Influenza treatment during pregnancy does not endanger newborns, study confirms
Newborns exposed to neuraminidase inhibitors during pregnancy did not have an increased risk for adverse outcomes or congenital malformations, according to the results of a large population-based, multinational observational cohort study.
“The effect of neuraminidase inhibitors during pregnancy on neonatal outcomes and congenital malformations has been assessed previously,” Sophie Graner, MD, PhD, of the department of medicine and obstetrics and gynecology at Karolinska University Hospital in Stockholm, Sweden, and colleagues wrote in BMJ. “However, this study is by far the largest, being almost twice the size of all other studies combined with respect to the number of exposed pregnant women, and our results confirm and expand on the findings in the previous studies of no association between neuraminidase inhibitors and a broad range of adverse neonatal outcomes.”
During the 2009-2010 influenza A(H1N1) pandemic, regulatory agencies in Europe and the United States recommended treatment and post-exposure prophylaxis in high-risk patients, including pregnant women, despite the lack of evidence of its safety and efficacy during pregnancy, according to the researchers.
“Accordingly, in the next virulent seasonal influenza pandemic, a large number of women may be targeted for post-exposure prophylaxis and treatment globally,” they added.
Graner and colleagues set out to further examine the effects of the neuraminidase inhibitors Tamiflu (oseltamivir, Roche) and Relenza (zanamivir, GlaxoSmithKline) during pregnancy. They assessed data on women and their singleton infants born at 154 days of gestation or later from January 2008 to December 2010 in Denmark, Norway, Sweden and France. The researchers defined influenza treatment exposure in newborns as mothers having filled a prescription during pregnancy.
More than 5,800 women and their infants were exposed to neuraminidase inhibitors during pregnancy. Most of the women (74%) were prescribed oseltamivir, and 441 received an inhibitor more than once during pregnancy. Overall, 1,220 infants were exposed during the first trimester, 2,408 were exposed during the second trimester, and 2,196 were exposed during the third trimester.
Exposure to oseltamivir or zanamivir did not increase the risk for stillbirth (adjusted OR = 0.81; 95% CI, 0.51-1.3) or being born preterm (aHR = 0.97; 95% CI, 0.86-1.1). In contrast, there was a decreased risk for having a low birth weight (aOR = 0.77; 95% CI, 0.65-0.91) and being small for gestational age (aOR = 0.72; 95% CI, 0.59-0.87).
An analysis restricted to data from Denmark, Norway and Sweden indicated that there was no association between treatment exposure and increased neonatal morbidity during the first 28 days of life (aOR = 0.92; 95% CI, 0.86-1). Further analyses showed a reduced risk for respiratory and cardiovascular disorders (aOR = 0.84; 95% CI, 0.75-0.95). Infants exposed only to oseltamivir had similar outcomes.
A final analysis using data on infants exposed during the first trimester showed that they did not have an increased risk for congenital malformations (aOR = 1.06; 95% CI, 0.77-1.48).
The researchers noted that there were several limitations to their study. For example, women who were prescribed neuraminidase inhibitors may not have taken the drug, or they may have started treatment at a later date than it was dispensed. However, they concluded that their results “support previously reported findings that the use of neuraminidase inhibitors is not associated with increased risks of adverse fetal or neonatal outcomes.” – by Stephanie Viguers
Disclosure: The researchers report no relevant financial disclosures.