Elevated Cord Blood IgE Research Articles

Association of the AhR, ARNT, and AhRR gene polymorphisms and cord blood AhR levels with elevated cord blood IgE susceptibility in Taiwan mother-infant pairs: a nested case–control study

ABSTRACT The roles of aryl hydrocarbon receptor (AhR), AhR-nuclear translocator (ARNT), and AhR repressor (AhRR) genes in the elevation of cord blood IgE (CbIgE) remained unclear. Our aims were to determine the polymorphisms of AhR, ARNT, and AhRR genes, cord blood AhR (CBAhR) level, and susceptibility to elevation of CbIgE. 206 infant-mother pairs with CbIgE>=0.35 IU/ml and 421 randomly selected controls recruited from our previous study. Genotyping was determined using TaqMan assays. Statistical analysis showed AhR rs2066853 (GG vs. AA+AG: adjusted OR (AOR)=1.5, 95%CI=1.10–2.31 and AOR=1.60, 95%CI=1.06–2.43, respectively) and the combination of AhR rs2066853 and maternal total IgE (mtIgE)>=100 IU/ml were significantly correlated with CbIgE>=0.35 IU/ml or CbIgE>=0.5 IU/ml. CBAhR in a random subsample and CbIgE levels were significantly higher in infants with rs2066853GG genotype. We suggest that infant AhR rs2066853 and their interactions with mtIgE>=100 IU/ml significantly correlate with elevated CbIgE, but AhRR and ARNT polymorphisms do not.

Gene\u2013gene and gene-environment interactions on cord blood total IgE in Chinese Han children

BackgroundIL13, IL4, IL4RA, FCER1B and ADRB2 are susceptible genes of asthma and atopy. Our previous study has found gene–gene interactions on asthma between these genes in Chinese Han children. Whether the interactions begin in fetal stage, and whether these genes interact with prenatal environment to enhance cord blood IgE (CBIgE) levels and then cause subsequent allergic diseases have yet to be determined. This study aimed to determine whether there are gene–gene and gene-environment interactions on CBIgE elevation among the aforementioned five genes and prenatal environmental factors in Chinese Han population.Methods989 cord blood samples from a Chinese birth cohort were genotyped for nine single-nucleotide polymorphisms (SNPs) in the five genes, and measured for CBIgE levels. Prenatal environmental factors were collected using a questionnaire. Gene–gene and gene-environment interactions were analyzed with generalized multifactor dimensionality methods.ResultsA four-way gene–gene interaction model (IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713) was regarded as the optimal one for CBIgE elevation (testing balanced accuracy = 0.5805, P = 9.03 × 10–4). Among the four SNPs, only IL13 rs20541 was identified to have an independent effect on elevated CBIgE (odds ratio (OR) = 1.36, P = 3.57 × 10–3), while the other three had small but synergistic effects. Carriers of IL13 rs20541 TT, IL13 rs1800925 CT/TT, IL4 rs2243250 TT and ADRB2 rs1042713 AA were estimated to be at more than fourfold higher risk for CBIgE elevation (OR = 4.14, P = 2.69 × 10–2). Gene-environment interaction on elevated CBIgE was found between IL4 rs2243250 and maternal atopy (OR = 1.41, P = 2.65 × 10–2).ConclusionsGene–gene interaction between IL13 rs20541, IL13 rs1800925, IL4 rs2243250 and ADRB2 rs1042713, and gene-environment interaction between IL4 rs2243250 and maternal atopy begin in prenatal stage to augment IgE production in Chinese Han children.

Relationship of cord blood IgE with maternal, fetal, and environmental factors in the Chinese population.

