Abstract

.Following the large outbreak of Zika virus in the Western Hemisphere, many infants have been born with congenital Zika virus infection. It is important to describe the functional outcomes seen with congenital infections to allow for their recognition and appropriate interventions. We evaluated 120 children conceived during the 2015–2016 Zika virus outbreak in Paraíba, Brazil, who were approximately 24 months old, to assess functional outcomes. All children met either anthropometric criteria or laboratory criteria suggestive of possible congenital Zika virus infection. We collected results of previous medical evaluations, interviewed parents, and performed physical examinations and functional assessments, for example, the Hammersmith Infant Neurological Examination (HINE). We compared patterns of neurologic outcomes and developmental delay at age 24 months by whether children met anthropometric or laboratory criteria, or both. Among children meeting both criteria, 60% (26/43) were multiply affected (had severe motor impairment, severe developmental delay, and suboptimal HINE scores), compared with 5% (3/57) meeting only laboratory criteria and none (0/20) meeting only anthropometric criteria. Of the remaining 91 children, 49% (45) had developmental delay, with more severe delay seen in children meeting both criteria. Although children meeting physical and laboratory criteria for potential congenital Zika virus infection were more severely affected, we did identify several children with notable adverse neurologic outcomes and developmental delay with no physical findings but potential laboratory evidence of Zika virus infection. Given this, all children who were potentially exposed in utero to Zika virus should be monitored in early childhood for deficits to allow for early intervention.

Highlights

  • Zika virus is believed to have been introduced in Brazil in 2013.1–3 it was not until August 2015, when healthcare providers in the state of Pernambuco noticed an unusual increase in newborns with microcephaly, that Zika virus was identified to cause congenital infections with serious outcomes.[4]

  • We found that 5% of children without physical findings but with some potential laboratory evidence of Zika virus infection had adverse neurologic outcomes and developmental delay

  • The fact that 37 of 100 children with some laboratory evidence of Zika virus infection in our study had neither developmental delay nor adverse neurologic outcomes suggests that either some children infected with Zika virus may not develop the functional outcomes we studied or the neutralizing antibodies detected in the children were only from the maternal transfer of these antibodies

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Summary

Introduction

Zika virus is believed to have been introduced in Brazil in 2013.1–3 it was not until August 2015, when healthcare providers in the state of Pernambuco noticed an unusual increase in newborns with microcephaly, that Zika virus was identified to cause congenital infections with serious outcomes.[4]. The increased incidence of severe microcephaly that first brought Zika virus to attention in Brazil has been likened to “the tip of the iceberg,”[16,17] yet the size and hallmarks of the rest of the presumed iceberg have been difficult to ascertain in part because of diagnostic challenges.[18] Aragao et al.[17] used neuroimaging to describe a spectrum of congenital infections that includes three levels of severity: microcephaly at birth, postnatal microcephaly, and without microcephaly. Other research suggests the possibility of impaired health and development in children without obvious manifestations of congenital infection at birth.[11,12] Subtle and delayed findings have been identified with congenital Zika virus infection, but their relation to functional deficits is unclear. Few studies have investigated functional outcomes of congenital Zika virus exposure among children aged 12 months or older, born with or without birth

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