SEARCH

SEARCH BY CITATION

Keywords:

  • aeroallergens;
  • antigen priming;
  • atopy;
  • intrauterine;
  • sensitization

Abstract

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

Background: The role of maternal allergen exposure during pregnancy in sensitization and development of atopic disease in the child remains controversial. In the spring of 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden. In 1994, the corresponding pollen levels were low. The aim of this study was to assess the influence of exposure during pregnancy to high/low doses of birch pollen on the risk of sensitization and development of atopic disease in children. In addition, a comparison was made with children exposed to birch pollen in early infancy.

Methods: Three hundred and eighty-seven children with atopic heredity, born in Stockholm in July–October 1993 or 1994 (mothers exposed during pregnancy), were investigated at age 4.5 years. The children were clinically examined and were skin prick tested (SPT) with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analysed in serum. A comparison was made with a similar group of children exposed during the same incident, but in the first 3 months of life, in 1993.

Results: The children of mothers high-dose exposed during pregnancy in 1993 tended to be more sensitized (SPT ≥ 3 mm) to birch pollen than the children with low-dose exposure during the corresponding period in 1994 (7.6 and 4.6%, respectively, OR: 1.7; 95% CI: 0.7–4.1). A similar but weak tendency was seen for positive RAST analyses (≥0.35 kU/l) against birch pollen and rBet v 1. Children of mothers high-dose exposed during pregnancy were significantly less sensitized to birch pollen than the children high-dose exposed in early infancy (17.9%, OR: 0.4; 95% CI: 0.2–0.7). There was an overall trend towards a slightly increased prevalence of bronchial asthma, allergic rhinoconjunctivitis and atopic dermatitis in the group with mothers high-dose exposed during pregnancy, compared to those with low exposure.

Conclusion: Exposure of the mother during pregnancy to high levels of birch pollen resulted in a tendency towards increased risk of sensitization to the same allergen and symptoms of atopic disease in children with atopic heredity. Furthermore, our data indicate that exposure of the mother during pregnancy to inhalant allergens is less likely to result in sensitization in the child than exposure of the child in early infancy.

Abbreviations
CI

confidence interval

i.u.

in utero

OR

odds ratio

rBet v 1

recombinant birch pollen allergen

SPT

skin prick test

Over the past decades, the prevalence of allergic diseases in childhood has increased considerably, especially in many western industrialized countries (1, 2). Changes in allergen exposure, early infections and life style factors may be contributing factors (3–6).

Several studies have tried to clarify the relation between early exposure to inhalant allergens, sensitization and development of atopic disease (7–13). It has been suggested that initial priming of the T-cell system to environmental allergens may occur before birth (14, 15). Several in vitro studies of immune stimulation of mononuclear cells from cord blood and the peripheral circulation have shown specific responses to allergen stimulation (16–19). It has been postulated that a specific allergen-induced response can occur from the 22nd week of gestation (20), and that this is specific to the foetus and not due to maternal contamination (19). In addition, the infants of atopic and nonatopic mothers may have different immune responses (21, 22). However, the clinical significance of these immune reactions remains unclear (11). Is it just a transient phenomenon, or could it contribute to long-lasting immune modulation?

In the spring of 1993, birch pollen levels in Stockholm were more than 50 times higher than in 1994. This phenomenon provided a unique opportunity to investigate the effect of allergen exposure in utero (i.u.) in groups of children born during the same season, but in different years. The aim of this study was to evaluate whether high-dose exposure to birch pollen of the mother during pregnancy correlated with sensitization and atopic disease in the child. Furthermore, a comparison is made with children high-dose exposed during the same incident in early infancy in 1993, which was the focus of a previous study (23).

Study population

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

Children living in southwestern Stockholm (Brännkyrka, Skärholmen, Hägersten, Huddinge and Botkyrka municipalities) and born in Stockholm County in July–October 1993 or 1994 (mothers exposed during pregnancy) were investigated (Table 1). A total of 1725 children were identified from birth records. When the children were 4 years old, the families were approached with a questionnaire concerning allergic symptoms in the children and their parents. Answers were obtained for 1405 children (81.4%), and 803 of these reported a family history (one or both parents) of atopic disease including asthma, allergic rhinoconjunctivitis, atopic dermatitis and/or food allergy. Among these, 538 children were randomly selected and invited to participate in the study. From this group, a total of 117 declined to participate or did not come to the clinical examination, which left 387 children for clinical assessment (189 and 198 children in the respective year-groups).

