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Background: To characterize neurodevelopmental abnormalities in children up to 36 months of age with congenital Zika virus exposure., Methods: From the U.S. Zika Pregnancy and Infant Registry, a national surveillance system to monitor pregnancies with laboratory evidence of Zika virus infection, pregnancy outcomes and presence of Zika associated birth defects (ZBD) were reported among infants with available information. Neurologic sequelae and developmental delay were reported among children with ≥1 follow-up exam after 14 days of age or with ≥1 visit with development reported, respectively., Results: Among 2248 infants, 10.1% were born preterm, and 10.5% were small-for-gestational age. Overall, 122 (5.4%) had any ZBD; 91.8% of infants had brain abnormalities or microcephaly, 23.0% had eye abnormalities, and 14.8% had both. Of 1881 children ≥1 follow-up exam reported, neurologic sequelae were more common among children with ZBD (44.6%) vs. without ZBD (1.5%). Of children with ≥1 visit with development reported, 46.8% (51/109) of children with ZBD and 7.4% (129/1739) of children without ZBD had confirmed or possible developmental delay., Conclusion: Understanding the prevalence of developmental delays and healthcare needs of children with congenital Zika virus exposure can inform health systems and planning to ensure services are available for affected families., Impact: We characterize pregnancy and infant outcomes and describe neurodevelopmental abnormalities up to 36 months of age by presence of Zika associated birth defects (ZBD). Neurologic sequelae and developmental delays were common among children with ZBD. Children with ZBD had increased frequency of neurologic sequelae and developmental delay compared to children without ZBD. Longitudinal follow-up of infants with Zika virus exposure in utero is important to characterize neurodevelopmental delay not apparent in early infancy, but logistically challenging in surveillance models., (© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Zika virus infection during pregnancy can cause serious birth defects of the brain and eyes, including intracranial calcifications, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities (1,2). The frequency of these Zika-associated brain and eye defects, based on data from the U.S. Zika Pregnancy and Infant Registry (USZPIR), has been previously reported in aggregate (3,4). This report describes the frequency of individual Zika-associated brain and eye defects among infants from pregnancies with laboratory evidence of confirmed or possible Zika virus infection. Among 6,799 live-born infants in USZPIR born during December 1, 2015-March 31, 2018, 4.6% had any Zika-associated birth defect; in a subgroup of pregnancies with a positive nucleic acid amplification test (NAAT) for Zika virus infection, the percentage was 6.1% of live-born infants. The brain and eye defects most frequently reported included microcephaly, corpus callosum abnormalities, intracranial calcification, abnormal cortical gyral patterns, ventriculomegaly, cerebral or cortical atrophy, chorioretinal abnormalities, and optic nerve abnormalities. Among infants with any Zika-associated birth defect, one third had more than one defect reported. Certain brain and eye defects in an infant might prompt suspicion of prenatal Zika virus infection. These findings can help target surveillance efforts to the most common brain and eye defects associated with Zika virus infection during pregnancy should a Zika virus outbreak reemerge, and might provide a signal to the reemergence of Zika virus, particularly in geographic regions without ongoing comprehensive Zika virus surveillance., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Amanda Elmore reports support from the Florida Birth Defects Registry, Surveillance, Intervention, and Referral to Services for Infants with Microcephaly or Other Adverse Outcomes linked with the Zika Virus in Florida. Jane Fornoff reports that she is vice-chair of the Illinois Department of Public Health’s Institutional Review Board. Nicole D. Longcore reports grant support from Epidemiology and Laboratory Capacity for Infectious Diseases. Amy E. Nance reports that the is co-chair for Communication and Health Promotion of the National Birth Defect Prevention Network. Brennan Martin reports being a member-at-large for the National Birth Defect Prevention Network (2019). No other potential conflicts of interest were disclosed.