#19,303
In late 2024, in EID Journal: Systematic Review of Avian Influenza Virus Infection and Outcomes during Pregnancy - among 30 pregnant women diagnosed with avian flu (H5N1 n = 16, H7N9 n = 13, and H5N6 n = 1) - researchers reported high mortality rates for both mothers (90.0%, 27/30) and their babies (86.7%, 26/30).As we've discussed often (see Pregnancy & Flu: A Bad Combination), novel flu often exacts a heavy toll on expectant mothers and their unborn children.
Even during the relatively mild H1N1 pandemic of 2009, we saw studies (see BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection) 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.
We also know that 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.
As bad as they were, most of these effects have been attributed to the mother's immune response (fever, cytokine production, etc.) to the infection; not the vertical transmission of the virus to the fetus in utero.
A 2012 CDC study, however (Effects of influenza on pregnant women and infants) does cite H5N1 as potentially being an exception, due to its ability to cause extrapulmonary infection & viremia. Their conclusion, however:
"Therefore, the limited evidence to date suggests that vertical transmission of influenza viruses can occur but is likely to be very rare."
Last November we looked at a preprint (see Vertical Transmission of Bovine H5N1 Influenza Virus during Pregnancy and Lactation in Mice) which demonstrated that in (lab inoculated) pregnant mice (2nd Trimester), the bovine B3.13 H5N1 virus crossed the placenta (in a subset of litters) and, in a separate late-gestation experiment, spread through milk, infecting pups.
Exposed offspring were typically smaller, reached developmental milestones later, and showed lasting behavioral changes into adolescence.
Interestingly, they used two different isolates (A/bovine/Texas/98638/2024 and A/bovine/Ohio/B24OSU-439/2024), which produced different clinical courses and pathology in mice.
The Texas isolate produced a faster, more lethal course and higher viral burdens in several tissues—including mammary, ovarian, and CNS tissues—than the Ohio isolate in mice. The authors elected to use the slower-progressing Ohio virus for their pregnancy experiments.
That (revised and renamed) preprint has now been published in Nature Comms, and is offered early (subject to additional edits) at the link below. The full study is lengthy, and at times, highly technical.
Those wanting a deeper dive should download the PDF. I'll have a postscript after the break.
Trimester-dependent vertical transmission of H5N1 influenza virus through placental and mammary routes impairs offspring development
We’re sharing this article early to provide faster access to peer-reviewed, accepted research. It is citable and carries a permanent DOI. This version is subject to further edits and will be replaced automatically by the final Version of Record. All legal disclaimers apply.
Abstract
Avian influenza H5N1 has pandemic potential and historically causes more severe disease in pregnant women than the general population. With increasing transmission of H5N1 detected among placental mammals, animal models are necessary for testing countermeasures, including during pregnancy. Pregnant outbred mice infected with a contemporary strain of bovine H5N1 during the second trimester equivalent causes in utero transmission, with infectious virus detected in the uterus, placenta, and fetus. Birth following third trimester infection results in offspring with decreased size, neurodevelopmental delays, and adolescent behavioral impairments, with infectious virus detected in the neonatal milk ring and lungs, as well as mammary tissues. H5N1 viral protein colocalizes with trophoblast cells in the placenta and epithelial cells in mammary tissue that spatially overlap with lectins for α2,3-linked SA. With the pandemic potential of H5N1, our vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.
But even without vertical transmission, pregnant women and their offspring are presumed at higher risk during any flu outbreak.
Last February, in Viruses: Avian Influenza H5N1 Infection During Pregnancy: Preparing for the Next Flu Pandemic and Improving Perinatal Outcomes, we looked at a review article published in Viruses that looked at the limited data we have on novel flu and pregnancy, and argued that H5N1 could be particularly dangerous to pregnant women and their offspring if it should begin to spread in humans.
The authors proposed a basic algorithm for initial clinical management of suspected H5N1 in pregnancy and lobbied for prioritizing both antivirals and vaccines (when available) for high-risk patients, including those who may be pregnant.
