Maternal Macro- and Micronutrient Intake During Pregnancy

INTRODUCTION

The in utero environment is not immune to the influence of maternal environmental exposures. One of the most dynamic maternal environmental exposures for the fetus results from variation in the maternal diet. The macro- and micronutrients in the maternal diet can vary based on choice, cultural background, food security, health-based dietary restrictions (eg, diabetic diet or cholestatic diet), and provider guidance (eg, supplementation of prenatal vitamins, folic acid, probiotics). The prevalence of challenge- proven food allergy¹ and atopic dermatitis² has increased in children, and environmental factors have been thought to play an important role in early programming.^3,4 Among these, maternal diet has been explored, and there is growing evidence that diet during pregnancy affects the allergic march in offspring. In this review, the authors briefly explore potential immune mechanisms of maternal diet–mediated effects on offspring, then dissect the evidence for the modulation by specific macro- and micronutrients during pregnancy on susceptibility to allergy development in offspring, and finally conclude with a discussion of the implications for the health care provider in providing nutritional guidance to women before and during pregnancy.

Potential Mediators of Maternal Diet Effects on Offspring Immunity

Maternal diet can alter the neonatal and maternal microbiome

Diet is a significant modifier of the intestinal microbiome. Changes in diet can shift the intestinal microbiome, although whether dietary modifications transiently or permanently alter the microbiome is still being investigated.^5–7 Observational studies suggest that changes in the maternal diet modify both the maternal and offspring microbiome. Several prospective observational studies sampling the oral, vaginal, and intestinal microbiome of mothers with gestational diabetes (GDM) demonstrate that they are unique at the phylum and genus level from those of control mothers without GDM.^8–10 In addition, GDM offspring have a unique gut microbiome, with a specific decrease in Bacteroides, Corynebacterium, and Brevundimonas.⁹ Whether these changes in the maternal microbiome are due to diet modification as a result of GDM diagnosis or hyperglycemia and metabolic derangements during pregnancy is still unclear, however. The microbiome is a potent modifier of the innate and adaptive immune response,^11–13 and early colonization changes as a result of maternal diet could influence the immune march in offspring¹⁴ and susceptibility to allergies.

Maternal diet can modify in utero and postnatal metabolite exposure

Metabolites produced by bacterial breakdown of diet or directly introduced in the diet, such as indole, short-chain fatty acids, and retinoids, are known to modify immune development. There is also some evidence that the fetus is exposed to these metabolites in utero,^15–17 either via the placenta to the fetal blood or in the amniotic fluid. Postnatally, microbiota-derived and dietary metabolites are also present in breast milk,^18–20 are modified by maternal diet, and can influence offspring immune development.

Maternal diet can modify epigenetic signatures in utero

Several studies have demonstrated that maternal diet can modify epigenetic signatures in offspring, including changes in DNA methylation, histone modifications, and noncoding RNA.²¹ These epigenetic changes can influence long-term immune development in offspring and potentially modify susceptibility to allergy.^22,23

Macronutrients, Pregnancy, and Offspring Susceptibility to Allergy Development

Macronutrient intake during pregnancy and offspring allergy susceptibility: the evidence

Validated food questionnaires provided to women during pregnancy have been used to determine if dietary intake during pregnancy influences development of allergy in offspring. In a prospective cohort more than 1200 women were given a validated food propensity questionnaire during pregnancy to determine if dietary intake correlated with development of allergies in offspring up to the age of 4 years ²⁴ Offspring were categorized as having no allergy or having atopic dermatitis, asthma, wheezing, allergic rhinitis, and/or food allergy. The investigators found that consumption of vegetables and yogurt was associated with prevention of allergy in offspring, whereas consumption of fried potatoes, cold cereals, rice, and red meats were associated with increased propensity to develop allergy. Another similar study using food questionnaires showed that the Mediterranean diet during pregnancy was protective for persistent wheeze, atopic wheeze, and atopy in children who were followed-up up to 6 years old.²⁵ Although most of the human studies demonstrate association with the use of these validated questionnaires, animal studies complement these studies and demonstrate how specific macronutrients during pregnancy can affect immunity and development of allergies in offspring (Table 1).