Previous studies reported that history of pregnancy and delivery and family environment might influence cord blood IgE (CB-IgE) levels and development of allergies; however, the association between them is not well-established. This study aimed at investigating the IgE level in the newborn's umbilical cord blood and its relationship with maternal, fetal, and environmental factors. A total of 989 mothers and their infants were analyzed in this study. Mothers were given a questionnaire that had a series of questions to evaluate demographic information, maternal allergic status, and environmental exposures during pregnancy. Neonatal cord blood samples were taken at the same time for IgE assay. By univariate analysis, we found statistically significant correlations between CB-IgE levels and gender (P = 0.000) and delivery mode (P = 0.017). By multivariate analysis, gender was found to have a significant association with CB-IgE levels (P = 0.001). No significant difference was found between CB-IgE levels and antenatal complications, the season of birth, birth weight, gestational age, and household income (P > 0.050). In this study, newborn gender was found to be a strong predictor of elevated CB-IgE. The delivery mode was a probable predictor.

Sex-moderated interactions between IL4/IL13 pathway genes and prenatal environment on cord blood IgE levels.

Elevated cord blood IgE (cIgE), a predictor of atopic diseases, is influenced by genetic and environmental factors. However, gene-environment interactions on cIgE elevation and their difference by sex remain largely unexplored. This study aimed to determine whether there are sex-moderated interactions between genetic variants in the IL4/IL13 pathway and prenatal environments on cIgE elevation. Comprehensive information on environmental tobacco smoke (ETS), home dampness (indexed by combining mildewy odour, visible mould and water stamp on the wall) and other household environments was obtained using a structured questionnaire during the third trimester of pregnancy in 1107 full-term newborns. The cord blood was collected for measuring cIgE levels, with elevation defined as ≥0.5IU/mL, and for genotyping of five single nucleotide polymorphisms of three candidate genes (IL-13 rs1800925, rs20541, rs848, IL-4 rs2243250 and STAT6 rs324011). Gene-environment interactions on cIgE elevation were observed in male but not female newborns, including those between ETS and IL13 rs20541, between home dampness and STAT6 rs324011, and between composite environmental exposure (combined ETS and the three home dampness indices) and STAT6 rs324011 (P for interaction=0.03, 0.006, and 0.001, respectively). Male newborns carrying STAT6 rs324011 CT or TT genotype manifested with a significant dose-response association of the composite environmental exposure with cIgE elevation. Sex moderates the gene-environment interactions involving IL4/IL13 pathway genes and prenatal household environments on cIgE elevation. The absence of prenatal exposure to ETS and home dampness in male neonates carrying the STAT6 rs324011 CT or TT genotype is least likely associated with cIgE elevation.

Effect of season of birth on cord blood IgE and IgE at birth: A systematic review and meta-analysis

BackgroundElevated cord blood IgE is important on the pathway to allergic disease. The association between season of birth and infant cord blood IgE is not well-established. Study findings differ on which birth season is associated with higher cord blood IgE risk and its magnitude. We conducted a systematic review and meta-analysis of studies on season of birth and cord blood IgE. MethodsWe searched Medline, Web of Science, Scopus and ProQuest Health databases, and reviewed reference lists of articles that met the inclusion criteria. All included studies measured IgE as a binary variable using various cut-off values. We performed multivariate-random-effects meta-analysis to handle an exposure with multiple categories of Season of Birth. ResultsOur search identified 275 records and 10 had sufficient data to be included in a meta-analysis. Relative to summer, winter birth had the greatest odds of high IgE (≥ 0.1IU/ml), meta-analysis OR = 1.24 (95%CI: 1.01–1.52). A similar OR, was found for IgE ≥ 0.5 IU/ml, OR = 1.30 (95%CI: 0.99–1.71). ConclusionsA winter season of birth was associated with statistically significant higher odds of elevated cord blood IgE at cut-off ≥ 0.1IU/ml but borderline at cut-off ≥ 0.5IU/ml. This winter effect is likely to be a marker for a range of other environmental exposures during specific stages of pregnancy, such as aeroallergen exposures, maternal infections and vitamin D levels. Further research is required to support our finding and to identify the exact mechanisms that lead to the winter season of birth effect on circulating IgE levels, as this may have implications for allergic disease prevention.

