Ige Levels In Umbilical Cord Blood Biology Essay

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Two hundred mothers and their infants were analyzed in this study. Mothers were given a questionnaire that had a series of questions to help elucidate family history of allergic status and environmental exposures during pregnancy. Plasma total IgE levels of mothers and plasma specific IgE levels of infants to house dust mite were analyzed by an immunoenzymatic assay.

Results: There was no significant correlation between plasma IgE positivity in mothers with regard to tobacco smoke, passive smoking or presence of atopy. A significant correlation was found between IgE presence in mothers and allergic reactions; however, no relationship between higher plasma IgE levels in mothers and positivity of plasma specific IgE levels in their infants was observed.

Conclusions: We concluded that prenatal maternal sensitivity to environmental allergens could not be evaluated as a predictive factor for in utero sensitization.

Key words: In utero sensitization, antigen-specific IgE, umbilical cord blood.

Introduction

Incidence of asthma and atopic reactions are increasing worldwide. Previous reports have suggested that maternal exposure to allergens during pregnancy may have potential effects on allergic sensitization in infants. Over the last several years, fetal exposures to environmental determinants such as tobacco, air pollutants, house dust mites and domestic pets have been investigated as potentially critical factors in the development of allergic diseases (1, 2, 3, 4, 5).

In this study, we analyzed maternal exposure to environmental factors, such as tobacco smoking, presence of domestic pets during pregnancy and history of atopy. Here, we evaluated plasma IgE levels of mothers and cord blood specific IgE levels of infants following delivery, to determine a potential relationship between environmental exposure and allergic sensitization early in life.

Methods

This study was a prospective birth cohort study that was approved by the Local Ethics Committee. The study included 200 infants born in the Department of Obstetrics of the HaydarpaÅŸa Numune Training and Research Hospital during 2012, along with their respective mothers. Mothers were divided into two groups according to the presence of higher plasma IgE levels. Additionally, mothers were given questionnaires to investigate family history of atopy, allergic rhinitis, asthma, while also inquiring about tobacco smoking or the presence of domestic pets during pregnancy.

Umbilical blood of infants was obtained by puncture of the umbilical veins; samples were then centrifuged, and plasma was frozen and stored at -70°C. Total concentrations of maternal IgE were determined by measuring chemilumine scence with a sandwich-type assay, using an Elecsys 2010 analyzer. Allergen specific IgE of infants were also assessed by utilizing an antibody kit specific to house dust mites (D. pteronyssinus, D. farinae).

Specific IgE was assessed using a non-competitive immunoenzymatic assay. Specific IgE concentrations over a threshold level of 0.35 IU/ml were accepted as positive.

All levels of significance were calculated by using tests for independence of two qualitative variables and the Mann-Whitney U test.

Results

Of the 200 mothers interviewed for this study, it was determined that 30.5% (61 mothers) smoked tobacco, 9.5% (19 mothers) displayed atopy and 93.5% (187 mothers) had asthma (Table I). 'In addition, it was determined that 5% of parents (10 families) kept domestic pets at home. When mothers were interviewed about family history, it was also established that atopy was seen in 8.5% of parents (17 families), allergy was present in 12.5% of parents (25 families), and presence of asthma in the family occurred in 22% of parents (44 families) (Table II).