Table 1.

Publications exploring association of maternal macronutrient intake with development of allergy in offspring

Maternal Macronutrient During Pregnancy	Allergy Development in offspring	Author
Dietary fat	High intake of margarine (aOR 1.49, 95% CI 1.08–2.04) and vegetable oils (aOR 1.48, 90% CI 1.14–1.91) positively associated with development of eczema in offspring up to 2 years old. High intake of fish (aOR 0.75, 95% CI 0.57–0.98) inversely associated with development of eczema up to 2 years old. High intake of deep-frying vegetable fat (aOR 1.61, 95% CI 1.02–2.54) associated with sensitization against inhalant allergens up to 2 years old. Low maternal linolenic acid (HR 1.67, 95% CI 1.12–2.48) and PUFA (HR 1.66, 95% CI 1.11–2.48) associated with increased risk of asthma in offspring up to 5 years old. High intake of total saturated fatty acids (HR 0.55, 95% CI 0.34–0.90) and palmitic acid (HR 0.51, 95% CI 0.31–0.83) associated with decreased risk of asthma up to 5 years old. Maternal supplementation with fish oil did not decrease food allergy susceptibility in offspring at 1 y (aRR 0.70, 95% CI 0.45–1.09). Meta-analyses show no consistent association between type of fat intake and susceptibility to offspring allergy development	German Birth Cohort LISA Study Lumia et al,27 2011 DOMInO study Venter et al, Garcia-Larsen et al,29 2018
High-fiber diet	High fiber intake throughout or during late pregnancy in mice protected adult offspring from asthma model Pregnant women who reported higher dietary fiber intake during pregnancy had decreased association of offspring presenting with cough or wheeze in first 12 mo of life	Thorburn et al Thorburn et al
Diabetic and cholestatic diet Vegan or elimination diet	Increased development of IgE-/IgG-mediated food hypersensitivity in offspring No association with offspring allergy development	Ogrodowczyk et al,38 2020 Ogrodowczyk et al,38 2020
Probiotic supplementation	Supplementation with Lactobacillus/Bifidobacterium/Propionibacterium from 36 wk and continued supplementation in infants up to 6 mo decreased allergic disease and eczema development only in subgroup delivered via C-section at 13 years old. Probiotic supplementation during pregnancy and lactation associated with reduced risk of eczema (RR 0.78, 95% CI 0.68–0.90)—meta-analysis Probiotic supplementation during pregnancy or infancy showed no association with protection from asthma (RR 0.99, 95% CI 0.81–1.21)— meta-analysis	Kallio et al,39 2019 Garcia-Larsen et al,29 2018 Azad et al,40 2013

Abbreviations: aOR, adjusted odds ratio; HR, hazard ratio; RR, risk ratio.

High-fat diet during pregnancy and allergy development in offspring

In a German prospective birth cohort study (LISA), maternal diet during the last 4 weeks of pregnancy was collected using a food-frequency questionnaire, and association with development of eczema and allergic sensitization in offspring up to 2 years old was determined.²⁶ The investigators found that high intake of margarine and vegetable oils was positively associated with development of eczema in offspring, and high intake of deep-frying vegetable fat was positively related to sensitization against inhalant allergens. In contrast, high intake of fish was inversely associated with development of eczema in offspring. Lumia and colleagues similarly showed that the type of maternal fat intake during pregnancy was associated with risk for development of asthma in offspring. They showed that low maternal intake of linolenic acid and polyunsaturated fatty acids was associated with an increased risk of asthma in offspring. In contrast, low intake of arachidonic acid and high intake of total saturated fatty acids were associated with protection from development of asthma in offspring.²⁷ These studies intriguingly suggest that the type of fat exposure is important; however, systemic reviews of available studies demonstrate no consistent association.^28,29 In a randomized study involving 706 pregnant women (The DOMInO study, Docosahexaenoic acid to Optimize Mother Infant Outcome) given either a fish oil capsule (omega- 3) or placebo supplement from 21 weeks’ gestation until birth ,no significant difference was found in the development of food allergies in offspring at 1 year of life.³⁰

