Parental history of atopic disease and concentration of cord blood IgE

Background A family history of atopy, and cord blood immunoglobulin E concentration, have been shown to be predictors of atopic disease in children. Several studies have suggested that parental atopy may be related to newborn immunoglobulin E. Objective The purpose of our analysis was to evaluate whether parental history of allergic disease was associated with cord blood immunoglobulin E concentration. Methods The study subjects were from a defined population of 777 newborns delivered between 1987 and 1989. The mothers of these children completed a questionnaire during pregnancy concerning themselves and the child's father, including parental history of physician diagnosis of allergic diseases (allergies, hay fever and asthma). Total immunoglobulin E levels were quantitated in cord blood samples with an enzyme-hnked immunoassay. Results Median cord blood immunoglobulin E concentration was higher among infants whose mothers had a history of atopic disease, particularly for those with a history of asthma (P<0.022) and allergen immunotherapy (P<0.016) vs infants whose mothers had no history of any atopic disease. Comparing all babies with a maternal history of asthma, to babies where neither parent had a history of any atopic disease, the median cord blood immunoglobulin E was significantly higher (0.36IU/mL vs 0.21 IU/mL; P<0.009). This association was found only among female infants (0.49IU/mL vs 0.20 IU/mL; P<0.001). Conclusion Maternal, but not paternal, history of atopic disease was associated with an elevated immunoglobulin E among newborns. For maternal asthma, this association was only evident in infant girls.     

Maternal smoking does not influence cord serum IgE or IgD concentrations

Increased cord blood IgE concentrations have been related to atopic risk in children, and a previous study reported increased cord blood IgE concentrations in smoking mothers. These associations suggest a relationship between maternal smoking during pregnancy and atopic risk. To evaluate this question, we prospectively studied parental smoking and cord blood IgE and IgD concentrations in a geographically defined group of women belonging to a health maintenance organization. Cord blood samples were obtained from 847 infants born to these women. Cotinine concentrations were measured in 114 cord blood samples to evaluate the veracity of the maternal smoking histories. Smoking during the prenatal period was reported by 144 mothers (17%) and 204 fathers (25%). Decreased birth weight and length were associated with maternal smoking (p less than 0.001 for both), confirming previous studies. Neither maternal nor paternal smoking was found to be associated with IgE level in univariate or multivariate analyses. Maternal and paternal smoking was associated with IgD (p = 0.03 and p = 0.06, respectively) in univariate analysis. In multiple regression analysis controlling for potentially confounding variables, the association between paternal, but not maternal, smoking and IgD was sustained (p = 0.05 and p greater than 0.20, respectively). Our data do not demonstrate that maternal or paternal smoking increases cord blood IgE.     

Cord serum IgE in relation to family history and as predictor of atopic disease in early infancy

Cord serum IgE was assayed by particle counting immunoassay (PACIA) in an unselected series of European newborns (n = 190; geom mean = 0.37 IU/ml) and a cutoff limit established (≥ 1.20 IU/ml) for prediction of atopy. At control follow-up by questionnaire 18 months after birth, 38 infants (20.0%) had developed definite (9.5%) or probable (10.5%) atopy with a significant predominance of boys ( P < 0.03). Infants with a positive immediate family history (IFH) had a higher risk of developing atopy ( P < 0.0025) and also had a higher incidence of elevated cord IgE ( P < 0.02) than infants with a negative IFH. Maternal atopy influenced cord IgE levels significantly ( P < 0.00005), whereas paternal atopy did not ( P = 0.23). No fetal IgE antibodies against five common allergens could be demonstrated in 36 cord sera tested. Breast-feeding for 3 months was not sufficient to prevent atopic symptoms. The predictive value of cord IgE was high since 26 of 36 newborns (positive predictive value = 72.2 %) with elevated cord IgE had developed atopic symptoms before follow-up. Of the 38 infants who developed atopic symptoms, 26 had elevated cord IgE (sensitivity = 68.4%) compared to only 10 (6.6%) of the 152 atopy-free infants (P < 0.00005). The data indicate that elevated cord IgE as determined by PACIA is a good predictor of early-onset atopy, better than family history ( P < 0.008), and that primarily maternal atopy seems to affect fetal IgE synthesis.     

