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