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Breast Milk Fatty Acid Composition Is Associated with Development of Atopic Dermatitis in the Infant

Hoppu, Ulla*†; Rinne, Minna*; Lampi, Anna-Maija; Isolauri, Erika*

Journal of Pediatric Gastroenterology and Nutrition: September 2005 - Volume 41 - Issue 3 - p 335-338
doi: 10.1097/01.mpg.0000168992.44428.fa
Original Articles: Gastroenterology

Objective: Breast milk fatty acids may have immunomodulatory properties related to the development of atopic disease. The aim of this study was to assess the impact of the breast milk fatty acid composition on the development of atopic dermatitis (AD) in high-risk infants.

Methods: Mothers with atopic disease were recruited at the end of gestation. Maternal food records and breast milk samples were collected at the infants' age of one month. Infants were clinically examined and AD diagnosed at one, three, six, and 12 months.

Results: Altogether 13 of 34 (38%) infants were diagnosed with AD during the first year of life. Infants developing AD had consumed breast milk with a higher ratio of saturated to polyunsaturated fatty acids and less n-3 fatty acids compared to infants not developing AD. Specifically, breast milk consumed by infants with AD contained more stearic acid, 8.9% of total fatty acids (95% confidence interval 7.9-10.0) in comparison to those without AD, 7.1% (95% CI 6.6-7.7).

Conclusion: Breast milk rich in saturated and low in n-3 fatty acids may be a risk factor for atopic dermatitis in the infant.

Departments of *Pediatrics and †Biochemistry and Food Chemistry, University of Turku, Finland; ‡Department of Applied Chemistry and Microbiology, University of Helsinki, Finland

Received January 3, 2005; accepted April 18, 2005.

Address correspondence and reprint requests to Ulla Hoppu, University of Turku, Itäinen Pitkäkatu 4 A, 5th floor, 20520 Turku, Finland. (e-mail:

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Breast milk is the single source of nutrients for the infant during the period of rapid growth and development in the first months of life. Besides providing the principal source of energy, breast milk fatty acids possess functional properties. Polyunsaturated fatty acids (PUFA) are essential particularly for the development of the infant's cognitive and visual functions (1), and certain PUFA have immunomodulatory properties (2).

The nutrition hypothesis for the increasing prevalence of atopic disease in Western countries rests on the conception of altered dietary habits. Increased consumption of vegetable oils and margarine contributes to a higher intake of n-6 in relation to n-3 PUFA, this being held to underlie the heightened risk of these conditions. Linoleic acid (18:2n-6) derived arachidonic acid can be converted to prostaglandin E2 that may favour the development of T helper (Th) type 2 cytokines, a hallmark of atopic disease (3).

Epidemiological as well as experimental evidence linking dietary fat to atopic disease is conflicting. Previous studies assessing dietary intake in relation to atopic disease have mainly reported on the one hand on the type of fat used as spread or in cooking (4,5) or on the effects of dietary supplementation of single polyunsaturated fatty acids on the other (6). Studies concerning breast milk fatty acids have either compared breast milk fatty acids between allergic and nonallergic mothers (7,8) or have concentrated on the breast milk PUFA composition in relation to infant's atopic disease (9). However, PUFA form only a part of breast milk fatty acids, and consequently the impact of breast milk total fatty acid composition on the infant's risk of developing atopic disease needs to be addressed before new dietary interventions are initiated. This preliminary study focuses on assessing the effect of the dietary fat intake of atopic mothers on the fatty acid composition of their breast milk, and further, on the development of atopic dermatitis (AD) in the infant.

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Clinical Evaluation

Mothers with atopic disease (asthma, allergic rhinitis, atopic dermatitis) were recruited for a follow-up study at 35-36 weeks of gestation. At the first study visit a detailed questionnaire on family history of atopic disease was completed. The extent of maternal atopic sensitisation was assessed by means of skin prick testing (SPT) (10). Allergens tested included milk, egg, wheat, cod, soy bean, peanut, hazelnut, birch, alder, mugwort, a mixture of six local grasses, cat, dog, house dust mite, and latex. Banana, potato, and carrot were tested by prick-prick technique.

