INTRODUCTION — The term "allergy" refers to a hypersensitivity reaction initiated by immunologic mechanisms. The available literature concerning manipulation of a woman's diet in pregnancy or lactation (or both) in an attempt to achieve primary prevention of allergic disease in her child will be reviewed here. The fetus can make immunologic responses to foods and other allergens . It is unclear if these responses represent normal immunologic phenomena, are related to the subsequent development of allergy, or both. The impact of breastfeeding and probiotics on the development of allergic disease and general issues related to food allergen avoidance are presented separately. (See "Management of food allergy: Avoidance" and "The impact of breastfeeding on the development of allergic disease" and "Prebiotics and probiotics for prevention of allergic disease".)
BACKGROUND — The most prevalent allergic or atopic disorders include atopic dermatitis, asthma, allergic rhinitis, and food allergies. These conditions afflict 20 percent of the population of the United States, and their prevalence is rising in developed nations. The increase in atopic diseases has been recognized as a pandemic, thus emphasizing the need for effective allergy prevention .
Early interventions — Three factors are needed to develop allergic disease: the appropriate genetic background, contact with the allergen(s), and environmental factors. Convincing studies support the existence of a critical time early in infancy and possibly even in prenatal life, in which the genetically predisposed atopic infant is at higher risk for becoming sensitized (ie, developing specific immunoglobulin E [IgE] to an allergen) . Therefore, dietary interventions instituted during pregnancy, lactation, and the first year of life have been proposed. These include maternal avoidance of allergenic foods and the addition of certain supplements to the maternal diet.
Types of prevention — There are three types of allergy prevention :
●Primary prevention, which blocks the initial immunologic sensitization (ie, the development of IgE specific to an allergen).
●Secondary prevention, which reduces the development of further disease after sensitization.
●Tertiary prevention, which reduces symptoms after disease expression.
The suggestions made in this review do not apply to infants who manifest signs of allergic disease shortly after birth, as dietary interventions during lactation may then represent treatment, rather than primary prevention. The signs and symptoms of food allergy are discussed elsewhere. (See "Clinical manifestations of food allergy: An overview".)
MATERNAL AVOIDANCE DIETS — The best studies and the majority of publications support the conclusion that maternal avoidance diets during pregnancy, lactation, or both are not effective in preventing allergic disease. A 2012 systematic review including five randomized trials [3-7] and over 900 patients also reached this conclusion . We will examine some representative studies in detail, as well as the limitations of the available data.
Study limitations — Studies of maternal and newborn diets are difficult to perform and have been attempted with varying degrees of experimental rigor. Such study designs often include variables that are difficult to separate or control for, such as length of breastfeeding, use of supplemental formulas, and the introduction of solid foods to infants, all of which may impact the development of allergic disease. (See "The impact of breastfeeding on the development of allergic disease" and "Introducing formula to infants at risk for allergic disease" and "Introducing highly allergenic foods to infants and children".)
In addition, the studies reviewed here were performed at different times over the span of several decades (during which the prevalence of atopy and recommendations regarding timing of introduction of allergenic foods have been changing) and on different populations, each with unique dietary and environmental influences.
The lack of protective effect in most studies could also be due (in part) to reverse causation. Specifically, even when not requested to do so, mothers who believed their infants were at higher risk for atopic disorders might have been more likely to avoid certain foods in their diet or to breastfeed and breastfeed longer, or mothers who were going to feed/supplement with formula might have been more likely to choose a hypoallergenic formula.
Finally, most of the studies examining the effects of maternal avoidance diets during pregnancy and lactation have been performed in "high-risk" populations. An infant's risk for developing allergic disease is based upon the family's atopic history. An infant is defined as "high risk" if there is at least one first-degree relative (parent or sibling) with documented allergic disease, a definition based upon a consensus among several committees representing the American Academy of Pediatrics (AAP), the joint guidelines of the European Society of Pediatric Allergy and Clinical Immunology (ESPACI), and the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) [9,10]. However, this definition of "high risk" is quite broad. An infant may be at high risk because the father has allergic rhinitis or because multiple siblings have severe asthma and life-threatening food allergy. These two circumstances are clearly not equivalent. The general nature of this definition ensures that the findings of studies can be applied to significant portions of the general population, although it also introduces some uncertainty about how such findings should be applied to specific individuals.
