Prenatal Oxidative Balance Affects Allergic Disease and Asthma into Adolescence

in utero fetus air pollution ultrafine particles
Pregnancy pollution risk to the unborn fetus as polluted smoke stacks and toxic waste in the umbilical cord with 3D illustration elements.
Investigators quantified the benefits and detriments in relation to asthma for patients who had been exposed in utero to pro-oxidant toxins.

Adolescents who were exposed in utero to pro-oxidant toxins (air pollution and maternal smoking) and/or potentially immunomodulatory beneficial nutrients (vitamin D and omega-3 polyunsaturated fatty acids [n-3 PUFAs]), but not antioxidants (vitamin C and beta-carotene), showed clear associations between these exposures and increases and reductions, respectively, in early teenaged asthma and allergic disease, according to a study published in the Journal of Allergy and Clinical Immunology.

Prenatal exposure to protective or damaging environmental factors that affect net fetal oxidative stress may play a crucial role in determining the risk for asthma and allergic disease into adolescence. Investigators sought to explore associations between protective vs adverse prenatal exposures (oxidative balance) and allergic disease outcomes in adolescence, hypothesizing that in utero exposures would correlate with disease outcomes in a study that, unlike prior research, modeled multiple factors simultaneously.

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Project Viva was a prebirth mother-child paired cohort study that recruited maternal-fetal pairs between 1999 and 2002; this analysis followed 996 (median age, 12.9 years; 51% male) of the children into adolescence to examine the effect that prenatal exposures had on the development of allergic disease.

Examined exposures included both pro-oxidant and potentially protective factors. The former group comprised maternal smoking, prepregnancy obesity and acetaminophen intake, and air pollution (measured as levels of third trimester residence-specific black carbon and particulate matter <2.5 microns in diameter [PM2.5]) during pregnancy. The latter group consisted of prenatal nutrient intake levels, including n-3 and n-6 PUFAs, folate, β-carotene, choline, and vitamins C, D, and E. The primary outcomes were offspring allergen sensitization, allergic rhinitis, and current asthma status.

Logistic regression analysis was performed to assess associations, with multivariable adjustments for confounders. Adjusted odds ratios (aORs) and 95% CIs were reported.

Alpha linolenic acid, an n-3 PUFA, was found to protect against allergen sensitization (aOR, 0.78; 95% CI, 0.64-0.95) and current asthma (aOR, 0.79; 95% CI, 0.64-0.99), whereas linoleic acid, an n-6 PUFA, protected against current asthma (aOR, 0.79; 95% CI, 0.63-0.99). Vitamin D protected against allergic rhinitis (aOR, 0.69; 95% CI, 0.53-0.89), and the combination of n-3 PUFAs eicosapentaenoic acid and docosahexaenoic acid protected against current asthma (aOR, 0.81; 95% CI, 0.66-0.99) and demonstrated a numerical trend toward protection against allergen sensitization (aOR, 0.85; 95% CI, 0.68-1.07).

Regarding adverse prenatal exposures, levels of black carbon (aOR, 1.35; 95% CI, 1.10-1.67) and PM2.5 (aOR, 1.34; 95% CI, 1.09-1.65) were linked with an approximately 30% increased risk for allergen sensitization. Intake of the nutrient choline was also correlated with an elevated risk for allergen sensitization (aOR, 1.33; 95% CI, 1.03-1.70). Maternal intake of acetaminophen was borderline associated with current asthma risk (aOR, 1.30; 95% CI, 0.99-1.70), whereas maternal “former smoker” status was positively associated with allergic rhinitis risk (aOR, 1.65; 95% CI, 1.03-2.67).

The remaining nutrients demonstrated no significant effects on outcomes. There were no multiplicative interactions detected between protective nutrient intakes and oxidative stress sources.

Study strengths included an extended follow-up period and the ability to simultaneously relate multiple exposure sources to allergic disease development. Study limitations included possibly having limited power to detect some associations, lack of trimester overlap for all exposures, and failure to account for cumulative pollutant and nutrient exposures.

“Protective nutrients may counterbalance the adverse effects of pro-oxidant exposures,” advised the authors.


Sordillo JE, Rifas-Shiman SL, Switkowski K, et al. Prenatal oxidative balance and risk of asthma and allergic disease in adolescence [published online August 19, 2019]. J Allergy Clin Immunol. doi:10.1016/j.jaci.2019.07.044