Michael Coston
Editor, Senior Moderator
Preprint: Vertical Transmission of Bovine H5N1 Influenza Virus during Pregnancy and Lactation in Mice
Updated CDC Case Count (n=71)
Does not include asymptomatic or `probable' cases'
#18,950
We've long known that influenza infection during pregnancy can lead to bad outcomes (see 2008 EID Journal article Pandemic Influenza and Pregnant Women), which we saw strongly manifest even during the relatively mild H1N1 pandemic of 2009.
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 (Effects of influenza on pregnant women and infants) does cite H5N1as 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.
Whether vertical transmission remains `very rare' with H5N1 (and potentially, other novel strains), is less certain. There is a paucity of detailed information published on (mild or severe) H5N1 infections globally, and long-term follow up reports are even less common.
All of which brings us to a preprint, published on the bioRxiv server, which uses a murine (mouse) model to investigate the vertical transmission of bovine (B3.13) H5N1 influenza A virus (during pregnancy and lactation) in outbred (genetically diverse) mice.
Essentially, they demonstrate that in (lab inoculated) pregnant mice (2nd Trimester), the bovine B3.13 H5N1 virus crossed the placenta (roughly 2/3rds of the time) and later spread through milk, infecting pups.
Exposed offspring were typically smaller, reached developmental milestones later, and showed lasting behavioral changes into adolescence.
Due to its length, and technical nature, I've just reproduced the abstract and a few excerpts. Follow the link to read it in its entirety. I'll have a brief postscript after the break.
Vertical Transmission of Bovine H5N1 Influenza Virus during Pregnancy and Lactation in Mice
Brittany A Seibert, Maclaine A Parish, Sattya N Talukdar, Tianle Zhang, Sabal Chaulagain, Jennifer A Liu, Jaiprasath Sachithanandham, Oscar Hernandez, Cosette Schneider, Lynda Coughlan, Andrew Bowman, Richard J. Webby, Jack R Harkema, Andrew Pekosz, Sabra L Klein
doi: https://doi.org/10.1101/2025.07.07.663583
This article is a preprint and has not been certified by peer review [what does this mean?].
Preview PDF
Abstract
Panzootic spillover of H5N1 virus clade 2.3.4.4b has resulted in expanded host range among placental mammals, with lactation transmission via milk documented. Whether infection during pregnancy leads to in utero or lactational vertical transmission remains unknown.
Pregnant outbred mice were infected with A/bovine/Ohio/B24OSU-472/2024 during the second or third trimester equivalent. Second trimester infection caused in utero infection, with infectious virus detected in the uterus, placenta, and fetus.
Birth following third trimester infection resulted in offspring with decreased size and neurodevelopmental delays, with infectious virus detected in the neonatal milk ring and lungs as well as mammary tissues.
Ongoing H5N1 infections present increased risk for human exposure and an H5N1 vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.
(SNIP)
(SNIP)
Although the current public health risk of H5N1 remains low, potential exposure and transmission from individuals working with infected cattle or poultry to multiple household pets raises the spillover risk for family members and veterinarians caring for these animals.
These results provide the groundwork for understanding the vertical transmission of bovine H5N1 viruses in humans and other placental mammals, including cattle, where adverse pregnancy outcomes have recently been reported following H5N1 infection. 14,15
(Continue . . . )
Admittedly, this study has some limitations and caveats; including a) mice have anatomical and immunological differences from humans. b) this study only looked at genotype B3.13, and c) andit is unknown how much these findings will actually translate to humans.
Even without vertical transmission, pregnant women and their offspring are at higher risk during any flu outbreak.
Many pregnant women remain reluctant to get the seasonal flu vaccine, despite numerous studies confirming the safety and benefits of vaccination (and the early use of antivirals) in protecting the lives of pregnant women and their unborn child, including:
Pediatrics: Maternal Flu Vaccination Extends Protection To Infants
Clinical Infectious Diseases: Flu Vaccine May Reduce Incidence of Stillbirth
JID: Benefits Of Early Use of Influenza Antivirals In Pregnancy
Complicating matters further, 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.
For more on the impact of maternal infection with influenza A, you may wish to revisits 2024's: CIMB Review: Maternal Influenza and Offspring Neurodevelopment
https://afludiary.blogspot.com/2025/11/preprint-vertical-transmission-of.html
Updated CDC Case Count (n=71)
Does not include asymptomatic or `probable' cases'
#18,950
We've long known that influenza infection during pregnancy can lead to bad outcomes (see 2008 EID Journal article Pandemic Influenza and Pregnant Women), which we saw strongly manifest even during the relatively mild H1N1 pandemic of 2009.
- In the fall of 2009 we learned that pregnant women were six times more likely to be hospitalized than non-pregnant women (see Pregnancy & Flu: A Bad Combination).
- In 2011, in BMJ: Perinatal Outcomes After Maternal 2009/H1N1 Infection we saw a study 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.
- And in 2019, in Study: Outcomes Of Infants Born To Women With Influenza A(H1N1)pdm09 found that women admitted to the ICU with H1N1 were more likely to deliverpreterm infants, low birth weight infants, and infants with low Apgar scores than women in the other groups.