Cord and blood levels of newborn IgE: Correlation,role and influence of maternal IgE

The role of cord blood immunoglobulin E (IgE) levels in predicting the development of atopy has been widely investigated. The aim of the study was to evaluate the correlation between serum and cord blood total IgE in newborns and the possible influence of the atopic status of the mother on them. It was also investigated the possible role of gestational age on neonatal total IgE levels. We considered 763 deliveries, 724 ≥ 37 weeks of gestation and 39 < 37 weeks of gestation. 14% of mothers (13.7% at term, 15.4% preterm) showed high total IgE levels. The results showed a significant correlation between serum and cord IgE levels both in preterm and term newborns. The data revealed also that mother’s total IgE levels affect both neonatal serum and cord total IgE levels. For the latters we also found child gender as an additional independent predictor. On the contrary total IgE levels are not affected by gestational age. Clinical limitations of total IgE is known but their determination can be useful to define atopy and to suggest follow-up of the children.     

Comparison of cord blood immunoglobulin E concentrations and maternal allergy for the prediction of atopic diseases in infancy

Total serum IgE levels were determined in 136 newborns and their mothers and in 54 of their fathers, using the paper radioimmunosorbent test (PRIST) technique. IgE specific antibodies for house dust (Dermatophagoides pteronyssinus), orchard grass, timothy grass, and cow's milk were measured with the radioallergosorbent test (RAST). One hundred thirty-three RAST assays were negative in newborns, and in three cases RAST for cow's milk was positive. Cord blood IgE ranged from 0 to 5.5 IU/ml (mean 0.32 ± 0.54 IU/ml); levels were significantly (p < 0.05) higher when maternal IgE was over 100 IU/ml and when mothers had received progesterone therapy during the pregnancy. Salbutamol administration or tobacco smoking during pregnancy did not influence newborn IgE. A clinical follow-up study was conducted in 83 infants for 9 mo. Nine infants developed definite atopic disease, and possible allergic diseases were noted in eight other infants. The IgE level at birth appeared to be more predictive for the development of allergy in infancy than the family history.     

The severity of atopic dermatitis and the relation to the level of total IgE,onset of atopic dermatitis and family history about atopy

The aim of this study is the evaluation, if the level of total IgE, onset of atopic dermatitis (AD) and the family history are in the significant dependence to the severity of AD. The statistical evaluation of the dependence between the severity of AD and the the level of total IgE, family history and onset of AD was performed. 296 patients were examined. The level of total IgE above 200 IU/ml is recorded in 93 % of patients suffering from severe form and the positive data about atopy in family history are recorded in 66 % of patients with severe form of AD. The significant dependence was recorded between the severity of AD and parameters such as the level of total IgE, and family history about atopy. No dependence was recorded between the severity of AD and the onset of AD.     

Are maternal psychosocial factors associated with cord immunoglobulin E in addition to family atopic history and mother immunoglobulin E?