Can family history and cord blood IgE predict sensitization and allergic diseases up to adulthood?

Long-term studies of the predictive value of family history and cord blood IgE level until adulthood are few, and their conclusions have been contradictory. Screening of total IgE in 1617 cord blood samples was performed in a Danish birth cohort. All infants with cord blood IgE (CB-IgE) ≥ 0.5 kU/l and a corresponding randomly chosen group with CB-IgE <0.5 kU/l were chosen for follow-up. Questionnaire-based interviews, physical examination, specific IgE testing, and from 10 yr also spirometry, were carried out at 1½, 5, 10, 15, and 26 yr. Predefined diagnostic criteria were used. A total of 455 infants were included, 188 with CB-IgE ≥ 0.5 kU/l and 267 with CB-IgE <0.5 kU/l. Follow-up rates were high, 288 (63%) attended the 26-yr follow-up. Family history and elevated CB-IgE were significantly associated to allergic disease until 26 yr. Concerning any allergic symptoms at 1½ yr the positive and negative predictive values (PPV and NPV), the sensitivity and specificity of CB-IgE ≥ 0.5 kU/l, was 29%, 81%, 54%, and 61%, respectively. The corresponding figures at 26 yr were 46%, 62%, 43%, and 65%. Overall, family history as well as CB-IgE ≥ 0.5 kU/l was associated with high NPV and specificity, but low PPV and sensitivity. Although family history and elevated CB-IgE were significantly associated with primarily atopic disease until 26 yr, none of these were strong predictors for subsequent sensitization and allergic symptoms from childhood until early adulthood. It appears that the predictive capacity of CB-IgE decreases in adolescence and early adulthood.

Asthma Heredity, Cord Blood IgE and Asthma-Related Symptoms and Medication in Adulthood: A Long-Term Follow-Up in a Swedish Birth Cohort

Cord blood IgE has previously been studied as a possible predictor of asthma and allergic diseases. Results from different studies have been contradictory, and most have focused on high-risk infants and early infancy. Few studies have followed their study population into adulthood. This study assessed whether cord blood IgE levels and a family history of asthma were associated with, and could predict, asthma medication and allergy-related respiratory symptoms in adults. A follow-up was carried out in a Swedish birth cohort comprising 1,701 consecutively born children. In all, 1,661 individuals could be linked to the Swedish Prescribed Drug Register and the Medical Birth Register, and 1,227 responded to a postal questionnaire. Cord blood IgE and family history of asthma were correlated with reported respiratory symptoms and dispensed asthma medication at 32–34 years. Elevated cord blood IgE was associated with a two- to threefold increased risk of pollen-induced respiratory symptoms and dispensed anti-inflammatory asthma medication. Similarly, a family history of asthma was associated with an increased risk of pollen-induced respiratory symptoms and anti-inflammatory medication. However, only 8% of the individuals with elevated cord blood IgE or a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication at follow-up. In all, 49 out of 60 individuals with dispensed anti-inflammatory asthma medication at 32–34 years of age had not been reported having asthma at previous check-ups of the cohort during childhood. Among those, only 5% with elevated cord blood IgE and 6% with a family history of asthma in infancy could be linked to current dispensation of anti-inflammatory asthma medication as adults. Elevated cord blood IgE and a positive family history of asthma were associated with reported respiratory symptoms and dispensed asthma medication in adulthood, but their predictive power was poor in this long-time follow-up.

Pro‐inflammatory and Th2‐type cytokine responses in PBMC in infants are associated with parental smoking

