Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age:
a prospective cohort study
Bright I. Nwaru, Tampere School of Public Health, FIN-33014, University of Tampere, Finland
Nwaru BI, Ahonen S, Kaila M, Erkkola M, Haapala A-M, Kronberg-Kippilä C, Veijola R, Ilonen J, Simell O, Knip M, Virtanen SM. Maternal diet during pregnancy and allergic sensitization in the offspring by 5 yrs of age: a prospective cohort study.
Pediatr Allergy Immunol 2010: 21: 29–37.
© 2009 John Wiley & Sons A/S
To examine the effect of maternal diet during pregnancy on allergic sensitization in the offspring by 5 yrs of age. The Finnish type 1 Diabetes Prediction and Prevention Nutrition Study. A population-based cohort study with 5-yr follow-up. A total of 931 children with human leukocyte antigen-conferred susceptibility to type 1 diabetes for whom maternal pregnancy food frequency questionnaire data and allergen-specific immunoglobulin E measurement at 5 yrs were available. Increasing maternal consumption of citrus fruits [odds ratio (OR) = 1.14, 95% confidence interval (CI) = 1.05–1.25] and total fruit (OR = 1.36, 95% CI = 1.09–1.70) were positively associated with sensitization to inhalant allergens, after adjustment for potential confounders. Maternal intake of vitamin D (OR = 0.56, 95% CI = 0.35–0.91) was inversely associated with sensitization to food allergens. Maternal consumption of citrus fruits during pregnancy may increase the risk to allergic sensitization in the offspring, whereas vitamin D intake may have a beneficial effect. Further studies are required to define more closely the putative effect of maternal intake of polyunsaturated fatty acids on development of allergic diseases in the offspring.
Allergen-specific immunoglobulin E (IgE) responses have been indicated as an important precursor to the development of allergic diseases in childhood (1, 2). IgE sensitization is believed to be initiated very early in life, possibly already in utero (3, 4). Maternal diet during pregnancy has been implicated to be associated with early IgE sensitization and subsequent development of allergic diseases in children (5, 6). During pregnancy, vital nutrients are transported from the mother to the fetus across the placenta (4). The intrauterine milieu plays an important role in regulating fetal immune responses. It may also serve as an avenue for the transfer of dietary allergen exposures from the mother to the fetus (7). This implies that allergy-related dietary factors might have already started exerting their influence before birth (3).
There are limited number of studies that have prospectively investigated the relation between maternal diet during pregnancy and the development of allergic diseases in childhood. Nevertheless, most studies have focused mainly on the relation between maternal nutrient intake during pregnancy and allergic outcomes; thus only a few studies have examined the effect of specific foods and food groups. Furthermore, not many studies have considered IgE sensitization as an end-point of allergic outcome.
Diet is a modifiable exposure. Therefore, ascertaining the role of maternal dietary intake during pregnancy in the development of allergic diseases in childhood may provide an important measure to early dietary prevention of childhood atopy. The aim of the present study was to examine whether maternal diet during pregnancy is associated with allergic sensitization in the offspring by 5 yrs of age. Our population-based prospective cohort study presents an opportunity to define the role of maternal diet during pregnancy on the development of allergic diseases in the offspring. We assessed maternal diet both on the food and nutrient levels.
Subjects and methods
The subjects in this study represent mother–child pairs participating in the Finnish Type 1 Diabetes Prediction and Prevention (DIPP) Nutrition Study, which falls within the framework of the larger DIPP study. Description of the DIPP and DIPP Nutrition Study has been presented elsewhere (8). Briefly, the DIPP study, which started in 1994, is an ongoing population-based prospective cohort study aimed at exploring possible means to prevent the development of type 1 diabetes. All newborn infants with human leukocyte antigen (HLA)-conferred susceptibility to type 1 diabetes are recruited from the university hospital areas of Turku, Oulu, and Tampere. A nutrition study was initiated within the framework of the DIPP Project in Oulu and Tampere in September 1996 and October 1997, respectively. Thus, the study aims at examining the effect of maternal diet during pregnancy and lactation in line with child’s diet during infancy and childhood on the development of type 1 diabetes, allergic diseases and asthma in children. At the age of 5 yrs, a questionnaire modified from the International Study of Asthma and Allergies in Childhood questionnaire was administered and blood sample measurement for IgE assessment was taken from each child.
