Congenital cerebral malformations and dysfunction in fetuses and newborns following the 2013 to 2014 Zika virus epidemic in French Polynesia

Abstract

We detected an unusual increase in congenital cerebral malformations and dysfunction in fetuses and newborns in French Polynesia, following an epidemic of Zika virus (ZIKV), from October 2013 to March 2014. A retrospective review identified 19 cases, including eight with major brain lesions and severe microcephaly, six with severe cerebral lesions without microcephaly and five with brainstem dysfunction without visible malformations. Imaging revealed profound neurological lesions (septal and callosal disruption, ventriculomegaly, abnormal neuronal migration, cerebellar hypoplasia, occipital pseudocysts, brain calcifications). Amniotic fluid was drawn from seven cases at gestation weeks 20 to 29. ZIKV RNA was detected by RT-PCR and infectious ZIKV isolates were obtained in four of five microcephalic, but not in two non-microcephalic cases with severe brain lesions. Medical termination of pregnancy was performed in eleven cases; two cases with brainstem dysfunction died in the first months of life; six cases are alive, with severe neurological impairment. The results show that four of seven tested fetuses with major neurological injuries were infected with ZIKV in utero. For other non-microcephalic, congenital abnormalities we were not able to prove or exclude ZIKV infection retrospectively. The unusual occurrence of brain malformations or dysfunction without microcephaly following a ZIKV outbreak needs further studies.

Possible Zika Virus Infection Among Pregnant Women — United States and Territories, May 2016

“…Case reports indicate that fetuses and infants of pregnant women with asymptomatic Zika virus infection might be at risk for microcephaly and other severe brain defects (9,10). Following pregnant women with laboratory evidence of possible Zika virus infection in the surveillance system, regardless of symptoms, allows better characterization of the full impact and consequences of infection to the mother and her offspring, and might allow for better stratification of risk for adverse congenital outcomes (1).…”

Zika virus: what do we know about the viral structure, mechanisms of transmission, and neurological outcomes?

“…Hydranencephaly, intracranial calcifications, destructive lesions of the posterior fossa, hydrothorax, ascites, subcutaneous edema, and arthrogryposis have been described in severe cases (68) (69) . It is important to rule out other infectious agents that are known to induce microcephaly (38) (70) before ascribing it to Zika virus infection.…”

Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia

“…The spectrum of disease caused by Zika virus among adults and children is still being investigated and defined, but it is clear in the most recent epidemic in South and Central America, Mexico, and the Caribbean islands that when infection occurs in pregnant women, fetuses appear to be at increased risk for a poor clinical outcome. [2][3][4][5][6][7][8][9] The most significant effect of the Zika virus on the fetus is the occurrence of neuronal necrosis and microcephaly-this has been demonstrated in neuroimaging studies performed both before delivery and following the birth of infected infants. 2,3,7 Pathology studies have been shown to be an important component of the public health investigation of emerging infections, contributing to the understanding of the mechanisms of tissue injury, for example, human immunodeficiency virus, Ebola virus, hantavirus, West Nile virus, and many others.…”