During infancy, a disturbed cytokine balance leads to an atopic immune response. Many risk factors have been associated with the development of atopy. These include parental smoking, elevated cord blood IgE, early exposure to pets and family history of atopy, but the knowledge of their impact on cytokine balance is limited. To assess the cytokines induced by mitogen in peripheral blood mononuclear cells (PBMC) of infants at 3months and 12months of age and their potential association with fatty acid (FA) intervention, parental atopy, atopic dermatitis and parental smoking. Infants from an intervention study using black currant seed oil (BCSO, n=34) or placebo (n=34) were included. PBMC samples were taken at the age of 3 and 12months. Signs of atopic dermatitis and parental smoking were registered. PBMC were isolated from heparinized blood samples, stimulated with ConcanavalinA mitogen and the cytokine responses were detected at 72h of stimulation by Luminex technology. Children of smoking parents had elevated levels of IL-4 (P=0.0004), IL-5 (P=0.0002), IFN-γ (P=0.039) and TNF (P=0.0003) at 12months of age. Children who had atopic dermatitis by the age of 3months showed elevated levels of IL-5 at 3months (P=0.0027) and 12months of age (P=0.022). The production of TNF at the age of 3months was higher (P=0.010) and the production of IL-12 at the age of 12months was lower (P=0.025) in infants whose parents were atopic. BCSO intervention did not have any effect on any cytokine production or mRNA expression. Children of smoking parents had highly significantly elevated levels of Th2-type cytokines IL-4, IL-5 and pro-inflammatory cytokine TNF. The detrimental effects of parental smoking on the child's immune function should lead us to pay more attention to supporting parents to stop smoking.

Environmental tobacco smoke and male sex modify the influence of IL‐13 genetic variants on cord blood IgE levels

Elevated cord blood IgE (cIgE) levels enhance the risk of childhood atopic diseases. However, genetic determinants of cIgE elevation and their potential modifiers remain inconclusive. We aimed to investigate the associations of single-nucleotide polymorphisms (SNPs) in the IL-13 gene (IL-13) with cIgE elevation and their interactions with prenatal environmental tobacco smoke (ETS) and neonatal sex. A structured questionnaire regarding prenatal environmental exposures was completed during pregnancy. Birth information was extracted from the medical records. Cord blood from 794 term neonates was genotyped for three SNPs (rs1800925, rs20541, and rs848) of IL-13 and measured for cIgE levels. SNP rs20541 and a 3-SNP haplotype containing rs1800925, rs20541, and rs848 (denoted as h011) were significantly associated with cIgE elevation (p = 0.04 and 0.003, respectively). Two-way interaction analysis revealed that the associations of IL-13 rs20541 and h011 with cIgE elevation were synergistically enhanced by prenatal ETS (p for interaction = 0.03 and 0.03, respectively), but not by male sex. If the association analyses were stratified by prenatal ETS and neonatal sex simultaneously, IL-13 rs20541 and h011 had the highest risks for cIgE elevation in male babies prenatally exposed to ETS, with adjusted odds ratios (95% confidence interval) being 3.03 (1.56-5.88) and 2.81 (1.54-5.15), respectively. When three-way interactions were examined, both IL-13 rs20541 and h011 exhibited significant interactions with male sex and ETS (p for interaction = 0.03 and 0.007, respectively). In conclusion, the influence of IL-13 genetic variants on cIgE elevation was modified by male sex and prenatal ETS.

Prenatal negative life events increases cord blood IgE: interactions with dust mite allergen and maternal atopy

Prenatal exposure to both stress and aeroallergens (dust mite) may modulate the fetal immune system. These exposures may interact to affect the newborn immune response. We examined associations between prenatal maternal stress and cord blood total IgE in 403 predominately low-income minority infants enrolled in the Asthma Coalition on Community, Environment, and Social Stress (ACCESS) project. We also examined potential modifying effects of maternal atopy and maternal dust mite exposure. The Crisis in Family Systems survey was administered to mothers prenatally, and a negative life event domain score was derived to characterize stress. Dust mite allergen was quantified in dust from pregnant mothers' bedrooms. Cord blood was analyzed for total IgE. Using linear regression, we modeled the relationship of stress with cord blood IgE and interactions of stress with dust mite and/or maternal atopy, adjusting for potential confounders. Higher prenatal maternal stress (β=0.09; P=0.01) was associated with increased cord blood IgE. The interactive effects between stress and dust mite groups (high vs low) were significantly different for children of atopic vs nonatopic mothers (P for three-way interaction=0.005). Among children of atopic mothers, the positive association between stress and IgE was stronger in the high dust mite group. In children of mothers without a history of atopy, the positive association between stress and IgE was most evident in the low allergen group. Prenatal stress was independently associated with elevated cord blood IgE. Mechanisms underlying stress effects on fetal immunomodulation may differ based on maternal atopic status.