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 (Effects of influenza on pregnant women and infants) does cite H5N1as 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.
Whether vertical transmission remains `very rare' with H5N1 (and potentially, other novel strains), is less certain. There is a paucity of detailed information published on (mild or severe) H5N1 infections globally, and long-term follow up reports are even less common.
All of which brings us to a preprint, published on the bioRxiv server, which uses a murine (mouse) model to investigate the vertical transmission of bovine (B3.13) H5N1 influenza A virus (during pregnancy and lactation) in outbred (genetically diverse) mice.
Essentially, they demonstrate that in (lab inoculated) pregnant mice (2nd Trimester), the bovine B3.13 H5N1 virus crossed the placenta (roughly 2/3rds of the time) and later spread through milk, infecting pups.
Exposed offspring were typically smaller, reached developmental milestones later, and showed lasting behavioral changes into adolescence.
Due to its length, and technical nature, I've just reproduced the abstract and a few excerpts. Follow the link to read it in its entirety. I'll have a brief postscript after the break.
Vertical Transmission of Bovine H5N1 Influenza Virus during Pregnancy and Lactation in Mice
Brittany A Seibert, Maclaine A Parish, Sattya N Talukdar, Tianle Zhang, Sabal Chaulagain, Jennifer A Liu, Jaiprasath Sachithanandham, Oscar Hernandez, Cosette Schneider, Lynda Coughlan, Andrew Bowman, Richard J. Webby, Jack R Harkema, Andrew Pekosz, Sabra L Klein
doi: https://doi.org/10.1101/2025.07.07.663583
This article is a preprint and has not been certified by peer review [what does this mean?].
Preview PDF
Abstract
Panzootic spillover of H5N1 virus clade 2.3.4.4b has resulted in expanded host range among placental mammals, with lactation transmission via milk documented. Whether infection during pregnancy leads to in utero or lactational vertical transmission remains unknown.
Pregnant outbred mice were infected with A/bovine/Ohio/B24OSU-472/2024 during the second or third trimester equivalent. Second trimester infection caused in utero infection, with infectious virus detected in the uterus, placenta, and fetus.
Birth following third trimester infection resulted in offspring with decreased size and neurodevelopmental delays, with infectious virus detected in the neonatal milk ring and lungs as well as mammary tissues.
Ongoing H5N1 infections present increased risk for human exposure and an H5N1 vertical transmission model in placental mammals is essential for understanding viral spread and evaluating treatments during pregnancy.
(SNIP)
Pregnancy represents a distinct physiological and immunological state, which causes more severe outcomes from influenza infections than in non-pregnant individuals. 6,7 The bovine H5N1 IAV outbreak, including reports of fatal infections in cats on affected farms, 9 multiple infections among dairy farm workers, 10,11 and a pediatric H5N1 case, 12,13 emphasizes the public health risk and heightened potential for household exposure among pregnant women.
Recent reports on cattle farms also indicate that H5N1-infected heifers exhibit reproductive complications, including abortions during mid- to late-gestation, and a reduced number of cattle in estrus during periods of high clinical disease. 14,15
Recent reports on cattle farms also indicate that H5N1-infected heifers exhibit reproductive complications, including abortions during mid- to late-gestation, and a reduced number of cattle in estrus during periods of high clinical disease. 14,15
While a previous study demonstrated that bovine H5N1 IAV inoculation of post-birth lactating female mice can result in transmission of virus to offspring through milk, 4 it remains unknown whether in utero transmission of bovine 30 H5N1 viruses occurs.
To address this gap, we established a pregnancy mouse model to study the pathogenesis and transmission dynamics of bovine H5N1 IAV from the 2024 outbreak
To address this gap, we established a pregnancy mouse model to study the pathogenesis and transmission dynamics of bovine H5N1 IAV from the 2024 outbreak
(SNIP)
Although the current public health risk of H5N1 remains low, potential exposure and transmission from individuals working with infected cattle or poultry to multiple household pets raises the spillover risk for family members and veterinarians caring for these animals.
These results provide the groundwork for understanding the vertical transmission of bovine H5N1 viruses in humans and other placental mammals, including cattle, where adverse pregnancy outcomes have recently been reported following H5N1 infection. 14,15
(Continue . . . )
Admittedly, this study has some limitations and caveats; including a) mice have anatomical and immunological differences from humans. b) this study only looked at genotype B3.13, and c) andit is unknown how much these findings will actually translate to humans.
Even without vertical transmission, pregnant women and their offspring are at higher risk during any flu outbreak.
Many pregnant women remain reluctant to get the seasonal flu vaccine, despite numerous studies confirming the safety and benefits of vaccination (and the early use of antivirals) in protecting the lives of pregnant women and their unborn child, including:
Pediatrics: Maternal Flu Vaccination Extends Protection To Infants
Clinical Infectious Diseases: Flu Vaccine May Reduce Incidence of Stillbirth
JID: Benefits Of Early Use of Influenza Antivirals In Pregnancy
Complicating matters further, 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.
For more on the impact of maternal infection with influenza A, you may wish to revisits 2024's: CIMB Review: Maternal Influenza and Offspring Neurodevelopment
https://afludiary.blogspot.com/2025/11/preprint-vertical-transmission-of.html