During pregnancy — The available studies suggest that maternal avoidance of allergenic foods during pregnancy does not reduce the risk of allergic disease in the offspring, regardless of whether the infant is high risk or not. Thus, the AAP, ESPACI, and ESPGHAN do not recommend maternal avoidance diets during pregnancy [11,12]. To the contrary, some studies suggest that avoidance may actually increase the risk in offspring.
●Few studies have been performed on unselected (ie, all levels of risk) populations of mothers and infants. One of the few was a cohort study of maternal intake of common allergenic foods during pregnancy and the subsequent development of allergic disease in the offspring in 1277 mother-child pairs from a multispecialty medical practice . Subjects completed questionnaires beginning at the first prenatal visit, throughout the pregnancy, and yearly after birth. Data from mid-childhood visits (mean 7.9 years of age) were evaluated for the presence of food allergy, asthma, allergic rhinitis, and atopic dermatitis, and serum-specific immunoglobulin E (IgE) levels were measured. Greater maternal intake of peanut during the first trimester of pregnancy was associated with reduced odds of a peanut-allergic reaction (odds ratio [OR] 0.53, 95% CI 0.30-0.94), and higher milk intake in the first trimester was associated with reduced odds of asthma and allergic rhinitis.
●Most studies have examined mothers of high-risk infants [4,14-21]. As an example, 212 pregnant women were randomly assigned to a diet free of cow's milk and egg or to a normal control diet from week 28 of gestation until delivery . Many of the women on the exclusion diet also chose to avoid these foods during lactation. At ages 18 months and five years, there were no differences in the prevalence of allergic rhinitis, atopic dermatitis, or asthma in the two groups of infants born of these mothers [4,15]. In contrast, at five years of age, egg allergy was significantly more common in the children of the mothers following restricted diets . Additionally, maternal weight gain during pregnancy was negatively affected by these dietary restrictions.
●In a prospective cohort study of 8205 children participating in the Growing Up Today Study 2, 140 children allergic to peanut or tree nut were identified by maternal report of a clinician's diagnosis of peanut or tree nut allergy. Allergy was confirmed by pediatrician and allergist/immunologist reviewers. The incidence of peanut or tree nut allergy was significantly lower among children of nut-nonallergic mothers who consumed peanuts or tree nuts greater than five times monthly in their peripregnancy diet compared with children of mothers who consumed peanuts or tree nuts less than once monthly (OR 0.31, 95% CI 0.13-0.75) .
In contrast to the above, a small number of studies support a protective effect of maternal avoidance of allergenic foods during pregnancy on the atopic status of the child [22,23]. The largest was an observational cohort study in which 503 infants, aged 3 to 15 months with evidence of cow's milk or egg allergy (ie, at high risk for food allergy) but without known peanut allergy and their mothers were evaluated . Because of these selection criteria, these infants were not representative of the general population. Mothers were questioned about peanut intake during pregnancy, and the infants' serum levels of peanut-specific IgE were measured, although challenges were not performed to determine if the children had clinical allergy. Maternal ingestion of peanut more than twice per week was associated with an increased risk of having a peanut-specific IgE level ≥5 kUA/L, a level considered likely indicative of peanut allergy (OR 2.9, 95% CI 1.7-4.9).
During lactation — It has been suggested for many years that the presence of food antigens in breast milk might sensitize nursing infants. Results of studies examining this hypothesis have been contradictory, and the cumulative data are not sufficient to support recommending food avoidance to breastfeeding mothers as a means of preventing allergy.
●One prospective study of high-risk families encouraged exclusive breastfeeding for the first three months of life and delayed introduction of solid foods. In addition, one group of mothers avoided cow's milk and egg in the last trimester of pregnancy and during the period of exclusive breastfeeding, a second group avoided cow's milk and egg only during lactation, and a third group had no dietary restrictions. The period prevalences of atopic dermatitis, as well as the rates of specific sensitization to cow's milk and egg at 6 and 12 months, were not significantly different among the groups .
●A longer-term study compared two groups of high-risk infants, both of which were breastfed and supplemented with protein hydrolysate formulas when necessary . The study group was composed of infants whose mothers avoided egg, cow's milk, and fish during the first three months of lactation, and the control group was composed of infants whose mothers had no dietary restrictions. Infants of mothers with restricted diets had less atopic dermatitis than the control group infants, although all other atopic manifestations were similar. However, in a 10-year follow-up study, there was no difference in the prevalence of allergic disease in these two groups of children .
