Estimation of the morbidity and mortality of congenital Chagas disease: A systematic review and meta-analysis

Chagas disease is caused by the parasite Trypanosoma cruzi which can be transmitted from mother to baby during pregnancy. There is no consensus on the proportion of infected infants with clinical signs of congenital Chagas disease (cCD). The objective of this systematic review is to determine the burden of cCD. Articles from journal inception to 2020 reporting morbidity and mortality associated with cCD were retrieved from academic search databases. Observational studies, randomized-control trials, and studies of babies diagnosed with cCD were included. Studies were excluded if they were case reports or series, without original data, case-control without cCD incidence estimates, and/or did not report number of participants. Two reviewers screened articles for inclusion. To determine pooled proportion of infants with cCD with clinical signs, individual clinical signs, and case-fatality, random effects meta-analysis was performed. We identified 4,531 records and reviewed 4,301, including 47 articles in the narrative summary and analysis. Twenty-eight percent of cCD infants showed clinical signs (95% confidence interval (CI) = 19.0%, 38.5%) and 2.2% of infants died (95% CI = 1.3%, 3.5%). The proportion of infected infants with hepatosplenomegaly was 12.5%, preterm birth 6.0%, low birth weight 5.8%, anemia 4.9%, and jaundice 4.7%. Although most studies did not include a comparison group of non-infected infants, the proportion of infants with cCD with clinical signs at birth are comparable to those with congenital toxoplasmosis (10.0%-30.0%) and congenital cytomegalovirus (10.0%-15.0%). We conclude that cCD burden appears significant, but more studies comparing infected mother-infant dyads to non-infected ones are needed to determine an association of this burden to cCD.