The infants were clinically examined at the ages of one, three, six, and 12 months. Skin prick tests for the infants were performed at 12 months. The diagnosis of atopic dermatitis was based on the Hanifin criteria (11). The outcome measure in this study was the emergence of atopic dermatitis during the first year of life. Altogether 34 mother-infant pairs were studied.

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Maternal Dietary Intake

Four-consecutive-day food records of the mothers were collected when the infants were one month old. Nutrient intakes were calculated with Nutrica software (version 3.0, Research Centre of Social Insurance Institution, Turku, Finland). Additional information on maternal dietary habits, including data on the type of spread usually consumed and the frequency of fish consumption was collected by means of a questionnaire.

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Collection and Analysis of Breast Milk Samples

Breast milk samples were collected at the infants' age of one month when the infants were exclusively or predominantly breastfed. Mothers were given standard written instructions on the collection of breast milk samples by manual expression in the morning prior to the study visit. Samples were stored at -70°C until analysed. Breast milk fatty acids were analysed with a gas chromatographic method as previously described (8).

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Ethics and Statistics

The research protocol was approved by the Ethical Committee of the Hospital District of South West Finland and all mothers gave written informed consent. The characteristics are described as mean with range and analyses as mean with 95% confidence interval (CI). Pearson's correlation analysis, chi-square test and t-test were used for statistical comparisons.

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Clinical Characteristics of the Infants

Altogether 13 of 34 (38%) infants were diagnosed as having AD, the outcome measure of this study. Of these, seven had positive SPT reactions at 12 months of age. In addition, two infants had positive SPT without AD. The mean birth weight of the infants was 3.6 kg (range 2.8-4.9) and length 51 cm (range 47-55). The mean duration of exclusive breastfeeding was 3.4 (range 0-6) and of total breastfeeding 8.6 months (range 2.5-12) and comparable between infants with or without AD.

Atopic disease in the mothers was the inclusion criterion for the study and 23 of 34 (68%) mothers had positive SPT reactions. Altogether 16 of 34 (47%) fathers had a clinical history of atopic disease, and 18 of 34 (53%) infants had siblings, of whom 14 (78%) had atopic disease. These clinical characteristics did not differ between infants developing or not developing AD.

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Maternal Dietary Intake

The mean energy intake of the mothers was 8.6 MJ per day (range 5.8-11.3). Their energy nutrient intakes are presented in Table 1. Nutrient intakes did not differ between mothers with positive or negative SPT (data not shown).



The type of spread usually consumed was margarine in 20 out of 34 (59%) mothers. None was using butter, but 9 (26%) consumed a butter-vegetable oil mixture while 5 (15%) used no spread at all. In the case of usual fish consumption, 19 of 34 (56%) mothers reported eating fish once a week, 6 (18%) mothers more and 9 (26%) mothers less frequently. None of the mothers was consuming fish oil preparations or other oil-containing supplements.

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Effect of Maternal Dietary Intake on Breast Milk Fat Composition

Mothers using margarine as spread had a higher proportion of total PUFA in their breast milk compared to those consuming butter-vegetable oil mixtures or no spread, 12.9 (95% CI 11.9-13.9) versus 11.3 (95% CI 10.1-12.5), p = 0.03. Frequency of fish consumption was not related to breast milk eicosapentaenoic acid (EPA) content. Dietary intake (g or E%) of total saturated fatty acids (SAFA), monounsaturated fatty acids, and PUFA did not correlate with the respective proportions in breast milk.

