Strengths and limitations
To the best of our knowledge, this study is the most extensive Brazilian
cohort study of women with confirmed ZIKV infection during gestation.
There are few large cohorts with robust estimates regarding ZIKV impact
on pregnancy losses and fetal malformations. Two early studies of
Brazilian cohorts reported very diverse results: -a high prevalence
(42%) of abnormal clinical or imaging findings distributed across
trimesters of maternal infection3; or -no microcephaly
but minor ultrasonography findings aside from ophthalmologic and/or
hearing loss in a third of infants8. It is possible
that referral bias, the relatively small number of mother-infant pairs,
and an extensive definition of adverse outcomes might have contributed
to the overestimation of the reported effects. Our results were
generated in a much more representative sample of the total population
once it contained all pregnant women with confirmed symptomatic ZIKV
infection living in a distinct geographic region. We used stricter
definitions of abnormalities potentially related to ZIKV infection,
systematically approached the gestational age of the maternal ZIKV
infection as a continuous variable and explored additional etiologies
for abnormal infants’ findings.
Our cohort set up which allowed obtaining birth data for all of the
women with confirmed infection and evaluate most of their infants during
the epidemics may be a model to investigate infection-related morbidity
in other epidemics such as COVID-19. Further, it demonstrates the need
to analyze the gestational age of infection to guide better clinical
practice for ZIKV maternal infection and the importance of long-term
follow-up for exposed infants, as known for other congenital infections.
Our study does have limitations. Only symptomatic women were selected,
and not all infants were followed from birth. Nevertheless, its size is
comparable to other country-specific studies, and it contained perinatal
outcome data for all women with confirmed ZIKV infection. Infant
findings potentially related to ZIKV infection were only considered
after ruling out other conditions with a large subgroup of infants
having complete clinical, neurological, and brain imaging data. Our
results likely reflect the real effect of the maternal ZIKV-symptomatic
infection in this population.