Preexisting Yellow Fever Virus and West Nile Virus Immunity and Pregnancy Outcomes in a Nigerian Cohort with Endemic Orthoflavivirus Exposure

Yellow fever virus (YFV) and West Nile virus (WNV) co-circulate with other arboviruses, including Zika (ZIKV), dengue (DENV), and chikungunya virus (CHIKV), in sub-Saharan Africa. Associations between preexisting YFV and WNV immunity with symptoms and adverse infant outcomes among pregnant women exposed to orthoflaviviruses are unknown. We retrospectively studied a prospective cohort of pregnant women enrolled between 2019 and 2022 in Jos, Nigeria. Rapid tests identified ZIKV, DENV, and CHIKV IgM/IgG reactivity for enrollment; 216 women underwent Western blot for YFV and WNV IgG. Logistic regression evaluated associations between arboviral seropositivity and maternal symptoms or adverse infant outcomes. Sequential serology of mother-infant pairs estimated the persistence of passively transferred maternal YFV antibodies. YFV IgG was detected in 50.5% (109/216) and WNV IgG in 5.1% (11/216) of maternal samples. YFV and WNV seropositivity was significantly associated with maternal symptoms (OR = 2.02, 95% CI: 1.35–3.02, P = 0.001), as was YFV seropositivity alone (OR = 1.77, 95% CI: 1.21–2.61, P < 0.004). CHIKV IgM reactivity was significantly associated with abnormal infant outcomes (OR = 2.38, 95% CI: 1.43–4.02, p = 0.001), but not ZIKV and DENV IgM reactivity. Passive maternal YFV IgG waned in infants at a median of 3.1 months (IQR: 1.65-5.35 months) after birth. YFV and WNV seropositivity was associated with maternal symptoms but not with adverse infant outcomes. Rapid waning of maternal YFV IgG highlights infant vulnerability and supports enhanced surveillance and maternal immunization strategies.