Table 1.  Selection of children for the study
 High-dose exposure to birch during pregnancy; children born in 1993Low-dose exposure to birch during pregnancy; children born in 1994
  1. * Randomly selected among those with atopic heredity who answered the screening questionnaire.

Screening stage
 Selected for screening863864
 Responded to screening questionnaire666 (77.2%)739 (86.0%)
 Atopic heredity by history375428
Clinical assessment
 Invited*269269
 Declined participation5859
 Did not come for examination2212
Final study groups189198

Another group of children exposed in early infancy has been described in detail in a previous study (23). The families of 781 children were approached with a questionnaire and 666 answered (85.3%). A total of 197 children were randomly selected for clinical assessment in the same way as described above. They were born in 1993 (February–April), and exposed to high doses of birch pollen at 0–3 months of age.

The local ethics committee at Huddinge University Hospital approved the study. Informed consent was obtained from parents and children.

Medical examination

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

All children were examined at the age of 4.5–5 years in the paediatric allergy clinic at Huddinge University Hospital by the same paediatrician (A.K.). The parents were asked to complete a questionnaire about atopic symptoms in the child as well as social and environmental factors, i.e. early infections, number of siblings, pets in the household, time of breastfeeding and parental smoking. Each child was clinically classified with respect to asthma, allergic rhinoconjunctivitis, atopic dermatitis and food allergy. Bronchial asthma was defined as three or more episodes of wheezing, or any episode of wheezing if related to exposure to pollen and/or furred pets. Among the children with bronchial asthma, allergic asthma was diagnosed if the children reacted with wheezing when exposed to pollen and/or furred pets, during a period free of airway infection. Allergic rhinoconjunctivitis was diagnosed if rhinitis and/or conjunctivitis appeared at least twice after exposure to a particular allergen and/or seasonal exposure and was unrelated to an infection. Atopic dermatitis was defined according to Hanifin and Rajka (24). Food allergy was diagnosed as acute onset of symptoms such as skin reactions, wheezing, vomiting or diarrhoea on more than one occasion after ingestion of or contact with a particular food.

Skin prick test (SPT) was performed against inhalant and food allergens. All SPTs were performed by the same nurse, on the volar side of the lower arm according to the manufacturer's instructions (ALK, Copenhagen, Denmark). The SPT included allergens from birch, timothy grass, cat, dog, horse, Dermatophagoides pteronyssinus, cladosporium species, (Soluprick, 10 Histamine equivalent potency, ALK), egg white (Soluprick, weight to volume ratio 1/100), codfish (Soluprick, 1/20), peanut (Soluprick, 1/20), hazelnut (Soluprick, 1/20), cow's milk (3% fat, standard milk), and soy bean protein (Soluprick, 1/20). Histamine chloride (10 mg/ml) was used as a positive control, and the allergen diluent as the negative control. A wheal diameter ≥3 mm recorded after 15 min was considered positive. In accordance with Pepys’ definition (25), a child with at least one positive SPT was classified as atopic.

For IgE assays, a blood sample was obtained from the arm vein after local anaesthesia (EMLA®). The blood was centrifuged at 1200 g and serum was separated and stored at –18°C. Circulating IgE antibodies against birch pollen and rBet v 1 were determined with the Pharmacia CAP-system (Pharmacia Upjohn, Uppsala, Sweden). An IgE antibody level ≥0.35 kU/l was considered significant.

Pollen measurements

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

Pollen counts have been recorded continuously since 1973 at the Swedish Museum of Natural History in Stockholm, using a Burkard trap. In this suction trap, pollen enters a narrow orifice, directed into the wind, and adheres to a Vaseline- and glycerine-coated celluloid tape on a slowly rotating drum. Once daily, the tape is transferred to microscope slides and examined for estimation of the pollen content of the air (26, 27).

