Cardiac findings in infants with in utero exposure to Zika virus – a follow up longitudinal study

BACKGROUND: Zika virus (ZIKV) is primarily known for its impact on the fetal central nervous system potentially leading to Congenital Zika Syndrome (CZS). Emerging evidence suggests ZIKV may also affect cardiac development. We conducted a follow-up study evaluating cardiologic findings in infants from ZIKV-exposed mothers. METHODS: Infants born to mothers with PCR-confirmed ZIKV infection during pregnancy and/or who had positive ZIKV PCR results at birth received echocardiograms in the first year of life. Repeat imaging within 12 months was requested for infants with identified abnormalities. Frequencies of cardiovascular (CV) abnormalities were evaluated using Pearson χ2 test, Fisher's exact test, and descriptive statistics. Predictors of CV abnormalities were assessed using multivariate logistic regression, as well as univariate and multivariate prevalence estimates. Sensitivity analysis assessed the robustness of associations when stratified by age at echocardiography (early vs late). RESULTS: One hundred sixty-nine children with antenatal ZIKV-exposure had echocardiograms; 30.8% were microcephalic (MC). Thirty (17.8%) had cardiac anomalies. MC children had a higher frequency of CV abnormalities than normocephalic (NC) children (26.9% vs 13.7%, p = 0.04). Twenty-four of 30 children (80.0%) returned for repeat imaging; of that group, 25.0% continued to demonstrate defects. Rates of persistent defects between the MC vs. NC cohorts were 33.3% vs 16.7%, respectively (p = 0.64). Presence of CV defects was significantly associated with MC (OR=3.40, 95% CI 1.15-10.02; p = 0.03). Among those with echocardiography performed later, MC was still associated with higher risk of abnormalities (OR=6.0, 95% CI 1.03-34.94; p = 0.046). CONCLUSIONS: A higher frequency of cardiac defects was noted in ZIKV-exposed infants than the general population. Most defects resolved on follow-up. The presence of a congenital heart defect (CHD) could be considered a parameter of CZS given its association with MC.