Teratogenic Effect of OROV Infection: An Analysis of Its Causality

Abstract

Oropouche virus (OROV) is an arbovirus that has caused multiple epidemic outbreaks in several Latin American countries. In 2024, cases of possible vertical transmission with congenital microcephaly were reported, raising concerns about potential teratogenic effects. However, the causal relationship between OROV infection during pregnancy and congenital anomalies remains poorly defined. This study aimed to analyze the evidence on the potential teratogenic effect of OROV in humans through a systematic literature review, applying Shepard's criteria for causality. The available evidence supports a temporal relationship between exposure during critical periods of prenatal development and observed effects in offspring. Reported cases share certain common characteristics that could suggest a specific syndrome. Experimental studies in animal models demonstrate vertical transmission of OROV and harmful effects in offspring. Considering the documented vertical transmission, viral presence in the central nervous system, and known pathogenic mechanisms, biological plausibility exists for a teratogenic effect. However, no epidemiological study has yet evaluated the association between OROV infection and teratogenicity. Furthermore, given that infection occurs during epidemic outbreaks rather than through sporadic environmental exposure, the criterion of infrequent exposure associated with an infrequent defect is not met. Therefore, Shepard's teratogenicity criteria are not yet fully fulfilled. In conclusion, while suggestive evidence exists, definitive proof of OROV teratogenicity remains lacking. Health authorities should prioritize research initiatives, strengthen epidemiological surveillance groups, ensure availability of serological testing for OROV infection, and enhance congenital defect surveillance systems to better characterize this potential association.