Interestingly, increased maternal high-fat diet intake during lactation may also contribute to the offspring risk for development of allergies. A prospective cohort study examined the association between maternal fat intake during lactation (based on a food questionnaire) and offspring development of atopic sensitization at 12 months. The investigators found that infants who had a positive skin prick test to at least one antigen were more likely born to mothers with a higher intake of total fat.³¹

Several animal studies have also explored the association between maternal high-fat diet intake and allergy sensitization in offspring. Myles and colleagues showed that offspring of pregnant mice fed a high-fat (western) diet had increased allergic sensitization when compared with pups born to mothers on standard (low-fat) diet.³² Similarly, MacDonald and colleagues showed that maternal high-fat diet exposure resulted in adult offspring that had increased airway hyperresponsiveness when compared with control offspring.³³

Maternal Fiber Intake During Pregnancy and Allergy Development in Offspring

Thornburn and colleagues demonstrated that maternal high fiber intake throughout or during late pregnancy in mice protected adult offspring from developing allergic airway diseases, mediated by altered transcription of Foxp3 genes linked to asthma development. ³⁴ Of note, high fiber intake during lactation did not similarly protect offspring. The investigators further showed that pregnant women who reported higher dietary fiber intake had higher levels of serum acetate with a decrease in their offspring presenting to their health care provider for cough or wheeze. This study demonstrated a potential association between maternal fiber intake and offspring susceptibility to development of asthma. Other animal studies have suggested that maternal high fiber intake can influence offspring T-cell differentiation, ³⁵ increase proteins in the offspring intestine associated with immune and inflammatory responses, ³⁶ and modify the offspring microbiome³⁷ mechanisms that can potentially alter the offspring allergic march. Further investigation on the impact of maternal dietary fiber intake on offspring susceptibility to allergy development is needed.

Maternal Diabetic and Cholestatic Diet and Allergy Development in Offspring

Pregnancy complications such as gestational diabetes and cholestasis prompt mothers to modify their diet to reduce carbohydrate and fat consumption. In a study examining mothers who were on these specific gestational diets and association of development of allergies in offspring, the investigators used bioinformatic and multivariate analysis for complex data sets and found that gestational diabetic and cholestatic diets were associated with development of immunoglobulin E (IgE)-/IgG-mediated food hypersensitivity.³⁸ They found no association of a gestational vegan or elimination diet with offspring allergy development.

Probiotic Supplementation During Pregnancy: Does It Affect Offspring Allergy Development?

The potential promise of modifying the maternal microbiome and the offspring microbiome and reducing the risk of development of allergies with probiotic supplementation led to several large studies. Unfortunately, to date, the evidence has not consistently supported maternal probiotic supplementation to modify allergy risk in offspring. Kallio and colleagues randomized pregnant women to receive either supplementation with probiotics (Lactobacillus/Bifidobacterium/Propionibacterium) or placebo during later pregnancy (36 weeks until birth) and continued supplementation of infants until 6 months.³⁹ They followed-up offspring to 13 years old and found that the probiotics protected only that subgroup who were delivered via C-section from allergic disease and eczema development. A meta-analysis of studies examining probiotic supplementation during pregnancy and lactation found that it was associated with reduced risk of eczema (risk ration [RR] 0.78, 95% confidence interval 0.68–0.90).²⁹ Another meta-analysis examining association of probiotics during pregnancy or infancy with development of childhood asthma found no protective association.⁴⁰ A potential confounder is the heterogeneity in the literature with the use of a broad range of probiotics and with the majority continuing supplementation during infancy, making it difficult to tease out the role of supplementation during pregnancy alone.

