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

Coutinho, Conrado Milani; de Moura Negrini, Silvia Fabiana Biason; de Almeida E Araujo, Daniel Cardoso; Teixeira, Sara Reis; Amaral, Fabiana Rezende; Moro, Marília Carolina Razera; Fernandes, Juliana Dias Crivelenti Pereira; da Motta, Márcia Soares Freitas; de Moura Negrini, Bento Vidal; Caldas, Carla Andréa Cardoso Tanuri; Anastasio, Adriana Ribeiro Tavares; Furtado, João Marcello; Bárbaro, Adriana Aparecida Tiraboschi; Yamamoto, Aparecida Yulie; Duarte, Geraldo; Mussi-Pinhata, Marisa Márcia

OBJECTIVE To define the prevalence of adverse outcomes 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's private and public health facilities. POPULATION Symptomatic ZIKV-infected mothers and their infants. METHODS Prenatal/early neonatal data were obtained for all mother-child pairs. A subgroup of infants had cranial ultrasonography, eye fundoscopy, hearing and neurological examinations, and Bayley III screening tests within three months of age. MAIN OUTCOME MEASURES Prevalence of pregnancy losses and anomalies detected at birth or within three months according to the gestational age of infection. RESULTS Overall, 511 ZIKV-infected women were identified from a total of 1116 symptomatic women; as there were two twins, there were a total of 513 fetuses included. In total, 13 of these 513 (2.5%;95%CI:1.5-4.3) presented with major signs of congenital Zika syndrome (CZS). Of the 511 women there were 489 livebirths and 24 (4.7%) pregnancy losses (20 miscarriages and 4 stillbirths). ZIKV-related anomalies occurred in the offspring of 42/511(8.2%) mothers. Microcephaly or other CNS malformations were diagnosed in 1/4 (25.0%) stillbirths and in 19/489(3.9%;95% CI:2.5-5.9) of the live-born infants. Fetal abnormalities were 14.0 (95%CI:7.6-26.0) times more likely with gestational infection occurring in ≤11 weeks. On follow up of 280 asymptomatic infants, 2/155(1.3%) had eye abnormalities, 1/207(0.5%) had CNS imaging findings, and 16/199(8%) presented neurological alert signs. CONCLUSIONS This prospective population-based study represents the largest Brazilian cohort study 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 three months of age.