An epidemic of Zika virus (ZIKV) infection began in Colombia in October 2015. Previous studies have identified a cause-effect relationship between fetal exposure to the ZIKV and the development of microcephaly and other central nervous system (CNS) anomalies with variable degrees of neurodevelopmental delay. Less is known about the neurodevelopmental outcome of infants without CNS anomalies born to symptomatic ZIKV RT-PCR-positive women. We aimed to compare the neurodevelopmental outcome of these infants to a control group of infants without CNS anomalies born to asymptomatic ZIKV RT-PCR negative women who did not seroconvert during pregnancy. Participating infants were categorized according to ZIKV maternal exposure. Women with symptomatology suggestive of ZIKV infection and a positive RT-PCR for ZIKV were categorized as ZIKV-exposed. Maternal controls (ZIKV unexposed) from the same geographic area were subsequently captured during the tail end of the epidemic through a partner project, the ZIKAlliance, whose aim was to determine the prevalence of ZIKV in pregnant women. Infant survivors from these two groups of pregnant women had a neurodevelopmental evaluation at 12, 18, and 24 months corrected age (CA). The ZIKV-exposed women were found to be older, had less subsidized health care, had a higher percentage of women in middle-class socioeconomic strata, had higher technical and university education, were less likely to be living with a partner, and had higher rates of pregnancy comorbidity and premature births than ZIKV unexposed women. Compared to infants born to ZIKV unexposed women (unexposed), infants born to ZIKV exposed women (exposed) were of lower gestational age and required more speech and occupational therapy services. No differences between groups were observed in the proportion of cut-off scores <70 on the Bayley-III Scale at 12, 18, and 24 months for motor, language, and cognitive domains. When a cut-off of <85 was used, a higher percentage of motor and cognitive impairment was observed in unexposed infants at 12 and 24 months CA, respectively. Median and IQR score on the Bayley-III scale showed higher scores in favor of exposed infants for motor development at 12 and 18 months CA, language at 12 months, and cognitive domain at 12, 18, and 24 months. The adjusted median and IQR compound score of the difference between exposed and unexposed was higher in favor of exposed infants at 12 to 24 months CA for motor (3.8 [95% CI 1.0 to 6.7]) and cognitive domains (10.6 [95% CI 7.3 to 13.9]). We observed no differences in the language domain (1.9 [95% CI -1.2 to 5.0]). We conclude that infants with no evidence of microcephaly or other CNS anomalies born to ZIKV-exposed women had normal neurodevelopment up to 24 months of CA, supporting an all-or-nothing effect with maternal ZIKV exposure. Long-term follow-up to evaluate school performance is required. Clinical Trial Registration: www.clinicaltrials.gov, NCT02943304.

T he emergence of Zika virus (ZIKV) in the Americas has coincided with an abnormal increase in prenatal and neonatal documented cases of microcephaly and other anomalies of the central nervous system (1) These alterations of the brain, along with animal models of vertical transmission of ZIKV, a single-stranded RNA fl avivirus, are evidence of the neurotropic nature of the virus (2-4).Vertical transmission and infection of the fetus during all 3 trimesters of pregnancy with ZIKV has been extensively reported, but little is known about perinatal transmission; only a few cases have been reported (5-8). We report 3 cases of perinatal ZIKV infection during the epidemic of Zika in Colombia and data on the neurodevelopmental outcome at 18 months of age (corrected). The StudyThe Institutional Review Board and Ethics Committee of the Universidad Industrial de Santander approved this study. Formal written consent was obtained from participating women.Case-patient 1 was a 26-year-old pregnant woman in labor who was admitted to the Hospital Universitario de Santander on August 7, 2015, after she reported fever, exanthema (maculopapular rash on the torso), and osteoid-muscular pains (Figure). Her initial hemogram showed mild thrombocytopenia (112,000 platelets/µL; reference range 150,000-400,000 platelets/µL). Test results for syphilis, toxoplasmosis, rubella, cytomegalovirus, herpes simplex virus, varicella zoster virus, and parvovirus B19 during hospitalization were negative, as was a test result for dengue virus (DENV) IgM.A boy was born vaginally at 37 weeks of gestation. Apgar scores were normal. Anthropometric measurements yielded a birthweight of 3.03 kg (32nd percentile), a head circumference (HC) of 32 cm (6th percentile), and a length of 54 cm (99th percentile). Results of a physical examination were unremarkable. The infant was admitted for observation, and cord blood samples were sent to the Instituto Nacional de Salud (INS) for additional testing by reverse transcription PCR (RT-PCR) for DENV and chikungunya virus. On the second day of life, the infant had a distal macular-papular rash with hyperalgesia and mild edema of the hands and feet; a test result for DENV IgM was negative. Hyperthermia developed on the sixth day, and generalized exanthema developed on the seventh day.Because of persistent fever, we initiated a sepsis work-up. Results for initial complete blood count/ differential count, erythrocyte sedimentation rate, blood culture, urine culture, and C-reactive protein were within reference ranges. Fever and exanthema

Transplacental transmission of Zika virus has been reported during all trimesters of pregnancy and might lead to central nervous system anomalies, including microcephaly. We report 3 cases of perinatal Zika infection identified during the epidemic in Colombia and provide detailed descriptions of clinical features, diagnosis, and neurodevelopmental outcome at 18 months of age (corrected).