Striking An (Oxidative) Balance: Prenatal Pro-oxidant Exposure, Protective Prenatal Nutrients And Asthma Risks In Adolescents

​Joanne Sordillo, ScD, MS

Childhood allergic disease is a significant public health problem, with over half of school-age children showing sensitization to allergens, and approximately 10% with asthma. Childhood asthma is responsible for more hospitalizations and emergency room visits than any other childhood disease in the U.S. While a child’s early life experience may influence his or her risk, susceptibility to allergies and asthma likely begins even before birth.  

Negative effects on the developing immune system of a fetus may be especially influential on the later development of allergic disease. Reactive molecules called free radicals can harm cells. A healthy immune system, beginning in fetal life, requires protection against them.  Many research groups, including our own, are interested in the potential health effects of the prenatal balance between free radicals (which cause a type of damage to cells called oxidative stress) and factors that protect against free radicals (antioxidants).  Potential sources of prenatal oxidative stress - air pollution, maternal smoking, obesity, prenatal acetaminophen intake - may enhance inflammatory responses and alter the expression of genes. If these effects persist after birth, there could be long-term health consequences much further down the road, including an increased risk of asthma that could persist into adolescence.  

In contrast, intake of prenatal nutrients, including antioxidants -- Vitamin D, omega-3 fatty acids, Vitamin C and others -- may have lasting protective effects. The roles of protective prenatal nutrients and of potential sources of oxidative stress are often considered individually in population-based studies and are rarely studied together.  Furthermore, associations between these prenatal exposures and allergic disease are typically reported for children up until the age of 6 or 7, but little is known about the persistence of these associations into adolescence.

In a recent study, we analyzed data from 961 mother-child pairs in Project Viva, a pre-birth cohort study.  We examined exposures that both promote and protect against oxidative stress and assessed how they were associated with asthma and allergic disease in adolescence.  Prenatal protective exposures were maternal intake of antioxidants and other beneficial nutrients (vitamins D, C, and E, β-carotene, folate, choline, and n-3 and n-6 polyunsaturated fatty acids (PUFAs)); harmful exposures were air pollutants, maternal body mass index, acetaminophen intake, and smoking.  We observed protective associations for prenatal Vitamin D (for allergic rhinitis), combined intake of n-3 PUFAs EPA and DHA (for asthma and allergen sensitization), and prenatal intake of n-3 PUFA ALA (for asthma and allergen sensitization).  All of the hypothesized prenatal exposures causing oxidative stress (maternal smoking, prenatal acetaminophen intakes, maternal BMI, prenatal air pollution) showed associations or trends toward increased risk of at least one health outcome.   On the other hand, we did not observe any beneficial effects of nutrients that function primarily as antioxidants (Vitamin C, Beta-carotene), nor did we detect any significant associations for a summary measure of all nutrients combined. Instead, our findings suggest that a few key prenatal nutrients, namely those with the strongest biological evidence for immune system modulation (Vitamin D and n-3 PUFAs), may reduce asthma and allergic disease risk.1 These protective nutrients may counterbalance the adverse effects of adverse exposures by decreasing risk of allergies and asthma in childhood and adolescence.
 
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1 For further reading, please see:
Adorini, L. et al. Dendritic cells as key targets for immunomodulation by Vitamin D receptor ligands. Journal of Steroid Biochemistry and Molecular Biology 89, 437–441 (2004).
Dunstan, J. A. et al. Maternal fish oil supplementation in pregnancy reduces interleukin-13 levels in cord blood of infants at high risk of atopy. Clinical & Experimental Allergy 33, 442–448 (2003).
Hossein-nezhad, M., Arash, MD, PhD|Holick, Michael F. PhD. Vitamin D for Health: A Global Perspective. Mayo Clinic Proceedings 88, 720–755 (2013).
Krauss-Etschmann, M., et al. Decreased cord blood IL-4, IL-13, and CCR4 and increased TGF-β levels after fish oil supplementation of pregnant women. Journal of Allergy and Clinical Immunology, The 121, 470.e6 (2008).
Provvedini, D. M., Tsoukas, C. D., Deftos, L. J. & Manolagas, S. C. 1,25-dihydroxyvitamin D3 receptors in human leukocytes. Science 221, 1181–1183 (1983).
Wada, M. et al. Enzymes and Receptors of Prostaglandin Pathways with Arachidonic Acid-derived Versus Eicosapentaenoic Acid-derived Substrates and Products. Journal of Biological Chemistry 282, 22254 (2007).