The relationship between cord blood immunoglobulin E levels and allergy-related outcomes in young adults

Elevated cord blood IgE may be associated with a higher risk of allergic disease. To determine whether cord blood IgE is associated with allergic biomarkers or allergic disorders in young adults. Data was collected from 670 subjects 18-21 years of age that were among 835 original participants in the Detroit Childhood Allergy Study, a general risk, population-based birth cohort. Cord blood IgE was assessed in relation to biomarkers associated with allergy and asthma including total IgE, allergen-specific IgE, blood eosinophilia, and spirometry. Cord blood IgE was also analyzed for associations to subsequent allergic disease including atopic dermatitis, allergic rhinitis, and asthma. Cord blood IgE, analyzed as a continuous measure, was modestly correlated with total IgE (r = 0.18, P < .001) and higher cord IgE was associated with a higher likelihood of sensitization to common allergens in young adults (OR = 1.18, 95% CI, 1.02-1.37; P = .031). The relationship between cord IgE and sensitization was stronger among teens with no pet exposure in the first year of life (OR = 1.43, 95% CI, 1.16-1.77; P = .001). No relationship was found between cord IgE and blood eosinophil counts or lung function. In addition, no consistent association of cord blood IgE to asthma, allergic rhinitis, or atopic dermatitis was apparent. An elevated cord blood IgE level modestly correlates with elevated total IgE and is associated with a slightly higher likelihood of allergic sensitization among young adults. However, cord IgE is not a strong predictor of clinical allergic disorders in this age group.

MicroRNA‐21 expression in neonatal blood associated with antenatal immunoglobulin E production and development of allergic rhinitis

The prevalence of allergic diseases has increased in the past decades. It is unknown whether expression of certain microRNAs (miRNAs) in neonatal leucocytes is correlated to IgE production and/or allergic diseases. This study investigated the association of miRNA expression in neonatal leucocytes with cord blood IgE (CBIgE) elevation and development of allergic disease. We screened for the expression of a panel of 157 miRNAs in mononuclear leucocytes from human umbilical cord blood (CB) samples with elevated CBIgE and tracked the association of down-regulated miRNA expression to the miRNA-targeted gene expression and to children with allergic rhinitis (AR). Among the initial screen of 10 CB samples with elevated CBIgE, expression of eight of the 157 miRNAs was low. Of these eight down-expressed miRNAs, three remained down-regulation in a validation with other 20 CB samples, and two of the three miRNAs, miR-21 and miR-126, were significantly lower in monocytes from AR children. Further analysis of mRNA expression of the miR-21-targeted genes identified that TGFBR2 expression on monocytes was significantly up-regulated in CB with elevated CBIgE, and in AR patients. Transfection of miR-21 precursor into monocytes from patients with AR increased miR-21 expression and decreased TGFBR2 expression. This study demonstrated the first in the literature that lower miR-21 expression in CB and increased TGFBR2 expression is associated with antenatal IgE production and development of AR.

Elevated cord blood IgE is associated with recurrent wheeze and atopy at 7 yrs in a high risk cohort

There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB-IgE in predicting asthma and other IgE-mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE-mediated allergic diseases. CB-IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB-IgE. Fifty-five (19.3%) of infants had detectable CB-IgE (>/=0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB-IgE. CB-IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB-IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.