Between August 1, 1998 and July 31, 2000, 1175 consecutively born children were invited to the allergy study at the age of 5 yrs. Out of these, 1067 (91%) participated in the study. However, serum IgE measurements were performed in 1018 participants (87% of those invited to the study) with a blood sample available. Of the 1018 children, 78 had only serum IgE available, while maternal Food Frequency Questionnaire (FFQ) data was available for 940. Nine FFQ of the 940 were rejected because of incompleteness of information. Therefore, the present analysis involves 931 children with complete FFQ information and IgE analysis. The study was approved by the Ethical Committees of the Universities of Oulu and Tampere, Finland.
Assessment of maternal diet during pregnancy
A validated 181-item FFQ was used to assess maternal food intake during the 8th month of pregnancy and use of dietary supplements during the whole pregnancy period (9). Mothers received the questionnaire after delivery and returned it at the 3-month visit of the child to the study center. The questionnaires were subsequently checked by a study nurse. The food frequency data were converted to each mother’s daily average food and nutrient intakes with a software developed by the National Public Health Institute in Helsinki, taking into account women’s individual choices of types of fat used in food preparations and baking, and oils used for salad dressing (10). The foods and food groups we have considered in the present analysis are presented in Appendix 1.
Immunoglobulin E measurement
Specific IgE concentrations were assayed from the children at 5 yrs of age, using ImmunoCAP fluoroenzyme immunoassay (Phadia Diagnostics, Uppsala, Sweden). Allergic sensitization for total IgE was set at >100 kU/l and specific IgE at ≥0.35 kU/l. For the present analysis specific IgE was measured for the following food and inhalant allergens: egg, cow’s milk, fish, wheat, house dust mite, cat, timothy grass, and birch.
Associations between background variables and allergic sensitization were analyzed using the Pearson chi-square test. Logistic regression analysis was used to study the association between maternal diet during pregnancy and allergic sensitization. We used the natural logarithmic transformed values for all food and nutrient variables. Nutrients were, in addition, adjusted for energy intake by the residual method (11). We used the continuous form of all dietary variables except for the polyunsaturated fatty acids (PUFA), which were categorized as quarters because of their nonlinear association with allergic sensitization. The two middle quarters were combined into one category and contrasted with the first and last quarters. Unadjusted logistic regression was first computed. We then performed multiple logistic regression model, adjusting for place of birth, season of birth, sex of the child, number of siblings, gestational age at birth, parental asthma, parental allergic rhinitis, maternal age at delivery, maternal smoking during pregnancy, and maternal basic education. Total energy intake was included to both the unadjusted and adjusted models of the association between foods and allergic sensitization. Statistical significance was defined as a two-sided p-value < 0.05. spss (SPSSwin 15) was used for all analyses.
Characteristics of the study subjects and prevalence of allergic sensitization
Table 1 shows the prevalence of allergic sensitization among children analyzed for IgE (n = 1018). Sensitization to any allergen was found in 30% of these children. Inhalant allergic sensitization (23%) was more prevalent than sensitization to food allergens (17%). Among inhalants, birch (15%) was the most common sensitized allergen, and cow’s milk (12%) among food allergens. Among the background characteristics, allergic sensitization was only related to place of birth, number of siblings, parental asthma, and parental allergic rhinitis (Table 2).
