FLU-IGIV

Objectives The objective of this study is to evaluate whether there is an association between in-utero exposure to nicotine and subsequent hearing dysfunction. Materials and Methods Secondary analysis of a multicenter randomized trial to prevent congenital cytomegalovirus (CMV) infection among gravidas with primary CMV infection was conducted. Monthly intravenous immunoglobulin hyperimmune globulin therapy did not influence the rate of congenital CMV. Dyads with missing urine, fetal or neonatal demise, infants diagnosed with a major congenital anomaly, congenital CMV infection, or with evidence of middle ear dysfunction were excluded. The primary outcome was neonatal hearing impairment in one or more ears defined as abnormal distortion product otoacoustic emissions (DPOAEs; 1 to 8 kHz) that were measured within 42 days of birth. DPOAEs were interpreted using optimized frequency-specific level criteria. Cotinine was measured via enzyme-linked immunosorbent assay kits in maternal urine collected at enrollment and in the third trimester (mean gestational age 16.0 and 36.7 weeks, respectively). Blinded personnel ran samples in duplicates. Maternal urine cotinine >5 ng/mL at either time point was defined as in-utero exposure to nicotine. Multivariable logistic regression included variables associated with the primary outcome and with the exposure (p < 0.05) in univariate analysis. Results Of 399 enrolled patients in the original trial, 150 were included in this analysis, of whom 46 (31%) were exposed to nicotine. The primary outcome occurred in 18 (12%) newborns and was higher in nicotine-exposed infants compared with those nonexposed (15.2 vs. 10.6%, odds ratio [OR] 1.52, 95% confidence interval [CI] 0.55–4.20), but the difference was not significantly different (adjusted odds ratio [aOR] = 1.0, 95% CI 0.30–3.31). This association was similar when exposure was stratified as heavy (>100 ng/mL, aOR 0.72, 95% CI 0.15–3.51) or mild (5–100 ng/mL, aOR 1.28, 95% CI 0.33–4.95). There was no association between nicotine exposure and frequency-specific DPOAE amplitude. Conclusion In a cohort of parturients with primary CMV infection, nicotine exposure was not associated with offspring hearing dysfunction assessed with DPOAEs. Key Points

Seasonal influenza causes significant morbidity and mortality around the world each year, even with the use of vaccines and antivirals. There is a need for more effective treatments for severe and hospitalized cases of influenza. In this study, we have tested the efficacy of a human plasma-derived IgG product (FLU-IGIV) against seasonal influenza in mouse and ferret models of influenza infection. FLU-IGIV successfully protected mice (100% survival) against lethal influenza infection. Also, the survival rate observed with FLU-IGIV treatment was better than the survival rate observed with oseltamivir (60% survival). FLU-IGIV significantly reduced the viral load in the lungs compared to placebo (PBS) in ferrets infected with influenza A/California/07/2009 (H1N1pdm09) virus. Overall, these studies demonstrate the efficacy of human plasma-derived FLU-IGIV in relevant animal models of influenza virus infection.