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Fatty Acid Composition of Breast Milk Associated with the Development of Atopic Dermatitis in the Infant

The mean total fat concentration of breast milk was 3.7 g/100 mL (range 1.8-5.9) and was comparable between infants subsequently developing or not developing AD. Table 2 compares the breast milk fatty acid composition (percent of total fatty acids) ingested by these infants. Infants developing AD had consumed breast milk with a significantly higher proportion of stearic acid (18:0) than infants without AD (p = 0.0009). The proportion of total SAFA tended to be higher and that of PUFA lower in the breast milk consumed by infants with AD. Thus, the ratio of SAFA to PUFA was higher in breast milk consumed by infants developing AD compared to those remaining healthy. Furthermore, the proportion of total n-3 PUFA and specifically EPA was lower in the breast milk of mothers whose infants developed atopic dermatitis.



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Identification of the risk factors for the increasing rates of atopic disease in Western societies may furnish novel prevention strategies. For future interventions, it is important to collect basic information on the total fat composition of diet and breast milk in different countries with distinct food culture. In this study a high ratio of SAFA to PUFA and specifically a high proportion of stearic acid in breast milk were determined as the factors underlying the development of AD in the infant. Breast milk saturated fatty acids have not previously been related to atopic disease while the evidence concerning breast milk n-3 fatty acids is contradictory, some studies showing n-3 fatty acids decreasing (13,14) and some increasing (15) the risk of atopic disease. Also the role of n-6 fatty acids in atopic disease still remains controversial, and in accord with the present study, some recent studies have found no association between breast milk n-6 fatty acids and atopic eczema (16).

The fat hypothesis explaining atopic disease has mainly concentrated on the ratio of n-6 to n-3 PUFA (3). It is of note, however, that in the USA, for example, this ratio in the diet has not changed during recent decades (17) parallel with the increase in the prevalence of atopic disease (18). Furthermore, evidence is accumulating to suggest that prostaglandins derived from n-6 and n-3 fatty acid precursors may not have different effects on the production of Th1 and Th2 cytokines (19). In a recent study, umbilical cord n-6 and n-3 fatty acids were not related to early childhood atopic disease (20). The effects of single fatty acids may also differ in terms of the development of atopic disease versus the control of symptoms of established disease and thus n-6 and n-3 fatty acids may have both positive and negative effects in various conditions. We hypothesised here that the n-6-n-3 theory may be an oversimplification and other fatty acids may also be involved in development of atopic disease.

Our result suggests that SAFA to PUFA ratio might be a useful indicator to be studied in relation to atopic disease. High dietary intake of SAFA has been associated with AD in adults (21), asthma in teenagers (22), and atopic sensitisation in infants (23). The demonstration of a negative correlation between the ratio of SAFA to PUFA in peripheral blood mononuclear cell phospholipids and interferon-γ production (24) tends to support this notion. Furthermore, our study identifies stearic acid in breast milk as being related to the development of AD. Interestingly, our clinical finding is supported by the recent demonstration that stearic acid is positively associated with the production of interleukin-4, a hallmark of atopic-type immune response (24). Besides SAFA, dietary monounsaturated fatty acids may also play a role in atopic disease (25).

The lack of direct quantitative relation between dietary intake during breastfeeding and breast milk composition in this study may be explained by the finding that the major determinant of breast milk fat composition is the maternal store accumulated during pregnancy and that only a minor proportion of breast milk fatty acids is derived directly from the diet during breastfeeding (26,27). Therefore, dietary interventions aiming at changing breast milk fatty acid composition and infant's fatty acid status should be started already at early pregnancy, and thus our research group has initiated a dietary intervention study beginning at the first trimester of pregnancy to address this issue thoroughly.

The maternal diet during pregnancy and breastfeeding, as well as breast milk, is a complex entity, where an increase in the amount of one item may reduce that of another. The approach in the prevention of atopic disease has shifted from passive elimination diets to active dietary modifications and supplementation of immunomodulatory nutrients such as fatty acids (28). However, supplementation of single fatty acids may be an unsuccessful approach if the total fat intake is high and the fatty acid composition of the diet is imbalanced. The result of the present study calls for the assessment of the total fat composition of diet and breast milk in attempts to reduce the risk of atopic disease in high-risk infants by dietary means.

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    Atopic dermatitis; Breast milk; Dietary intake; Fatty acid

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