Table 1. Prevalence of allergic sensitization to food and inhalant allergens measured by specific immunoglobulin E antibodies in children aged 5 yrs (n = 1018)
|Any food or inhalant allergen||305 (30)|
|Any food allergen||169 (17)|
| Egg||95 (9.3)|
| Cow’s milk||119 (12)|
| Fish||11 (1.1)|
| Wheat||46 (4.5)|
|Any inhalant allergen||234 (23)|
| House dust mite||26 (2.6)|
| Cat||79 (7.8)|
| Timothy grass||85 (8.3)|
| Birch||152 (15)|
Table 2. Characteristics of participating mothers and children in relation to specific allergic sensitization
|Place of birth|
| Tampere||566 (56)||99 (18)||0.393||145 (26)||0.026|
| Oulu||452 (44)||70 (16)||89 (20)|
|Season of birth|
| Spring (April–May)||189 (19)||32 (17)||0.985||41 (22)||0.905|
| Summer (June–August)||227 (22)||38 (17)||50 (22)|
| Autumn (September–November)||258 (25)||44 (17)||60 (23)|
| Winter (December–March)||344 (34)||55 (16)||83 (24)|
| Boys||551 (54)||89 (16)||0.676||136 (25)||0.162|
| Girls||467 (46)||80 (17)||98 (21)|
|No. siblings at child’s birth|
| None||428 (42)||79 (19)||0.309||130 (30)||<0.001|
| One||326 (32)||56 (17)||64 (20)|
| Two or more||245 (24)||34 (14)||38 (16)|
| Missing information||19 (2))||–||–|
|Gestational age at birth (quarter)|
| 1st||260 (26)||40 (15)||0.773||56 (22)||0.6|
| 2nd||225 (22)||35 (16)||48 (21)|
| 3rd||275 (27)||47 (17)||64 (23)|
| 4th||255 (25)||47 (19)||66 (26)|
| Missing information||3 (0.3)||–||–|
| No||740 (73)||112 (15)||0.008||177 (24)||0.979|
| Yes||126 (12)||31 (25)||30 (24)|
| Missing information||152 (15)||–||–|
|Parental allergic rhinitis|
| No||299 (29)||35 (12)||0.003||56 (18)||0.006|
| Yes||528 (52)||105 (20)||146 (28)|
| Don’t know||40 (4)||3 (8)||6 (15)|
| Missing information||151 (15)||–||–|
| <25||166 (16)||32 (19)||0.275||39 (24)||0.967|
| 25–29.9||343 (34)||64 (19)||82 (24)|
| 30–34.9||312 (31)||46 (15)||71 (23)|
| ≥35||197 (19)||27 (14)||43 (22)|
|Maternal smoking in pregnancy|
| No||909 (89)||154 (17)||0.84||206 (23)||0.424|
| Yes||86 (9)||14 (16)||22 (26)|
| Missing information||23 (2)||–||–|
|Maternal basic education|
| Elementary school||374 (37)||65 (17)||0.803||84 (22)||0.68|
| High school||617 (60)||103 (17)||145 (24)|
| Missing information||27 (3)||–||–|
|Total length of breastfeeding (months)|
| <6||380 (37)||65 (17)||0.736||88 (23)||0.991|
| ≥6||614 (60)||100 (16)||142 (23)|
| Missing information||24 (3)||–||–|
|Total||1018 (100)||169 (17)|| ||234 (23)|| |
Maternal food and nutrient intakes during pregnancy
The mean daily intake of total energy during pregnancy by the mothers (n = 931) was 11639 (s.d. = 3396) kJ. Their mean (s.d.) daily consumption of fruits was 207 (161) g, vegetables and roots 359 (160) g, milk products 871 (405) g, fish products 23 (20) g, and cereals 192 (68) g. Mean daily dietary intake of total fat was 109 (37) g, vitamin A 1705 (953) μg, vitamin C 202 (121) mg, vitamin D 5.2 (2.8) μg, vitamin E 14.2 (4.8) mg, zinc 16.9 (5.0) mg, copper 2.3 (1.0) mg, and iron 16.8 (5.4) mg. Of the women, 28% had taken vitamin D supplements during pregnancy with a mean intake of 1.1 (2.4) μg; whereas 73% of them had taken iron supplements with a mean intake of 28 (19) mg.
Maternal diet during pregnancy and allergic sensitization in 5-yr-old children
Increasing maternal consumption of total fruit (OR = 1.36, 95% CI = 1.09–1.70, p = 0.008) and citrus fruits (OR = 1.14, 95% CI = 1.05–1.25, p = 0.016) were positively associated with allergic sensitization against inhalants (Table 3). Increasing maternal intake of vitamin D (OR = 0.56, 95% CI = 0.35–0.91, p = 0.026) was inversely associated with sensitization to food allergens (Table 4). The associations between PUFA and allergic sensitization were not linear; accordingly, we present that data as quarters. Low maternal intakes of total PUFA and n-6 PUFA, and both low and high intake of n-3 PUFA during pregnancy were inversely associated with sensitization to inhalant allergens in the unadjusted model; in the adjusted model, low maternal intakes of total PUFA and n-6 PUFA were borderline significantly associated with sensitization to inhalant allergens (Table 5).
