Yellow Fever in Pregnancy: Reassessing Risks, Outcomes, and Vaccination in the 2024–2026 Americas Outbreak

Key Takeaways:

• Pregnancy does not appear to increase susceptibility to or severity of yellow fever, but adverse maternal and fetal outcomes—including miscarriage and preterm birth—remain possible.
• Vertical transmission is rare but can be severe, with limited documented cases showing high neonatal mortality.
• Vaccination during pregnancy is generally safe and beneficial in high-risk settings, with evidence supporting a risk-based, individualized approach.

The resurgence of yellow fever (YF) across South America during the 2024–2026 outbreak has renewed attention on vulnerable populations, particularly pregnant women. A comprehensive review published in Tropical Medicine and Infectious Disease synthesizes current evidence on the epidemiology, clinical course, and prevention of YF in pregnancy, highlighting both reassuring findings and critical knowledge gaps.

Despite longstanding concerns, available data suggest that pregnancy does not significantly increase susceptibility to YF infection or worsen disease severity. Physiological and immunological adaptations during gestation—while theoretically capable of altering antiviral responses—have not translated into higher case-fatality rates or more severe clinical presentations compared to non-pregnant individuals. However, the consequences of infection can still be substantial. Reported maternal complications include severe hepatitis, hemorrhage, and multiorgan failure, while fetal risks encompass miscarriage, stillbirth, and preterm delivery. These outcomes, though inconsistently documented, underscore the potential impact of YF on maternal–fetal health.

One of the most striking findings is the rarity—but severity—of vertical transmission. Only a handful of confirmed cases exist, typically occurring near delivery. In these instances, neonates initially appeared asymptomatic before rapidly progressing to fulminant disease characterized by hepatic failure, coagulopathy, and death. The scarcity of systematic data limits accurate estimation of transmission risk, reflecting broader deficiencies in surveillance systems that rarely capture pregnancy-specific outcomes.

Clinically, diagnosing YF in pregnancy remains challenging. Early symptoms overlap with other endemic infections such as dengue, malaria, and viral hepatitis, as well as obstetric conditions like HELLP syndrome. Definitive diagnosis relies on molecular or serologic testing, but access to these tools is often limited in outbreak settings. As a result, clinicians must rely heavily on epidemiologic context and clinical suspicion to guide early management.

Treatment options are similarly constrained. There is no antiviral therapy for YF, and care is largely supportive, focusing on hemodynamic stabilization, management of liver dysfunction, and prevention of complications. In severe cases, intensive care—including transfusion support and renal replacement therapy—may be required. Multidisciplinary management is essential, with maternal stabilization prioritized as the most effective strategy for improving fetal outcomes.

Prevention, therefore, remains paramount. Vector control and personal protective measures are foundational, particularly in endemic and outbreak settings. Yet vaccination stands as the most effective intervention. Historically, the use of the live-attenuated YF vaccine during pregnancy raised concerns about fetal safety. However, accumulating observational evidence and real-world experience now provide reassurance. Multiple studies have not demonstrated increased risks of miscarriage, congenital anomalies, or adverse neonatal outcomes associated with vaccination.

This evolving evidence base has informed a shift toward risk-based vaccination strategies. In high-transmission settings—such as active outbreaks—the benefits of maternal immunization clearly outweigh theoretical risks. Public health authorities increasingly recommend vaccination during pregnancy when exposure risk is substantial, particularly after the first trimester. Conversely, in low-risk settings, deferral may still be appropriate.

Importantly, the review emphasizes persistent gaps in knowledge. The lack of prospective studies, incomplete surveillance data, and historical exclusion of pregnant women from clinical research all limit the strength of current evidence. Addressing these gaps through pregnancy registries, improved pharmacovigilance, and targeted research will be critical for refining clinical guidance.

As YF continues to re-emerge in the Americas, integrating maternal health considerations into outbreak response is essential. The current evidence supports a pragmatic approach: prioritize prevention, individualize vaccination decisions, and strengthen systems to better capture and understand the impact of this disease in pregnancy.