During the 2009 influenza A (H1N1) pandemic, many pregnant women experienced severe illness and some gave birth while ill with suspected or confirmed pandemic (H1N1) 2009 influenza. Because of concerns about possible transmission of this novel virus to immunologically naïve newborns, and the absence of definitive studies regarding this risk, the Centers for Disease Control and Prevention (CDC) reviewed relevant literature to understand the potential burden of disease and routes of transmission affecting newborns. This report describes the issues considered during the 2009 H1N1 pandemic as CDC developed guidance to protect newborns in hospital settings. Also presented is a framework of protection efforts to prevent novel influenza infection in fetuses/newborns before birth and in hospital settings. Although developed specifically for the pandemic, the framework may be useful during future novel influenza outbreaks.