Table 3. Association between maternal food intakes (as continuous variables) during pregnancy and allergic sensitization in the offspring at 5 yrs of age
|Total fruits||0.97 (0.78–1.20)||0.97 (0.77–1.23)||1.32 (1.08–1.62)*||1.36 (1.09–1.70)*|
| Malaceous fruits||0.95 (0.83–1.09)||0.97 (0.84–1.13)||0.98 (0.87–1.11)||1.00 (0.87–1.14)|
| Citrus fruits||0.98 (0.91–1.06)||1.00 (0.92–1.09)||1.11 (1.03–1.20)*||1.14 (1.05–1.25)*|
|Berries||1.05 (0.92–1.19)||1.07 (0.92–1.25)||1.06 (0.94–1.19)||1.12 (0.88–1.28)|
|Juices||0.98 (0.91–1.07)||0.99 (0.90–1.08)||0.99 (0.92–1.06)||0.98 (0.90–1.06)|
|Vegetables and roots||0.77 (0.50–1.18)||0.80 (0.49–1.31)||1.16 (0.79–1.69)||1.28 (0.82–1.99)|
|Potatoes||0.74 (0.51–1.07)||0.73 (0.48–1.23)||0.74 (0.54–1.03)||0.92 (0.63–1.35)|
|Pulses and nuts||1.07 (0.91–1.26)||1.11 (0.92–1.33)||1.15 (0.99–1.32)||1.10 (0.94–1.28)|
|Cereals||0.87 (0.50–1.52)||1.26 (0.66–2.43)||1.00 (0.61–1.64)||0.94 (0.53–1.66)|
| Wheat||0.98 (0.65–1.49)||1.20 (0.75–1.93)||1.12 (0.78–1.62)||1.16 (0.77–1.74)|
|Dietary fats||0.79 (0.49–1.29)||0.86 (0.50–1.48)||0.91 (0.60–1.41)||1.07 (0.66–1.73)|
| Butter and butter spreads||1.05 (0.81–1.35)||1.08 (0.81–1.43)||1.15 (0.92–1.43)||1.20 (0.94–1.54)|
| Margarine and low fat spreads||0.96 (0.78–1.17)||0.95 (0.76–1.20)||0.93 (0.79–1.10)||0.96 (0.79–1.17)|
| Oils||0.86 (0.55–1.36)||0.83 (0.51–1.36)||1.19 (0.75–1.67)||0.97 (0.62–1.49)|
|Fish and fish products||0.96 (0.87–1.05)||0.98 (0.88–1.09)||0.98 (0.90–1.07)||1.00 (0.91–1.10)|
| Fish||0.97 (0.89–1.06)||0.99 (0.89–1.09)||0.99 (0.91–1.07)||1.02 (0.93–1.12)|
|Milk and milk products||0.81 (0.56–1.19)||0.88 (0.57–1.35)||0.76 (0.54–1.06)||0.76 (0.52–1.11)|
| Milks||0.92 (0.75–1.14)||0.95 (0.76–1.20)||0.87 (0.73–1.04)||0.91 (0.75–1.12)|
| Fermented milk products||0.97 (0.83–1.15)||1.00 (0.83–1.21)||1.10 (0.94–1.28)||1.04 (0.88–1.23)|
| Cheese||0.96 (0.78–1.18)||0.96 (0.77–1.19)||1.09 (0.91–1.31)||1.05 (0.86–1.29)|
|Egg||0.80 (0.55–1.16)||0.75 (0.50–1.13)||0.92 (0.66–1.27)||0.91 (0.64–1.29)|
|Chocolate and sweets||1.00 (0.88–1.13)||0.99 (0.86–1.14)||1.01 (0.90–1.13)||1.00 (0.88–1.14)|
Table 4. Association between maternal nutrient intakes from foods (as continuous variables) in pregnancy and specific allergic sensitization in the offspring at 5 yrs of age
|Total fat||1.01 (0.29–3.58)||0.68 (0.17–2.76)||1.14 (0.37–3.45)||1.12 (0.32–3.93)|
|Saturated fatty acids||1.05 (0.44–2.52)||0.91 (0.34–2.43)||0.87 (0.41–1.87)||0.83 (0.35–1.99)|
|Vitamin A||0.83 (0.58–1.21)||0.84 (0.55–1.27)||0.84 (0.61–1.16)||0.22 (0.64–1.33)|
|α-Carotene||0.88 (0.70–1.09)||0.98 (0.76–1.26)||1.04 (0.86–1.26)||1.11 (0.89–1.39)|
|β-Carotene||0.85 (0.63–1.14)||0.94 (0.67–1.32)||1.11 (0.86–1.43)||1.19 (0.88–1.60)|
|Vitamin C||0.81 (0.57–1.16)||0.83 (0.56–1.22)||1.18 (0.87–1.61)||1.25 (0.89–1.76)|
|Vitamin D||0.56 (0.37–0.86)*||0.56 (0.35–0.91)*||0.72 (0.50–1.05)||0.76 (0.50–1.17)|
|α-Tocopherol||0.80 (0.37–1.73)||0.62 (0.26–1.52)||2.06 (1.05–4.02)*||1.97 (0.91–4.26)|