Information about the infants in the study was gathered, and it was observed that gestational ages of the infants were between 35 and 42 weeks, (mean age was 38.81 ± 1.86 weeks), and birth weights were between 2400 g and 4750 g (mean weight was 3334.33 ± 389.65 g). Of the 97 infants born from mothers who had positive maternal IgE levels, 50.5% (49 infants) were male (Table III). Similarly, of the 103 infants born from mothers who had negative IgE levels, 50.5% (52 infants) were male (Table III). There was no significant correlation between maternal IgE positivity and gestational age, birth weight, gender of infants or presence of in-door domestic pets (p>0.05) (Table III). With regard to the presence of domestic pets, only 4.1% of mothers (4 of 97) who had positive maternal IgE levels kept domestic pets at home, and likewise, only 5.8% of mothers (6 of 103) who had negative maternal IgE levels kept domestic pets as well (Table III). It was also observed that 3.9% of mothers (4 of 103) who had negative maternal IgE levels had allergic rhinitis, compared with those that did not have allergic rhinitis (p < 0.005). In contrast, 15.5% of mothers (15 of 97) who had positive maternal IgE levels had allergic rhinitis. Furthermore, 2.9% of mothers (3 of 103) with negative maternal IgE levels had asthma, compared to the remaining 97.1% (100 of 103) that did not have asthma (pË‚0.05). Finally, 10.3% of mothers (10 of 97) with positive maternal IgE levels had asthma, in relation to those that did not (pË‚0.05) (Table IV). There was no significant correlation between plasma IgE positivity of mothers who smoked tobacco, were exposed to passive smoking or had incidences of atopy (p>0.05). However, a statistically significant correlation was found between maternal IgE positivity and allergic rhinitis, as well as asthma symptomatology (pË‚0.05) (Table IV). There was no correlation between plasma IgE levels of mothers and plasma specific IgE levels of infants. Only in one case, however, did plasma IgE levels of the mother and infant seem to match (Table V).

Discussion

Currently, there is a high incidence of allergy worldwide, perhaps related to increasing environmental pollution, and changing life-styles with respect to hygienic and nutritional status (7). An infant is defined as high risk if there is at least one first-degree relative (parent or sibling) with documented allergic disease. This definition is based on a consensus among several committees representing the European Society for Pediatric Allergology and Clinical Immunology (ESPACI) and the American Academy of Pediatrics (8).

In this study, we investigated whether life-style and maternal allergen sensitization status influenced in utero allergen sensitization. We analyzed allergen-specific IgE levels in cord blood samples of infants and plasma IgE levels of their mothers. Mothers were asked about their environmental exposure to tobacco smoke, outdoor pollutants, indoor pet keeping and family history of atopy. Based on these environmental factors during pregnancy, we evaluated for potential effects on intrauterine sensitization.

The most common immunologic abnormalities detected early in life among children who went on to have asthma included diminished IFN- Æ´ production and reduced T Helper 2 responses (9).

Sybilski et al analyzed 173 newborns and mothers to evaluate the effects of environmental factors on their total IgE levels and on the presence of selected antigen specific IgE in umbilical cord blood plasma. In this study, 519 assays (173-3) for antigen specific IgE were performed (10).

Most previous reports point to the presence of maternal atopic diseases in causing elevated levels of IgE in umbilical cord blood. In this study, total cord blood IgE levels were significantly higher in male infants, compared with females. Additionally, the number of siblings (family size) correlated with a decrease in cord blood IgE levels. Maternal contact with a domestic cat during pregnancy resulted in increased levels of IgE against grass, cereals and food. Sybilski et al found a significant association between the level of antigen specific IgE against domestic dust mites and maternal tobacco smoking in which they detected specific IgE in 34 newborns (6.6% with a positive test). Of the 40 positive tests, 20 were to grass, 11 to house dust mites and 9 were to food. No correlations were noted between familial history of allergy and the presence of specific immunoglobulin. There was no statistically significant correlation between antigen-specific IgE in umbilical cord plasma and pregnancy associated factors (10). The results of this study were similar to ours because they showed no correlation between pregnancy, environmental factors and the presence of IgE in umbilical cord plasma.

In a study conducted in the USA, Peters et al examined 301 mother-infant pairs to evaluate the effects of prenatal and early life social and physical environmental exposures. Elevated prenatal dust mite levels increased cord blood IgE levels by 29%. Continuous dust mite concentrations were associated with a significant increase in cord blood IgE levels. These results demonstrated that maternal prenatal exposure to household allergens might affect cord blood IgE levels (11). However, in our study, we did not find a correlation between maternal prenatal exposure to allergens and cord blood IgE levels.