Micronutrients Supplementation During Pregnancy and Offspring Susceptibility to Allergy Development

Allergic conditions are common among children. Various studies have postulated the association between micronutrient levels such as vitamin D, vitamin E, vitamin A, selenium, iron, copper, and iron during pregnancy and numerous allergic outcomes such as asthma, rhinitis, food sensitization as well as pulmonary function testing at differing stages of childhood. Complex relationships seem to exist between low and excessive vitamin D and folate levels and allergic outcomes, whereas there is no clear association between vitamin A and E levels and such outcomes. Several studies seem to show an association with low maternal iron status and allergic outcomes in offspring; however, in the largest maternal-child pair study this finding was not consistent.⁴¹ Here the authors further examine a select group of micronutrient levels in pregnancy, cord blood, and allergic outcomes in offspring (Table 2).

Table 2.

Publications exploring association of maternal micronutrient intake with development of allergy in offspring

Maternal Micronutrient During Pregnancy	Allergy Development in Offspring	Author
Increasing maternal vitamin D intake	Decreased wheeze (Camargo et al.) and nonsignificant lower incidence of asthma/ recurrent wheeze at age 3y Decreased asthma at 7 y, decreased admissions due to asthma, no difference in asthma at 18 mo, no difference in allergic rhinitis at 7 y Reduced rate of wheezing/ asthma, no change in atopic dermatitis or food allergy	Camargo et al,482007 Li et al,502019 Maslova et al,492013 Litonjua et al
Maternal vitamin D levels	No association between level and any allergic outcome at 1 y of age Positive correlation between level and risk of food allergy by age 2 y	Woon et al,54 2020 Weisse et al,55 2013
Maternal folate supplementation	Increased risk of wheeze and URI up to 18 mo No association with wheezing/shortness of breath/atopic dermatitis, no association with asthma in childhood Supplementation with >500 mcg/ d increased eczema in offspring	Haberg et al,60 2009 Kiefte-de Jong et al,60 2012 Crider et al,64 2013
Maternal folate levels	Positive association with atopic dermatitis in highest quartile Folate level greater than the median resulted in decreased risk for lower respiratory tract infections at 6 mo of age and atopic dermatitis at 24 mo	Kiefte-de Jong et al,61 2012 Kim et al,62 2015
Cord blood folate levels	Levels 50–75 nmol/L were optimal to minimize sensitization	Dunstan et al,63 2012
Maternal vitamin E levels	No association with atopy, food allergy, wheezing up to age 2 y	Gromadzinska et al,66 2018
Maternal vitamin E intake	Positive association between low levels and childhood asthma Decreased asthma up to age 10 y with higher maternal intake	Hijazi et al,67 2000 Devereux et al,68 2019
Maternal vitamin A intake	Increased risk of asthma as intake becomes greater than recommended amount No association with asthma, rhinitis, or eczema Higher intake may be protective against development of eczema	Parr et al,73 2018 Nwaru et al,83 2014 Miyake et al,76 2010
Maternal vitamin A supplement	No difference in asthma/ wheeze in supplemented groups	Checkley et al,74 2011
Maternal hemoglobin	Lower values may be a risk factor for allergic sensitization; no association with asthma No association with allergic outcomes in childhood	Shaheen et al,812004 Yang et al,41 2021
Maternal/Fetal iron status	Reduced iron status in mothers is adversely associated with childhood wheeze, lung function, and atopic sensitization Increased risk of inhalant allergy; no difference in lung function, asthma, or inhalant allergic sensitization Negative association with late-onset wheeze and eczema	Nwaru et al,83 2014 Quezada-Pinedo et al,84 2021 Shaheen et al.

Abbreviation: URI, upper respiratory illness.

