Photo Credit – CDC
# 6877
We’ve known for a long time that influenza and pregnancy are a bad combination - one that can endanger both the mother and unborn child’s life – and that women are more susceptible to influenza when they are pregnant.
During the 1918 pandemic an abnormally high number of pregnant women died from the influenza, and those that survived endured a very high miscarriage rate. Again, during the much milder 1957 Asian Flu, pregnant women reportedly suffered disproportionately higher mortality rates than non-pregnant women of the same age.
Historical reviews of both events are available in a Perspective, written by 3 CDC physicians (Sonja A. Rasmussen, Denise J. Jamieson, Joseph S. Bresee) and published in the CDC Journal of EID article, Pandemic Influenza and Pregnant Women in February of 2008.
True to form, the 2009 H1N1 pandemic saw similarly high rates of influenza complications among pregnant women.
An open access research article in the BMJ in 2011 (Perinatal outcomes after maternal 2009/H1N1 infection: national cohort study) found that 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.
Over the past decade we’ve also seen a handful of studies tentatively linking prenatal exposure to influenza (or an influenza-like-illness) with a variety of child and adolescent development disorders (see Of Pregnancy, Flu & Autism).
All of which explains why the CDC, the WHO, and other public health stress the importance of seasonal flu vaccination for pregnant women.
Despite all of this evidence of harm from influenza - there remains some reluctance among pregnant women to get the shot - in part due to the persistent anti-vaccine rhetoric on the internet and in the media.
Despite studies showing exactly the opposite effect, during and after the 2009 H1N1 pandemic there were unfounded claims that the 2009 H1N1 vaccine was responsible for `thousands’ of miscarriages.
Our first stop then is a study that recently appeared in the NEJM that looked at a large cohort of pregnant Norwegian women during the pandemic, and found that while influenza increased the rate of fetal deaths, that vaccination did not, and may have reduced the number fetal deaths.
Risk of Fetal Death after Pandemic Influenza Virus Infection or Vaccination
Siri E. Håberg, M.D., Ph.D., Lill Trogstad, M.D., Ph.D., Nina Gunnes, Ph.D., Allen J. Wilcox, M.D., Ph.D., Håkon K. Gjessing, Ph.D., Sven Ove Samuelsen, Ph.D., Anders Skrondal, Ph.D., Inger Cappelen, Ph.D., Anders Engeland, Ph.D., Preben Aavitsland, M.D., Steinar Madsen, M.D., Ingebjørg Buajordet, Ph.D., Kari Furu, Ph.D., Per Nafstad, M.D., Ph.D., Stein Emil Vollset, M.D., Dr.P.H., Berit Feiring, M.Sc.Pharm., Hanne Nøkleby, M.D., Per Magnus, M.D., Ph.D., and Camilla Stoltenberg, M.D., Ph.D.
N Engl J Med 2013; 368:333-340J anuary 24, 2013 DOI: 10.1056/NEJMoa1207210
Conclusions
Pandemic influenza virus infection in pregnancy was associated with an increased risk of fetal death. Vaccination during pregnancy reduced the risk of an influenza diagnosis.
Vaccination itself was not associated with increased fetal mortality and may have reduced the risk of influenza-related fetal death during the pandemic. (Funded by the Norwegian Institute of Public Health.)
This was not the first study to show the safety of the 2009 pandemic flu vaccination in pregnancy, only the latest.
Last year, in BMJ: H1N1 Vaccination & Fetal Death Rates, we looked at a study on a large cohort of pregnant women from Demark that reassuringly found no increase in miscarriage among those who received the 2009 H1N1 vaccine.
We saw similar results in 2010 (see Hong Kong: No Increase In Fetal Death Among Vaccine Recipients). For more studies on the safety of flu vaccines in pregnancy, see IDSA: Flu Vaccines In Pregnancy.
Our second study, published overnight in PLoS One, looks at transplacental transfer of antibodies following vaccination with the AS03A-Adjuvanted H1N1 2009 Vaccine.