Keil et al examined the interaction of passive smoking and allergic sensitization during the first ten years of life. In their study, 18% of the children were exposed to regular maternal smoking since pregnancy and 43% to paternal smoking and irregular maternal smoking. They concluded that maternal smoking was a strong risk factor for allergic sensitization and asthma symptoms during the first 10 years of life, but only in children with allergic parents. Our study did not show that the environmental factor of maternal smoking influenced allergic in uteri sensitization of infants, but we could not follow them for a long duration (12).

Lannerö et al analyzed 4089 families with children for environmental factors and symptoms of allergic disease. They found no evident association between maternal smoking during pregnancy and risk of IgE sensitization. However, a different study showed that there was an increased risk of sensitization to inhalant and/or food allergens among children exposed to environmental tobacco smoke (13). Our data indicated that maternal smoking during pregnancy did not influence the allergic sensitization of the infants in our study.

Aichbaumik et al investigated whether maternal exposure to pets affected cord blood IgE level. A total of 1258 mothers were evaluated by demographic and allergic history characteristics. Cord IgE data were also available from 1049 infants. Presence of indoor cats or dogs, maternal smoking during pregnancy, maternal atopy, birth weight and gestational age were analyzed. When they investigated for any affect of indoor pet exposure on umbilical cord IgE levels, they found that maternal exposure to indoor dogs or cats during pregnancy was associated with lower cord blood IgE levels (14). Their findings were similar to those of Kerkhof et al, who measured IgE levels by heal prick from 1027 infants in the Netherlands during the first week of life to assess for IgE to specific prenatal exposures, including pets. They determined that when dogs or cats were present in the home during pregnancy, there was a lower likelihood of having a detectable level of total IgE at birth. In addition to the effects of pet keeping on attenuating total and allergen specific IgE, there are many reports suggesting that pets decrease the risk for clinical atopy-related disorders. A predictor of elevated cord blood IgE level in their study, as well as in others, was positive for family history of atopy and allergic disease (14). In our study, the presence of indoor cats or dogs did not affect in utero sensitization. Infants did not reveal lower IgE levels, although pets were kept indoors during the intrauterine period. This study showed no correlation between cord blood levels of IgE and family history of atopy.

Bønnelykke et al examined for the relevance of allergen-specific IgE in cord blood to sensitization in early infancy. Inhalant and food allergen specific IgE in cord blood was analyzed and compared with specific IgE in infant blood at 6 months of age. Allergen specific IgE levels against inhalant allergens were detected in 14% of cord blood samples. Specific IgE in cord blood completely matched specific IgE in maternal blood, with respect to allergen specificity. Allergen specific IgE in cord blood did not reflect intrauterine sensitization but seemed to be the result of maternal-fetal transfer of IgE (15). Our study was supported by this study that did not confirm intrauterine sensitization.

Rowe J et al suggested that the development of atopic sensitization to peanut occurs postnatally rather than in uteri. T-cell cytokine responses and antibody assays of peanut-specific IgE and IgG were investigated in a cohort of 200 high-risk infants at birth and 6, 12 and 24 months of age. No association was found between cord blood T-cell reactivity and subsequent postnatal IgE sensitization at birth, whereas an increasingly strong association developed between these parameters at 6 months of age (16). In our study, maternal atopic sensitization did not reveal IgE sensitization in the cord blood of infants, but we could not perform a subsequent analysis of the infants' IgE levels at the 6-month follow-up.

A 2008 report sponsored by the American Academy of Pediatrics concluded that there was insufficient evidence to recommend that a woman whose child is at high-risk for allergic disease because of documented parental allergic disease avoid environmental allergens for the purpose of preventing allergic disease (17).

