Thursday, February 04, 2016

JID: Benefits Of Early Use of Influenza Antivirals In Pregnancy

Credit - CDC


With a warning earlier this week that severe H1N1 cases are beginning to be reported in younger adults around the country, the timing for a study and commentary on the benefits of early antiviral treatment for pregnant women with influenza that appears today in the Journal of Infectious Diseases couldn't be much better. 

Pregnant women have an enhanced risk for serious complications from influenza, something we've looked at repeatedly over the years:

  • During the 2009 H1N1 pandemic, pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).
  • And in 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study where pregnant women who were admitted to the hospital with an  H1N1 infection experienced a 3 to 4 times higher rate of preterm birth, 4 to 5 times greater risk of stillbirth, and a 4 to 6 times higher rate of neonatal death.

It is for this reason that flu vaccinations are so highly recommended for women who are pregnant (see CDC's Pregnancy and Influenza Vaccine Safety). But even with the vaccine, infection can sometimes occur, and here is where antivirals come into play.

Despite their frequent demonization in the press, antivirals have a proven track record of reducing the impact of severe influenza when taken early in one's illness, particularly for those at greatest risk of complications

I've reviewed the evidence for using antivirals many times over the years, including The Conversation: The Rise & Fall Of The Challenge To Tamiflu and Revisiting Tamiflu Efficacy (Again).

Although we've seen evidence of the value of treating pregnant women with antivirals in the past (see Study: Antivirals Saved Lives Of Pregnant Women), we have another study showing the outcomes for pregnant women hospitalized with lab-confirmed influenza, who either received antivirals early (< 48 hrs after onset), late (> 48hrs) , or not at all.

The benefit of early influenza antiviral treatment of pregnant women hospitalized with laboratory-confirmed influenza


Background. We describe the impact of early antiviral treatment among pregnant women hospitalized with laboratory-confirmed influenza (2010−14 influenza seasons). 

Methods. Severe influenza was defined as intensive care unit admission, mechanical ventilation, respiratory failure, pulmonary embolism, sepsis, or death. Within severity stratum, we used parametric survival analysis to compare length of stay (LOS) by timing of antiviral treatment, adjusting for underlying conditions, influenza vaccination, and pregnancy trimester.

Results. Among 865 pregnant women, median age was 27 years (interquartile range [IQR], 23−31). Most (68%) were healthy, and 85% received antiviral treatment. Sixty-three (7%) women had severe influenza, 4 died. Severity was associated with preterm delivery and fetal loss.
Women with severe influenza were less likely to be vaccinated than those without (14% vs. 26%, p=0.03). Comparing women treated with antivirals ≤2 vs. >2 days from illness onset, median LOS (days) was respectively 2.2 (IQR 0.9−5.8; n=8) vs. 7.8 (IQR 3.0−20.6; n=7) for severe (p=0.03), and 2.4 (IQR 2.3−2.5; n=153) vs. 3.1 (IQR 2.8−3.5; n=62) for non-severe influenza (p<0 .01="" span="">

Conclusions.  Early influenza antiviral treatment for pregnant women hospitalized with influenza may reduce LOS, especially if severe influenza. Influenza during pregnancy is associated with maternal and infant morbidity and annual influenza vaccination is warranted.

The full study can be downloaded at Full Text (PDF).

The IDSA (Infectious Disease Society of America) has a press release on this study, excerpts of which follow:

For pregnant women with flu, the earlier the better for antiviral treatment

Prompt use of medication beneficial, especially in cases of severe illness, study suggests Infectious Diseases Society of America

Pregnant women are at higher risk for serious illness and complications, including death, from influenza. For expectant mothers hospitalized with flu, early treatment with the influenza antiviral drug oseltamivir may shorten their time in the hospital, especially in severe cases, suggests a new study published in The Journal of Infectious Diseases and available online. The findings also underscore the importance of flu vaccination for this risk group.

"Treating pregnant women who have influenza with antiviral drugs can have substantial benefit in terms of reducing length of stay in the hospital," said Sandra S. Chaves, MD, MSc, of the Centers for Disease Control and Prevention (CDC) and senior author of the study. CDC recommends treatment of suspected cases of flu among pregnant women with antiviral drugs as soon as possible, without waiting for test results to confirm influenza. "The earlier you treat, the better chances you have to modify the course of the illness."

Past studies have suggested that flu antiviral therapy is safe and beneficial for pregnant women. The current study, based on data from a nationwide flu surveillance network including 14 states, focused on pregnant women hospitalized with laboratory-confirmed flu over four recent flu seasons, from 2010 to 2014.
During the study period, 865 pregnant women were hospitalized with flu. Sixty-three of these patients, or about 7 percent, had severe illness.
After adjusting for underlying medical conditions, vaccination status, and pregnancy trimester, the researchers found that early treatment with the antiviral drug oseltamivir was associated with a shorter hospital stay. Among pregnant women with severe flu illness who were treated early -- within two days of the start of symptoms -- the median length of stay was about five days shorter compared to hospitalized pregnant women with severe flu illness who were treated later (2.2 days vs. 7.8 days). Pregnant women hospitalized with less severe illness who were treated early also had a shorter hospital stay than those treated later, but the difference was not as great.

In the study, pregnant women hospitalized with severe flu illness were half as likely to have been vaccinated as women hospitalized with milder illness (14 percent vs. 26 percent). CDC recommends annual flu vaccination for everyone 6 months of age and older, including pregnant women during any trimester of their pregnancy. Earlier studies have suggested that immunization during pregnancy may protect not only the mother from flu, but also her newborn baby during the first 6 months of life.

"All pregnant women should receive annual influenza vaccination to prevent influenza and associated complications for themselves and their infants," the study authors wrote.

A related editorial commentary by Alan T. N. Tita, MD, PhD, and William W. Andrews, PhD, MD, of the University of Alabama at Birmingham, accompanies the new study in The Journal of Infectious Diseases.

"Overall, considering the accumulating evidence of fetal benefit and safety, influenza vaccination of pregnant and postpartum women should be a public health priority in accordance with national recommendations," the commentary authors wrote. "Prompt initiation of antiviral therapy if infection occurs, preferably within two days of suspected or confirmed influenza infection, is encouraged."
Fast Facts
  • Among pregnant women hospitalized with severe flu who were treated early with an antiviral medication, the median length of their hospital stay was about five days shorter compared to similar patients treated later.
  • Pregnant women who were hospitalized with severe cases of flu illness were half as likely to have been vaccinated as women with non-severe illness.
  • Annual vaccination against flu is recommended for everyone 6 months of age and older, including pregnant women, who are at high risk of serious flu illness and complications.

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