●Another study found that a maternal exclusion diet of egg, cow's milk, fish, and nuts during lactation actually increased the presence of atopic dermatitis and allergy in the offspring .
Subsequently, research shifted to investigating the possible mechanisms by which maternal ingestion of allergenic foods during lactation might protect infants from developing food allergy or other allergic diseases:
●One study examined the effect of maternal elimination diets on breast milk and found that women avoiding cow's milk had lower levels of milk-specific immunoglobulin A (IgA) in their breast milk compared with women consuming milk . IgA in human milk is believed to perform functions that are generally protective to the infant gut and discourage the development of food allergy. Infants of mothers avoiding milk had lower serum levels of immunoglobulin G1 (IgG1) and immunoglobulin G4 (IgG4) to milk allergens, and these findings were associated with the development of infant milk allergy, since allergen-specific IgG4, in particular, is believed to be a marker of tolerance. (See "Structure and biologic functions of IgA", section on 'Secretory IgA in milk'.)
●In the prospective, population-based cohort Finnish type 1 diabetes prediction and prevention study, in mothers with simultaneous consumption of cow's milk during pregnancy and lactation, the highest quartile intake only during pregnancy was associated with a lower risk of cow's milk allergy in offspring (OR 0.30, 95% CI 0.13-0.68) . When stratified by maternal allergic rhinitis or asthma, the association between high consumption of cow's milk products during pregnancy and lower risk of cow's milk allergy persisted only in children of nonallergic mothers (OR 0.30, 95% CI 0.13-0.69). Cord blood IgA correlated positively with the consumption of milk products during pregnancy.
●A similar study investigated the impact of maternal egg ingestion during lactation on egg protein levels in breast milk by comparing women ingesting high-egg (>4 eggs a week), low-egg, and egg-free diets . Average maternal egg ingestion was positively associated with egg ovalbumin (EO) concentration in breast milk, although one-third of the women eating egg had no detectable EO in their breastmilk, for unclear reasons. Serum IgG4 specific to EO in the infants at six months of age was positively correlated with maternal egg ingestion. These findings support those of the earlier study.
MATERNAL DIET DIVERSITY — While avoidance of foods during pregnancy is not recommended, there are emerging data that show the quality and diversity of the mother's diet may impact allergy outcomes in infants. To investigate this, a maternal allergy-preventive diet index (MDI) was developed and validated; the MDI includes weighted measures of intake of vegetables, yogurt, fried potatoes, rice/grains, red meats, 100 percent fruit juice, and cold cereals .The MDI was applied to infant allergy outcomes in the Healthy Start Study, a United States pre-birth cohort of 1410 mother/offspring dyads. Offspring allergic diseases were assessed at age 4 years. Vegetables and yogurt were associated with the reduced odds of offspring allergic rhinitis (odd ratio [OR] 0.82, 95% CI 0.72-0.94), atopic dermatitis (OR 0.77, 95% CI 0.69-0.86), asthma (OR 0.84, 95% CI 0.74-0.96), and wheeze (OR 0.80, 95% CI 0.71-0.90) but not food allergy (OR 0.84, 95% CI 0.66-1.08). The consumption of more red meat, fried potatoes, rice/grains, cold cereals, and 100 percent fruit juice were associated with increased risk of allergic diseases.
SUPPLEMENTATION OF THE MATERNAL DIET — Women may ask if there is any benefit to purposefully ingesting allergenic foods during pregnancy or lactation for the purpose of preventing food allergy or other allergic disorders in the child or if there is value in any specific supplements for preventing allergic disease in general.
Adding allergenic foods — Some women who already have food-allergic children may be avoiding a certain food because it is easier to eliminate that food from the household altogether. If the woman becomes pregnant and is not personally allergic to a food she has been avoiding, she may want to introduce that food into her own diet during pregnancy or lactation in an effort to prevent her future child from developing an allergy to that food. As an example, a pregnant woman who is avoiding peanut because she has a peanut-allergic child at home, might ask if she should start eating peanuts when away from the house. In this situation, our approach is first to offer dietary counseling to ensure adequate maternal nutrition if milk or multiple foods are being avoided because if nutrition is possibly inadequate, there is a clear justification for expanding the mother's diet and including foods that she has been avoiding. However, if the woman's diet is nutritionally adequate, the decision can be made on an individual basis, taking into consideration the woman's preferences and concerns, since the relative importance of maternal diet compared with genetic factors and other risk factors is not fully understood.
