Relative and attributable risks of neurological and perinatal adverse outcomes among children with and without prenatal Zika virus exposure in Northeast Brazil: A prospective cohort study (2015-2018).

BACKGROUND: Although there has been substantial progress in the characterization of Congenital Zika Syndrome, the lack of a control group in the majority of published studies on Zika virus (ZIKV) infections during pregnancy limits our understanding of, first, the magnitude by which prenatal ZIKV exposure may increase risks of adverse outcomes for offspring and, second, the fraction of abnormalities that are attributable to this exposure. METHODS: To overcome this limitation, this study harmonized and integrated data collected prospectively in Recife, Pernambuco, Brazil, from offspring of ZIKV-exposed women in the Microcephaly Epidemic Research Group (MERG) Pregnant Women Cohort and from offspring of ZIKV-unexposed women in the Zika in Infants and Pregnancy (ZIP) Study. We compared the data to estimate the relative risk (RR) and attributable risk percent (AR%) of: (i) adverse birth outcomes including low birth weight (LBW), prematurity and small for gestational age (SGA) and (ii) developmental abnormalities including microcephaly and neurological, ophthalmological, audiological, and neuroimaging alterations. FINDINGS: We observed similar odds of adverse birth outcomes and ophthalmological deficits in ZIKV-exposed and unexposed children. However, as compared to ZIKV-unexposed children, ZIKV-exposed children presented with markedly increased risks of microcephaly (RR, 95%-CI: 3.61, 1.70 to 7.63 AR 72%), neurological abnormalities (RR, 95%-CI: 5.64, 3.04 to 10.47.79AR 82%), audiological screening failures (RR, 95%-CI: 9.20, 2.59 to 32.69 AR 89%), and neuroimaging abnormalities (RR, 95%-CI: 22.06, 2.90 to 167.5; AR 95%). The risk of having concurrent abnormalities was lower than the risk of having just one abnormality. Our results provide new insights into the relative and attributable risks related to prenatal ZIKV exposure and demonstrate that, overall, the risks of congenital abnormalities are elevated among children exposed to ZIKV during pregnancy compared to their ZIKV-unexposed peers.