Association Between Antenatal Exposure to Zika Virus and Anatomical and Neurodevelopmental Abnormalities in Children.

Importance: Zika virus (ZIKV) is a mosquito-borne flavivirus recognized as teratogenic since the 2015 to 2016 epidemic. Antenatal ZIKV exposure causes brain anomalies, yet the full spectrum has not been delineated. Objective: To characterize the clinical features of ZIKV infection at a pediatric referral center in Rio de Janeiro, Brazil, among children with antenatal ZIKV exposure. Design, Setting, and Participants: Retrospective cohort study conducted from May to July 2019 of a prospective cohort of 296 infants with antenatal ZIKV exposure followed up since December 2015 at a tertiary maternity-pediatric hospital. Exposures: Zika virus infection during pregnancy. Main Outcomes and Measures: Characterization of clinical features with anthropometric, neurologic, cardiologic, ophthalmologic, audiometric, and neuroimaging evaluations in infancy and neurodevelopmental assessments (Bayley Scales of Infant and Toddler Development, Third Edition) from 6 to 42 months of age, stratified by head circumference at birth (head circumference within the reference range, or normocephaly [NC] vs microcephaly [MC]). Results: Antenatal exposure to ZIKV was confirmed for 219 of 296 children (74.0%) referred to Instituto Fernandes Figueira with suspected ZIKV infection through positive maternal or neonatal polymerase chain reaction analysis or IgM serology results. Of these children, 110 (50.2%) were boys, ages ranged from 0 to 4 years, and 53 (24.2%) had congenital microcephaly. The anomalies observed in ZIKV-exposed children with MC or NC were failure to thrive (MC: 38 of 53 [71.7%]; NC: 73 of 143 [51.0%]), cardiac malformations (MC: 19 of 46 [41.3%]; NC: 20 of 100 [20.0%]), excess nuchal skin (MC: 16 of 22 [72.7%]; NC: 35 of 93 [37.6%]), auditory abnormalities (MC: 13 of 50 [26.0%]; NC: 14 of 141 [9.9%]), and eye abnormalities (MC: 42 of 53 [79.2%]; NC: 28 of 158 [17.7%]). Although they experienced fewer neurologic abnormalities than children born with MC, those with NC also had frequent neurologic abnormalities (109 of 160 [68.1%]), including hyperreflexia (36 of 136 [26.5%]), abnormal tone (53 of 137 [38.7%]), congenital neuromotor signs (39 of 93 [41.9%]), feeding difficulties (15 of 143 [10.5%]), and abnormal brain imaging results (44 of 150 [29.3%]). Among 112 children with NC with Bayley-III evaluations, 72 (64.3%) had average or above-average scores; 30 (26.8%) scored 1 SD below average in at least 1 domain; and 10 (8.9%) scored 2 SD below average in at least 1 domain. Among 112 children with NC, a smaller head circumference at birth was significantly associated with subsequent below-average cognitive scores (U = 499.5; z = -2.833; P = .004) and language scores (U = 235.5; z = -2.491; P = .01). Conclusions and Relevance: Children without MC who were exposed to ZIKV in utero had a high frequency of anatomical and neurodevelopmental abnormalities. The head circumference at birth for children with NC was associated with neurocognitive development. Recognition of the wide spectrum of clinical phenotypes is critical to ensure early referral to rehabilitative interventions.

Early Clinical Infancy Outcomes for Microcephaly and/or Small for Gestational Age Zika-Exposed Infants.

BACKGROUND: Zika-exposed infants with microcephaly (proportional or disproportional) and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.Antenatal Zika virus (ZIKV) exposure may lead to adverse infant outcomes including microcephaly and being small for gestational age (SGA). ZIKV-exposed infants with a diagnosis of microcephaly (proportional [PM] or disproportional [DM]) or SGA at birth were evaluated with anthropometric measurements and health outcomes. METHODS: Infants had laboratory-confirmed ZIKV exposure in Brazil. PM, DM, or SGA classification was based on head circumference and weight. First-year growth parameters and clinical outcomes were recorded with analyses performed. RESULTS: Among the 156 ZIKV-exposed infants, 14 (9.0%) were SGA, 13 (8.3%) PM, 13 (8.3%) DM, and 116 (74.4%) were neither SGA nor had microcephaly (NSNM). High rates of any neurologic, ophthalmologic, and hearing abnormalities were observed for PM (100%), DM (100%), and SGA (42.9%) vs NSNM infants (18.3%; P <.001); odds ratio [OR], 3.4 (95% confidence interval [CI], 1.1-10.7) for SGA vs NSNM. Neuroimaging abnormalities were seen in 100% of PM and DM and in 42.9% of SGA vs NSNM infants 16%; (P <.001); OR 3.9 (95% CI, 1.2-12.8) for SGA vs NSNM. Growth rates by z score, particularly for microcephaly infants, were poor after birth but showed improvement beyond 4 months of life. CONCLUSIONS: ZIKV-exposed infants with microcephaly (PM and DM) had similarly high rates of adverse outcomes but showed improvement in growth measurements beyond 4 months of life. While SGA infants had fewer adverse outcomes compared with microcephaly infants, notable adverse outcomes were observed in some; their odds of having adverse outcomes were 3 to 4 times greater compared to NSNM infants.Zika-exposed infants with microcephaly, irrespective of being proportional or disproportional, and those who are small for gestational age without microcephaly should be closely followed, particularly their growth trajectories. They are at high risk of adverse outcomes in the first year of life.