|γ-Tocopherol||1.05 (0.644–1.70)||0.99 (0.58–1.70)||0.99 (0.65–1.51)||0.98 (0.61–1.58)|
|Zinc||0.81 (0.25–2.62)||0.92 (0.25–3.37)||0.50 (0.18–1.38)||0.53 (0.17–1.63)|
|Copper||0.94 (0.35–2.53)||1.21 (0.40–3.69)||1.11 (0.46–2.65)||1.12 (0.42–3.01)|
|Iron||1.08 (0.42–2.79)||1.47 (0.51–4.23)||1.18 (0.51–2.70)||1.37 (0.54–3.49)|
Table 5. Association between maternal polyunsaturated fatty acid intakes during pregnancy and specific allergic sensitization in the offspring at 5 yrs of age
|Total polyunsaturated fatty acids (quarter)|
| 1st||0.95 (0.62–1.44)||0.787||1.03 (0.65–1.62)||0.664||0.63 (0.43–0.92)**||0.028||0.63 (0.41–0.97)**||0.062|
| 2nd and 3rd||1||1||1||1|
| 4th||0.86 (0.56–1.32)||0.81 (0.50–1.33)||0.70 (0.48–1.02)||0.71 (0.47–1.09)|
|n-3 PUFA (quarter)|
| 1st||0.89 (0.59–1.36)||0.604||0.91 (0.58–1.43)||0.66||0.65 (0.45–0.95)*||0.013||0.67 (0.44–1.02)||0.075|
| 2nd and 3rd||1||1||1||1|
| 4th||0.81 (0.53–1.24)||0.80 (0.49–1.31)||0.62 (0.42–0.90)*||0.68 (0.45–1.05)|
|n-6 PUFA (quarter)|
| 1st||0.77 (0.50–1.19)||0.346||0.78 (0.49–1.25)||0.269||0.60 (0.41–0.89)**||0.028||0.60 (0.39–0.93)**||0.059|
| 2nd and 3rd||1||1||1||1|
| 4th||0.77 (0.50–1.19)||0.69 (0.42–1.13)||0.76 (0.53–1.10)||0.78 (0.52–1.17)|
Further analysis of total nutrient intakes (foods and supplements combined) as quarters showed no significant associations (data not shown) between most of the nutrients and allergic sensitization except for vitamin D. The last quarter vs. the middle quarters of maternal intake of total vitamin D was inversely associated with sensitization against inhalant allergen, but with a borderline statistical significance (OR = 0.62, 95% CI = 0.40–0.95, overall p = 0.069).
In the present population-based cohort study, increasing maternal consumption of citrus and total fruits during pregnancy increased the risk of sensitization to inhalant allergens in children aged 5 yrs. On the other hand, increasing maternal intake of vitamin D was inversely associated with sensitization to food allergens. These findings support earlier notions that maternal food intake during pregnancy may play a role in the development of allergic diseases in the offspring.
Our measurement of atopic sensitization as an allergic outcome may limit generalizing these findings to actual asthma, atopic eczema or allergic rhinitis. As a result of lack of statistical power based on the small number of children having asthma, atopic eczema, and allergic rhinitis at the age of 5 yrs, we were not able to assess the association of maternal diet with these outcomes in the present subject series. Although there are no definite knowledge on the predictive value of later allergic diseases by early allergic sensitization, a recent study from eastern Finland suggests that early sensitization to inhalant allergens predicted wheezing and asthma until adolescence (12). Prolonged follow-up of our study cohort will clarify whether our findings could be translated into clinical allergic diseases.