BACKGROUND: Atopy in maternal and family histories is known to be a risk factor for elevated umbilical cord immunoglobulin E (cIgE). However, the association between cIgE and psychosocial factors remains under investigation. OBJECTIVE: To explore whether psychosocial factors in addition to atopy contribute to elevated cIgE. METHODS: Four private maternity hospitals fitting the quantile levels of SO(2) in 2000 cooperated with us by recruiting participants for this study: pairs of mothers and neonates living within 3-km catchment areas of air-monitoring stations. We used a questionnaire to collect exposure data, and the Pharmacia UniCap IgE assay test system to determine the levels of IgE in gravidas and cord blood. RESULTS: Between July 2001 and March 2003, 334 mother and neonate pairs participated in this study. The frequencies of sensitization, serum IgE (sIgE)>100 IU/mL, or cIgE> or =0.35 IU/mL were not different between the four different hospitals. By multi-variate logistic regression analysis adjusted for environmental factors, genetic factors, and psychosocial factors, the risk factors for elevated cIgE were being a male neonate (odds ratio (OR)=3.5, 95% confidence interval (CI)=[1.5, 8.5]), carpets at home (OR=3.0, 95% CI=[1.02, 8.4]), maternal allergy to dog dander (OR=9.7, 95% CI=[1.2, 98.8], maternal total serum IgE>100 IU/mL (OR=5.1, 95% CI=[2.2, 12.8]), maternal regularly/mostly/often self-reported nervousness (OR=4.0, 95% CI=[1.3, 12.8]), family income 11,574-17 361 US dollars/year (OR=3.7, 95% CI=[1.3, 11.5]), incense burning (OR=4.0, 95% CI=[1.4, 13.3]), and atopy in maternal grandparents (OR=4.8, 95% CI=[1.7, 14.0]). By principle component analysis and logistic regression, psychosocial stress (beta +/- standard error=0.26+/-0.13, P=0.04) was associated with increased cIgE. CONCLUSION: Psychosocial factors are potentially important risk factors for elevated cIgE.     

Head circumference at birth and maternal factors related to cord blood total IgE

BACKGROUND: A recent study reported an association between a large head circumference at birth and adult total IgE. However, no study has yet looked at the relation between head circumference and cord blood IgE. OBJECTIVES: To assess the relationship between child's cord blood total IgE and head circumference at birth taking parental allergy and smoking habits as well as placental calcifications into account. METHODS: Two samples of unselected newborns and their mothers with uncomplicated pregnancies were studied: 235 in study A with data on parental allergy and 99 in study B with data on placental calcifications. RESULTS: In both studies, cord blood IgE was significantly related to large head circumference at birth (0.07 vs 0.15 IU/mL for newborns < 37 cm vs >/= 37 cm, respectively, P = 0. 03 for study A and 0.09 vs 0.28 IU/mL, P = 0.04 for study B). Cord blood IgE was unrelated to parental smoking habits. Maternal IgE significantly increased in mothers exposed to both active and passive smoking during pregnancy compared with other pregnant women. High cord blood IgE were associated with high maternal IgE (r = 0. 38; P < 0.001). Multiple linear regression showed that large head circumference, maternal IgE and clinical manifestations of maternal, but not paternal, allergy were independently related to cord blood IgE (study A). Large head circumference and placental calcifications were independently related to a higher cord blood IgE level (study B). CONCLUSIONS: Besides the role of genetic factors, results on the preferential role of maternal vs paternal allergy and associations to large head circumference and placental calcifications support the hypothesis of the role of environmental factors during pregnancy on the level of cord blood IgE.     

Cultures of human cord blood metachromatic cells in relation to family history of atopy, development of atopic disease, nasal metachromatic cells and perinatal factors

The appearance of basophilic cells by maturation from progenitors was studied in cultures of cord blood mononuclear cells (CB-MNC) from 83 newborns. In unstimulated cultures, the numbers of basophilic cells increased 5-fold after 14 days of cultivation. This increase and the cell numbers were similar in cultures from atopic individuals and controls. Other cultures were stimulated with conditioned medium (CM) prepared from 3-day cultures of blood cells from atopic individuals activated with allergen or with CM from the Mo leukemic cell line. The addition of such CM resulted in an increase in the number of basophilic cells, as compared to the cultures which were unstimulated (p less than 0.01). No correlation was found between the maturation of basophils and heredity for atopy, development of atopic disease, appearance of metachromatic cells in the nasal mucosa and perinatal factors, such as maternal infections, perinatal stress, birth weight, month of birth and IgE levels. The study confirmed that basophilic cells can be driven to mature in cultures of CB-MNC, although the maturation did not seem to depend on atopic predisposition as indicated by family history of allergy and CB IgE levels nor on symptoms and signs of atopic disease during the first 18 months of life. Therefore, the predictive value of elevated basophilic cell numbers in CB or CB-MNC cultures with regard to allergic disease seemed to be limited.     