Statistical analysis

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

Data were analysed by using Stata 7.0 software (Stata Corporation, College Station, TX). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for signs and symptoms of atopy in children of mothers exposed during pregnancy in 1993 in relation to children of mothers exposed during the corresponding period in 1994. Similar calculations were performed for children of mothers exposed during pregnancy in 1993 and children exposed in early infancy during the same year. Data were adjusted for differences in background variables using multiple logistic regression analysis. These variables reflected the situation after birth of the child: breastfeeding exclusively during the first 4 months of life, maternal smoking and furred pets (cats, dogs, rodents) in the household.

Results

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

The total pollen counts for the two spring seasons (April–May, mainly birch pollen) reported in Stockholm were 26 805 counts/m3 in 1993 and 435 counts/m3 in 1994 (Fig. 1). The total pollen counts for the two corresponding summer seasons (June–August, mainly grass pollen) were 826 counts/m3 in 1993 and 1534 counts/m3 in 1994. In comparison, the pollen counts in 1995 were 9069 counts/m3 for the spring season and 2523 counts/m3 for the summer season.

image

Figure 1. The total pollen counts for the two spring seasons (April–May, mainly birch pollen). 1993, 26 805 and 1994, 435 counts/m3 air.

Download figure to PowerPoint

The 387 children participating in the study included 200 boys and 187 girls. The mean age at examination was 4.6 years (range 4.5–4.8 years). Demographic data are presented in Table 2. The groups were generally comparable regarding breastfeeding, maternal smoking and exposure to pets. However, the mothers of the children born in 1994 smoked less during pregnancy and the first 3 months of the baby's life, than the mothers of the children born in 1993. The number of older siblings and family history of asthma, atopic eczema or food allergy did not differ between groups (not shown in Table 2).

Table 2.  Demographic data and risk factors for atopic disease in children of Stockholm, mothers exposed to pollen during pregnancy in 1993 or 1994
Characteristics (%)High-dose exposure to birch during pregnancy; children born in 1993 (n = 189)Low-dose exposure to birch during pregnancy; children born in 1994 (n = 198)
Demographic
 Age, mean (years)4.64.6
 Age, range4.5–4.84.5–4.8
 M/F98/91102/96
Risk factors
Breast-feeding
 Exclusively ≤4 months51 (27.0%)48 (24.2%)
Household pets
 Ever (after birth of child)72 (38.1%)70 (35.4%)
 0–3 months of age51 (25.9%)45 (22.7%)
Cat
 Ever (after birth of child)37 (19.6%)35 (17.7%)
 0–3 months of age29 (16.0%)30 (15.5%)
 Only during pregnancy4 (2.2%)4 (2.2%)
Maternal smoking
 Ever50 (26.5%)41 (20.7%)
 Present39 (20.6%)29 (14.7%)
 0–3 months of age43 (22.8%)23 (11.6%)
 During pregnancy43 (22.8%)24 (12.1%)
Paternal smoking
 Ever47 (24.9%)46 (23.2%)
 Present38 (20.1%)38 (19.1%)
Parental atopy (heredity by history)
 Mother137 (72.5%)139 (70.2%)
 Father104 (55.0%)118 (59.6%)
 Both55 (29.1%)61 (30.9%)

Clinical data as well as SPT and RAST results are presented in Table 3. Five children refused the SPT, and nine declined intravenous blood test. There was an overall trend that the children of mothers exposed during pregnancy in 1993 (high-dose exposed) tended to develop more symptoms of atopic disease than children of mothers exposed during the corresponding period in 1994 (low-dose exposed). The cumulative incidences (by case history) of pollen- and/or animal dander-induced asthma were 7.4% (1993) and 5.1% (1994), respectively, and for bronchial asthma in general 28.6 and 22.7%. The cumulative incidences of atopic dermatitis were 49.7 and 38.9%, and for allergic rhinoconjunctivitis 15.3 and 11.6%.

