See also asthma prevention.

Immune system starts development in the first trimester, in the womb. Some parts (eg IFN gamma) are constrained, probably to protect the placenta. Immunoglobulin (particular A) still developing through early years – airway mucosal dendritic cells still expanding up until puberty.

The major driving force behind postnatal immune development in all mammalian species is microflora of the gastrointestinal tract – “healthy” development requires not just the right balance of microflora, but also at a crucial window in time.

The hygiene hypothesis (David Strachan) has now been modified to include “old friends” (Graham Rook, talking about microbes that have co-evolved with humans) and finally the biodiversity hypothesis.

So lifestyle becomes important – time spent outdoors, time spent in contact with natural habitats, having diverse, unprocessed diets. Fresh fruit and vegetables have their own microbiome, for instance. And these things are heavily linked to socioeconomic status, particularly housing and green space. Role of artificial sweeteners, emulsifiers, plasticisers and other waste organic compounds?

Mode of birth/delivery affects neonatal colonisation (elective vs emergency section or vaginal) – although so far maternal-infant microbial seeding studies have failed to demonstrate health benefits.

More than 20 studies of probiotics and prevention of allergy.  No safety concerns.  15 found supplementation during pregnancy and lactation may reduce eczema, but no effect in asthma, food allergy, rhinitis.

Fish oil (omega-3) supplementation during pregnancy may reduce risk of allergic sensitisation to egg.

Cochrane 2013 review of prebiotics concluded “promising results in high risk populations”, WAO find in favour (probiotics too), but others institutions have not!

Other dietary exposures, including maternal allergenic food avoidance, vitamin, mineral, fruit and vegetable intake did not appear to influence risk of allergic or autoimmune disease.

There is limited evidence to suggest that supporting mothers to breastfeed for longer reduces risk of eczema in the first year. Longer exclusive breastfeeding duration reduces risk of type 1 diabetes.

EAACI have recommended hypoallergenic formula (“one with documented preventive effect”) for 4/12  (Grade I, evidence A-B).  2024 Chinese systematic review found low quality evidence for extremely hydrolysed formula (EHF) reducing risk of cow’s milk allergy [relative risk (RR): 0.62]. Moderate quality evidence for partially hydrolysed (PHF) and EHF reducing risk of eczema in children (even after 2 y – RR: 0.71-0.79). Moderate quality evidence that PHF only reduced risk of wheeze at age 0-2 y compared with CMF (RR: 0.50), but cf with breast milk, both PHF and EHF increased the risk (RR: 1.61 and 64).

[PLoS Med metanalysis 2018]

Sun exposure around time of birth protects against allergy/atopy, according to French study – for one change in interquartile range, sun exposure prenatally had adjusted odds ratio of 0.47 for sensitisation at age 8-9yrs, and 0.32 for asthma. Postnatal effects less strong. Maternal vitamin D supplementation seemed to increase the risk. All the children were from Paris – sun exposure was calculated from meterological data around time of birth, not time spent outdoors. Ethnicity was not reported.  The suggestion is that the mechanism is vitamin D mediated. Previous studies have had mixed results.

Skin

Since eczema commonly precedes food allergy, it is assumed that disruption of the epithelial barrier is the first step in sensitisation (even when a baby is not eating any food) – the “dual allergen exposure” hypothesis. Peanut protein levels in household correlate with peanut sensitisation in high risk babies.

A couple of different skin “endotypes” – protein/ceramide expression, staph aureus abundance – that seem to predict food allergy. Filaggrin mutations are the strongest genetic risk factor for eczema, and the associated disruption in keratinocytes allows for allergens and irritants to penetrate the skin and trigger inflammation. Detergents/pollutants can further disrupt the skin barrier. Low humidity/temperature also affects (autumn/winter births more at risk).

S aureus colonisation is more likely with eczema, and is associated with severity and persistence – it is also associated with reduced tolerance to egg/peanut, and higher IgE milk/egg/peanut.

Cochrane review of emollients as preventive strategy found no evidence of benefit and possibly more infection. Frequent bathing and oil based bath additives increased the risk of eczema. STOP-AD study (ceramide based emollient, first 2 months of life) found reduced eczema incidence at 1yr in high risk infants. Other studies are looking at trilipid rather than petrolatum based emollients.

Japanese study of “proactive topical steroids” at 7-13 weeks of age (including non-affected skin) found 25% reduction in egg allergy but also reduced weight/length! Calcineurin inhibitors may get around the issue of steroid side effects, if safety data in infants becomes available (so far, so good). [Review, 2024]