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Incense smoke: clinical, structural and molecular effects on airway disease

In Asian countries where the Buddhism and Taoism are mainstream religions, incense burning is a daily practice. A typical composition of stick incense consists of 21% (by weight) of herbal and wood powder, 35% of fragrance material, 11% of adhesive powder, and 33% of bamboo stick. Incense smoke (fumes) contains particulate matter (PM), gas products and many organic compounds. On average, incense burning produces particulates greater than 45 mg/g burned as compared to 10 mg/g burned for cigarettes. The gas products from burning incense include CO, CO2, NO2, SO2, and others. Incense burning also produces volatile organic compounds, such as benzene, toluene, and xylenes, as well as aldehydes and polycyclic aromatic hydrocarbons (PAHs). The air pollution in and around various temples has been documented to have harmful effects on health. When incense smoke pollutants are inhaled, they cause respiratory system dysfunction. Incense smoke is a risk factor for elevated cord blood IgE levels and has been indicated to cause allergic contact dermatitis. Incense smoke also has been associated with neoplasm and extracts of particulate matter from incense smoke are found to be mutagenic in the Ames Salmonella test with TA98 and activation. In order to prevent airway disease and other health problem, it is advisable that people should reduce the exposure time when they worship at the temple with heavy incense smokes, and ventilate their house when they burn incense at home.

Prenatal Environmental Tobacco Smoke and Null Genotypes of Glutathione S-Transferase T1 were Associated with Fetal Cord Blood IgE

P-120 Introduction: Elevated cord blood IgE (cbIgE) is a predictor for atopic diseases. Environmental tobacco smoke (ETS) exposure are known associated with cbIgE levels. However, interactive effects on cbIgE is unclear between ETS and genotypes of glutathione s-transferase (GST) T1. A birth-cohort study was conducted to assess the association between gene-environmental interaction and cbIgE. Methods: Between July 2001 and July 2005, 1080 mother-infant pairs are recruited from 8 maternity hospitals in Taiwan. Questionnaires were completed by mothers prior to and immediately following birth. CAP system were used to measure maternal IgE, specific IgE to common allergens, and cbIgE levels. GSTT1/M1 (null/non-null) was determined by polymerase chain reaction (PCR). Results: A total of 745 mother-infant pairs had all measurements satisfactorily completed. The prevalence of elevated cbIgE (≥ 0.35 IU/ml) and maternal prenatal ETS exposure was 23.7% and 39.3%, respectably. The frequency of null GSTT1, M1 genotype was 48.0% and 57.0%, respectively. Male infants (p=0.0002), birth season in Spring (p=0.019), maternal history of atopy (p=0.0008), elevated maternal total IgE (p<0.0001) were associated with elevated cbIgE. Birth weight, gestational age, birth order, parental socioeconomical status, paternal atopy history, and GSTM1 genotype was not associated with cbIgE. Both maternal prenatal ETS exposure (OR=0.48, 95% CI =0.28∼0.80) and GSTT1 null genotype (OR=0.54, 95% CI=0.33∼0.86) were negatively associated with high cbIgE, while OR for those with both GSTT1 null genotype and ETS exposure were 0.30 (95% CI=0.16∼0.54) after adjusting for the above variables. Discussion and Conclusions: Our study found maternal prenatal ETS exposure and GSTT1 null genotype associated with lower cbIgE, adjusting for confounding factors. When both ETS and GSTT1 null genotypes were present, the OR for high IgE were even lower. This finding is somewhat different from previous studies about ETS effects on asthma occurrence. Further follow-up of these children on their development of asthma, allergic rhinitis, or atopic dermatitis will provide valuable information about the prenatal and early childhood risk factors for atopic diseases.

Predictability of early onset atopic dermatitis by cord blood IgE and parental history.