Serum total IgE in normal subjects and the influence of a family history of allergy

The purpose of this study was to establish the range of serum total immunoglobulin E (IgE) in a healthy population free of personal and family history of allergy, and to determine whether a family history of allergy influenced serum IgE levels. Using commercially available Phadebas reagents, the mean serum IgE in eighty-four adults aged 17–30 years with no personal or family history of allergy was found to be 38.8 iu/ml. Seventy-five percent of subjects had a serum IgE below 50 iu/ml and in only one subject was serum IgE in excess of 150 iu/ml, which we suggest be taken as the upper limit of normal. When healthy subjects with no personal history but with a family history of allergy were included with this normal population, the mean serum IgE in 207 subjects was 95.4 iu/ml and the upper limit of the distribution curve over 200 iu/ml, suggesting an influence of genetic factors on IgE production.     

Common variants in FCER1A influence total serum IgE levels from cord blood up to six years of life

Background:  In a recent genome wide scan, a functional promoter variant (rs2251746) in the gene encoding the alpha chain of the high affinity receptor for immunoglobulin E (IgE) (FCER1A) was identified as major determinant of serum IgE levels.
Objective:  The aim of this study was to investigate the role of rs2251746 on total IgE levels measured at different stages of life from birth (cord blood) up to the age of 6 and to evaluate its interaction with the environmental influences in two German birth cohorts.
Method:  Data from two German birth cohorts were analysed ( n  = 1043 for the LISA cohort and n  = 1842 for the GINI cohort). In the studies, total serum IgE was measured from cord blood, and blood samples taken at the age of 2/3 and 6 years. In a subgroup of the LISA study, house dust samples were collected at age of 3 months and the amount of endotoxin was determined. Random effect models were used to analyse the longitudinal health outcomes.
Results:  In the two cohorts, the heterozygote and the rare homozygote of rs2251746 was consistently associated with lower total IgE levels from birth up to the age of 6 years with an allele-dose effect ( P  < 0.02 for blood samples taken at each time point in both cohorts). No interaction between the two FCER1A encoding gene and environmental exposures including endotoxin, worm infestation and day care centre attendance during early childhood were observed.
Conclusion:  Common variants in FCER1A strongly influence basal IgE production independently from environmental stimuli. These effects can be observed already in cord blood pointing to altered gene expression in foetus.     

Expression of sCD23 in atopic and nonatopic blood donors: correlation with age, total serum IgE, and allergic symptoms

Although structure, biologic activities, and expression of the low-affinity IgE receptor (Fc_eRII, CD23) have been investigated, the diagnostic value for allergies of this molecule and its soluble circulating fragment (sCD23) remains unclear. Therefore, serum sCD23 levels were measured in 203 blood donors. They were divided into atopic and nonatopic subjects by allergy history, physical findings of allergic symptoms, and corresponding specific circulating IgE antibodies. The group consisting of nonatopic subjects was divided into four age categories in order to exclude age-dependent variations in the expression of the low-affinity IgE receptor. In our study population, sCD23 serum levels were not influenced by age. Furthermore, no significant differences, especially no decrease in serum sCD23 levels, between the four nonatopic age groups were detected. There was no significant increase of sCD23 serum levels in atopic subjects in comparison with nonatopic blood donors. In addition, no correlation between total IgE levels and sCD23 serum levels could be detected, in either the group of atopic donors or the group of nonatopics. Our data suggest that the circulating low-affinity IgE receptor does not appear to be an additional general marker for the diagnosis of allergies, as previously suggested.     

Seasonal influence on serum and receptor-bound IgE in pollinosis

Analysis of the correlation between bound and free IgE in 32 patients with pollinosis before and during the pollen season disclosed no correlation between bound and free IgE in rhinitic patients before the pollen season, while there was correlation during the season. In the asthmatic patients there was good correlation before the pollen season rather than during it.     

