Pregnant women with influenza are at increased risk of morbidity, particularly 
due to respiratory complications. A high excess mortality rate among pregnant 
women has been observed in previous influenza pandemics and healthcare agencies 
have provided recommendations on the use of oseltamivir to treat pregnant women 
who are infected with the pandemic (H1N1) 2009 virus. This article reviews 
pre-clinical and clinical data to assess the safety of oseltamivir administered 
during pregnancy, in the context of the effects of influenza on adverse 
pregnancy outcomes and fetal malformations. The effects of influenza during 
pregnancy, whether mediated directly by the virus or by fever or other events 
secondary to the underlying infection, are not yet well understood, but some 
data indicate an increased risk of birth defects in women infected with 
influenza during the first trimester. Animal and toxicology studies do not 
suggest that clinically effective dosages of oseltamivir have the potential to 
produce adverse effects on fetal development. Additionally, transplacental 
transfer of the drug and its active metabolite was very limited and not 
detectable at normal therapeutic doses in an ex vivo human placenta model. To 
investigate the safety of oseltamivir in pregnancy, the Roche oseltamivir safety 
database was searched for all exposures to oseltamivir during pregnancy in the 9 
years up to 14 December 2008. In addition, a search of the literature was 
carried out. Of 232 maternal exposures to oseltamivir in the Roche database, 
pregnancy outcomes were known for 115 of these exposures. The incidence of 
adverse pregnancy outcomes was as follows: spontaneous abortions 6.1% (7/115), 
therapeutic abortions 11.3% (13/115) and pre-term deliveries 2.1% (2/94 live 
births), values that are not higher than background incidence rates. Fetal 
outcomes were known in 100 of the 232 exposures. For the nine cases of birth 
defect that were reported, the timing of oseltamivir exposure in relation to the 
sensitive period for inducing the birth defect was analysed. Two cases of 
ventricular septal defect, a more common birth defect, and one case of 
anophthalmos, an uncommon birth defect, were consistent with exposure to 
oseltamivir during the sensitive period for these birth defects. For other birth 
defects, there was either no exposure to oseltamivir during the sensitive period 
for the defect or insufficient information for assessment. These findings were 
consistent with other reports in the published literature, including a series of 
79 Japanese women exposed to oseltamivir during the first trimester. Together 
with the other evidence reviewed herein, review of the company safety database 
suggests that oseltamivir is unlikely to cause adverse pregnancy or fetal 
outcomes, but available data are limited. Clinicians who use oseltamivir in 
pregnant women should consider the available safety information, the 
pathogenicity of the circulating influenza virus strain, the woman's general 
health and the guidance provided by health authorities. Roche will continue to 
monitor all reports of oseltamivir use during pregnancy.