Another limitation to the present study is that our birth cohort has been selected based on HLA-conferred susceptibility to type 1 diabetes, which may limit the generalizability of our findings to the general population. However, the present cohort represents about 14% of the general population, and there is very weak and inconsistent evidence that the HLA genotype should have any impact on the development of allergic diseases. In addition, there are conflicting findings on the frequency of co-morbidity of type 1 diabetes and IgE-mediated allergy at the population level (13–15). Moreover, our subject series constitute unselected children with regard to the family history of allergic diseases (16).
It has been observed that estimates derived from FFQ data may be susceptible to dietary misreporting, leading to a random misclassification of intakes and portion. This may weaken the associations observed (17). However, the FFQ used in our study was validated against two 5-day food records and was found to reasonably well assess dietary intakes of pregnant women in a prospective study (9). Except for duration of breastfeeding, we did not take into account in the present analysis the diet during the infant period. Maternal food intake during pregnancy may be a surrogate for the child’s, indicating that associations found from this type of analysis may be strongly determined by the post-natal diet of the child. Therefore, intervention studies may be warranted to disentangle the effect of maternal food intake during pregnancy on allergic outcomes from that of the child (18).
The present study has the advantage of being population-based and of having a prospective design, which is superior to other observational epidemiological designs in detecting plausible causal relationships. Secondly, the evaluation of the association between dietary intake and disease outcomes based on both food consumption and nutrient intake represents a novel approach in establishing plausible effects in epidemiological analyses. This approach will better guide any future dietary intervention related to allergic diseases (17).
Our observation regarding the association between maternal citrus fruit consumption during pregnancy and allergic sensitization to inhalants is consistent with a previous prospective cohort study from Germany (18), which reported a positive association between high consumption of citrus fruit and allergic sensitization against inhalants in the offspring by 2 yrs of age. That study observed in addition a positive association between high consumption of citrus fruits and allergic sensitization against foods, which could not be confirmed in the present study. Nonetheless, the allergenicity of citrus fruits has been well characterized (19, 20). Particularly, profilin and germin-like proteins are suggested to have strong pro-inflammatory properties and have been identified as major classes of allergens in oranges (20). In Finland, citrus fruit allergy has been one of the most commonly reported food allergies among children, with a frequency of about 3% at the age of 3 yrs (21). The positive association between total maternal fruit consumption and allergic sensitization against inhalants in our study may be largely explained by citrus fruit, considering that none of the other fruit types was related to allergic sensitization. Interestingly, the association between total maternal fruit consumption, except that of citrus fruit, lost its statistical significance when it was added into the same model with citrus fruits (data not shown), while the effect of citrus fruit did not change. Therefore, we postulate that increasing maternal consumption of citrus fruits during pregnancy may have an independent positive association with allergic sensitization in the offspring. An intervention trial may be warranted to confirm these observations.
Increasing maternal dietary vitamin D intake decreased risk of sensitization to food allergens in the present study, and an inverse borderline significance was observed for total vitamin D intake. The effect of vitamin E seems unlikely to confound this result, because further adjustment for vitamin E did not change the direction or strength of our finding (data not shown). This inverse effect of vitamin D on allergic sensitization in our study is discordant with the result of a birth cohort study from the UK (22), which reported no association between maternal vitamin D intake and sensitization to any specific allergen in the offspring by 5 yrs of age. However, vitamin D was inversely related to early childhood wheezing in the same UK study. This result was also confirmed in another cohort study from the US (23). Vitamin D plays important physiological roles and has been noted to influence the regulation of the immune system, which may contribute to the development of allergic diseases (24, 25). These immunological characteristics indicate that maternal intake of vitamin D during pregnancy might be important in modulating the development of allergic diseases in the offspring.
The mean total daily intake of vitamin D (6.25 μg) among mothers in our study decreased below national recommendation of 10 μg/day (26). Vitamin D deficiency is prevalent around the world, particularly among pregnant women (27). This deficiency has been linked to diverse chronic disorders and autoimmune diseases (24). Therefore, there is a need for active promotion of consumption of foods rich in vitamin D and/or adequate use of its supplements among pregnant women, especially in populations living at northern latitude. Our observation, along with the previous UK and US follow-up studies show that high maternal vitamin D intake in pregnancy may decrease the risk of development of allergic diseases in the offspring.
