Introduction
Influenza is an acute infectious disease caused by the influenza A, B,
and C viruses that threatens pregnant mothers[1]. During seasonal
influenza and pandemic influenza outbreaks, pregnant women have
increased susceptibility to severe infection and worse clinical outcomes
from influenza[2]. Maternal influenza exposure during pregnancy is
associated with adverse maternal and neonatal outcomes[3],
suggesting that influenza should be prevented and treated in pregnant
women.
The neuraminidase-inhibitor antiviral medications oseltamivir and
zanamivir have been recommended for preventing and treating influenza
among exposed and/or infected pregnant women since the 2009 HIN1
pandemic[4]. Since then, there has been a notable increase in the
number of pregnant women treated with neuraminidase inhibitors[5].
However, little is known about the reproductive safety of these drugs. A
study using an ex vivo human placental model showed that
transplacental transfer of the oseltamivir metabolite is incomplete and
its accumulation is minimal[6]. Several cases of adverse outcomes
have been reported in mothers exposed to oseltamivir[7, 8]. Some
studies without control women suggest that maternal exposure to
laninamivir does not increase the rate of adverse pregnancies or fetal
outcomes[9, 10]. Previous systematic reviews with small sample sizes
have summarized this association and reported that exposure to a
neuraminidase inhibitor during pregnancy does not appear to increase the
overall risk of congenital malformations[11, 12]. Additional studies
have been published since that systematic review, enabling a more
detailed analysis of the association between neuraminidase-inhibitor use
during pregnancy and congenital malformation risk. Those studies also
investigated the effects of neuraminidase inhibitors on other pregnancy
outcomes, but the results were inconsistent. Therefore, we conducted a
meta-analysis to collect evidence-based, relevant research regarding
maternal neuraminidase-inhibitor exposure during pregnancy and neonatal
outcomes to provide a scientific basis for recommendations to avoid
adverse outcomes.