Table 3.  Signs and symptoms of atopy in children aged 4–5 years in Stockholm, mothers exposed to birch pollen during pregnancy during the pollen season in 1993 or 1994
  High-dose exposure to birch during pregnancy; children born in 1993 (n = 189)Low-dose exposure to birch during pregnancy; children born in 1994 (n = 198)
Clinical symptoms or history of atopic disease
Total100 (52.9%)91 (46.0%)
 Bronchial asthma54 (28.6%)45 (22.7%)
 Previous23 (12.2%)16 (8.1%)
 Current31 (16.4%)29 (14.7%)
 Allergic asthma14 (7.4%)10 (5.1%)
 Atopic dermatitis94 (49.7%)75 (38.9%)
 Previous22 (11.6%)14 (7.1%)
 Current72 (38.1%)60 (30.3%)
 Allergic rhinoconjunctivitis29 (15.3%)23 (11.6%)
 Food allergy18 (9.5%)17 (8.6%)
Skin prick test
 Test done187 (98.9%)195 (98.5%)
 Any positive result35 (18.9%)35 (18.0%)
 Birch14 (7.6%)9 (4.6%)
 Timothy grass15 (8.1%)7 (3.6%)
 Cat18 (9.7%)18 (9.2%)
 Dog10 (5.4%)11 (5.6%)
 Horse4 (2.1%)5 (2.6%)
 D. pteronyssinus1 (0.5%)3 (1.5%)
 Cladosporium1 (0.5%)2 (1.0%)
 Hen's egg1 (0.5%)1 (0.5%)
 Hazelnut5 (2.7%)1 (0.5%)
 Peanut9 (4.9%)9 (4.6%)
 Cod fish0 (0.0%)1 (0.5%)
 Milk2 (1.1%)0 (0.0%)
 Soy1 (0.5%)1 (0.5%)
RAST, birch
 Test done183 (96.8%)194 (97.9%)
 Positive test14 (7.6%)12 (6.2%)
RAST, rBet v 1
 Test done179 (94.7%)195 (98.4%)
 Positive test13 (7.3%)11 (5.6%)

Furthermore, the children of mothers exposed during pregnancy in 1993 tended to be more sensitized (i.e. a larger proportion of them had positive SPT) to birch than children of mothers exposed during the corresponding period in 1994 (7.6 and 4.6%, respectively). They also more frequently had positive SPT to timothy grass (8.1 and 3.6%, respectively) and positive SPT to hazelnut (2.7 and 0.5%, respectively). The results from SPT for cat and the other allergens tested were comparable in the two groups. The number of positive RAST analyses against birch was similar in the two groups of children, 7.6% (1993) and 6.2% (1994), when the cut-off level used was ≥0.35 kU/l. The RAST analyses against rBet v 1 followed the same pattern.

After adjusting for potential confounders (gender, maternal smoking, breastfeeding and domestic pets), an overall trend towards increased risk of atopic symptoms and sensitization in the high-dose exposed group was seen (Table 4). Asthma, allergic asthma and allergic rhinoconjunctivitis tended to be increased among children of mothers high-dose exposed during pregnancy. For atopic dermatitis the increase was statistically significant (OR: 1.6; 95% CI: 1.1–2.5). The occurrence of SPT-positivity to birch as well as RAST-positivity to birch and rBet v 1 also tended to be increased among mothers high-dose exposed during pregnancy. For sensitization to timothy grass the increase was statistically significant (OR: 2.4; 95% CI: 1.0–6.1).

Table 4.  Odds ratio for signs and symptoms of atopy in children aged 4 to 5 years in Stockholm, and exposed during pregnancy to the pollen season in 1993 (high-dose exposure), in relation to children exposed during pregnancy in 1994 (low-dose exposure), or exposed postnatally in 1993
 1993 i.u./1994 i.u. Odds ratio (95% CI)*1993 i.u./1993 p.n. Odds ratio (95% CI)*
  1. * Odds ratio (95% confidence interval) adjusted for gender, maternal smoking, breastfeeding and pets in the household. If the confidence interval did not include 1.0, the result is statistically significant at the P < 0.05 level.

  2. † Clinical symptoms or history of atopic disease.

  3. i.u., in utero; p.n., postnatally.