Vitamin D: maternal supplementation and levels

Two vitamin D isoforms exist. One form (vitamin D3) can be made in the human dermis with exposure to ultraviolet B light. Vitamin D2 is synthesized in plants and fungi.⁴² Although both isoforms are available as dietary supplements, vitamin D3 is more effective at increasing serum levels of 25(OH)D levels.⁴³ Insufficiency is defined by serum 25(OH)D concentrations of less than 10 to 30 ng/mL depending on which reference is used.⁴⁴ Options for improving vitamin D levels exist outside of supplementation via fortified foods such as cereals and milk.⁴⁵ Vitamin D deficiency remains common among pregnant women, with up to 60% of those in Asian countries meeting criteria for deficiency. Current recommendations for supplementation of 200 to 400 IU/day exist but it is not entirely clear if improved outcomes occur.⁴⁶ Vitamin D is potentially influential over many cellular mechanisms including those in the immune system affecting macrophages, monocytes, T cells, and B cells.⁴² The vitamin D receptor is expressed on T cells, B cells, and antigen-presenting cells, and these cells can make the active form of vitamin D (1,25 (OH)₂.D).⁴⁷ In addition, vitamin D has been shown to alter regulatory T cells and transforming growth factor β production.⁴²

Possible role in allergic disease

Several studies have assessed the association of vitamin D levels in pregnancy with allergic outcomes in offspring. Using questionnaires, Camargo and colleagues found that higher maternal vitamin D intake was associated with a lower risk of wheezing in children at age 3 years.⁴⁸ A large Danish study was conducted using questionnaires to assess the dietary intake of vitamin D during pregnancy at week 25 and outcomes such as a diagnosis of asthma at 18 months of age (via phone report from parent) and asthma or allergic rhinitis at age 7 years via record review. This study found a weak inverse relationship between total vitamin D and asthma outcomes in later childhood. The relationship did not hold true for early asthma. There was no association found with allergic rhinitis.⁴⁹ A meta-analysis conducted by Li and colleagues found an inverse relationship between the intake of vitamin D during pregnancy and wheezing or asthma in offspring. This analysis was primarily concerned with finding an optimal dose of vitamin D to prevent outcomes of wheezing or asthma, and their data suggest an optimal dose of 800 IU/day during pregnancy with a U-shaped association between vitamin D supplementation dosing and asthma outcomes.⁵⁰ The VDAART study, a randomized clinical trial, enrolled more than 400 pregnant women to receive either placebo plus 400 IU/day vitamin D or 4000 IU plus the standard 400 IU/day vitamin D. This group analyzed outcomes of physician-diagnosed asthma/wheezing by 3 years of age and third trimester vitamin D levels. Vitamin D levels in pregnant women were significantly higher in the supplemented group, and this study group did have a lower report of asthma in offspring; however, this did not reach significance.⁵¹ A later 6-year follow-up study also did not show a difference in asthma or wheezing in this study group.⁵² A meta-analysis by Venter and colleagues showed maternal supplementation with vitamin D may help prevent asthma in offspring, but there was no association with atopic dermatitis or food allergy.²⁸

Other studies investigating maternal vitamin D levels in pregnancy and outcomes of food allergy, wheezing, or asthma have shown mixed results. Adams and colleagues concluded that the odds of wheezing/asthma decreased with increasing vitamin D levels in white mothers, but the odds of wheezing increased with increasing vitamin D levels in black mothers.⁵³ A study of maternal vitamin D levels in late pregnancy and risk of allergy in offspring showed that the nondeficient group did not have offspring with a significantly different amount of any type of allergic disease including food sensitization, inhalant allergen reaction, wheeze, or eczema.⁵⁴ The data are further confused by a study by Weisse and colleagues, which found that high maternal vitamin D levels and higher cord blood levels were associated with worsened outcomes with respect to food allergies.⁵⁵ It seems that normal vitamin D levels may lead to a protective effect, whereas either deficiency or excess vitamin D may incur increased risk of allergy or asthma.⁵⁶ Further studies are needed to fully elucidate the details of this complex relationship.

