Scientists are urging caution in interpreting an observational study—funded by CDC and published in Vaccine—that found women who had a miscarriage were more likely to have received a certain version of the flu vaccine two years in a row.
The researchers emphasized that their findings did not demonstrate that the flu vaccine causes miscarriages, pointing to confounding factors—including potential differences between mothers who do and do not receive regular vaccines—that could help explain the study's results.
The study authors, CDC, and the American College of Obstetricians and Gynecologists continue to recommend that pregnant women receive a flu shot at any point in pregnancy because of the danger flu presents to women and developing fetuses.
In the late 1990s, CDC recommended that pregnant women in the second or third trimester get a flu shot. CDC's Advisory Committee on Immunization Practices (ACIP) in 2004 extended the recommendation to all pregnant women.
About 10 years ago, CDC funded a project, called Vaccine Safety Datalink, to investigate whether miscarriage rates were higher among women who had a flu shot. Data from the 2005-2006 and 2006-2007 flu seasons did not find a higher rate among women who'd gotten the shot.
However, following the 2009 H1N1 swine flu pandemic, scientists changed the flu shot composition. In response, CDC asked research involved in the Vaccine Safety Datalink project to redo the miscarriage study to assess the effects of the new vaccine composition.
For the new study, epidemiologists compared 485 pregnant women ages 18 to 44 who had a miscarriage with 485 women of similar ages who had either carried to term or suffered a stillbirth—a pregnancy loss late in pregnancy—during the 2010-2011 flu season and the 2011-2012 season. According to the Washington Post's "To Your Health," the compositions of vaccines against H1N1 in 2010-2011 and 2011-2012 were identical.
The researchers found that 17 of the women who had a miscarriage had gotten a flu shot within 28 days of the miscarriage and had been immunized the flu season prior. In comparison, only four of the women who had normal deliveries had gotten a flu shot within the last 28 days and had gotten a flu shot the season prior.
James Donahue, an epidemiologist and lead author, noted, "We only saw the link between vaccination and miscarriage if they had been vaccinated in the season before."
Limitations and explanations
The researchers cautioned that the study had several limitations. For instance, only a limited number of women in the study had had a miscarriage and received the flu shot in two consecutive years.
Further, the researchers said the results could be biased if women who sought care for a miscarriage were also more likely to get a flu shot. Miscarriages typically happen early in pregnancy, and women might have a miscarriage before they or their health care provider learns of the pregnancy. So if women who receive a flu shot every year are likely to be aware of their pregnancy sooner than other women or seek care before or after miscarriage, that could explain the findings, "To Your Health" reports.
In addition, women were more likely to get a flu shot during and after the 2009 H1N1 pandemic than they were before. The researchers said the possible association could be tied to getting the same vaccine for two years in a tow. According to STAT News, the researchers are already assessing data on subsequent years to see if the findings hold up, and—if so—whether it is ongoing.
Experts voice caution on findings
Health officials and study authors said the findings do not warrant a change in the recommendation that pregnant women get a flu shot. Amanda Cohn, senior adviser for vaccines at CDC, said ACIP will discuss the findings at its next meeting at the end of October.
"I think it's really important for women to understand that this is a possible link, and it is a possible link that needs to be studied and needs to be looked at over more (flu) seasons," Cohn said. "We need to understand if it's the flu vaccine, or is this a group of women (who received flu vaccines) who were also more likely to have miscarriages."
Gregory Poland—director of vaccine research at the Mayo Clinic and the editor-in-chief of Vaccine—said he does not believe the vaccines caused the miscarriages but said the study was well designed and raised a question that shouldn't be ignored. According to the Associated Press, two medical journals declined to publish the article before Vaccine accepted it.
Separately, Edward Belongia—an author on the study, ACIP member, and a senior epidemiologist at the Marshfield Clinic Research Institute—said the findings are "not a message that we welcome or want[,] [b]ut it is what we found, and we have an obligation to let people know about that." He added, "Science is an incremental process, and a lot of people don't understand that very seldom does a single study provide a definitive answer that can lead to changes in recommendations."
Gaston De Serres, an infectious diseases epidemiologist with the Quebec Public Health Institute who has written about flu vaccine safety in pregnancy, said, "I wouldn't take these results at face value." He added, "This paper is not a game changer by itself." According to De Serres, an estimated 10 to 15 percent of pregnancies end in miscarriage, and if that rate had increased steeply, obstetric practices would have noticed a change and raised concerns.
Laura Riley, a member of ACIP and vice chair of obstetrics at Massachusetts General Hospital, echoed De Serres' thoughts, saying she "remain[s] skeptical" that repeated flu shots could cause miscarriage. She added the findings are "not going to change my practice, that's for sure."
Providers prepare for questions, concerns
Health officials said they expect the study will raise questions among pregnant women, and they urged those with concerns to speak with their health care providers.
CDC has posted new guidance in anticipation of questions from providers and patients alike, "To Your Health" reports, and ACOG is drafting fact sheets and talking points for members. Riley, chair of ACOG's immunization committee, said, "Your average OB-GYN is not reading Vaccine, ... so they're not going to have the details" (Stobbe, AP/Sacramento Bee, 9/13; Sun, "To Your Health," Washington Post, 9/13; Branswell, STAT News, 9/13).
It's that time of the year again: How to avoid the flu when you fly
We spoke with the University of Arizona's Chuck Gerba—a microbiologist and expert in "fomites," or inanimate objects that are capable of spreading disease—about some of the most alarming hot spots on a plane, and the measures travelers can take to protect themselves. It was a mildly terrifying conversation.