Atopy†1.3 (0.9–2.0)1.0 (0.7–1.5)
Bronchial asthma1.3 (0.8–2.1)1.3 (0.8–2.1)
Allergic asthma1.5 (0.6–3.4)0.6 (0.3–1.1)
Allergic rhinoconjunctivitis1.4 (0.7–2.4)0.9 (0.5–1.5)
Atopic dermatitis1.6 (1.1–2.5)1.5 (1.0–2.2)
Any Pos SPT response1.1 (0.6–1.8)0.6 (0.4–0.9)
Pos SPT response to birch1.7 (0.7–4.1)0.4 (0.2–0.7)
Pos RAST result to birch1.3 (0.5–2.8)0.4 (0.2–0.9)
Pos RAST result to rBet v 11.3 (0.6–3.0)0.4 (0.2–1.0)
Pos SPT response to timothy grass2.4 (1.0–6.1)1.0 (0.5–2.1)
Pos SPT response to cat1.1 (0.5–2.1)0.8 (0.4–1.6)

Children of mothers high-dose exposed during pregnancy were less sensitized to birch pollen than the children exposed in early infancy in 1993 (measured by SPT and RAST). No consistent difference was seen for sensitization to other allergens or for atopic symptoms.

Discussion

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

This study suggests that exposure of the mother to high levels of airborne birch pollen during pregnancy may be associated with a slightly increased prevalence of positive SPT to birch in children with atopic heredity. RAST analysis against birch pollen and rBet v 1 supported the SPT results. The clinical outcome of atopic symptoms was more moderate. An increase of atopic dermatitis was seen, and an overall trend towards increase of other symptoms of atopic disease. In a previous publication, we have shown in children with atopic heredity that exposure to high levels of birch pollen in early infancy (i.e. the first 3 months of life) significantly increases the risk of sensitization (number of positive SPT and/or RAST) to the same allergen, as well as of allergic asthma. In addition, some susceptibility could remain during the first year of life (23).

Can our observations on sensitization towards tree and grass pollens be explained by the present knowledge of maternal–foetal immune regulation and pre- and postnatal exposure to antigens/allergens? There appears to be both a maternal and a placental influence on the developing foetal immune response. Thus, in a double-sided ex vivo placenta model, Bet v 1 and other allergens were shown to cross the placenta (28). Besides, antigens could be introduced to the foetus by antigen-presenting cells in the placenta and/or through the foetal gut when the foetus swallows the amniotic fluid (29). Signs of foetal IgE production can be detected already from 8 weeks of gestation (30). In addition, from 22 weeks of gestation foetal T-cells appear to respond to several allergens (house dust mite, cat fur, birch tree pollen, β-lactoglobulin and ovalbumin) (20). This response is of foetal origin and is not due to maternal contamination, as shown by DNA extracted from foetal T-cell clones (19). It was recently shown that mononuclear cells from cord blood can proliferate after stimulation with inhalant and food allergens, indicating possible allergen priming i.u. (16–18, 28). Taken together, these observations point towards a possibility for birch pollen to induce an immune response in the growing foetus, including synthesis of allergen-specific IgE. However, the significance of a foetal or neonatal response to allergens is not clear, and these responses could be different from more mature postnatal memory responses. Furthermore, the mechanisms of sensitization and further development of atopic disease might not be identical.

Little is known about the importance of high or low dose of allergen exposure of the pregnant woman/foetus. In animal models, low-dose allergen exposure has induced IgE synthesis, while high doses resulted in development of tolerance (31). Furthermore, low- and high-dose allergen exposure might induce different cytokine patterns (32). Since allergen exposure induces IgG synthesis, it has been postulated that these antibodies, passing the placenta, might contribute to tolerance by protecting the baby from IgE sensitization during early infancy (14, 17, 28, 33). A corresponding protective mechanism has been discussed for newborn infants of mothers undergoing immunotherapy during pregnancy (34) or pregnant women who consume different amounts of cow's milk and hen's egg during the third trimester (35). If maternal IgG antibodies can influence the postnatal IgE immune regulation of the child, these antibodies might also interfere in IgE regulation already i.u. Maternal pollen-antigen-specific IgG levels have been considered low during the months prior to the pollen season (33). Thus, maternal birch-pollen-specific IgG, transferred to the foetus during pregnancy, might have been insufficient to protect an infant exposed postnatally to the extremely high levels of birch pollen noted in the year of 1993. This could explain why children high-dose exposed during early infancy (0–3 months) were more sensitized (positive SPT and/or RAST) to birch pollen than the children exposed i.u. In addition, the birch pollen doses reaching the foetus would be low compared to the airborne levels, and the foetus is most likely protected to a large extent from normal seasonal fluctuations.

