Photo Credit – CDC
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We've known for quite some time that that novel influenza viruses often take a heavy toll among pregnant women and their unborn children (see 2009's Pregnancy & Flu: A Bad Combination)- and some novel viruses (like H5N1) - appear to attack younger individuals more robustly (see 2007's A Predilection For The Young).During the 1918 pandemic an abnormally high number of pregnant women died from the influenza, while during the much milder 1957 Asian Flu, pregnant women reportedly suffered disproportionately higher mortality rates than non-pregnant women of the same age.
In a Perspective, written by 3 CDC physicians (Sonja A. Rasmussen, Denise J. Jamieson, Joseph S. Bresee) and published in the EID journal article, Pandemic Influenza and Pregnant Women in 2008, we got this assessment of the historic impact of influenza on pregnant women.
Although appropriate nonpregnant control groups were generally not available, mortality rates among pregnant women in the pandemics of 1918 and 1957 appeared to be abnormally high (5,7). Among 1,350 reported cases of influenza among pregnant women during the pandemic of 1918, the proportion of deaths was reported to be 27% (5).
Similarly, among a small case series of 86 pregnant women hospitalized in Chicago for influenza in 1918, 45% died (6). Among pregnancy-associated deaths in Minnesota during the 1957 pandemic, influenza was the leading cause of death, accounting for nearly 20% of deaths associated with pregnancy during the pandemic period; half of women of reproductive age who died were pregnant
A year after the end of the 2009 H1N1 pandemic we looked at BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection, which found 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.
Other studies over the years have linked maternal (usually severe) influenza infection with a variety of physical and developmental deficits in the unborn offspring (see Nature: Severe Influenza in Pregnancy Linked to Neurodevelopmental Disorders in Offspring).
Despite these dangers, pregnant women and young children are often the last cohort to be approved to receive a novel flu (or CoV) vaccine, since most early clinical trials exclude them over safety concerns.
With the global H5N1 epizootic raising concerns, and the ever-present potential of another pandemic virus to emerge - we have a systematic review of outcomes on a (limited) number of H5N1 infected pregnant women over the past 2 decades.
This is a lengthy review, and I've only posted some excerpts, so follow the link to read it in its entirety. I'll have a postscript after the break.
Synopsis
Systematic Review of Avian Influenza Virus Infection and Outcomes during Pregnancy
Rachael Purcell, Michelle L. Giles, Nigel W. Crawford, and Jim Buttery
Abstract
Human cases of avian influenza A(H5N2) and A(H5N1) viruses associated with outbreaks in birds and mammals are increasing globally, raising concerns about the possibility of a future avian influenza pandemic.
We conducted a systematic review examining 30 reported cases of avian influenza in pregnant women. We found high mortality rates for mothers (90.0%, 27/30) and their babies (86.7%, 26/30) when women were infected with avian influenza virus during pregnancy.
Despite being a high-risk population and having worse health outcomes across multiple pandemics, pregnant women are often excluded from vaccine trials.
However, as the risk for a new pandemic increases and human vaccines against avian influenza are developed, early inclusion of pregnant women in clinical trials can inform the risk–benefit analysis for both the mother and their newborn infant. Early inclusion of pregnant women in public health vaccination programs is vital for protecting this high-risk population.
During pandemics, special risk populations are often more vulnerable to severe disease and death. Pregnant women experienced higher mortality and critical illness rates during the 2009 influenza pandemic (1), the SARS-CoV-2 pandemic (2), and the 2014–2016 Ebola epidemic in Africa (3). Global efforts are needed to proactively recognize and mitigate risks to pregnant women before the onset of a pandemic, rather than as a reactive process after a pandemic has started.
Recent case reports of human infection with avian influenza A(H5N2) and A(H5N1) viruses have renewed concerns regarding the heightened risk for a pandemic. An increasing number of cases of human avian influenza virus infection have been reported since 2004, and increasing case numbers have been seen since 2023 (4), exceeding 1,400 cases across different subtypes (5). Avian influenza is commonly caused by influenza A virus subtypes H5, H7, and H9. Occurring naturally among wild water birds, a rising number of avian influenza infections have been reported in domestic poultry and in mammals, including domestic cats and dogs and humans (6).
(SNIP)
In previous influenza pandemics, pregnant women experienced worse health outcomes and higher mortality rates than the general population. In some studies, pregnant women accounted for up to 9% of intensive care unit (ICU) admissions and up to 10% of patients who died (1). The risk for severe disease or adverse outcomes among pregnant women was observed again during the COVID-19 pandemic (2), before the introduction of vaccination, when pregnant women were at an increased risk for critical illness requiring ICU admission, extracorporeal membrane oxygenation, or mechanical oxygenation compared with nonpregnant women of a similar age.
Despite the increased risks, in the past, pregnant women have been excluded from clinical prelicensure trials of vaccines and therapeutic agents aiming to address pandemics (15,16). Pregnant women also have been excluded or have had delayed entry into population-level public health vaccination programs (15). As avian influenza virus infections in humans increase (11,13,17), understanding which populations are likely to be most vulnerable will be critical to pandemic preparedness efforts. We conducted a systematic review of avian influenza virus infection during pregnancy to assess adverse effects among this population.
(SNIP)
Conclusions
We used PRISMA guidelines to conduct a systematic review of avian influenza virus during pregnancy to assess infection effects on pregnancy outcomes. We found limited reports of outcomes for pregnant women infected with avian influenza virus in the literature. Of those reports, mortality rates for infected women and their infants was >90%.
As human cases of avian influenza A(H5N1) and A(H5N2) virus infection increase, awareness of the vulnerability of pregnant women to a new pandemic is needed. A paradigm shift is required to routinely include that population in pandemic preparedness programs and avoid preventable deaths. Inclusion could be achieved through using the capacity of existing surveillance systems, planning vaccine trials to include the complex needs of pregnancy, and scaling up signal detection systems to identify pregnancy outcomes.
About the Author
Dr. Purcell is a pediatric infectious diseases physician at Monash Health ad Department of Paediatrics, The University of Melbourne, Clayton, Victoria, Australia. Her research interests include perinatal infection and vaccination, and vaccination and infection in childhood.
Based on the evidence gathered over the past 20 years, an H5Nx pandemic would likely impact pregnant women, young children, and adolescents the hardest. But even if we get lucky, and H5N1 fizzles, history suggests (see examples below) these same groups may suffer disproportionately in the next pandemic.
- During the 1918 Spanish flu, the death rates among those in their teens, 20s, and 30s was reportedly much higher those in their 50's and 60's.
- While the average (mean) age of a flu-related fatality in a `normal’ flu season here in the United States is about 76 years, the average during the (relatively mild) 2009 H1N1 pandemic was half that; at 37.4 years (see Study: Years Of Life Lost Due To 2009 Pandemic).
