Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of ZIKA Virus Infection in Gestation (NATZIG) cohort study

Abstract

Objective: To define the prevalence of adverse outcomes according to the gestational age of maternal infection in a large cohort of ZIKV-infected Brazilian women and their infants. Design: Prospective, population-based cohort study. Setting: Ribeirão Preto's region private and public health facilities. Population: All pregnant women with confirmed ZIKV-infection and their infants. Methods: Prenatal/early neonatal data were obtained for all pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing, neurological exam, and Bayley III screening test within 3 months of age. Main Outcome Measures: Prevalence of pregnancy losses, anomalies detected at birth or within 3 months according to the gestational age of infection. Results: 511 women with ZIKV were identified from a total of 1116 women with flavivirus-type symptoms. Pregnancy losses 24/511(4.7%) and/or ZIKV-related anomalies occurred in 43/511(8.4%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4(25.0%) of the stillbirths and 19/489[3.9%;CI95%:2.5-5.9] of the live-born infants, with 13/513[2.5%;CI95%:1.5-4.3] neonates presenting major signs of CZS. Fetal abnormalities were 14.0(CI95%:7.6-26.0) times more likely with gestational infection <11 weeks. Among 280 asymptomatic evaluated infants, 2/155(1.3%) had eye abnormalities, 1/207(0.5%) CNS imaging significant findings, and 16/199(8%) neurological alert signs. Conclusions: This prospective, population-based study represents the largest Brazilian cohort of ZIKV in pregnancy. Congenital anomalies potentially associated with CZS are less frequent than previously thought. There is a strong relationship between the gestational age of infection (<11 weeks) and worse early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age. Funding: FAEPA/SES-SP Manuscript title: Early maternal Zika infection predicts severe neonatal neurological damage: results from the prospective Natural History of ZIKA Virus Infection in Gestation (NATZIG) cohort study.

Brazilian Protocol for Sexually Transmitted Infections 2020: Zika virus infection

“…Even considering the inaccuracies regarding these complications' prevalence, since the real infection incidence is unknown (considering the asymptomatic cases), the causal link between gestational and neurological complications and Zika virus infection has already been scientifically established [41][42][43] . Considering gestational complications, it is estimated that miscarriage rates (1.2% to 3.9 %), eye defects (1.0% to 7.5%), fetal death (0.7% to 1.6%) and malformations (3.1% to 22.8%) are increased due to infection during pregnancy 35,[44][45][46] . The most feared neurological complication in adults is Guillain-Barré syndrome, whose frequency, estimated by meta-analytical studies, ranges from 0.01% to 1.23% 47,48 .…”

“…Embryonic or fetal central nervous system afflicting spectrum causing malformations and its pathogenesis are not yet fully established. It is known that Zika virus presents neural progenitor cells tropism and that, in the embryonic or embryonic/fetal brain, it stops growth, proliferation, migration, and differentiation of neuronal cells, with severe consequences for neurodevelopment 40,[44][45][46]67,68 .…”

Protocolo Brasileiro para Infecções Sexualmente Transmissíveis 2020: infecção pelo vírus Zika

“…41,43 Considerando las complicaciones del embarazo, se estima que las tasas de aborto (1,2% a 3,9% %), defectos oculares (1,0% a 7,5%), óbito fetal (0,7% a 1,6%) y malformaciones (3,1% a 22,8%) aumentan debido a la infección durante el embarazo. 35,[44][45][46] La complicación neurológica más temida en adultos es el síndrome de Guillain-Barré, cuya frecuencia estimada por estudios metanalíticos oscila entre el 0,01% y el 1,23% . 47,48 Fuente: Informaciones numéricas retiradas de las referencias 9, 10, 11 y 12.…”

“…Se sabe que el virus Zika tiene tropismo por las células progenitoras neuronales y que, en el cerebro embrionario o embrionario/fetal, detiene el crecimiento, la proliferación, la migración y la diferenciación de células neuronales, con graves consecuencias para el neurodesarrollo. 40,[44][45][46]67,68 Cuando la infección ocurre durante el primer y el segundo trimestre del embarazo, existe un mayor riesgo de anomalías estructurales del sistema nervioso central del embrión y del feto. Estas infecciones presentan frecuentemente un cuadro variado de cambios anatómicos, que resultan en ventriculomegalia, calcificaciones intracraneales y microcefalia.…”

“…Geraldo Duarte y colaboradoreselectroencefalográficas y convulsiones, entre otros problemas de salud 45. Solamente estudios de los niños expuestos al virus Zika en la vida intrauterina puede respaldar una comprensión más amplia del síndrome congénito del virus Zika 70.…”