Abstract Objective To better understand the clinical spectrum and course of congenital Zika syndrome (CZS) during the first 18 months of life of children whose mothers had rash during pregnancy. Methods This longitudinal observational study evaluated the clinical progress from birth until 18 months of life of children of mothers who developed rash during or up to 3 months before gestation. Maternal rash occurred from November 2015 to May 2017. The study subjects were divided into three groups: children whose mothers tested positive by RT-qPCR for Zika virus (ZIKV) (Group 1), children whose mothers tested negative by RT-qPCR for ZIKV (Group 2), and children whose mothers did not undergo any testing for ZIKV (Group 3) but tested negative for other congenital infections. Results Between April 2016 and July 2018, we studied 108 children: 43 in Group 1, 26 in Group 2 and 39 in Group 3. The majority of children were admitted into the study within 6 months of life. CZS was diagnosed in 26 children, equally distributed in Groups 1 and 3. Of 18 children with microcephaly, 6 were in Group 1 (1 postnatal) and 12 were in Group 3 (5 postnatal). Maternal rash frequency was 10 times higher during the first trimester than in the other trimesters (OR: 10.35; CI 95%: 3.52–30.41). CZS was diagnosed during the follow-up period in 14 (54%) cases. Developmental delays and motor abnormalities occurred in all children and persisted up to 18 months. Epilepsy occurred in 18 (69%) of the cases. Conclusions Infants born of mothers exposed to ZIKV during pregnancy showed progression of developmental, motor and neurologic abnormalities even if they were born asymptomatic. Continued postnatal monitoring of such newborns is necessary to preclude disability-associated complications.