Depner et al investigated whether allergen specific memory was primed prenatally and whether it would cause persistent immunologic sensitization. The Protection against Allergy: Study in Rural Environments (PASTURE) birth control study included 793 children from rural regions of 5 European countries. Specific IgE levels for 6 food and 13 common inhalant allergens were analyzed from cord blood samples and compared with blood samples collected once the children turned one year old. Sensitization was more common in the one-year-old children than at birth for nearly all specificities. Persistent sensitization to the same allergen was rare (1%), whereas transient sensitization (only at birth, 11%) and specific incidents of sensitization (only at 12 months, 34%) were more common. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, IgE sensitization pattern, change between birth and 12 months and were related to maternal and environmental influences (18). Our study, did not confirm in utero sensitization because antigen specific IgE was not determined in the cord blood samples of infants.

Here, we observed that infants born from atopic mothers who had high IgE levels, showed no allergic sensitization. One limitation of this study was that we could not evaluate whether the sensitization patterns of infants would change during a one year follow up. In this study, we wanted to evaluate the immunological responses of neonates at risk of atopy, in relation to specific intrauterine exposures to environmental allergens; however, we did not find a relationship between maternal immune status and environmental factors on intrauterine sensitization. We feel that future comprehensive studies that include more subjects should be assessed to evaluate the influence of maternal exposure to allergens on intrauterine sensitization.

Table I. Evaluation of Maternal Immune Status

n

%

Tobacco smoking

Present

61

30.5

Absent

139

69.5

Passive smoking

Present

129

64.5

Absent

71

35.5

Maternal atopy

Present

19

9.5

Absent

181

90.5

Maternal allergic reaction

Present

19

9.5

Absent

181

90.5

Maternal allergic rhinitis

Present

19

9.5

Absent

181

90.5

Maternal bronchial asthma

Present

13

6.5

Absent

187

93.5

Maternal presence of IgE

Positive

97

48.5

Negative

103

51.5

Table II. Familial Evaluation of Allergic Status

n

%

Families keeping domestic pets

present

10

5

absent

190

95

Family history of atopy

present

17

8.5

absent

183

91.5

Family history of allergy

present

25

12.5

absent

175

87.5

Family history of asthma

present

44

22

absent

156

78

Table III. Evaluation of Neonatal Status According to Maternal IgE Levels

Maternal IgE

p

Negative

Positive

Mean ± SD

Mean ± SD

a Gestational age

38.87±1.09

38.75±1.27

0.472

a Birth weight

3298.80±397.22

3372.06±379.84

0.185

n (%)

n (%)

b Gender

Male

52 (50.5%)

49 (50.5%)

0.997

Female

51 (49.5%)

48 (49.5%)

b Domestic pets

Present

6 (5.8%)

4 (4.1%)

0.581

Absent

97 (94.2%)

93 (95.9%)

a Student t test b Chi-square test SD: Standard deviation

Table IV. Evaluation of Maternal Allergic Status According to Maternal IgE Levels

Maternal IgE

p

Positive

Negative

n (%)

n (%)

Tobacco Smoke

Present

33 (34%)

28 (27.2%)

0.294

Absent

64 (66%)

75 (72.8%)

Passive smoking

Present

60 (61.9%)

69 (67%)

0.448

Absent

37 (38.1%)

34 (33%)

Maternal Atopy

Present

12 (12.4%)

7 (6.8%)

0.179

Absent

85 (87.6%)

96 (93.2%)

Maternal Allergy

Present

13 (13.4%)

6 (5.8%)

0.068

Absent

84 (86.6%)

97 (94.2%)

Maternal Allergic Rhinitis

Present

15 (15.5%)

4 (3.9%)

0.005**

Absent

82 (84.5%)

99 (96.1%)

Maternal Asthma

Present

10 (10.3%)

3 (2.9%)

0.034*

Absent

87 (89.7%)

100 (97.1%)

Chi-square test was performed *p<0.05 **p<0.01

Table V. Evaluation of Neonatal IgE Levels According to Maternal IgE Levels

Neonatal IgE

Maternal IgE

p

Positive

Negative

n (%)

n (%)

Positive

1 (0.5%)

0

0.001**

Negative

96 (48%)

103 (51.5%)

Mc Nemar test was performed **p<0.01

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