Vitamin D — Vitamin D supplementation of the maternal diet during pregnancy has been studied for prevention of asthma/wheeze, allergic rhinitis, food allergy, atopic dermatitis, and allergic sensitization to allergens.
●Vitamin D supplementation for the prevention of asthma in offspring has shown promise. Studies focusing on asthma prevention, as well as current recommendations for pregnant persons, are discussed in detail separately. (See "Risk factors for asthma", section on 'Maternal diet during pregnancy' and "Management of asthma during pregnancy", section on 'High-dose vitamin D'.)
●A 2020 systematic review and meta-analysis of maternal vitamin D supplementation during pregnancy found that there was a trend towards reduction in the risk of allergen sensitization and allergic rhinitis, but no clear impact on the risk of eczema or food allergy .
Antioxidants — Supplementation of the maternal diet with vitamins C and E has not been shown to reduce the risk of allergic disease in the offspring .
Omega-3 fatty acids — In the 2020 systematic review mentioned previously, omega-3 fatty acid supplementation was associated with nonsignificant reduction in the risk of asthma/wheeze (OR 0.70, 95% CI 0.45-1.08) and allergic rhinitis (OR 0.76, 95% CI 0.56-1.04) but did not impact the risk of atopic dermatitis or food allergy . The risks and benefits of long-chain polyunsaturated fatty acid (LCPUFA) supplements during pregnancy and current recommendations are reviewed separately. (See "Fish consumption and marine omega-3 fatty acid supplementation in pregnancy", section on 'Marine omega-3 fatty acid supplements and fortified foods'.)
Prebiotics and probiotics — Studies on the use of prebiotics and probiotics for the prevention of allergic disease in pregnant women and infants are discussed elsewhere. (See "Prebiotics and probiotics for prevention of allergic disease".)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Food allergy" and "Society guideline links: Breastfeeding and infant nutrition".)
SUMMARY AND RECOMMENDATIONS
●Primary prevention – Primary prevention of allergic disease involves interventions designed to prevent immunologic sensitization to an allergen(s). The following suggestions do not apply to infants who manifest signs of allergic disease shortly after birth, as dietary interventions during lactation may then represent treatment rather than primary prevention. (See 'Types of prevention' above.)
●Maternal avoidance of allergenic foods is not helpful – We do not suggest that women avoid specific allergenic foods during pregnancy or lactation for the purpose of reducing food allergy or other allergic diseases in offspring (Grade 2B). These interventions have not proven effective in preventing persistent allergic disease in children and may compromise maternal and/or fetal nutrition. (See 'Maternal avoidance diets' above.)
●Mixed evidence about ingesting allergenic foods – There is some preliminary evidence that ingesting allergenic foods during pregnancy and lactation may protect against the development of food and other allergies in children, although there is not enough evidence to justify purposefully supplementing a woman's diet during pregnancy or lactation with allergenic foods. Therefore, we counsel women as follows:
•Women who are ingesting unrestricted diets before pregnancy should not change their diets when they become pregnant for the purpose of preventing allergic disease in their offspring.
•For women who already have food-allergic children and are avoiding certain foods because it is easier to eliminate those foods from the household altogether, we offer dietary evaluation to determine the nutritional adequacy of their diets, especially if milk or multiple foods are being avoided. Based on that evaluation, as well as the patient's preferences and concerns, we make an individualized decision about adding back foods. (See 'Adding allergenic foods' above.)
●Increased vegetable and yogurt consumption may help – There are emerging data that show the quality and diversity of the maternal diet during pregnancy, with consumption of more vegetables and yogurt and less fried potato products, rice/grains, red meats, 100 percent fruit juice, and cold cereals, decreases the risk of allergic diseases in children. (See 'Maternal diet diversity' above.)
●Vitamin D may help prevent asthma in the first years of life – Studies of supplementation of the maternal diet during pregnancy for the purpose of preventing allergic diseases in the offspring have mostly reached inconclusive results, with the exception of vitamin D during pregnancy for the prevention of asthma, which is discussed in detail separately. (See "Risk factors for asthma", section on 'Maternal diet during pregnancy' and "Management of asthma during pregnancy", section on 'High-dose vitamin D'.)
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