Pregnant women who have pandemic H1N1 influenza infection appear to be at greater risk of complications, but some healthcare providers have been hesitant to treat them early with antivirals despite recommendations to do so, researchers from the US Centers for Disease Control and Prevention (CDC) reported today.

The latest details on the health risks of novel H1N1 infection in pregnant women come on the same day the CDC´s Advisory Committee on Immunization Practices voted to place pregnant women at the top of a priority list to receive a vaccine against the virus that is now being developed.

The study findings, which also reveal that pregnant women were four times more likely than the general population to be hospitalized for their flu infections, appear today an in early online edition of The Lancet. The analysis is based on enhanced surveillance in pregnant women that the CDC ordered shortly after the first US deaths in these women.

Pregnant women have been identified as a high-risk group for season flu and have been hit hard during previous influenza pandemics. In the early weeks of the novel H1N1 outbreak, the CDC raised an alarm on the risks in pregnant women through case reports in the May 12 issue of Morbidity and Mortality Weekly Report (MMWR) and held a media briefing to stress the importance of early antiviral treatment in this population.

Illness and death tolls
The authors reported that from Apr 15 through May 18, 34 confirmed novel H1N1 cases in pregnant women of various ages and races from 13 states were reported to the CDC. Seventeen of the women were prescribed oseltamivir (Tamiflu), but only eight began treatment within 2 days of symptom onset. Six of these had confirmed or suspected pneumonia and two were diagnosed with dehydration. The group´s symptoms resembled those of patients who were not pregnant, though pregnant women were more likely to report shortness of breath.

Although the authors found that the pregnant women were four times more likely to be hospitalized, the CDC investigators cautioned that doctors may be more likely to admit ill women if they are pregnant.

Of the 45 deaths that were reported in the United States through Jun 16, 13% (6) were in pregnant women. One woman was in the first trimester, one in the second trimester, and four in the third trimester. The authors reported that all were fairly healthy before they contracted pandemic H1N1 influenza. The time interval between presentation for medical care and antiviral treatment ranged from 2 to 14 days, with a median of 4.5 days.

All of the women who died had primary viral pneumonia and experienced acute respiratory distress syndrome that required mechanical ventilation. None who died were treated with oseltamivir within 48 hours of symptom onset, the time when the drug is expected to provide the most benefit. None of five infants born to the women who died had any evidence of influenza infection.

A call for quick antiviral treatment
The CDC investigators concluded that the high proportion of flu-related deaths in the United States is concerning. Denise Jamieson, MD, a medical officer in the division of reproductive health at the CDC and lead author of the study, said in a statement that reports of deaths in pregnant women are always heartbreaking. "If a pregnant woman feels like she may have influenza, she needs to call her healthcare provider right away," Jamieson said.

Healthcare providers who treat pregnant women should have a triage system in place for those who have flu symptoms and should not delay starting antiviral treatment, according to Jamieson. "Some clinicians hesitate treating pregnant women with antiviral medications because of concerns for the developing fetus, but this is the wrong approach. It is critical for pregnant women, in particular, to be treated promptly."

Implications for vaccination
The benefits of antiviral therapy outweigh the risks for pregnant women, and healthcare providers will likely face resistance again when a pandemic H1N1 vaccine becomes available. Though the CDC and the American College of Obstetrics and Gynecology have recommended that pregnant women in all trimesters receive their annual flu shot, vaccine coverage rates in this group are lowest, about 14%, of all adults groups for whom vaccination is recommended.

Vaccinating pregnant women may have an extra benefit, the authors noted. They pointed to an October 2008 study in the New England Journal of Medicine that suggested maternal influenza vaccination reduced influenza illness by 63% in babies aged 6 months and younger.

Laura E. Reilly, MD, medical director for labor and delivery at Massachusetts General Hospital in Boston, told CIDRAP News that in general, many people believe it´s not safe to take any medications during pregnancy, a concern that is magnified by worries over vaccine safety in young children.

However, she said epidemiologic studies show that pregnant women are at risk for worse outcomes when they have influenza infections. Reilly said vaccines aren´t an easy sell to pregnant women, "but it´s a reasonable conversation to have with a pregnant woman."

An extra challenge providers will face when talking to pregnant women about the pandemic H1N1 vaccine is that little is known about its effects and that two doses will likely be needed.

Reilly said physicians may feel uncomfortable pushing the new vaccine. "Whenever you´re a provider you have to feel like you´re not doing any harm," she said. Federal officials could help doctors become more confident in administering the vaccine by making efforts after immunization campaigns to begin tracking outcomes.

After participating in a discussion with a group from the US Department of Health and Human Services on Jul 27, Reilly said she was encouraged that federal officials take the pandemic H1N1 vaccine safety tracking issue seriously.

The venue for delivering the pandemic H1N1 vaccine to pregnant women should probably be doctors´ offices, she said. "Pregnant women want to have a discussion about this with their doctors. Pregnant women aren´t going to want to line up at CVS," Reilly added.

Jamieson DJ, Honein MI, Rasmussen SA, et al. H1N1 2009 influenza virus infection during pregnancy in the USA. Lancet 2009 Jul 29 (early online publication) [Abstract]