaction between maternal smoking during pregnancy and prematurity on childhood wheezing  in this urban , multiethnic birth cohort BACKGROUND Less microbial exposure in early childhood is associated with more allergic disease later . Allergic children have a different fecal microflora , with less lactobacilli and bifidobacteria . Beneficial effects regarding the development of allergy have been suggested to come through probiotic supplementation . OBJECTIVE We sought to study the effect of probiotic and prebiotic supplementation in preventing allergies . METHODS In a double-blinded , placebo-controlled study we r and omized 1223 mothers with infants at high risk for allergy to receive a probiotic mixture ( 2 lactobacilli , bifidobacteria , and propionibacteria ) or placebo during the last month of pregnancy and their infants to receive it from birth until age 6 months . Infants also received a prebiotic galacto-oligosaccharide or placebo . At 5 years , we evaluated the cumulative incidence of allergic diseases ( eczema , food allergy , allergic rhinitis , and asthma ) and IgE sensitization . RESULTS Of the 1018 intent-to-treat infants , 891 ( 88 % ) attended the 5-year visit .  Frequencies of allergic and IgE-associated allergic disease and sensitization in the probiotic and placebo groups were similar : 52.6 % versus 54.9 % and 29.5 % versus 26.6 % , respectively , and 41.3 % in both . No significant difference appeared in frequencies of eczema ( 39.3 % vs 43.3 % ) , atopic eczema ( 24.0 % vs 25.1 % ) , allergic rhinitis ( 20.7 % vs 19.1 % ) , or asthma ( 13.0 % vs 14.1 % ) between groups . However , less IgE-associated allergic disease occurred in cesarean-delivered children receiving probiotics ( 24.3 % vs 40.5 % ; odds ratio , 0.47 ; 95 % CI , 0.23 % to 0.96 % ; P = .035 ) . CONCLUSIONS No allergy-preventive effect that extended to age 5 years was achieved with perinatal supplementation of probiotic bacteria to high-risk mothers and children . It conferred protection only to cesarean-delivered children OBJECTIVE To evaluate the influence of early antiinflammatory therapy in the development of asthma 3 years after hospitalization for wheezing in infancy . In addition , the effects of allergic sensitization and respiratory syncytial virus ( RSV ) infection on the development of asthma were investigated . DESIGN AND SETTING A r and omized , controlled follow-up study in a university hospital that provides primary hospital care for all pediatric patients in a defined area . PATIENTS Eighty-nine infants under 2 years of age who had been hospitalized for infection associated with wheezing and followed up for 3 years . INTERVENTION Early antiinflammatory therapy was given for 16 weeks ; 29 patients received cromolyn sodium and 31 received budesonide .  Twenty-nine control patients received no therapy . OUTCOME MEASURES Clinical diagnosis of current asthma , defined as having at least 3 episodes of physician-diagnosed wheezing and either a wheezing episode during the preceding year or ongoing antiinflammatory medication for asthma . RESULTS Fourteen ( 48 % ) patients in the former cromolyn group , 15 ( 48 % ) in the former budesonide group , and 16 ( 55 % ) in the control group had current asthma . The significant predictors of asthma were age over 12 months ( risk ratio [ RR ] 4.1 ; 95 % confidence interval [ CI ] = 1.59 - 10.35 ) , history of wheezing ( RR 6.8 ; CI = 1.35 - 34.43 ) , and atopic dermatitis on study entry ( RR 3.4 ; CI = 1.17 - 9.39 ) . Skin prick test positivity at the age of 16 months significantly predicted asthma ( RR 9.5 ; CI = 2.45 - 36.72 ) . In addition , all of the 18 ( 20 % ) children sensitized with furred pet developed asthma . RSV identification ( RR 0.3 ; CI = 0.08 - 0.80 ) and early furred pet contact at home ( RR 0.3 ; CI 0.10 - 0.79 ) were associated with the decreased occurrence of asthma . CONCLUSIONS Antiinflammatory therapy for 4 months has no influence on the occurrence of asthma 3 years after wheezing in infancy . Early sensitization to indoor allergens , especially to pets , and atopic dermatitis predict subsequent development of asthma . RSV infection in wheezing infants may have a better outcome than other infections It is uncertain whether B group vitamins are risk or preventive factors for allergic disorders . We prospect ively investigated the association between maternal intake of folate and vitamins B(12 ) , B(6 ) , and B(2 ) during pregnancy and the risk of wheeze and eczema in the infants aged 16 - 24 months . Subjects were 763 Japanese mother-child pairs . Data on maternal intake during pregnancy were assessed with a  diet history question naire ( DHQ ) . Symptoms of wheeze and eczema were based on criteria of the International Study of Asthma and Allergies in Childhood . Among 763 infants , 169 ( 22.1 % ) and 142 ( 18.6 % ) had symptoms of wheeze and eczema  , respectively . There were no evident relationships between maternal consumption  of folate , vitamin B(12 ) , vitamin B(6 ) , and vitamin B(2 ) during pregnancy