The increasing trend in allergic diseases observed in the developed world has been suggested to be partly related to the decrease in consumption of foods rich in n-3 PUFA and increase in consumption of foods rich in n-6 PUFA (28). PUFA are nutrients with immunomodulatory effects. While n-6 PUFA are believed to possess pro-inflammatory properties that may be associated with allergic diseases (3, 28), n-3 PUFA are thought to antagonize these effect, thus decreasing the risk of allergic diseases (29). Our observation of no clear association between the PUFA and allergic sensitization neither support the hypothesis of a decreased risk of atopy along with an increased intake of n-3 PUFA; nor does our result support the hypothesis of increased risk of atopy with increasing intake of n-6 PUFA.
Few prospective cohort studies have investigated the effect of maternal intake of PUFA during pregnancy on allergic outcomes in children. Nevertheless, the protective effect of n-3 PUFA has been mainly ascribed to fish oil (30). It has been suggested that supplementation with fish oil may modulate neonatal immune responses to allergens (31). Two large cohort studies have reported a protective effect of maternal consumption of oily fish during pregnancy on the risk of asthma (17) and allergic sensitization (32). A randomized placebo-controlled clinical trial (33) and its follow-up study (34), respectively, showed reduction of interleukin-13 levels in cord blood of infants and lesser sensitization to egg allergen by 1 yr of age in children of mothers who received fish oil capsules containing n-3 PUFA compared with those in the control group. However, in a recent randomized controlled trial (35) and another observational study (36), no association was observed between n-3 fatty acids as supplements, plasma levels, and dietary intakes and any respiratory or allergic outcome in children. The effect of fish oil on allergic outcomes thus seems inconclusive. Therefore, further prospective studies will be essential to assess the putative role of PUFA in the development of allergic diseases.
In conclusion, we observed in this study that increasing maternal consumption of citrus fruits during pregnancy may increase the risk to allergic sensitization in the offspring, whereas vitamin D may have a beneficial effect. The role of maternal intakes of PUFA on allergic sensitization were not clear, thus further studies will be required to assess the putative effect of PUFA on allergic outcomes.
The authors are thankful to the mothers and children who participated in this study. The authors are grateful to the DIPP doctors, research nurses, nutritionists, and laboratory staff for their continuous collaboration through the years. The authors also express our gratitude to Sirpa Pohjola and Ilona Kalliomäki for their expert technical assistance. Supported by the Academy of Finland (grants 44105, 48724, 80846, 201988, 126813, 129492), the Finnish Pediatric Research Foundation, the Juho Vainio Foundation, the Yrjö Jahnsson Foundation, Medical Research Funds, Turku, Oulu and Tampere University Hospitals, JDRF, Novo Nordisk Foundation, the University of Tampere Foundation, and EU Biomed 2 Program (BMH4-CT98-3314).
BIN designed, analyzed, and prepared the present manuscript under the supervision of SMV, M Kaila, and ME. SMV designed and is responsible for the DIPP Nutrition Study. SMV and M Kaila have planned the allergy study. SA and CKK were responsible in preparing the dietary data and AMH IgE analysis. RV, JI, OS, and M Knip were responsible for data collection in the clinics and for pediatric expertise in this study. All authors have commented and approved the final version.
Appendix 1. Foods and food groups considered in this study
|Fruits||Apple, pear, peach, plum, brune, orange, lemon, grapefruit, mandarine, all canned fruits, melons, pineapple, grapes, banana, kiwi fruits, avocado, and dried fruits|
|Malaceous fruits||Apple, pear, peach, plum, and brune|
|Citrus fruits||Orange, lemon, grapefruit, and mandarine|
|Juices||Fruit and berry juices|
|Vegetables and roots||All cabbages, canned vegetables, cucumber, tomato, sweet pepper, courgette, egg plant, salads, spinach, celery, corn, Chinese cabbage, fresh herbs, onions, leek, garlic, carrot, swede, turnip, beetroot, parsnip, Jerusalem artichoke, and potatoes|
|Pulses and nuts||Pulse vegetables, nuts, and seeds|
|Cereals||Rye, wheat, oats, barley, rice, pasta, macaroni, starches and other grains|
|Fats||Butter, butter spreads, animal fat, margarine and fat spreads, fats for cooking and industrial use, oil, and other fat products|
|Butter and butter spreads||Butter and butter spreads|
|Margarine and low fat spreads||All margariness and fat spreads|
|Fish and fish products||All fishes and fish products|
|Milk and milk products||Milks, cheese, yoghurt, sour milk, curd, creams, and ice creams|
|Fermented milk products||Yoghurt, sour milk, and curd|
|Chocolate and sweets||Chocolates and sweets|