Early and Long-Term Adverse Outcomes of In Utero Zika Exposure.

BACKGROUND Zika virus (ZIKV) infection during pregnancy can lead to congenital Zika syndrome (CZS) and may result in neurodevelopmental alterations in exposed children, with and without CZS. This study aimed to evaluate ZIKV infection during pregnancy as a risk factor for early and long-term adverse outcomes. METHODS This retrospective-prospective, matched cohort study was conducted in Mato Grosso do Sul, Brazil. Mother-infant pairs exposed and unexposed to ZIKV during pregnancy were enrolled in the study from 2018 to 2022. Clinical and epidemiological data from the gestational period and neonatal evaluations were obtained from the Brazilian health surveillance system. Children were assessed for early (congenital anomalies) and long-term adverse outcomes (neurodevelopmental delay). Incidence risk ratio (IRR) and crude odds ratio (OR) were used to assess associations. RESULTS The risk of adverse outcomes in exposed children was nearly 3-fold higher (IRR, 2.7; 95% CI, 1.4-5.1) compared with the control group. The risk of motor (IRR, 3.4; 95% CI, 1.2-9.6) and cognitive delay (IRR, 4.7; 95% CI, 1.7-13.0) was significantly higher in exposed children. In 44% of pregnancies wherein maternal infection occurred in the first trimester, at least 1 adverse event was identified in the child, with 11.2-fold greater odds of adverse outcomes (OR, 11.2; 95% CI, 3.6-35.0) compared with children of mothers infected in the third trimester. CONCLUSIONS Children exposed to ZIKV in utero, even without CZS, demonstrate a greater risk for neurodevelopmental delay in early childhood, with the timing of maternal infection being a significant predictive risk factor.