Diet during pregnancy and infancy and risk of allergic or autoimmune disease: A systematic review and meta-analysis

Abstract

Background: There is uncertainty about the influence of diet during pregnancy and infancy on a child's immune development. We assessed whether variations in maternal or infant diet can influence risk of allergic or autoimmune disease.

Methods and findings: Two authors selected studies, extracted data, and assessed risk of bias. Grading of Recommendations Assessment, Development and Evaluation (GRADE) was used to assess certainty of findings. We searched Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica dataBASE (EMBASE), Web of Science, Central Register of Controlled Trials (CENTRAL), and Literatura Latino Americana em Ciências da Saúde (LILACS) between January 1946 and July 2013 for observational studies and until December 2017 for intervention studies that evaluated the relationship between diet during pregnancy, lactation, or the first year of life and future risk of allergic or autoimmune disease. We identified 260 original studies (964,143 participants) of milk feeding, including 1 intervention trial of breastfeeding promotion, and 173 original studies (542,672 participants) of other maternal or infant dietary exposures, including 80 trials of maternal (n = 26), infant (n = 32), or combined (n = 22) interventions. Risk of bias was high in 125 (48%) milk feeding studies and 44 (25%) studies of other dietary exposures. Evidence from 19 intervention trials suggests that oral supplementation with nonpathogenic micro-organisms (probiotics) during late pregnancy and lactation may reduce risk of eczema (Risk Ratio [RR] 0.78; 95% CI 0.68-0.90; I2 = 61%; Absolute Risk Reduction 44 cases per 1,000; 95% CI 20-64), and 6 trials suggest that fish oil supplementation during pregnancy and lactation may reduce risk of allergic sensitisation to egg (RR 0.69, 95% CI 0.53-0.90; I2 = 15%; Absolute Risk Reduction 31 cases per 1,000; 95% CI 10-47). GRADE certainty of these findings was moderate. We found weaker support for the hypotheses that breastfeeding promotion reduces risk of eczema during infancy (1 intervention trial), that longer exclusive breastfeeding is associated with reduced type 1 diabetes mellitus (28 observational studies), and that probiotics reduce risk of allergic sensitisation to cow's milk (9 intervention trials), where GRADE certainty of findings was low. We did not find that other dietary exposures-including prebiotic supplements, maternal allergenic food avoidance, and vitamin, mineral, fruit, and vegetable intake-influence risk of allergic or autoimmune disease. For many dietary exposures, data were inconclusive or inconsistent, such that we were unable to exclude the possibility of important beneficial or harmful effects. In this comprehensive systematic review, we were not able to include more recent observational studies or verify data via direct contact with authors, and we did not evaluate measures of food diversity during infancy.

Conclusions: Our findings support a relationship between maternal diet and risk of immune-mediated diseases in the child. Maternal probiotic and fish oil supplementation may reduce risk of eczema and allergic sensitisation to food, respectively.

Fig 1. PRISMA flow chart.

CENTRAL, Central Register of Controlled Trials; EMBASE, Excerpta Medica dataBASE; LILACS, Literatura Latino Americana em Ciências da Saúde; MEDLINE, Medical Literature Analysis and Retrieval System Online.

Fig 2

Observational study findings for a relationship between breastfeeding ever and recurrent wheeze at age 5–14 years (A) and a Funnel plot for this analysis showing evidence of publication bias (B). Egger test P = 0.012. CI, confidence interval; OR, odds ratio; W, weight.

Fig 3

Observational study findings for a relationship between breastfeeding ever (A) or exclusive breastfeeding for ≥3–4 months (B) and type 1 diabetes mellitus. CI, confidence interval; OR, odds ratio; W, weight.

Fig 4

RCT findings for probiotic supplementation compared with no probiotics and risk of eczema (A) or atopic eczema (B) at age ≤4 years. CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 5

RCT findings for probiotic supplementation compared with no probiotics and risk of allergic sensitisation to any allergen (A), any inhalant allergen (B), any food allergen (C), egg (D), milk (E), or peanut (F). CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 6. RCT findings for prebiotic supplementation compared with no prebiotics and risk of eczema at age ≤4 years.

CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 7

RCT findings for omega-3 polyunsaturated fatty acid supplementation compared with no polyunsaturated fatty acids and risk of allergic sensitisation to any allergen (A), any inhalant allergen (B), any food allergen (C), milk (D), egg (E), or peanut (F). CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 8

Randomised controlled trial findings for multifaceted dietary interventions compared with no multifaceted intervention and risk of allergic rhinitis at age ≤4 years (A) or 5–14 years (B), wheeze (C) or recurrent wheeze (D) at age 5–14 years, and wheeze (E) or recurrent wheeze (F) at age ≤4 years. CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 9

RCT findings for vitamin supplementation compared with no vitamin supplementation and risk of wheeze (A), recurrent wheeze (B), or eczema (C) at age ≤4 years. CI, confidence interval; RCT, randomised controlled trial; RR, risk ratio; W, weight.

Fig 10

TSA of intervention trials evaluating the effect of probiotics on risk of eczema (A) and the subgroups of studies that did (B) or did not (C) supplement lactating mothers during the postnatal period. The vertical red line is the optimal information size, i.e., the cumulative sample size required to establish with 80% power and 5% 2-sided significance whether the intervention reduces risk of the outcome by ≥20%, allowing for repeatedly meta-analysing the accumulating studies. The horizontal green line is a z score of +1.96, equal to two-sided P = 0.05. The cumulative Z-statistic (blue line) does not reach the optimal information size in analysis of all studies (A) or maternal supplementation studies (B) but does cross the trial sequential monitoring boundary (curved red line), showing evidence for ≥20% relative risk reduction. The cumulative Z-statistic (blue line) for studies without maternal supplementation (C) crosses the futility boundary and reaches the optimal information size without crossing ±1.96, indicating evidence of futility such that further trials of this intervention are not required. Findings were similar for ≥30% relative risk reduction and for eczema associated with allergic sensitisation. No., number; TSA, trial sequential analysis.

Fig 11. TSA of intervention trials evaluating the effect of fish oil supplementation on risk of allergic sensitisation to egg.

The vertical red line is the optimal information size, i.e., the cumulative sample size required to establish with 80% power and 5% 2-sided significance whether the intervention reduces risk of the outcome by ≥20%, allowing for repeatedly meta-analysing the accumulating studies. The horizontal green line is a z score of +1.96, equal to two-sided P = 0.05. The cumulative Z-statistic (blue line) does not reach the optimal information size and does not cross the trial sequential monitoring boundary (curved red line), indicating no clear evidence for ≥20% relative risk reduction. Findings were similar for ≥30% relative risk reduction. No., number; TSA, trial sequential analysis.