Interestingly, the children of mothers exposed to birch pollen during pregnancy in 1993 were more sensitized to timothy grass, although the levels of grass pollen in 1993 were considerably lower than in 1994 and 1995. It has been suggested that grass allergen more easily passes the placenta barrier than rBet v 1 (16, 36). Furthermore, certain allergens such as timothy grass and cow's milk proteins seem to induce foetal T-cell-priming more often than other allergens (36). The intense birch pollen season in 1993 may have initiated priming of the foetal immune system, which was further activated during the grass pollen season the same year.

The differences in clinical outcome between the study groups were moderate. There was a tendency that high-dose exposure of mothers during pregnancy increased the risk of development of asthma and rhinoconjunctivitis in the child. Furthermore, the excess of atopic dermatitis among the infants of mothers exposed to a high dose of birch pollen during pregnancy was significant. An explanation for the discrepancy in prevalence between eczema and respiratory allergies might be that most cases of atopic dermatitis have appeared from birth to the age of 5 years while the prevalence of bronchial asthma and allergic rhinoconjunctivitis will further increase with age of the children. The cumulative incidences of bronchial asthma were 28.6% (exposed i.u. in 1993) and 22.7% (exposed i.u. in 1994), respectively. These results are in agreement with our previous study on postnatal exposure to birch pollen and the development of atopic disease (23), and could partly be explained by the selection of children with atopic heredity. At least 20% of the children had one or two parents with asthma. Besides, all families lived in an urban area. These factors could increase the risk of development of asthma (36). In addition, the group of infants born in July–September 1993 (high-dose exposed in 1993), were only a few months old in the winter of 1993–1994 when there was an unusually intense epidemic of respiratory syncytial virus (RSV) in Stockholm County (37). RSV infections early in life can have an influence on the development of childhood asthma (38). The cumulative incidence of allergic asthma in children exposed during pregnancy, when children reacted to pollen and/or furred pets, was only 7.4% (1993) and 5.1% (1994), respectively. This could be compared with the incidence of allergic asthma in children exposed in early infancy in 1993 (12.2%, high-dose exposure) and 1994 (5.1%, low-dose exposure) (23). Our data indicate that high dose allergen exposure in early infancy increases the risk of allergen-induced asthma (23), whereas the children of mothers exposed during pregnancy are not as strongly affected.

In cross-sectional studies, certain types of bias must be taken into consideration, such as recall bias from disease-related misclassification of exposure and selection bias (39). In our study, the year-groups of children were selected in exactly the same way and allergen exposure was assessed objectively. Furthermore, the children were less than 5 years old at the time of the investigation, and parents probably still remember quite well. In addition, our data were adjusted for potential confounding factors like heredity, gender, parental smoking, breastfeeding and domestic pets. Even if the information of these factors was partly inaccurate, we do not believe that the degree differed between the year-groups.

In conclusion, exposure of the mothers to high levels of birch pollen during pregnancy resulted in an overall tendency towards increased risk of sensitization to the same allergen and symptoms of atopic disease in children with atopic heredity. Exposure of the mother during pregnancy to inhalant allergens appeared less likely to result in sensitization and allergic asthma in the child than exposure in early infancy. However, it should be kept in mind that the birch pollen doses reaching the foetus should be considerably lower than in children exposed after birth.

Acknowledgments

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References

We thank Rosie Boo, Yvonne Hyllensved and Monica Nordlund for excellent assistance, The Swedish Museum of Natural History, Palynological laboratory for providing the pollen records and Pharmacia Diagnostic AB for supply of reagents. This grant was supported by the Swedish Foundation for Health Care Sciences and Allergy Research, the Swedish Asthma and Allergy Association, Consul Th C Bergh's Foundation, Swedish Order of Freemasons and the Samariten Foundation.

