Zika virus infection in pregnancy and its fetomaternal repercussions: findings from a prospective cohort study in São Paulo, Brazil

Not availablePrior to its arrival in The Americas in 2014, Zika Virus was thought to cause only mild disease. Following the outbreak in Brazil and the declaration of a Public Health Emergency of International Concern by WHO in February 2016, epidemiological and biological evidence has been published which supports a causal link between prenatal Zika Virus (ZIKV) infection and congenital brain abnormalities including microcephaly. This doctoral thesis uses data from The Jundiaí Zika Cohort, a prospective pregnancy and birth cohort which was set up in The State of São Paulo in 2016 to investigate this causal hypothesis further. A total of 748 pregnant women were recruited from the high-risk pregnancy clinic at Jundiaí University Hospital in the period March 2016 to August 2017. Baseline sociodemographic and medical data were collected at recruitment. Biological samples (blood, saliva, urine) were collected from women at enrolment and regular intervals throughout pregnancy. Women were asked to report any symptoms consistent with ZIKV infection (as per the WHO clinical case definition) and to attend the hospital to be assessed clinically and for samples to be taken. Further biological specimens (colostrum, umbilical cord, placenta, neonatal blood, saliva, urine and cerebro-spinal fluid when appropriate) were obtained at delivery. Urine samples were processed for ZIKV RT-PCR and the rest of the biological material has been stored in a secure biorepository. Anthropometric measures were obtained from the neonates at birth. After creating the master database and carrying out the first thorough analysis of the dataset, I created a cohort profile manuscript which thoroughly detailed the creation, the specific methodology and the preliminary findings of The Jundiaí Zika Cohort. I then employed a prospective cohort study design to investigate the extent to which specific symptoms can be utilized to differentiate ZIKV-infected pregnant women from those with other pregnancy-related problems. Finally, I compared the prevalence of adverse fetal outcomes (prematurity, low birth weight, small-forgestational- age, fetal death and microcephaly) by prenatal Zika Virus (ZIKV) exposure status. The main findings are that most pregnant women positive for ZIKV in urine are asymptomatic and do not deliver a baby with microcephaly, that physical symptoms alone do not differentiate between high risk pregnant women positive or negative for ZIKV and that current clinical case definitions have a low sensitivity for detecting ZIKVpositive women living in active ZIKV transmission areas. In addition, ZIKV infection in high risk pregnant women substantially increases the risk of disproportionate microcephaly but not other adverse fetal outcomes. As a result of this research, we propose clinical case definitions for use in pregnant women living in areas with active ZIKV transmission be revised and that disproportion between head circumference and weight during fetal development should be considered as a diagnostic tool for the presence of a ZIKV-infected fetus