Limited information on avian influenza virus infections in pregnancy is available, and we found only 30 reported cases despite >1,400 infected humans described in the literature (5). What we do know from the cases reported is that outcomes for mothers and their fetuses were poor, and most cases ended in both maternal and in utero fetal death. Although less severe cases could be more likely to be detected and reported, the limited description of outcomes for pregnant women infected with avian influenza virus paints a concerning picture.

We noted no obvious pattern between the timing of infection during pregnancy and maternal or fetal and infant outcomes. We found no reported cases of pregnant women infected with H5N2 virus. The last case of H5N1 virus infection in a pregnant woman was reported in 2019 (23), and we found no cases associated with the outbreaks occurring in 2024 through June.

Pregnancy is a unique physiologic state, and often renders otherwise healthy women vulnerable to worse outcomes after some infections than nonpregnant persons. That phenomenon has been seen in multiple infectious disease epidemics, including influenza (1), the COVID-19 pandemic (25), and viral hemorrhagic fever outbreaks, such as Lassa fever and Ebola (3,26). Health impacts of infections are not limited to the mother, and reports of premature birth or infant death related to maternal death are increasing. Adverse effects on the infant have been noted not only with maternal death, but also among infants born to women admitted to an ICU (27).

The viral infections described in poultry and other mammals in 2024 are primarily avian viruses, and no genetic changes which would increase transmission to, and between, humans have been observed (28). A 2024 report on H5N1 viral whole-genome sequencing from dairy cattle, birds, domestic cats, and a raccoon in association with epidemiologic data supported efficient cow-to-cow transmission, increasing concern about the potential ability of avian influenza H5N1 clade 2.3.4.4b to cross species and efficiently transmit within new species (29). On April 23, 2024, joint analysis of the World Health Organization, World Organisation for Animal Health, and Food and Agriculture Organization of the United Nations assessed the overall public health risk posed by H5N1 as low (30). However, persons who have exposure to infected animals or contaminated environments are at an increased risk level (31). Nonetheless, efforts in vaccine development have been made to provide human protection against acquisition and severe disease, and antigenic analysis demonstrated that the avian influenza virus detected in humans in 2024 would be well covered by candidate vaccine viruses (31). A vaccine for humans against H5N1 influenza virus has been developed, and major investments have been made to promote development using mRNA technology (32).

The European Commission’s Health Emergency Preparedness and Response Authority procured 665,000 zoonotic avian influenza virus vaccine doses (33), and vaccination for persons working in high-risk occupations, such as fur farmers, was commenced in Finland (33). However, vaccination during pregnancy is listed as a contraindication, and health providers cautioned against vaccinating pregnant women because of insufficient safety data (34).

The inclusion of women as early as possible is a key priority in pandemic planning (16,35). The presumption of inclusion described in advocacy attempts to change the default approach and aims to normalize the position of pregnant women being included in vaccine development, research, and deployment programs (36). Although efforts have been made by leading public health bodies to preempt the impact of respiratory viral pandemics on pregnant women (37), those efforts have yet to result in a universal systemic approach. During the COVID-19 pandemic, pregnant women were largely excluded from vaccine trials, and only 2 of 90 studies included pregnant women (15). Although the speed of SARS-CoV-2 vaccine development was unprecedented, the noninclusion of pregnant women, who were known to experience more severe infections than the general population (2), highlights how inclusion and equality of access to vaccination remains a core issue.

Ethical pandemic preparedness to avoid preventable deaths requires early inclusion of vulnerable populations in vaccine development, monitoring, and trials (38,39). The dogma of presumptive exclusion of pregnant women needs to change (36,38), and a pregnancy-focused research agenda should be developed and implemented by ethically informed oversight from institutional review boards, regulators, and policy makers (38).

Harnessing existing monitoring systems and resources to identify and include pregnant women and infant outcomes through use of administrative endpoints (38)—for example by using International Classification of Diseases, 10th Revision ,codes (37) —could be a method of providing systematic and timely prospective data. That strategy must be parallelled with a commitment to the rapid development and deployment of codes used to report new infections. Investment in the upkeep and readiness of pregnancy registries is also required. Although platforms in some jurisdictions have data available in a timely manner (40), others often report outcomes several years later (39). As recommended by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group, suitability for administration during pregnancy should be a consideration when funding bodies are reviewing vaccine candidates, and the early initiation of preclinical development toxicology studies should be prioritized before efficacy studies (38). Vaccine trials that include women of childbearing age should be structured to systematically collect data on pregnancy-related safety outcomes and immunogenicity in the event of pregnancy occurring (36). Those data may also help inform outcomes from vaccine exposures earlier in pregnancy than would occur in planned antenatal vaccine trials. Similarly, using existing Rapid Cycle Analyses structures (41), such as the signal detection systems developed by the Global Vaccine Data Network or the Vaccine Safety Datalink (40,42), gives real-time data around population level vaccine safety.

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.