References

  1. Top of page
  2. Abstract
  3. Methods
  4. Study population
  5. Medical examination
  6. Pollen measurements
  7. Statistical analysis
  8. Results
  9. Discussion
  10. Acknowledgments
  11. References
  • 1
    The International Study of Asthma and Allergies in Childhood (ISAAC) Steering Committee. Worldwide variation in prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and atopic eczema. Lancet 2001;351: 12251232.
  • 2
    Aberg N, Hesselmar B, Aberg B, Eriksson B. Increase of asthma, allergic rhinitis and eczema in Swedish schoolchildren between 1979 and 1991 (see comments). Clin Exp Allergy 1995;25: 815819.
  • 3
    Alm JS, Lilja G, Pershagen G, Scheynius A. Early BCG vaccination and development of atopy (see comments). Lancet 1997;350: 400403.
  • 4
    Von Mutius E, Braun-Fahrlander C, Schierl R, Riedler J, Ehlermann S, Maisch S et al. Exposure to endotoxin or other bacterial components might protect against the development of atopy. Clin Exp Allergy 2000;30: 12301234.
  • 5
    Alm JS, Swartz J, Lilja G, Scheynius A, Pershagen G. Atopy in children of families with an antrophosophic lifestyle. Lancet 1999;353: 14851488.
  • 6
    Braun-Fahrlander C, Gassner M, Grize L, Neu U, Sennhauser FH, Varonier HS et al. Prevalence of hay fever and allergic sensitization in farmer's children and their peers living in the same rural community. SCARPOL team. Swiss Study on Childhood Allergy and Respiratory Symptoms with Respect to Air Pollution. Clin Exp Allergy 1999;29: 2834.
  • 7
    Wahn U, Lau S, Bergmann R, Kulig M, Forster J, Bergmann K et al. Indoor allergen exposure is a risk factor for sensitization during the first three years of life. J Allergy Clin Immunol 1997;99: 763769.
  • 8
    Miller RL, Chew GL, Bell CA, Biedermann SA, Aggarwal M, Kinney PL et al. Prenatal exposure, maternal sensitization, and sensitization in utero to indoor allergens in an inner-city cohort. Am J Respir Crit Care Med 2001;164: 9951001.
  • 9
    Custovic A, Simpson BM, Simpson A, Kissen P, Woodcock A. Effect of environmental manipulation in pregnancy and early life on respiratory symptoms and atopy during first year of life: a randomised trial. Lancet 2001;358: 188193.
  • 10
    Chan-Yeung M, Ferguson A, Chan H, Dimich-Ward H, Watson W, Manfreda J et al. Umbilical cord blood mononuclear cell proliferative response to house dust mite does not predict the development of allergic rhinitis and asthma. J Allergy Clin Immunol 1999;104: 317321.
  • 11
    Smillie FI, Elderfield AJ, Patel F, Cain G, Tavenier G, Brutsche M et al. Lymphoproliferative responses in cord blood and at one year: no evidence for the effect of in utero exposure to dust mite allergens. Clin Exp Allergy 2001;31: 11941204.
  • 12
    Lau S, Illi S, Sommerfeld C, Niggemann B, Bergmann R, Von Mutius E et al. Early exposure to house-dust mite and cat allergens and development of childhood asthma: a cohort study. Multicentre Allergy Study Group. Lancet 2000;356: 13921397.
  • 13
    Lindfors A, Wickman M, Hedlin G, Pershagen G, Rietz H, Nordvall SL. Indoor environmental risk factors in young asthmatics: a case-control study. Arch Dis Child 1995;73: 408412.
  • 14
    Warner JO, Jones CA, Kilburn SA, Vance GH, Warner JA. Pre-natal sensitization in humans. Pediatr Allergy Immunol 2000;11(Suppl. 13):68.
  • 15
    Devereux G, Seaton A, Barker RN. In utero priming of allergen-specific helper T cells. Clin Exp Allergy 2001;31: 16861695.
  • 16
    Duren-Schmidt K, Pichler J, Ebner C, Bartmann P, Forster E, Urbanek R et al. Prenatal contact with inhalant allergens. Pediatr Res 1997;41: 128131.
  • 17
    Szepfalusi Z, Nentwich I, Gerstmayr M, Jost E, Todoran L, Gratzl R et al. Prenatal allergen contact with milk proteins. Clin Exp Allergy 1997;27: 2835.
  • 18
    Piccinni MP, Mecacci F, Sampognaro S, Manetti R, Parronchi P, Maggi E et al. Aeroallergen sensitization can occur during fetal life. Int Arch Allergy Immunol 1993;102: 301303.
