Risk of adverse outcomes in offspring with RT-PCR confirmed prenatal Zika virus exposure: An individual participant data meta-analysis of 13 cohorts in the Zika Brazilian Cohorts Consortium

Abstract

Background: Knowledge regarding the risks associated with Zika virus (ZIKV) infections in pregnancy has relied on individual studies with relatively small sample sizes and variable risk estimates of adverse outcomes, or on surveillance or routinely collected data. Using data from the Zika Brazilian Cohorts Consortium, this study aims, to estimate the risk of adverse outcomes among offspring of women with RT-PCR-confirmed ZIKV infection during pregnancy and to explore heterogeneity between studies.

Methods: We performed an individual participant data meta-analysis of the offspring of 1548 pregnant women from 13 studies, using one and two-stage meta-analyses to estimate the absolute risks.

Findings: Of the 1548 ZIKV-exposed pregnancies, the risk of miscarriage was 0.9%, while the risk of stillbirth was 0.3%. Among the pregnancies with liveborn children, the risk of prematurity was 10,5%, the risk of low birth weight was 7.7, and the risk of small for gestational age (SGA) was 16.2%. For other abnormalities, the absolute risks were: 2.6% for microcephaly at birth or first evaluation, 4.0% for microcephaly at any time during follow-up, 7.9% for neuroimaging abnormalities, 18.7% for functional neurological abnormalities, 4.0% for ophthalmic abnormalities, 6.4% for auditory abnormalities, 0.6% for arthrogryposis, and 1.5% for dysphagia. This risk was similar in all sites studied and in different socioeconomic conditions, indicating that there are not likely to be other factors modifying this association.

Interpretation: This study based on prospectively collected data generates the most robust evidence to date on the risks of congenital ZIKV infections over the early life course. Overall, approximately one-third of liveborn children with prenatal ZIKV exposure presented with at least one abnormality compatible with congenital infection, while the risk to present with at least two abnormalities in combination was less than 1.0%.

Keywords: Adverse outcomes; Children; Cohort; Meta-analysis; Pregnant women; Zika.

Fig. 1

Absolute risk^a of adverse outcomes at delivery or at first evaluation of children born to women with rt-PCR-confirmed ZIKV infections during pregnancy participating in studies of the ZBC-consortium. ^aEstimated using a two-stage random effects meta-analyses with the metaprop STATA command.

Fig. 2

Absolute risk^a of neurological, ophthalmological and audiological adverse outcomes at birth or at first evaluation of children born to women with rt-PCR-confirmed ZIKV infections during pregnancy participating in studies of the ZBC-consortium. ^aEstimated using a two-stage random effects meta-analyses with the metaprop STATA command. ∗median age of 11.7 months; ∗∗median age of 11.2 months; ∗∗∗median age of 6.5 months; ∗∗∗∗median age of 14.9 months.