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