Background The signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome. Methods and findings A systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age. Conclusions Zika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.

Purpose To report the findings of a cross-sectional study of visual function in infants with confirmed or suspected antenatal Zika virus (ZIKV) infection seen at a single referral center in Rio de Janeiro. Methods Infants were examined following the ZIKV outbreak period at Fernandes Figueira Institute/FIOCRUZ. Visual function was considered abnormal if an infant could not fix and follow a standardized high-contrast target (10 cm) by 3–6 months of age. Visual function and associations with structural eye abnormalities, central nervous system (CNS) abnormalities, microcephaly, and nystagmus were assessed. Sensitivity and specificity of screening criteria for structural eye abnormalities was assessed. Results A total of 173 infants met inclusion criteria. Reduced visual function was found in 52 infants (30.0%) and was significantly associated with eye abnormalities (40/52; OR = 44.2; 95% CI, 16.6–117.6), CNS abnormalities (50/52; OR = 64.0; 95% CI, 14.7–277.6), microcephaly (44/52; OR = 31.5; 95% CI,12.7–77.8), and nystagmus (26/52; OR = 120.0; 95% CI, 15.6–924.5). Using microcephaly as screening criteria for the detection of eye abnormalities provided a sensitivity of 88.9% (95% CI,76.0–96.3) and specificity of 82.8% (95% CI, 75.1–88.9). Using both abnormal visual function and microcephaly increased sensitivity to 100% (95% CI, 92.1–100.0) and decreased specificity to 80.5% (95% CI, 72.5–86.9). Conclusions Infants with suspected antenatal ZIKV infection and reduced visual function should be referred to an ophthalmologist. Visual function assessments are helpful in screening for antenatal ZIKV exposure in resource-limited settings and can identify infants who may benefit from visual habilitation.

Similar eye manifestations were identified regardless of laboratory confirmation. Well-appearing infants were also found to have eye abnormalities. Therefore, all infants born after ZIKV outbreaks should be universally screened for eye abnormalities.