Zika virus infection in pregnancy and adverse fetal outcomes in São Paulo State, Brazil: a prospective cohort study

Abstract

Robust epidemiological and biological evidence supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. However, it remains uncertain if ZIKV infection in pregnancy also increases the risk for other adverse fetal and birth outcomes. In a prospective cohort study we investigated the influence of ZIKV on the prevalence of prematurity, low birth weight, small-for-gestational-age, and fetal death as well as microcephaly (i.e., overall and disproportionate) in the offspring of women attending a high-risk pregnancy clinic during the recent ZIKV outbreak in Brazil. During the recruitment period (01 March 2016–23 August 2017), urine samples were tested for ZIKV by RT-PCR from all women attending the high-risk pregnancy clinic at Jundiaí University Hospital and from the neonates after delivery. Of the 574 women evaluated, 44 (7.7%) were ZIKV RT-PCR positive during pregnancy. Of the 409 neonates tested, 19 (4.6%) were ZIKV RT-PCR positive in the first 10 days of life. In this cohort, maternal ZIKV exposure was not associated with increased risks of prematurity, low birth weight, small-for-gestational-age, or fetal death. However, relative to ZIKV-negative neonates, ZIKV-positive infants had a five-fold increased risk of microcephaly overall (RR 5.1, 95% CI 1.2–22.5) and a ten-fold increased risk of disproportionate microcephaly (RR 10.3, 95% CI 2.0–52.6). Our findings provide new evidence that, in a high-risk pregnancy cohort, ZIKV RT-PCR positivity in the neonate at birth is strongly associated with microcephaly. However, ZIKV infection during pregnancy does not appear to influence the risks of prematurity, low birth weight, small-for-gestational-age or fetal death in women who already have gestational comorbidities. The results suggest disproportion between neonatal head circumference and weight may be a useful screening indicator for the detection of congenital microcephaly associated with ZIKV infection.

Fetal, neonatal, and infant outcomes associated with maternal Zika virus infection during pregnancy: A systematic review and meta-analysis

“…The variation in the number of pregnant women in the studies ranged from 28 [ 19 ] to 19,963 [ 39 ]. The overall studies were conducted in the Americas: Brazil [ 25 , 26 , 29 , 33 , 34 , 38 ], Puerto Rico [ 18 ], United States of America (USA) [ 19 , 21 , 22 , 24 , 35 , 37 , 40 ], Peru [ 30 ], French territories of the Americas: French Guiana, Guadeloupe and Martinique [ 20 , 36 ] and Colombia [ 23 , 27 , 28 , 39 ]. Quality scores for the studies are available in S3 Table .…”

“…In nine studies, only symptomatic pregnant women were included [ 23 , 25 , 27 – 29 , 33 , 34 , 36 , 40 ], in the other 12 studies, both symptomatic and asymptomatic pregnant women were included. Only four studies had a control group with pregnant women without ZIKV infection [ 19 , 20 , 26 , 34 ], with different bivariate analysis methods used. The pregnant women included in the studies were infected with ZIKV in different trimesters of pregnancy.…”

“…The pregnant women included in the studies were infected with ZIKV in different trimesters of pregnancy. Only six studies described the trimester of ZIKV infection [ 20 , 24 , 26 , 33 , 34 , 36 ]. The analysis of potential confounding factors was performed in a few cohorts such as serology for dengue and Chikungunya [ 18 , 34 ], other serologies [ 36 ], maternal comorbidities [ 26 , 34 ] and sociodemographic data [ 19 , 20 , 26 , 30 , 34 , 36 ].…”

Knowledge of Zika Virus Transmission and Its Prevention among High-Risk Pregnant Women in Brazil

“…We conducted a cross-sectional study, part of the Thematic Project: “Vertical infection by the ZIKA virus and its impact on the mother-child area”, a Cohort Study that recruited women with high-risk pregnancies between March 2016 and August 2017 [ 23 , 24 ]. The inclusion criteria were (1) high-risk pregnant women, defined as pregnancies more likely to have an adverse outcome due to previous pregnancy loss or preterm delivery, preexisting autoimmune, hormonal or hypertensive conditions, the presence of hormonal, infectious, or hypertensive disorders in the current pregnancy, or maternal age <16 or >35 [ 25 ], (2) participation in the Thematic Project, and (3) residents of Jundiaí.…”

COVID-19 in comparison with other emerging viral diseases: risk of geographic spread via travel

“…The Zika epidemic presents the first ever known association between a flavivirus, carried by the Aedes aegypti mosquito, and congenital disease. The congenital disease most closely linked to the Zika virus in the 2015 epidemic was microcephaly where the occipitofrontal head circumference is smaller than 98% of all newborns, but many more neurodevelopmental anomalies were observed [ 95 , 96 ]. Mortality in adults is extremely low.…”