Maternal Zika virus exposure and neurodevelopmental outcomes: A longitudinal study of preschool children in the ZIKAlliance Colombian Cohort

Background Zika virus (ZIKV) infection has been inconsistently associated with neurodevelopmental delay (ND). We aimed to compare the incidence of ND between ZIKV-exposed and ZIKV-unexposed children within the ZIKAlliance (ZA) cohort, in Colombia, assessed 2 years after birth (2018–2021). Methods We performed a neurodevelopmental evaluation on normocephalic children (aged 40–72 months) from the ZIKAlliance cohort. Children were classified as ZIKV-exposed (maternal positive RT-qPCR or virus neutralization test – VNT) or unexposed (maternal negative IgG ELISA or VNT in paired antenatal samples). A trained psychologist, blinded to exposure status, administered the Denver Developmental Screening Test II (DDST-II). Children were considered at ND risk if they presented ≥1 delay or ≥2 cautions in one or more areas, within their age range in the DDST-II scale. Inconclusive initial tests were re-evaluated. Adjusted odds ratios were estimated using logistic regression. Results We analyzed conclusive DDST-II results from 153 children (mean age: 4.7 years; 53.8% male). Overall, 57.2% (n = 83) were classified as cases of ND. Children with ND were more likely to be male (61.4% versus 43.5%) and less likely to attend daycare or school (42.2% versus 11.3%) than children with normal development. After adjusting for child age, sex, household size, and education, the association between in utero ZIKV exposure and ND was not statistically significant (OR = 0.71; 95% CI: 0.32–1.59, p = 0.320). However, children attending daycare or school had a significantly lower risk of ND compared to those who stayed at home. Conclusions Prenatal ZIKV exposure was not associated with ND in this cohort of normocephalic preschool children. Instead, attending a community daycare or school emerged as a significant protective factor against developmental delays.