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

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.

Timing of Allergenic Food Introduction to the Infant Diet and Risk of Allergic or Autoimmune Disease: A Systematic Review and Meta-analysis.

IMPORTANCE: Timing of introduction of allergenic foods to the infant diet may influence the risk of allergic or autoimmune disease, but the evidence for this has not been comprehensively synthesized. OBJECTIVE: To systematically review and meta-analyze evidence that timing of allergenic food introduction during infancy influences risk of allergic or autoimmune disease. DATA SOURCES: MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS databases were searched between January 1946 and March 2016. STUDY SELECTION: Intervention trials and observational studies that evaluated timing of allergenic food introduction during the first year of life and reported allergic or autoimmune disease or allergic sensitization were included. DATA EXTRACTION AND SYNTHESIS: Data were extracted in duplicate and synthesized for meta-analysis using generic inverse variance or Mantel-Haenszel methods with a random-effects model. GRADE was used to assess the certainty of evidence. MAIN OUTCOMES AND MEASURES: Wheeze, eczema, allergic rhinitis, food allergy, allergic sensitization, type 1 diabetes mellitus, celiac disease, inflammatory bowel disease, autoimmune thyroid disease, and juvenile rheumatoid arthritis. RESULTS: Of 16 289 original titles screened, data were extracted from 204 titles reporting 146 studies. There was moderate-certainty evidence from 5 trials (1915 participants) that early egg introduction at 4 to 6 months was associated with reduced egg allergy (risk ratio [RR], 0.56; 95% CI, 0.36-0.87; I2 = 36%; P = .009). Absolute risk reduction for a population with 5.4% incidence of egg allergy was 24 cases (95% CI, 7-35 cases) per 1000 population. There was moderate-certainty evidence from 2 trials (1550 participants) that early peanut introduction at 4 to 11 months was associated with reduced peanut allergy (RR, 0.29; 95% CI, 0.11-0.74; I2 = 66%; P = .009). Absolute risk reduction for a population with 2.5% incidence of peanut allergy was 18 cases (95% CI, 6-22 cases) per 1000 population. Certainty of evidence was downgraded because of imprecision of effect estimates and indirectness of the populations and interventions studied. Timing of egg or peanut introduction was not associated with risk of allergy to other foods. There was low- to very low-certainty evidence that early fish introduction was associated with reduced allergic sensitization and rhinitis. There was high-certainty evidence that timing of gluten introduction was not associated with celiac disease risk, and timing of allergenic food introduction was not associated with other outcomes. CONCLUSIONS AND RELEVANCE: In this systematic review, early egg or peanut introduction to the infant diet was associated with lower risk of developing egg or peanut allergy. These findings must be considered in the context of limitations in the primary studies.

Guidance for the Conduct and Reporting of Clinical Trials of Breast Milk Substitutes.

Importance: Breast milk substitutes (BMS) are important nutritional products evaluated in clinical trials. Concerns have been raised about the risk of bias in BMS trials, the reliability of claims that arise from such trials, and the potential for BMS trials to undermine breastfeeding in trial participants. Existing clinical trial guidance does not fully address issues specific to BMS trials. Objectives: To establish new methodological criteria to guide the design, conduct, analysis, and reporting of BMS trials and to support clinical trialists designing and undertaking BMS trials, editors and peer reviewers assessing trial reports for publication, and regulators evaluating the safety, nutritional adequacy, and efficacy of BMS products. Design, Setting, and Participants: A modified Delphi method was conducted, involving 3 rounds of anonymous questionnaires and a face-to-face consensus meeting between January 1 and October 24, 2018. Participants were 23 experts in BMS trials, BMS regulation, trial methods, breastfeeding support, infant feeding research, and medical publishing, and were affiliated with institutions across Europe, North America, and Australasia. Guidance development was supported by an industry consultation, analysis of methodological issues in a sample of published BMS trials, and consultations with BMS trial participants and a research ethics committee. Results: An initial 73 criteria, derived from the literature, were sent to the experts. The final consensus guidance contains 54 essential criteria and 4 recommended criteria. An 18-point checklist summarizes the criteria that are specific to BMS trials. Key themes emphasized in the guidance are research integrity and transparency of reporting, supporting breastfeeding in trial participants, accurate description of trial interventions, and use of valid and meaningful outcome measures. Conclusions and Relevance: Implementation of this guidance should enhance the quality and validity of BMS trials, protect BMS trial participants, and better inform the infant nutrition community about BMS products.

Hydrolysed formula and risk of allergic or autoimmune disease: systematic review and meta-analysis.

OBJECTIVE: To determine whether feeding infants with hydrolysed formula reduces their risk of allergic or autoimmune disease. DESIGN: Systematic review and meta-analysis, as part of a series of systematic reviews commissioned by the UK Food Standards Agency to inform guidelines on infant feeding. Two authors selected studies by consensus, independently extracted data, and assessed the quality of included studies using the Cochrane risk of bias tool. DATA SOURCES: Medline, Embase, Web of Science, CENTRAL, and LILACS searched between January 1946 and April 2015. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective intervention trials of hydrolysed cows' milk formula compared with another hydrolysed formula, human breast milk, or a standard cows' milk formula, which reported on allergic or autoimmune disease or allergic sensitisation. RESULTS: 37 eligible intervention trials of hydrolysed formula were identified, including over 19,000 participants. There was evidence of conflict of interest and high or unclear risk of bias in most studies of allergic outcomes and evidence of publication bias for studies of eczema and wheeze. Overall there was no consistent evidence that partially or extensively hydrolysed formulas reduce risk of allergic or autoimmune outcomes in infants at high pre-existing risk of these outcomes. Odds ratios for eczema at age 0-4, compared with standard cows' milk formula, were 0.84 (95% confidence interval 0.67 to 1.07; I(2)=30%) for partially hydrolysed formula; 0.55 (0.28 to 1.09; I(2)=74%) for extensively hydrolysed casein based formula; and 1.12 (0.88 to 1.42; I(2)=0%) for extensively hydrolysed whey based formula. There was no evidence to support the health claim approved by the US Food and Drug Administration that a partially hydrolysed formula could reduce the risk of eczema nor the conclusion of the Cochrane review that hydrolysed formula could allergy to cows' milk. CONCLUSION: These findings do not support current guidelines that recommend the use of hydrolysed formula to prevent allergic disease in high risk infants. REVIEW REGISTRATION: PROSPERO CRD42013004252.