Congenital Zika Virus Infection: Beyond Neonatal Microcephaly.
OBJECTIVE
Recent studies have reported an increase in the number of fetuses and neonates with microcephaly whose mothers were infected with the Zika virus (ZIKV) during pregnancy. To our knowledge, most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects.


OBJECTIVE
To describe the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurological damage associated with ZIKV infection in Brazil.


METHODS
We observed 11 infants with congenital ZIKV infection from gestation to 6 months in the state of Paraíba, Brazil. Ten of 11 women included in this study presented with symptoms of ZIKV infection during the first half of pregnancy, and all 11 had laboratory evidence of the infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by magnetic resonance imaging. Histopathological analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis.


METHODS
Description of the major lesions caused by ZIKV congenital infection.


RESULTS
Of the 11 infants, 7 (63.6%) were female, and the median (SD) maternal age at delivery was 25 (6) years. Three of 11 neonates died, giving a perinatal mortality rate of 27.3%. The median (SD) cephalic perimeter at birth was 31 (3) cm, a value lower than the limit to consider a microcephaly case. In all patients, neurological impairments were identified, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence (ie, arthrogryposis). Results of limited testing for other causes of microcephaly, such as genetic disorders and viral and bacterial infections, were negative, and the ZIKV genome was found in both maternal and neonatal tissues (eg, amniotic fluid, cord blood, placenta, and brain). Phylogenetic analyses showed an intrahost virus variation with some polymorphisms in envelope genes associated with different tissues.


CONCLUSIONS
Combined findings from clinical, laboratory, imaging, and pathological examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported. The term congenital Zika syndrome is preferable to refer to these cases, as microcephaly is just one of the clinical signs of this congenital malformation disorder.
Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Adriana Suely de Oliveira
AS
Melo
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Renato Santana
RS
Aguiar
Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil6Universidade Federal de Campina Grande, Paraíba, Brazil.
Melania Maria Ramos
MM
Amorim
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Monica B
MB
Arruda
Instituto de Pesquisa Professor Amorim Neto (IPESQ), Campina Grande, Paraíba, Brazil2Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil.
Fabiana de Oliveira
FO
Melo
Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil3Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil.
Suelem Taís Clementino
ST
Ribeiro
Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Alba Gean Medeiros
AG
Batista
Universidade Federal de Campina Grande, Paraíba, Brazil.
Thales
T
Ferreira
Instituto de Saúde Elpidio de Almeida, Campina Grande, Paraíba, Brazil.
Mayra Pereira
MP
Dos Santos
Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Virgínia Vilar
VV
Sampaio
Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Sarah Rogéria Martins
SR
Moura
Faculdade de Ciências Médicas de Campina Grande, Campina Grande, Paraíba, Brazil4Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Luciana Portela
LP
Rabello
Hospital Municipal Pedro I, Campina Grande, Paraíba, Brazil.
Clarissa Emanuelle
CE
Gonzaga
Division of Ultrasound in Obstetrics and Gynecology, Lis Maternity Hospital, Tel Aviv Sourasky Medical Center, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Gustavo
G
Malinger
Fundação de Medicina Fetal Latino Americana, Campinas, São Paulo, Brazil.
Renato
R
Ximenes
Fundação Instituto de Pesquisa e Ensino de Diagnostico por Imagem, Universidade Federal de São Paulo, São Paulo, Brazil.
Patricia Soares
PS
de Oliveira-Szejnfeld
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil11Instituto D'Or de Pesquisa e Ensino, Rio de Janeiro, Rio de Janeiro, Brazil.
Fernanda
F
Tovar-Moll
Laboratório de Neuropatologia do Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
Leila
L
Chimelli
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Paola Paz
PP
Silveira
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Rodrigo
R
Delvechio
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Luiza
L
Higa
Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
Loraine
L
Campanati
Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Rita M R
RM
Nogueira
Laboratório de Flavivírus, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, Rio de Janeiro, Brazil.
Ana Maria Bispo
AM
Filippis
Departamento de Diagnóstico por Imagem, Universidade Federal de São Paulo, São Paulo, Brazil.
Jacob
J
Szejnfeld
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Carolina Moreira
CM
Voloch
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Orlando C
OC
Ferreira
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Rodrigo M
RM
Brindeiro
Departamento de Genética, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Rio de Janeiro, Brazil.
Amilcar
A
Tanuri
D000015:Abnormalities, Multiple / Q000209:etiology; D001176:Arthrogryposis / Q000209:etiology*; D001938:Brazil; D002531:Cerebellum / Q000473:pathology; D054022:Cerebrum / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006849:Hydrocephalus / Q000209:etiology*; D007223:Infant; D066088:Infant Death; D007231:Infant, Newborn; D054082:Lissencephaly / Q000209:etiology; D008297:Male; D008831:Microcephaly / Q000209:etiology; D009421:Nervous System Malformations / Q000209:etiology*; D066087:Perinatal Death; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious; D000071244:Zika Virus / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity; D000071243:Zika Virus Infection / Q000150:complications* / Q000151:congenital