and the risk of wheeze or eczema in the offspring after adjustment for maternal age , gestation at baseline , residential municipality at baseline , family income , maternal and paternal education , maternal and paternal history of asthma , atopic eczema , and allergic rhinitis , changes in maternal diet in the previous 1 month , season when data at baseline were collected , maternal smoking during pregnancy , baby 's older siblings , baby 's sex , baby 's birth weight , household smoking in the same room as the infant , breastfeeding duration , age at which solid foods were introduced , age of infant at the third survey , and maternal intake of docosahexaenoic acid , n-6 polyunsaturated fatty acids , vitamin D , calcium , vitamin E , and β-carotene during pregnancy . Further investigation is warranted to draw conclusions as to the question of whether maternal B vitamin intake during pregnancy is related to the risk of childhood allergic disorders IMPORTANCE Asthma and wheezing begin early in life , and prenatal vitamin D deficiency has been variably associated with these disorders in offspring . OBJECTIVE To determine whether prenatal vitamin D ( cholecalciferol ) supplementation can prevent  asthma or recurrent wheeze in early childhood . DESIGN , SETTING , AND PARTICIPANTS The Vitamin D Antenatal Asthma Reduction Trial was a r and omized , double-blind , placebo-controlled trial conducted in 3 centers across the United States . Enrollment began in October 2009 and completed follow-up in January 2015 . Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were r and omized at 10 to 18 weeks ' gestation . Five participants were deemed ineligible shortly after r and omization and were discontinued . INTERVENTIONS Four hundred forty women were r and omized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D , and 436 women were r and omized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D. MAIN OUTCOMES AND MEASURES Co primary outcomes of ( 1 ) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and ( 2 ) third trimester maternal 25-hydroxyvitamin D levels . RESULTS Eight hundred ten infants were born in the study , and 806 were included in the analyses for the 3-year outcomes . Two hundred eighteen children developed asthma or recurrent wheeze : 98 of 405 ( 24.3 % ; 95 % CI , 18.7%-28.5 % ) in the 4400-IU group vs 120 of 401 ( 30.4 % , 95 % CI , 25.7%-73.1 % ) in the 400-IU group ( hazard ratio , 0.8 ; 95 % CI , 0.6 - 1.0 ; P = .051 ) . Of the women in the 4400-IU group whose blood levels were checked , 289 ( 74.9 % ) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 ( 34.0 % ) in the 400-IU group ( difference , 40.9 % ; 95 % CI , 34.2%-47.5 % , P < .001 ) . CONCLUSIONS AND RELEVANCE In pregnant women at risk of having a child with asthma , supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women . The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1 % , but this did not meet statistical significance ; however , the study may have been underpowered . Longer follow-up of the children is ongoing to determine whether the difference is clinical ly important . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00920621 OBJECTIVE To investigate the incidence of  allergic and respiratory diseases  through age 3 years in children fed docosahexaenoic acid (DHA)- and arachidonic acid (ARA)-supplemented formula during infancy . STUDY DESIGN Children who completed r and omized , double-blind studies of DHA/ARA-supplemented  ( 0.32%-0.36%/0.64%-0.72 % of total fatty acids , respectively ) versus nonsupplemented ( control ) formulas , fed during the first year of life , were eligible . Blinded study nurses review ed medical charts for upper respiratory infection ( URI ) , wheezing , asthma , bronchiolitis , bronchitis , allergic rhinitis , allergic conjunctivitis , otitis media , sinusitis , atopic dermatitis ( AD ) , and urticaria . RESULTS From the 2 original cohorts , 89/179 children participated ; 38/89 were fed DHA/ARA formula . The DHA/ARA group had significantly lower odds for developing URI ( odds ratio [ OR ] , 0.22 ; 95 % confidence interval [ CI ] , 0.08 - 0.58 ) , wheezing/asthma ( OR , 0.32 ; 95 % CI , 0.11 - 0.97 ) , wheezing/asthma/AD ( OR , 0.25 ; 95 % CI , 0.09 - 0.67 ) , or any allergy ( OR , 0.28 ; 95 % CI , 0.10 - 0.72 ) . The control group had significantly shorter time to first diagnosis of URI ( P = .006 ) , wheezing/asthma ( P = .03 ) , or any allergy ( P = .006 ) . CONCLUSIONS DHA/ARA supplementation was associated with delayed onset and reduced incidence of URIs and common allergic diseases up to 3 years of age
We found no evidence to support a protective association between perinatal use of probiotics and doctor diagnosed asthma or childhood wheeze .
R and omised controlled trials to date have not yielded sufficient evidence to recommend probiotics for the primary prevention of these disorders .
OBJECTIVE To evaluate the association of probiotic supplementation during pregnancy or infancy with  childhood asthma and wheeze .