Functional Outcomes among a Cohort of Children in Northeastern Brazil Meeting Criteria for Follow-Up of Congenital Zika Virus Infection

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.

Early Growth Parameters as Predictors of Developmental Delay among Children Conceived During the 2015–2016 Zika Virus Outbreak in Northeastern Brazil

“…Our results illustrate that early growth parameters are predictive of developmental delay among children conceived during a Zika virus outbreak and likely exposed to Zika virus in utero, who met anthropometric and/or laboratory criteria for Zika virus infection [ 24 ]. Identifying whether children without the Zika-specific phenotype were congenitally infected with Zika virus was challenging, and prevented the specific attribution of observed early growth patterns to Zika virus infection.…”

“…For the ZODIAC follow-up investigation, eligibility was restricted to children living in macroregions 1 and 2 of Paraíba state because of logistical constraints. The mothers of infants in the case group had to have resided in Paraíba state for 80% of their pregnancy [ 24 ]. Children included in the earlier case-control study were eligible for the ZODIAC follow-up investigation if they met the following anthropometric or laboratory criteria: Laboratory: non-negative test for Zika-specific neutralizing antibodies in an infant sample, and/or Anthropometric: met case-control study criteria for assignment to the microcephaly, small, or disproportionate group [ 23 ], as defined above.…”

Case Fatality Rate Related to Microcephaly Congenital Zika Syndrome and Associated Factors: A Nationwide Retrospective Study in Brazil †

“…Congenital microcephaly is characterized by the reduction greater than −2 standard deviations from the mean adjusted for gestational age, in the fetuses and newborn's head circumference, which may be accompanied by abnormal brain development that causes complications such as delayed physical, neuromotor and cognitive development [7][8][9][10][11]. In addition, congenital ZIKV infection can cause several other damages, such as craniofacial disproportion, dysphagia, hyper-reflexia, spasticity, seizures, arthrogryposis, low birth weight and prematurity, among others [12][13][14][15][16]. Therefore, this spectrum makes it possible to recognize a new congenital syndrome that came to be named microcephaly/congenital Zika syndrome (microcephaly/CZS) [17][18][19].…”

Cross-sectional study of the anthropometric characteristics of children with congenital Zika syndrome up to 12 months of life

“…The long-term effects on the growth and development of children with congenital ZIKV exposure are not yet well known. So far, some of the main reported clinical abnormalities are low birth weight, arthrogryposis, heart disease, microcephaly with a specific pattern of brain damage, delay in neuromotor and cognitive development, impaired vision and hearing, seizures, dysphagia and failure to thrive [3][4][5][6][7].…”