As infants are highly susceptible to influenza, and vaccination is not recommended before the age of 6 months, the receipt of vaccine derived antibodies from the mother while still in the womb might provide needed protection.
This study looked for antibodies in cord blood samples taken from babies shortly after delivery from 77 vaccinated and 27 unvaccinated women during the fall and winter of 2009.
Multi-Centre Observational Study of Transplacental Transmission of Influenza Antibodies following Vaccination with AS03A-Adjuvanted H1N1 2009 Vaccine
Richard Puleston , George Bugg, Katja Hoschler, Justin Konje, James Thornton, Iain Stephenson, Puja Myles, Joanne Enstone, Glenda Augustine, Yvette Davis, Maria Zambon, Karl Nicholson, Jonathan Nguyen-Van-Tam
Abstract
Introduction
Illness and death from influenza increase during pregnancy. In the United Kingdom pregnant women were targeted in a national programme for vaccination during the H1N1 2009–10 pandemic.
Methods
In this study, pregnant women were recruited in labour from November 9, 2009 to March 10, 2010. Pandemic vaccination status was determined. Venous cord blood collected at delivery was evaluated for transplacental transfer of antibodies by measurement of haemagglutination inhibition and microneutralization titres.
Results
Samples were collected from 77 vaccinated and 27 unvaccinated women. Seroprotection (HI titre ≥1:40) was detected in 58 (75.3%, 95% CI 64.2–84.4) cord blood samples from vaccinated women and 5 (18.5%, 95% CI 6.3–38.1) from unvaccinated women (P<0.0001). There was evidence of transplacental seroprotection 8 days after maternal immunization (77.9%, 95 CI 66.2–87.1), maintained in most cases for at least 16 weeks.
Discussion
Immunization of pregnant women with AS03A-adjuvanted vaccine is followed by transplacental transfer of passive immunity at titres consistent with clinical protection in three-quarters of new-born infants. The findings support national and international pandemic H1N1 2009 recommendations for immunization during pregnancy.
In the body of the study, the authors caution:
Although there are no established correlates of protection for HI or MN in children and infants, evidence is accumulating that antibodies against seasonal influenza viruses, at levels that are normally associated with protection, can be found in a high proportion of cord blood samples and neonates following immunization during pregnancy.
Our study found that three-quarters of vaccinated women had ‘seroprotective’ cord blood HI antibody titres of ≥1:40 that are associated with at least 50% protection against symptomatic influenza in adults.
Once again, this is not the first study to show a potential `protective effect’ to the fetus from maternal flu vaccination. In 2011, in saw:
Impact of maternal immunization on influenza hospitalizations in infants
American Journal of Obstetrics and Gynecology, 2011; 204 (6): S141 DOI:
Katherine A. Poehling, Peter G. Szilagyi, Mary A. Staat, Beverly M. Snively, Daniel C. Payne, Carolyn B. Bridges, Susan Y. Chu, Laney S. Light, Mila M. Prill, Lyn Finelli, Marie R. Griffin, Kathryn M. Edwards.
This study analyzed data collected by CDC and the New Vaccine Surveillance Network between 2002 and 2009 (before the H1N1 pandemic), and found that infants born to mothers who had received the flu vaccine during pregnancy were more than 45% less likely to be hospitalized with laboratory confirmed influenza.
In October of 2010, in Study: Protecting Two With One Shot I blogged on Lisa Schnirring’s CIDRAP News story regarding a study that showed that babies born to mothers who received the flu vaccination experienced fewer infections and hospitalizations during their first six months than babies whose mothers did not.
And two years before that, we saw a study conducted in Bangladesh (see CIDRAP’s Study: Flu shots in pregnant women benefit newborns) that offered pretty much the same conclusion.
While we may wish that flu shots were more effective in preventing illness (see CIDRAP: The Need For `Game Changing’ Flu Vaccines), flu shots are still considered the best preventative action you can take against influenza, and serious side effects are extremely rare.
And for pregnant women and their unborn child, the evidence continues to show that the real risks come from influenza virus, not from the vaccine.