  • 19
    Prescott SL, Macaubas C, Holt BJ, Smallacombe TB, Loh R, Sly PD et al. Transplacental priming of the human immune system to environmental allergens: universal skewing of initial T cell responses toward the Th2 cytokine profile. J Immunol 1998;160: 47304737.
  • 20
    Jones CA, Kilburn SA, Warner JA, Warner JO. Intrauterine environment and fetal allergic sensitization. Clin Exp Allergy 1998;28: 655659.
  • 21
    Williams TJ, Jones CA, Miles EA, Warner JO, Warner JA. Fetal and neonatal IL-13 production during pregnancy and at birth and subsequent development of atopic symptoms. J Allergy Clin Immunol 2000;105: 951959.
  • 22
    Kopp MV, Zehle C, Pichler J, Szepfalusi Z, Moseler M, Deichmann K et al. Allergen-specific T cell reactivity in cord blood: the influence of maternal cytokine production. Clin Exp Allergy 2001;31: 15361543.
  • 23
    Kihlström A, Lilja G, Pershagen G, Hedlin G. Exposure to birch pollen in infancy and development of atopic disease in childhood. J Allergy Clin Immunol 2002;110: 7884.
  • 24
    Hanifin JM, Rajka G. Diagnostic features of atopic dermatitis. Acta Derm Venereol 1980;92(Suppl.):4447.
  • 25
    Pepys J. Clinical aspects of immunology, 3rd edn. Oxford: Blackwell Scientific Publications, 1975;877902.
  • 26
    Hirst JM. An automatic volumetric spore trap. Ann Appl Biol 1952;39: 257265.
  • 27
    Berggren B, Nilsson S. Pollensäsongen 1992–1995. Swedish Museum of Natural History, Palynological laboratory Stockholm, 1995.
  • 28
    Szepfalusi Z, Loibichler C, Pichler J, Reisenberger K, Ebner C, Urbanek R. Direct evidence for transplacental allergen transfer. Pediatr Res 2000;48: 404407.
  • 29
    Jones CA, Vance GH, Power LL, Pender SL, Macdonald TT, Warner JO. Costimulatory molecules in the developing human gastrointestinal tract: a pathway for fetal allergen priming. J Allergy Clin Immunol 2001;108: 235241.
  • 30
    Lima JO, Zhang L, Atkinson TP, Philips J, Dasanayake AP, Schroeder HW, Jr. Early expression of iepsilon, CD23 (FcepsilonRII), IL-4Ralpha, and IgE in the human fetus. J Allergy Clin Immunol 2000;106: 911917.
  • 31
    Jarrett E, Hall E. Selective suppression of IgE antibody responsiveness by maternal influence. Nature 1979;280: 145147.
  • 32
    Friedman A, Weiner HL. Induction of anergy or active suppression following oral tolerance is determined by antigen dosage. Proc Natl Acad Sci USA 1994;91: 66886692.
  • 33
    Jenmalm MC, Holt PG, Bjorksten B. Maternal influence on IgG subclass antibodies to Bet v 1 during the first 18 months of life as detected with a sensitive ELISA. Int Arch Allergy Immunol 1997;114: 175184.
  • 34
    Glovsky MM, Ghekiere L, Rejzek E. Effect of maternal immunotherapy on immediate skin test reactivity, specific rye I IgG and IgE antibody, and total IgE of the children. Ann Allergy 1991;67: 2124.
  • 35
    Lilja G, Dannaeus A, Falth-Magnusson K, Graff-Lonnevig V, Johansson SG, Kjellman NI et al. Immune response of the atopic woman and foetus: effects of. Clin Allergy 1988;18: 131142.
  • 36
    Szepfalusi Z, Pichler J, Elsasser S, Van Duren K, Ebner C, Bernaschek G et al. Transplacental priming of the human immune system with environmental allergens can occur early in gestation. J Allergy Clin Immunol 2000;106: 530536.
  • 37
    Reyes M, Eriksson M, Bennet R, Hedlund KO, Ehrnst A. Regular pattern of respiratory syncytial virus and rotavirus infections and relation to weather in Stockholm, 1984–1993. Clin Microbiol Infect 1997;3: 640646.
  • 38
    Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B. Respiratory syncytial virus bronchiolitis in infancy is an important risk factor for asthma and allergy at age 7. Am J Respir Crit Care Med 2000;161: 15011507.
  • 39
    Pershagen G. Challenges in epidemiologic allergy research. Allergy 1997;52: 10451049.