Cord blood IgE and atopic family history have been used as predictors of atopic disease in infants for more than 20 years. In recent years, the value of cord blood IgE in predicting the development of atopic dermatitis has been questioned, while family history of atopy has consistently been regarded as a useful predictor for atopic dermatitis. A birth cohort was followed-up to 6 months of age to record the development of atopic dermatitis and to study its association with cord blood IgE levels and parental history of atopy. The cumulative incidence of atopic dermatitis over the 1st, 3rd and 6th months of life amounted to 5.0%, 8.2% and 14.0%, respectively. When the cutoff value for cord blood IgE was set at 0.5 kU/L, there was a significant association between elevated cord blood IgE level and atopic dermatitis at 1, 3 and 6 months of age; when the cutoff value was set at 0.9 kU/L, the association was only found at 3 months of age. There was a significant association with atopic history of the mother. The effect of maternal atopic history on atopic dermatitis seen only at 1 month was lost by 3 months of age. There was no correlation between paternal history and atopic dermatitis. In our study, the predictive capacity of maternal history and cord blood IgE was not high enough to recommend them as screening factors.

Prevention of allergic disease in childhood: clinical and epidemiological aspects of primary and secondary allergy prevention.

The development and phenotypic expression of atopic diseases depends on a complex interaction between genetic factors, environmental exposure to allergens,and non-specific adjuvant factors, such as tobacco smoke, air pollution and infections. Preventive measures may include both exposure to allergens and adjuvant risk/protective factors and pharmacological treatment. These measures may address the general population, children at risk for development of atopic disease (high-risk infants), children with early symptoms of allergic disease or children with chronic disease. The objective for this review was to evaluate possible preventive measures as regards prevention of development of allergic disease in childhood--primary prevention--and also some aspects of the effect of specific allergy treatment as regards secondary prevention in children with allergic asthma and allergic rhinoconjunctivitis. In one prospective observational study of a birth cohort of unselected infants we evaluated possible predictive/risk factors. In two prospective intervention studies including 1 yr birth cohorts of high-risk(HR) infants we investigated the effect of feeding HR infants exclusively breast milk (BM) and/or hydrolyzed cow's milk-based formula the first 4-6 months as regards: (i) the allergy preventive effect of BM/extensively hydrolysed formula (eHF) compared with ordinary cow's milk-based formula, (ii) the effect of two different eHFs, a whey (Profylac) and a casein-based (Nutramigen) formula, as regards development of cow's milk protein allergy (CMA), and (iii) a comparison of the preventive effect of eHF (Profylac/Nutramigen) with a partially hydrolyzed cow's milk-based formula (pHF) (NanHA) as regards development of CMA. None of the mothers had a restricted diet during pregnancy or lactation period. In two prospective randomized intervention studies we evaluated the preventive effect of specific allergen avoidance and specific immunotherapy (SIT) in children with allergic asthma and allergic rhinoconjunctivitis, respectively. The combination of atopic heredity and elevated cord blood IgE resulted in the best predictive discrimination as regards development of allergic disease. The optimal high-risk group was defined by either double parental atopic predisposition or single atopic predisposition, the latter combined with a cord blood IgE > or = 0.3 kU/1. 66% of unselected infants were daily exposed to tobacco smoke, which was a significant risk factor for recurrent wheezing until the age of 1.5 yr. HR infants were breastfed for a longer period and less exposed to tobacco smoke than unselected infants. Exclusively BM/eHF for at least 4 months was associated with a significantly reduced cumulative prevalence of CMA [3.6% (5/141) vs. 20%(15/75) in the control group] up to 5 yr. The effect of the two different eHFs was similar. Exclusively breastfed infants were significantly less exposed to tobacco smoke and pets, had solid foods introduced later and belonged to higher social classes. pHF was significantly (p = 0.05) less effective than eHF as regards prevention of development of CMA. A diet period of 4 months seems to be as efficient as 6 months or more as regards development of CMA. A few ongoing prospective, randomized intervention studies have produced the first indication that avoidance of indoor allergens such as house dust mite (HDM) in HR infants may reduce the incidence of severe wheeze and sensitization during the first 1-4 yr of age. Long-term follow-up is awaited. In a prospective, double-blind placebo-controlled study in children with doctors diagnosed asthma and documented HDM allergy, we found that semipermeable polyurethane mattress and pillow encasings (Allergy Control) when compared with placebo encasings resulted in a significant perennial reduction of HDM exposure and a significant reduction in the needed dose of inhaled steroids by approximately 50% (mean dose: 408 microg--227 microg/day) after 1-yr follow-up. In another randomized prospective study we investigated the possible preventive effect of SIT in children with allergic rhinoconjunctivitis and grass/birch pollen allergy as regards development of asthma. Among those without asthma significantly fewer in the SIT group developed asthma when compared with the control group (19/79 = 24% vs.32/72 = 44%) after the first 3 yr; and methacholinebronchial provocation test results improved significant in the SIT group. The results of our studies support the evidence that the risk for development of early allergic manifestations e.g. CMA and atopic dermatitis can be reduced significantly by simple dietary measures for the first4 months of life. In all infants breastfeeding should beencouraged for at least 4-6 months, and exposure to tobacco smoke should be avoided during pregnancy and early childhood. In HR infants a documented hypoallergenic formula (at present eHF) is recommended if exclusive breastfeeding is not possible for the first 4 months. In homes of HR-infants, current evidence supports measures to reduce the levels of indoor allergens. e.g. HDM and pets. In symptomatic children allergen-specific treatment may influence both the symptoms and the prognosis. Allergen avoidance can reduce the need for pharmacological treatment, SIT may have the potential for preventing the development of asthma in children with allergic rhinoconjunctivitis. and it may be possible to interfere with the natural course of allergic diseases.

