The Japan Society of Obstetrics and Gynecology (JSOG) recommended the use of oseltamivir or zanamivir for the treatment of pregnant patients or for the prophylaxis in pregnant women in close contact with an infected person during the influenza pandemic (H1N1) in 2009. As data on the safety of these antivirals during pregnancy were limited, the JSOG initiated a prospective study to collect information on the outcomes of exposed infants.
Compared with Japanese national data, there appeared to be no increase in miscarriage or preterm deliveries among women who took oseltamivir or zanamivir (although the frequency of the latter was higher for zanamivir, the 95% confidence interval did not exceed that in national data). Similarly, infants exposed to oseltamivir or zanamivir in utero did not have higher rates of perinatal complications compared to previous reports, and their rates of birth weight below 2500 g or small-for-gestational age did not exceed those for Japan's general population.
A total of 14 infants (2.1%) were confirmed to have congenital malformations within 1 to 18 months after birth (all cases were exposed to oseltamivir). Only two of these were exposed during the first trimester (1.3% rate of malformations). In infants exposed during the second and third trimesters, the rate of malformations was 2.6%. The authors comment that generally, the rate of congenital abnormalities diagnosed up to the eight month of life ranges from 2.2-3%.
Based on their results, the authors say that the use of oseltamivir and zanamivir during pregnancy does not appear to increase the number of adverse pregnancy outcomes, including congenital malformation. The study was however limited by the examination of only short-term outcomes, and longer-term follow-up of the exposed infants (at least until the age of two years) is required to clarify long-term prognosis. As miscarriages are more common in early pregnancy, and many women were not enrolled in this study until after this period, it is difficult to compare rates of miscarriage to that in the general population. The authors comment on the sample size for zanamivir in the study, and how it was too small to determine safety.