Neurodevelopment in Children Exposed to Zika in utero: Clinical and Molecular Aspects

Abstract

Five years after the identification of Zika virus as a human teratogen, we reviewed the early clinical manifestations, collectively called congenital Zika syndrome (CZS). Children with CZS have a very poor prognosis with extremely low performance in motor, cognitive, and language development domains, and practically all feature severe forms of cerebral palsy. However, these manifestations are the tip of the iceberg, with some children presenting milder forms of deficits. Additionally, neurodevelopment can be in the normal range in the majority of the non-microcephalic children born without brain or eye abnormalities. Vertical transmission and the resulting disruption in development of the brain are much less frequent when maternal infection occurs in the second half of the pregnancy. Experimental studies have alerted to the possibility of other behavioral outcomes both in prenatally infected children and in postnatal and adult infections. Cofactors play a vital role in the development of CZS and involve genetic, environmental, nutritional, and social determinants leading to the asymmetric distribution of cases. Some of these social variables also limit access to multidisciplinary professional treatment.

The Alberta Infant Motor Scale: A tool for the assessment of motor aspects of neurodevelopment in infancy and early childhood

“…Moreover, 35 of 39 participants met the criteria for the diagnosis of cerebral palsy (CP) ( 32 ). The current prevalence of CP in children infected by the Zika virus prenatally is about 80–100 % ( 33 ). CP related to Zika virus infection is thought to stem from prenatal brain abnormalities (microcephaly is the most prominent one) ( 33 ).…”

“…The current prevalence of CP in children infected by the Zika virus prenatally is about 80–100 % ( 33 ). CP related to Zika virus infection is thought to stem from prenatal brain abnormalities (microcephaly is the most prominent one) ( 33 ). The clinical manifestation of CP in this group has been characterized as an occurrence of hypertonia, spasticity, and hyperreflexia related to pyramidal tract involvement during the first months of life and extrapyramidal signs, such as dystonia and dyskinetic movements observed in the second year ( 33 ).…”

Drosophila as a Model for Human Viral Neuroinfections

“…Viral infections can trigger neurodevelopmental disturbances [ 182 ]; one that has recently received much attention has been those reported following Zika virus infection. ZIKV infection in pregnant women can cause microcephaly (a birth defect resulting in smaller than typical head size and brain atrophy) in newborns [ 183 ]. Drosophila have been a useful model to assess why amongst Flaviviruses, ZIKV drives microcephaly pathology.…”

Early and mid-gestation Zika virus (ZIKV) infection in the olive baboon (Papio anubis) leads to fetal CNS pathology by term gestation

“…Studies show poor developmental prognosis for children with CZS including severe developmental injuries by 30 months of age [ 7 ] and below average neurodevelopmental assessment (cognitive, language, motor, autism spectral disorder) between 7 and 32 months of age [ 8 ]. Neurological impairment, including development of microcephaly in infants born with normal head circumference, have also been reported in infants born without clinical abnormalities [ 9 , 10 ] [ 11 , 12 ]. In the USA, 9% of children born to ZIKV infected mothers were reported to have at least one neurodevelopmental abnormality prior to 2 years of age [ 13 ].…”