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

## TL;DR

This study finds that infants exposed to Zika virus in the womb have a higher risk of heart defects, especially if they have microcephaly, suggesting heart issues may be a new sign of Congenital Zika Syndrome.

## Contribution

The study is the first to longitudinally assess cardiac outcomes in Zika-exposed infants and links microcephaly with increased heart defect risk.

## Key findings

- 17.8% of Zika-exposed infants had cardiac anomalies, higher than the general population.
- Microcephalic infants had significantly more cardiovascular abnormalities than non-microcephalic infants.
- Most heart defects resolved over time, but microcephaly remained a strong predictor of persistent defects.

## Abstract

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.

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).

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).

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.

Zika virus (ZIKV) is best known for affecting the fetal brain and causing Congenital Zika Syndrome (CZS), but growing evidence suggests it may also impact heart development. We studied infants born to mothers with PCR-confirmed ZIKV infection during pregnancy or infants who tested positive at birth, and all received echocardiograms in their first year. Those with abnormalities were asked to return for repeat imaging. We analyzed how often heart findings occurred and whether certain factors, like microcephaly (MC), were linked to these abnormalities. Among 169 ZIKV-exposed infants, 30% had MC and 17.8% had heart defects. Children with MC had a higher rate of abnormalities than those without MC (26.9% vs 13.7%). Of the infants who returned for repeat imaging, most defects resolved, although persistent defects were more common in the MC group. MC was significantly associated with a higher chance of having a heart defect, even when looking at infants who had later echocardiograms. Overall, ZIKV-exposed infants had a higher rate of heart defects than expected in the general population, and while most findings improved over time, the presence of a congenital heart defect may be considered another feature of CZS.