Prenatal exposure to RSV season influences first-year risk of RSV lower respiratory illness and RSV-specific immune responses assessed at birth.

Maternal-to-fetal transmission of respiratory syncytial virus (RSV) has been shown to occur but whether late prenatal exposure to RSV season influences offspring postnatal RSV-lower respiratory illness (LRI) risk in early life or RSV immune status at birth is unclear. In this study, the duration of third trimester RSV season exposure was determined for 1,094 newborns of the Tucson Children's Respiratory Study (TCRS) and found to show an inverse relation to risk for first RSV-LRI in the first year. Cord blood anti-RSV antibody is related to third trimester RSV season exposure but not to first year RSV-LRI risk. In a separate birth cohort (the Infant Immune Study), supernatants from cord blood mononuclear cells stimulated with the recall antigen, UV-inactivated RSV, were assayed for IFN-γ and IL-4. The frequency of detectable IFN-γ (but not IL-4) was increased for those with at least 2 mo of third trimester RSV season exposure, suggestive of a fetal immune response to RSV. IMPORTANCE Our study found that duration of third trimester exposure to RSV season related inversely to subsequent risk of postnatal RSV-LRI in the first year, thus implicating this exposure as an important factor in reducing risk of postnatal RSV-LRIs, a risk reduction that appears to be independent of maternally transferred anti-RSV antibody level. The increase in frequency of detectable IFN-γ and not IL-4 in response to UV-inactivated RSV in cord blood immune cells for infants with greater third trimester exposure to RSV season is suggestive of a Type-1 immune response to RSV occurring in utero .

Competing Interests: F.D. Martinez reports grants from the National Institutes of Health (NIH)/National Heart, Lung and Blood Institute (HL139054, HL132523, HL130045, HL147016), NIH/National Institute of Allergy and Infectious Diseases (AI135108, AI146131, AI148104), NIH/Office of Director (OD023282) and OM Pharma (UANLID46205). M. Halonen reports grants from the NIH during the conduct of the study. A.L. Wright reports grants from the NIH during the conduct of the study. T.F. Carr reports grants from the NIH, consulting fees from AstraZeneca and Novartis, honoraria from GSK and Regeneron, and editorial fees from Wolters Kluwer Health during the conduct of this study, unrelated to this work. D.A. Stern and A. Spangenberg report salaries paid by NIH grants noted earlier during the conduct of the study. Raffaella Nenna reports no conflict of interest.