Analysis of congenital Zika syndrome clinicopathologic findings reported in the 8 years since the Brazilian outbreak

Aim: A Zika virus outbreak that began in Brazil, developed into an international public health emergency that extended from February 2015 until November 2016. Zika-infected pregnant women gave birth to a cohort of infants with congenital Zika syndrome (CZS) originally defined by severe microcephaly, retinal scarring, joint deformities, and hypertonia. This study examines the nature, extent, and severity of all CZS clinicopathologic findings described to date, compiled and analyzed by system. It reviews studies monitoring disease progression and proposing classification schemes for CZS stages. The teratogenic cellular and molecular mechanisms implicated in CZS pathogenesis are also discussed. Methods: A systematic review was conducted by literature search through WorldCat.org and ProQuest Central databases to identify studies on case series from the 2015–2016 CZS outbreak. Results: Twenty-six reports were included describing radiologic, ophthalmologic, audiologic, orthopedic, and laboratory test results in CZS cases including stillborns between 2016 and 2023. CZS neuropathology included prenatal and postnatal microcephaly, cerebral calcifications, quadriparesis, epilepsy, ventriculomegaly, reduced cerebral parenchyma, malformation of cortical development, and sleep electroencephalogram disturbances. Visual deficits were due to retinal and optic nerve lesions. Conductive and sensorineural hearing deficits were stable. Hypertonia, hypotonia, and spasticity with foot, hip, knee, and shoulder deformities resulted in arthrogryposis and restricted joint mobility. There was enlargement of immune organs, increased leukocyte counts, and cytokine dysregulation. Oro-craniofacial deformities affected the midface and caused dental eruption delay. Additional studies proposed that these systemic teratogenic effects could be attributable to transplacental Zika virus infection of multiple fetal progenitor cell lineages. Conclusions: The CZS-associated impairments in brain, eye, musculoskeletal, and immunologic functions caused disabilities that varied from moderate to severe, and significantly increased age-specific mortality rates. Further research is warranted to assess progression, classify stages, elucidate the precise molecular mechanisms mediating Zika teratogenicity, develop suitable therapeutic strategies, and design supportive social policies.