Preterm birth may be protective against development of allergies

Preterm birth appeared to have an inverse association with long-term IgE sensitization, according to a study published in Allergy.

Niki Mitselou, a doctoral student in the department of pediatrics at Örebro University Hospital in Sweden, and colleagues aimed to assess the impact that gestational age at birth has on long-term IgE sensitization to common food and inhalant allergens through early adulthood.

The analysis included data from the ongoing and longitudinal Children, Allergy, Milieu, Stockholm, Epidemiology, or BAMSE, population-based prospective birth cohort, which includes 4,089 infants born between 1994 and 1996 in Stockholm, Sweden. When the infants were aged 2 to 3 months, parents completed questionnaires about their background experience, with additional periodic questionnaires completed up to age 24 years (75% completion rate; n = 3,069).

The researchers also used the Swedish Twin study On Prediction and Prevention of Asthma (STOPPA) cohort to replicate their findings.

Researchers analyzed blood samples for IgE antibodies against milk, egg, cod, soy, peanut and wheat, and against cat, dog, horse, birch, timothy, mugwort, Dermatophagoides pteronyssinus and Cladosporium herbarum allergens at 4, 8, 16 and 24 years in the BAMSE cohort (n = 3,522) and between 9 and 14 years in the STOPPA cohort (n = 675).

Researchers examined the risk for sensitization — defined as allergen-specific IgE of at least 0.35 kU_A/L to fx5 and/or to Phadiatop — to these common food and inhalant allergens up to 24 years among participants based on their gestational age, with birth before 37 weeks considered preterm and at 42 weeks or later considered post-term.

Of those with IgE data in the BAMSE cohort, 197 (5.6%) were born preterm and 330 (9.4%) post-term.

Longitudinal analyses of these data from BAMSE showed preterm birth was associated with lower odds of sensitization to all the allergens tested up to age 24 years (adjusted OR = 0.71; 95% CI, 0.52-0.98), with a greater benefit seen when evaluating food allergens alone (aOR = 0.6; 95% CI, 0.38-0.93).

Replication analyses using data from STOPPA showed a similar risk estimate for all food and inhalant allergens (aOR = 0.72; 95% CI, 0.42-1.21), as did a meta-analysis combining data from both cohorts (aOR = 0.71; 95% CI, 0.54-0.94). The meta-analysis revealed adjusted ORs of 0.73 (95% CI, 0.55-0.96) for sensitization to inhalant allergens alone and 0.71 (95% CI, 0.48-1.04) for sensitization to food allergens.

These associations were independent of birth weight, mode of delivery, family history of allergic disease, furred pets at home and other broadly measured confounders.

The researchers wrote that their findings agree with the hygiene hypothesis, which posits that early microbial exposure protects against atopy by driving a shift from Th2 to Th1-type response to produce greater tolerance. Because preterm infants are exposed to microbes earlier, a Th1-skewed predominance may lead to primary prevention against long-term allergy conditions.

The dual-allergen hypothesis, meanwhile, suggests that food allergen sensitization occurs through low-dose transcutaneous exposure and that immunologic tolerance is the result of early high-dose oral consumption.

“Although preterm birth is associated with significant comorbidities, some outcomes seem to be beneficial,” the researchers wrote. “In contrast, post-term birth was not associated with sensitization. We believe the insights obtained in this paper add to the knowledge on how gestational age and perinatal factors may influence immune tolerance. Further large

prospective cohort studies with power to study extreme prematurity are warranted, as well as studies on early life nutrition and allergen exposure in order to identify the underlying mechanisms for the observed trend.”