Folate (Vitamin B9): Maternal Levels, Supplementation, and Allergic Outcomes

Folate functions as a coenzyme necessary for multiple chemical reactions including purine synthesis.⁵⁷ The primary means of folate supplementation in pregnancy is via folic acid, the more stable and better-absorbed form. Dietary sources including fortified cereals, leafy greens, and liver are readily available in developed countries.⁴² Current recommendations to consume 400mcg/d of folic acid remain in place due to known reduction of neural tube defects.⁵⁸ Increased folic acid intake can potentially influence gene expression involved in T-cell differentiation, which may affect allergic predisposition in an infant.⁴²

Possible role in allergic disease

No randomized trials have been conducted to assess the role of folate levels during pregnancy and allergic outcomes in infants.⁵⁹ A large Norwegian study showed that folic acid supplementation in pregnancy seems to increase the risk of wheezing and upper respiratory infections in the first 18 months of life.⁶⁰ Similarly, a study conducted in the Netherlands found that a higher maternal folate level was associated with an increased risk of atopic dermatitis in children up to 4 years of age but there was no association seen with wheezing outcomes in this cohort.⁶¹ Conversely, a study using maternal reporting of allergic and respiratory outcomes in comparison to folate levels in pregnancy found that a folate level greater than the median value in midpregnancy was associated with decreased risk of atopic dermatitis at age 2 years and lower respiratory tract infections by 6 months of age.⁶² Dunstan and colleagues found that maternal folate supplementation greater than 500 mcg/d was associated with an increased presence of subsequent eczema in offspring. This study also investigated cord blood levels of folate and found a nonlinear relationship, showing a specific range of fetal levels (50–75 nmol/L) that seemed to optimize minimized sensitization.⁶³ Many of the studies conducted on this relationship are observational and require accurate maternal reporting of folic acid intake, dietary intake, and offspring outcomes. Overall study outcomes seem to be inconsistent with some displaying positive associations with increasing folate intake or maternal level with increasing allergic outcomes, whereas others seem to show no evidence of an association.⁶⁴

Maternal vitamin E intake and offspring outcomes

Vitamin E acts as an antioxidant to aid in the decreased production of reactive oxygen species during fat oxidation. Maternal vitamin E intake may affect fetal growth and subsequently fetal lung growth and capacity and hence subsequent outcomes regarding lung health.⁶⁵ A Polish study of 252 mother-infant dyads aimed to assess the association of both vitamin A and vitamin E levels of pregnancy/cord blood and allergic outcomes. There was no association found for either vitamin with atopy, food allergy, or wheezing in the infants followed-up to age 2 years.⁶⁶ Hijazi and colleagues investigated the relationship between maternal vitamin E intake and asthma in offspring. This group found that childhood asthma was positively associated with a history of a maternal diet low in vitamin E.⁶⁷ A study conducted in the United Kingdom by Devereux and colleagues measured vitamin E intake during pregnancy and found decreased rates of asthma in children up to age 10 years who were born to women with higher intake of the vitamin. The decreased asthma outcome seemed to be lost by age 15 years.⁶⁸ There is unclear and insufficient evidence to suggest an association between vitamin E intake or maternal levels and outcomes of allergy/ asthma.

Vitamin A–rich diets and supplementation: an unclear effect

Vitamin A and other retinoids are likely relevant to immune response by affecting the Th1/Th2 responses and maintaining mucosal immune homeostasis.^69,70 Lower levels of vitamin A are observed in both children and adults with asthma versus healthy controls.^71,72 Parr and colleagues studied the role of maternal intake of vitamin A on the presence of asthma in children at age 7 years. This large Norwegian cohort showed an increased rate of asthma, as the vitamin A intake increased to greater than the recommended quantity during pregnancy.⁷³ Several other studies have failed to show an association between either maternal vitamin A supplementation or diets shown to be higher in vitamin A with an outcome of asthma or allergic rhinitis.^74,75 Confounding evidence from other sources showed a lowered risk of eczema and wheezing in offspring with diets higher in ß-carotene.^76,77 It remains unclear if allergy, wheeze, or asthma can be truly correlated with vitamin A levels and vitamin A–rich diets during pregnancy.