Induction of an auto-anti-IgE response in rats I. Effects on serum IgE concentrations

With a view to specifically suppressing the IgE isotype, rats of high (BN) and low (PVG.RT1u) IgE-responding phenotypes were immunized with a highly purified rat IgE myeloma (IR2) in an attempt to induce an anto-anti-IgE response. Rat IgE antibodies against epsilon determinants were detected in the serum of IR2-immunized animals using a solid-phase (plate) radioimmunoassay. The auto-anti-IgE antibodies detected were found to bind to IR2, to a second rat IgE myeloma (IR162) and to mouse monoclonal IgE but not rat IgG. The specificity of the anti-epsilon binding was shown by inhibition studies. The raising of an auto-anti-IgE response in PVG.RT1u rats severely depleted the serum level of circulating IgE for at least 8 weeks. In BN rats, immunization with IR2 caused marked fluctuations in serum IgE levels. The rats in both strains remained healthy throughout the experiment. The rate and route of IgE break down was not altered in anti-IgE-producing rats. The relevance of the present model in understanding and possibly controlling allergic disorders is considered.     

Pregnancy induces nonimmunoglobulin insulin-binding activity in both maternal and cord blood serum.

To evaluate whether pregnancy has any effect on insulin antibody levels and to test the concordance between a conventional radioimmunoassay and a new microassay for the detection of insulin antibodies, insulin antibodies were analysed in 104 mothers in early pregnancy and at delivery and in their newborn infants. Thirty-eight of the mothers had type 1 diabetes. The concordance between the assays was high in the samples taken in early pregnancy (95%), but substantially lower in the samples taken at delivery (40%) and in the cord blood samples (68%). A considerable proportion of the mothers at delivery, especially the unaffected mothers (71%), and the newborn infants of the unaffected mothers (32%) were positive for insulin antibodies in the conventional assay but not in the microassay. Insulin antibody levels increased in the mothers, significantly so in the unaffected mothers (P < 0.001), during pregnancy in the conventional assay, whereas in the microassay they decreased significantly (P < 0.01) in affected mothers and remained negative in the unaffected mothers. Since immune complexes are precipitated with protein A specific for IgG in the microassay and with polyethylene glycol lacking specificity for immunoglobulins in the conventional assay, our data indicate that insulin antibody levels decrease on average during pregnancy and that the increasing non-IgG anti-insulin activity observed in the conventional assay is induced by pregnancy and is present in both the maternal and the foetal circulation.     

Predictive value of cord blood IgE in the development of atopic disease and role of breast-feeding in its prevention

The predictive value of cord blood IgE in the development of atopic disease was evaluated in a prospective study of two groups of infants. Total serum IgE level was ≥ 0.7 U/ml in 44.3% of the infants with positive family history of atopy and in 16.0% among those with negative family history. The level of cord blood IgE correlated significantly with the subsequent development of atopic disease in both groups. Cord blood IgE higher than 0.7 U/ml was associated with a high risk of development of atopic eczema and wheezing, 52.8% and 58.8% respectively in the groups with or without family history of atopy; compared with 13.4% and 1.1% in the groups with IgE levels less than 0.7 U/ml. Among newborns fed exclusively on breast milk for a minimum of 3 months, the incidence of eczema and wheezing was significantly lower (12%) compared with findings in the formula-fed group (32%).     

巨大儿孕母血清、羊水、脐血瘦素水平测定及意义

目的探讨瘦素(1eptin)与巨大儿发病的关系.方法应用酶联免疫法(ELISA)检测20例巨大儿(巨大儿组)及20例正常体重儿(对照组)孕母血清.羊水及脐血瘦素水平.结果(1)巨大儿组孕母血清瘦素平均(25.6±8.2ng/rml),羊水瘦素平均(5.9±1.7ng/m1)与对照组(18.8±7.8ng/ml)及(3.9±1.7ng/ml)比较相差显著.分别为(P＜0.05)(P＜0.01).(2)巨大儿组脐血瘦素水平平均(16.8±7.0ng/m1)明显高于对照组(7.7±4.6rg/ml)(P＜0.001).(3)两组孕母血清瘦素与胎儿出生重量无相关性,而脐血瘦素水平与胎儿出生重量呈正相关.(r=0.65,P＜0.01)结论脐血瘦素来源于胎盘及胎儿组织.巨大儿的发病与脐血瘦素水平相关.