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.
Highlights
Zika Virus (ZIKV) has been detected sporadically in entomological and immunologic surveillance studies across Africa and Southeast Asia since the 1 950s1,2
Case control study evidence from Recife in the Northeast of Brazil has shown that intra-uterine ZIKV exposure is associated with microcephaly[22,23], and prospective cohort data in symptomatic women with suspected ZIKV in Rio de Janeiro have shown an association between congenital ZIKV infection and abnormal neurological examination and/or brain imaging at birth[24,25], Studies quantifying the risk of other adverse fetal outcomes associated with ZIKV infection during pregnancy are lacking
For the purposes of answering this particular study question, twin pregnancies and 15 women who were recruited because of suspected ZIKV infection but who did not have other risk factors were excluded from the analysis
Summary
Zika Virus (ZIKV) has been detected sporadically in entomological and immunologic surveillance studies across Africa and Southeast Asia since the 1 950s1,2 This mosquito-borne infection, which was previously considered to cause only mild disease[3], spread to the Americas in 20144,5. Case control study evidence from Recife in the Northeast of Brazil has shown that intra-uterine ZIKV exposure is associated with microcephaly[22,23], and prospective cohort data in symptomatic women with suspected ZIKV in Rio de Janeiro have shown an association between congenital ZIKV infection and abnormal neurological examination and/or brain imaging at birth[24,25], Studies quantifying the risk of other adverse fetal outcomes (i.e., prematurity, low birth weight, small-for-gestational age, and fetal death) associated with ZIKV infection during pregnancy are lacking. Differentiation between proportionate and disproportionate microcephaly (i.e., disproportion between neonatal head circumference and weight) has been made in some ZIKV s tudies[25,30], its importance in helping to characterise the Congenital Zika Syndrome has still not been established
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