Conclusions
The 2000 AAP policy167 recommended avoidance of allergenic foods for breastfeeding mothers and delayed introducing allergenic foods to infants to prevent FA was based on expert opinion informed by a limited number of low quality studies.168 These guidelines influenced infant feeding practices for almost 20 years,169 while FA only continued to increase, rather than decrease. These guidelines were reversed in 2008, but not replaced with comprehensive guidelines, only limited recommendations.168With publication of data from higher-quality studies, recent guidelines offer a comprehensive approach to maternal/infant diet.16,17,166,170The foundation for these studies and ongoing efforts to study the prevention of atopy was laid throughout the 1900s by pioneers in the field (Table 1).
It is critical to not only have consistent diagnostic criteria for the conditions being studied, but also to have comparable outcomes that are patient-relevant when possible. This will allow for valid and complete comparisons across studies in diverse populations, including high and general risk populations, regionally and globally. Reliable estimates of the global burden of atopic disease and improved epidemiologic data for these conditions is crucial to gain support for and acceptance of prevention guidelines.
Interventions to prevent AD and FA targeted at the first few months of life are not early enough for some babies. There are likely factors already in place within the first few weeks of life, or earlier, particularly in at-risk infants who may start the march towards atopy and a Th2 milieu in the womb.  The proposed increased risk for FA with more than daily application of moisturizer in the EAT study cohort highlights the need for earlier assessments and interventions among diverse and representative populations employing consistent disease definitions using easily applied and clinically relevant assessments.171 This finding further cautions against drawing potentially premature conclusions when important confounders cannot be adequately accounted for. These most recent findings add to the conflicting evidence about the potential to prevent AD to reduce the risk of FA.172 Further, this supports the need for intervention trials designed from the outset to study FA using a broadly accepted definition as the primary outcome, beginning in the first weeks of life, with intentionally developed treatment groups and carefully planned assessments in hopes of Stopping Eczema and ALlergy (SEAL, NCT03742414). The SEAL Study will also attempt to answer ongoing research questions identified in this review, summarized in Box 1.
It is unlikely that there is a single way to stop the atopic march once underway or a master switch that could render all the external factors discussed in this review ineffective at inducing a Th2 response. It remains important to investigate these potential targets for prevention (Figure 7) and continue to search for others. Given the remarkably conflicting results within and between studies on the microbiome and a wide variety of dietary factors, it seems that well-informed guidelines in these areas are farther off in the future, and may require extensive public health campaigns to slowly change behaviors if successful approaches can be identified.
It is of course still necessary to provide recommendations before definitive evidence that is applicable to diverse populations is available. In the interim, recent updates from North America16 and the UK17 are more unified and coming aligned with those from Australasia.170 There will certainly be disagreement with some aspect of any guideline, but these do represent a responsible approach toward prevention of atopic conditions, based on the presently limited evidence base. Well-designed trials must continue, and future trials move forward in the face of unprecedented challenges faced today by study subjects, clinical researchers, and scientists so that the field can move closer to an understanding of the complex mechanisms driving allergic sensitization early in life. Effective strategies for the prevention of atopic conditions, particularly AD and FA will almost certainly be the result.
Table 1A: Major Milestones Laying the Foundation for Prevention Studies