Prenatal prediction of infant atopy by maternal but not paternal total IgE levels

Background The atopic history of parents has long been used to predict infant atopy. However, bias from questionnaires of allergic history are also frequently suspected, because a large number of vasomotor rhinitis, intrinsic asthma, and seborrheic dermatitis cases are probably misinterpreted to be atopic diseases. Objective We attempted to identify a risk factor other than parental atopic history to predict elevated infant IgE levels and infant atopy. Methods A total of 655 core families were prenatally recruited, and finally 545 families completed the study for the prospective analysis of infant atopy at 6 months of age. Atopic history and blood samples of parents were collected in the third trimester during pregnancy. Cord blood (CB) was collected immediately after birth. Infant blood samples and history of infant eczema were collected in the 6-month physical checkup clinic. Blood total IgE and specific IgE levels were determined by use of the Pharmacia CAP system. Results In univariate analysis, maternal, but not paternal, atopic history correlated with elevated CB IgE levels and the occurrence of infant eczema. Elevated maternal, but not paternal, total IgE levels (>150 KU/L) significantly correlated with increases of CB IgE levels (median, 0.54 vs 0.17 KU/L, P < .001), infant IgE levels (log-transformed mean values, 1.32 ± 0.51 vs 1.13 ± 0.51 KU/L, P < .001), and infant eczema ( P = .008). Multivariate logistical regression analysis, however, showed that only maternal total IgE levels correlated with CB and infant IgE levels and the development of infant eczema. Conclusions The maternal, but not paternal, total IgE level correlates with elevated infant IgE levels and infant atopy. This provides a high specificity (83%) and a sensitivity of 34% for prediction of infant atopy. This suggests that maternal factors, placental factors, or both have an impact on perinatal allergic sensitization.

Early sensitisation and development of allergic airway disease - risk factors and predictors.

The development and phenotypic expression of allergic airway disease depends on a complex interaction between genetic and several environmental factors, such as exposure to food, inhalant allergens and non-specific adjuvant factors (e.g. tobacco smoke, air pollution and infections). The first months of life seem to be a particularly vulnerable period and there is evidence that sensitisation is related to the level of allergen exposure during early life. At present, the combination of atopic heredity and elevated cord-blood IgE seems to result in the best predictive discrimination as regards development of allergic disease at birth. Early sensitisation, cow's milk allergy and atopic eczema are predictors for later development of allergic airway disease. Exposure to indoor allergens, especially house dust mite allergens, is a risk factor for sensitisation and development of asthma later in childhood in high-risk infants and infants with early atopic manifestations.