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

Abstract

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 3 months of age.

Main outcome measures: Prevalence of pregnancy losses and anomalies detected at birth or within 3 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. Of these, 13 (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 four 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 liveborn 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 association between the gestational age of infection (≤11 weeks) and a poorer early infant prognosis. A notable proportion of apparently asymptomatic newborns can present with subclinical findings within 3 months of age.

Tweetable abstract: ZIKV and pregnancy: adverse outcomes are less common, more prevalent for first-trimester infections, and potentially subclinical.

Keywords: Adverse outcomes; Zika virus; congenital Zika syndrome; infant; pregnancy.