Iron status in mothers and offspring may affect allergic outcomes

Iron is essential for normal immune development.^78,79 In addition, low iron status at birth is associated with eosinophilia, a marker of allergic disease. Weigert and colleagues conducted a prospective study of healthy newborns at risk for iron deficiency anemia. This study showed that infants who developed eosinophilia had lower cord ferritin values.⁸⁰ In addition, cord blood iron concentrations were shown to be negatively associated with the development of wheezing and eczema.⁸¹ Shaheen and colleagues also showed that lower maternal hemoglobin during pregnancy may be a risk factor for allergic sensitization, higher IgE levels, and lower forced vital capacity during childhood. There was no association shown for childhood asthma or other allergic diseases.⁸² A large birth cohort in Japan, The Japan Environment and Children’s Study (JECS), examined the relationship between maternal iron status and allergy in early childhood. More than 90,000 mother-child pairs took part in this study, which showed low maternal hemoglobin and hematocrit were not associated with allergic outcomes.⁴¹ An additional maternal-child pair study conducted in the United Kingdom involved 157 pairs assessed for maternal iron status using hemoglobin concentrations and serum iron status at 11 weeks gestation and at delivery. As first trimester iron status decreased, an increased risk of wheezing was shown, and increased serum ferritin concentration was associated with increased pulmonary function measures in offspring. Increased maternal transferrin receptor–ferritin index was associated with increased risk of offspring with atopic sensitization.⁸³ Finally, a cohort study conducted in the Netherlands with more than 3800 mother-child pairs examined the relationship between maternal ferritin, transferrin concentrations, and transferrin saturation in early pregnancy and childhood lung function, asthma, allergic sensitization, and diagnosed inhalant allergy. Higher maternal transferrin concentrations during pregnancy and lower serum iron levels were associated with higher likelihood of childhood allergy as diagnosed by physicians. There was no difference in pulmonary outcomes.⁸⁴

SUMMARY

In conclusion, there is some overall evidence that maternal macro- and micronutrient intake during pregnancy can affect allergic susceptibility in offspring, but specific recommendations based on the studies are difficult to conclude; this is due to multiple challenges with the studies evaluated here, including the use of food questionnaires and necessity for maternal recall, heterogeneity of the studies, timing of initiation of the supplement, continuation of supplementation in offspring after birth, and varied age of assessment of development of allergy in offspring ranging from 1 to 13 years. Based on the current evidence, advice to the pregnant woman would include avoiding a high-fat diet, increasing fiber intake, and maintaining normal micronutrient levels, as some studies suggest higher intake of certain vitamins can increase risk of allergies in offspring (see Table 2). Further studies are needed that are focused on both the micro-and macronutrient intake during pregnancy, as well as interaction with the maternal microbial and metabolic environment. This combined approach would help guide nutrition advice to pregnant women in the future to avoid allergic susceptibility in their offspring.

KEY POINTS.

• Maternal diet can influence offspring immune and microbiome development.

• Maternal diet may play a role in the allergic march in offspring.

• Maternal macronutrient intake, including fat, fiber, and carbohydrate, has recently been examined for association with susceptibility to offspring allergy.

• Maternal micronutrient supplementation with various vitamins and iron have been studied in several large trials for association with offspring allergy development.

CLINICS CARE POINTS.

• Maternal diet is potentially relevant to allergic outcomes in offspring.

• Maternal high-fat diet may lead to increased risk of allergic outcomes, although current supporting data are not conclusive.

• There is some evidence that probiotic supplementation or high-fiber diet during pregnancy may offer a protective effect against allergy development in offspring.

• Excess or depletion of vitamin D during pregnancy may impart higher risk of allergic outcomes in offspring.

• Supplementation of vitamin A and vitamin E during pregnancy do not seem to clearly affect offspring allergy risk.

• Specific recommendations for micronutrient or macronutrient supplementation are limited given the current heterogeneity of study outcomes.